Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

The improvement of health and social care needs the introduction of shared solution at transnational level. The SI4CARE (Social Innovation for Integrated Health Care) project is a transnational initiative within the Adriatic-Ionian regions aiming to develop strategies to improve the current status of health and social care. The Municipality of Miglierina, a small rural town in Calabria, which is a member the project, is developing a pilot action related to the use of wearable device for monitoring people affected by dementia with the project partner Ra.Gi.. Ra.Gi. is a non-profit organization dedicated to assisting people with dementia in day care centers and so-called dementia-friendly communities. The pilot is based on the use of smart wearable devices to monitor these patients during their daily lifetime. This paper focuses on the design and implementation of the system discussing the proposed application, the strengths and weaknesses. Finally, the possibility of extending the experiment to the other Adriatic-Ionian region is presented.

α-synuclein is a constituent of Lewy bodies and mutations of its gene cause familial PD. A previous study showed that a variant of α-synuclein gene (SNCA), namely the 263bp allele of Rep1 was associated to faster motor progression in PD. On the contrary, a recent report failed to detect a detrimental effect of Rep1 263 on both motor and cognitive outcomes in PD. Aim of this study was to evaluate the influence of the Rep1 variants on disease progression in Parkinson’s Disease (PD) patients. We recruited and genotyped for SNCA-Rep1 426 PD patients with age at onset ≥40 years and disease duration ≥4 years. We then analyzed frequency and time of occurrence of wearing-off, dyskinesia, freezing of gait, visual hallucinations and dementia. SNCA Rep1 263 carriers showed increased risk of both dementia (HR=3.03) and visual hallucinations (HR=2.69) compared to 263 non-carriers. In conclusion, SNCA Rep 1 263 allele is associated to a worst cognitive outcome in PD.

The most common form of mixed dementia (MixD) is constituted by abnormal protein deposits associated with Alzheimer´s disease (AD) that coexist with vascular disease. Although olfactory dysfunction is considered a clinical sign of AD-related de-mentias, little is known about the impact of this sensorial impairment in MixD at molecular level. To address this gap in knowledge, we have assessed olfactory bulb (OB) proteome-wide expression in MixD subjects (n=6) respect to neurologically intact controls (n=7). Around 9% of the quantified proteins were differentially expressed, pinpointing aberrant proteostasis involved in synaptic transmission, nucleoside monophosphate and carbohydrate metabolisms and neuron projection regeneration. In addition, net-work-driven proteomics revealed a modulation in cell-survival related pathways such as ERK, AKT and PDK1-PKC axis. Part of the differential OB protein set was not specific of MixD, being also deregulated across different tauopathies, synucleinopathies and tardopathies. However, the comparative functional analysis of OB proteome data between MixD and pure AD pathologies deciphered commonalities and differences between both related phenotypes. Finally, olfactory proteomics allowed to propose serum Prolow-density lipoprotein receptor-related protein 1 (LRP1) as a candidate marker to differentiate AD from MixD phe-notypes.

Dementia is a public health priority, in which memory impairments are prevalent and affects an individual’s daily activities. Research has tried to find ways to support memory problems of individuals with dementia. Self reference effect (SRE) has been shown to benefit memory in healthy, non-dementia group. The study aimed to investigate if SRE will improve memory performance of individuals with dementia. We used ecologically valid Ownership Procedure and the Remember/Know Paradigm to examine the Self-Reference Effect (SRE) on memory. It was hypothesised that participants living with dementia will perform differently in the recall of items that were self-referentially encoded compared to items other-referentially encoded and that the memory will be different in control participants than in those that live with dementia. The research found that self-referential processes did not have effect on memory in individuals with dementia. We suggest that impaired self-awareness may have contributed to the lack of this effect. However, we had a small sample size and these findings should be treated with caution.

Alzheimer's disease is characterized by a progressive decline of cognitive functions. The class of drugs used for the treatment are acetylcholinesterase inhibitors. Essential oils have contributed to folk medicine and discovery of new drugs for a long time. The purpose of the study was to investigate the in vitro and in silico the anti-acetylcholinesterase activity, as well as acute toxicity of the essential oil of Lippia origanoides. EOLO was obtained by hydrostelting and analyzed by gas chromatography-mass spectrometry. The inhibition assay of acetylcholinesterase enzyme activity was evaluated in vitro, as well as in silico by docking. The effects of EOLO on hematological, biochemical and behavioral parameters were analyzed in mices. We expose that EOLO shows good anti-acetylcholinesterase activity and low toxicity, possibly resulting from the action of the majority compounds thymol, carvacrol and p-cymene. The anti-acetylcholinesterase potential in vitro demonstrating a 70% inhibition. The docking results elucidated the participation of the major phenolics in AChE inhibition by interacting with the catalytic cavity of AchE. The acute oral toxicity test classified as low toxicity. These results contribute to expand the knowledge about essential oil of Lippia origanoides. Therefore, appears to be promising for herbal medicine production with anti-acetylcholinesterase and antioxidant activity.

Young dementia carers (YDCs) rarely receive appropriate training and support. Their visibility and identification remain dangerously low and as a consequence, support initiatives being developed are failing to reach them. This study explored the success (or failure) of YDCs identification pathways as well as the barriers and enablers to their implementation. An explorative qualitative approach was followed drawing on the experiences of parents of YDCs, dementia researchers, professionals in the field of dementia/young carers and young adult carers. Data collection involved semi-structured interviews (n=17) and a participatory 2-hour workshop to discuss and critique preliminary themes as well as explore strategies to increase the visibility and identification of YDCs. Five themes were identified: A ‘whole family approach’ (as a pathway to identification); ‘Not a carer’ (self/family identification); A postcode lottery (high variability of support services); Tailored support that is ‘fit for purpose’ and the ‘power’ of peer support. Recommendations on potential initiatives and actions that can help raise awareness and increase identification success of YDCs are proposed. Our findings support the need for a broad and holistic approach to the identification of YDCs that runs alongside the development of support initiatives that are accessible and relatable. The support itself will play a role in improving subsequent identification or hindering it if not ‘fit for purpose’.

Ageing of the world population makes of dementia a challenge for health systems worldwide. The cognitive disturbance is a serious but not the only issue in dementia; behavioural and psychological syndromes known as neuropsychiatric or behavioural and psychological symptoms of dementia remarkably reduce the quality of life of patients. Rising evidence is unraveling the pathophysiology of these symptoms in which all the neurotransmitter systems in the Central Nervous System (CNS) are implicated, with a pivotal role of alterations of the glutamatergic neurotransmission. Pharmacological agents for the treatment of these disorders endowed with efficacy and safety are not available yet; aromatherapy provides the best evidence in the control of agitation, the most resistant symptom. Basic research effort demonstrates that the essential oil of bergamot induces anxyolitic-like effects, devoid of sedation, typical of benzodiazepines, with noteworthy advantage for demented patients. People suffering from dementia often cannot verbalize pain, thus resulting unrelieved and contributing to agitation. Bergamot essential oil provides extensive evidence of analgesic properties independent from the route of administration. Among other mechanisms, modulation of autophagy, a process involved in neuropathic pain, seems to be implicated in the analgesic activity of bergamot essential oil. These data, together with the reported safety profile form the rational basis for bergamot as a neurotherapeutic to be trialed for the control of behavioural and psychological symptoms of dementia.

In dementia, particularly Alzheimer's Disease (AD), communication challenges are evident, especially in vocabulary and pragmatic aspects. Affected individuals often use vague, non-specific words, and their speech lacks informative nouns and verbs, leading to imprecise communication. However, aspects like sentence structure, phonology, and articulation are believed to remain intact until later stages, though this view is debated in the research community. The rise of Large Language Models (LLMs) has made significant strides in various domains, including sentiment analysis and question-answering. These advancements have been applied to dementia research, with studies using LLMs to analyze textual data. Some research incorporates pauses in text to enhance performance, while others utilize transfer learning techniques. However, limited datasets for dementia detection pose challenges in training LLMs. Our research presents a novel approach to measuring the impact of in-text encoding strategies by embedding special characters within the text to enhance model performance and incorporating sequences and summaries of their frequency. Our best model achieves 0.88 and 0.86 in f1-score and accuracy, respectively, whereas the baseline has 0.42 and 0.56 in f1-score and accuracy.

Hospitalizations for patients with diabetes and dementia take a significant health and economic toll on older adults in the United States. The present study sought to examine the differences in hospitalization characteristics and outcomes associated with diabetes and dementia separately and together using discharge record data of Los Angeles County residents aged 50+ from the California Department of Health Care Access and Information for the period 2019-2021. Results from multiple linear regression analyses indicated that when compared to those with no diabetes or dementia, patients with diabetes alone exhibited the highest total charges, while those with comorbid diabetes and dementia exhibited lower charges (p≤.05). Results of a multinomial logistic regression found that patients with comorbid diabetes and dementia had the highest odds of having a length of stay of 7+ days (AOR=1.49; 95% CI=1.44-1.53). A matched-case control analysis found that comorbid diabetes and dementia was associated with significantly lower odds of hypertensive disease than diabetes alone (MOR=0.81; 95% CI=0.67-0.97). These results highlight the complexity of factors affecting variation in hospitalization outcomes across these distinct disease profiles. Findings suggest a need to carefully consider this complexity when developing health policies or strategies to improve hospitalization outcomes involving these disease conditions.

Background. Amyotrophic Lateral Sclerosis (ALS) is a devastating disease involving motor neuron degeneration. The few drugs approved for treatment have at most a marginal benefit, and death usually occurs 2-5 years after diagnosis. Methods. A thorough manual examination of the relevant literature, covering over 35,000 papers. Results. Two major phenomena that are generally not known to clinicians were found. First, insulin signaling is impaired in ALS even in patients not diagnosed with diabetes (DB). Almost all studies that have explicitly tested insulin function in non-DB ALS patients using glucose tolerance tests (18 out of 20, 1964-2022, different groups) have found it to be impaired. Second, there is strong evidence for excessive insulin-independent glucose uptake (IIGU) in ALS. In addition, (i) early/late diabetes are associated with increased/decreased risk, respectively; (ii) insulin-based diabetes drugs are protective in ALS in large retrospective human studies; and (iii) strong animal and human evidence shows that insulin opposes all of the major pathological processes in ALS. Conclusion. Most ALS patients have insulin impairment, yet this is commonly not diagnosed, likely because excessive IIGU normalizes glucose levels. The impairment promotes disease progression. Late diabetes is associated with decreased risk because high glucose levels indicate non-excessive IIGU, and because diabetes drugs are protective. Insulin-based treatment (e.g., GLP1 agonists, insulin) is beneficial and can be disease-modifying in ALS and in frontotemporal dementia variants comorbid with ALS. ALS patients should be routinely tested for insulin function and treated if test results are positive.

Background: The psychomotor agitation of the behavioural and psychological symptoms of dementia (BPSD) is one of the common issues in aged care facilities, leading to the poor functional and medical consequences. Psychotropic interventions are the preferred choice of treatment, but which medication should be the prescribers first preference? This review aims to compare pharmacological interventions for psychomotor agitation, judging them according to their effectuality and justifiability profiles. This is to be achieved by retrieving information from Randomised Control Trials (RCTs) and systematic reviews. Objectives: This review evaluates evidence from RCTs, systematic reviews, and meta-analyses of BPSD patients who have taken agitation treatments. Assessing the efficacy of selective serotonin reuptake inhibitors (SSRI) and antipsychotic treatments when compared to each other for the purpose of improving agitation outcomes. Methods: This review includes RCT that compared one or more active ingredient medications with another medication or with a placebo, along with systematic reviews comparing citalopram (SSRI) with antipsychotics such as quetiapine, olanzapine, and risperidone. Studies were extracted by searching and accessing databases, such as PubMed, OVID, and Cochrane with restrictions of date from 2000 to 2021 and English language. Conclusion: There is still limited studies of SSRIs for the treatment of agitation in BPSD. SSRIs such as citalopram were associated with a reduction in symptoms of agitation, and lower risk of adverse effects compared to antipsychotics. Future studies are required to assess the long-term safety and efficacy of SSRI treatments for agitation in BPSD.

Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

Context: A clinical video telehealth (CVT) program was implemented improve access and quality of dementia care to patients and their caregivers in rural areas. The program was offered as part of an established dementia clinic/geriatric primary care clinic in collaboration with five community-based outpatient clinics (CBOC’s) affiliated with the Tennessee Valley Healthcare System (TVHS) in middle Tennessee. Telehealth support was provided by a physician – social worker team visit. Methods: Telehealth training and equipment were provided to clinic personnel, functioning part-time with other collateral clinical duties. Patients and caregivers were referred by primary care providers and had an average of 1 to 2 CVT encounters originating at their local CBOC lasting 20 to 30 minutes. Clinical characteristics and outcomes of patients and caregivers receiving CVT support were collected by retrospective electronic medical record (EMR) review. Results: Over a 3-year period 45 CVT encounters were performed on patient-caregiver pairs, followed for a mean of 15 (1-36) months. Some 80% patients had dementia confirmed and 89% of these had serious medical comorbidities, took an average of 8 medications, and resided at a distance of 103 (76-148) miles from the medical center. Dementia patients included 33% with late stage dementia, 25% received additional care from a mental health provider, 23% took antipsychotic medications, 19% transitioned to a higher level of care, and 19% expired an average of 10.2 months following consultation. Caregiver distress was present in 47% of family members. Consult recommendations included 64% community-based long-term care services and supports (LTSS), 36% medications, and 22% further diagnostic testing. Acceptance of the CVT encounter was 98%, with 8770 travel miles saved. Conclusion: CVT is well received and may be helpful in providing dementia care and supporting dementia caregivers to obtain LTSS for high-need older adults in rural areas.

Volunteering has many social, emotional and health benefits and could be an option for people with younger/early onset dementia to engage in stage and age-appropriate, personally meaningful activities within their local communities. This study explored how people with young onset dementia volunteer in the UK, the benefits and barriers, and how we can improve access to volunteering opportunities. Audio data of people with young onset dementia discussing their experiences of volunteering were taken from the Dementia Diaries audio and video diary project (https://dementiadiaries.org/). The data were co-analysed by a co-production team, (X), made up of six researchers living with young onset dementia and two facilitators. The findings suggest that stigma is the overarching concept (or net) which influences people’s experiences of volunteering with dementia. Within the stigma net, three themes were developed that employed a lifespan approach to challenging said stigma: 1) Valuing the past, 2) Valuing the present and 3) Valuing the future, each with additional subthemes. This research contributes to the limited pool of literature that highlights the clear benefits of volunteering for people with young onset dementia, while also considering how dementia stigma can create practical and institutional barriers to accessing volunteering. Guidance is provided for how to deliver meaningful and accessible volunteering opportunities.

This study investigated co-constructed research poetry as a way to understand the lived experiences of people affected by rarer dementia and as a means to use poetry to convey those experiences to healthcare professionals. Using mixed-methods, 71 people living with rarer dementia and care-partners (stakeholders) contributed to co-constructing 27 poems with professional poets; stakeholders’ verbatim words were analysed with descriptive qualitative analysis. Stakeholders were also surveyed and interviewed about their participation. Healthcare professionals (n = 93) were surveyed to elicit their responses to learning through poetry and its acceptability as a learning tool. Poems conveyed a shared narrative of different aspects of lived experience, often owing to atypical symptoms, misunderstandings by professionals, lack of support pathways, and a continuous struggle to adapt. Stakeholder surveys indicated it was a valuable experience to both co-create and respond to the poems, whilst group interviews revealed people’s experiences of the research poetry were characterised by reflection on lived experience, curiosity and exploration. Healthcare professionals’ responses reinforced the poetry’s capacity to stimulate cognitive and affective learning specific to rare dementia support and prompt both empathy and critical thinking in practice. As the largest poetry-based study that we are aware of, this novel accessible approach of creating group poems yielded substantial information about the experiences and needs of those affected by rarer dementia and how poetry can contribute to healthcare education and training.

Sensory processing is a crucial function of the nervous system that significantly affects a large portion of the population, particularly older individuals who may be dealing with different forms of dementia. The global population of people aged 65 or older has reached a substantial count of around 703 million, representing approximately 9% of the total global population. Within this demographic, an estimated 5-8% of those aged 60, highlighting the growing need to address sensory modulation challenges for healthy aging. Sensory diet, derived from sensory integration theory, provide a tailored approach to modulating sensory experiences and triggering neuroplastic changes in the brain. Recent neuroimaging studies have revealed intricate structural and functional alterations in the brain associated with the implementation of sensory diets. Furthermore, the integration of the Metaverse, augmented reality, and virtual reality has opened up personalized experiences, fostering cognitive stimulation and emotional well-being for individuals during aging. This article offers a comprehensive exploration of the effectiveness of sensory diets in enhancing attentional control, self-regulation, and alleviating sensory-related distress among the healthy aging and dementia population. By employing precise quantitative evaluations such as sensory processing scales and advanced neuroimaging methodologies, it presents solid evidence of the tangible impact of these interventions. Emphasizing the importance of interdisciplinary cooperation and leveraging technological advancements, the article underscores the crucial need for customized sensory diets to optimize sensory processing and improve the overall well-being of older individuals contending with sensory modulation challenges and dementia.

Schizophrenia is a spectrum of neuropsychiatric deformities, characterized by hallucination, delusion, mood disorders, speech pathology, and neurocognitive deficits. Among various clinical manifestations, hallucination has been recognized as a core psychotic symptom that occurs more frequently in schizophrenia. A significant number of subjects with neurocognitive disorders like Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and other neurological diseases like stroke and epileptic seizure also experience hallucinations. While aberrant neurotransmission has been linked to the neuropathogenic events of schizophrenia, the specific cellular mechanism contributing to hallucinations remains ambiguous. Neurodegeneration in the hippocampus of the brain has been identified as a predominant pathogenic determinant of dementia. While the scientific proof for the neurodegeneration in schizophrenia is limited, the occurrence of dementia in schizophrenia has become increasingly evident. To note, both neurodegenerative, neurodevelopmental, and neuropsychiatric disorders display impaired neurogenesis in the brain. Impaired neurogenesis in the hippocampus has been linked to dementia and mood disorders. Notably, the early phase of many neurodegenerative disorders has been characterized by reactive neuroblostosis and aberrant cell cycle activation in mature neurons leading to the fluctuation in neurogenic processes leading to abnormal synaptogenesis and neurotransmission in the brain. Thus, this article emphasizes a hypothesis that aberrant neurogenic processes could be an underlying mechanism of hallucination in schizophrenia and other neurological diseases.

Background: Demonstrate a theoretical and empirical justification for including potentially protective factors in Sporadic Creutzfeldt-Jakob case-controlled studies alongside the almost exclusively studied risk-enhancing factors. Methods: Synthesize existing sCJD and Alzheimer's disease (AD) research to suggest the plausibility of shared neuroprotective factors. A fixed effects longitudinal analysis of 26 countries across 10 time periods examines whether factors identified to protect against AD are associated with population-level sCJD incidence rates. Results: Increased consumption of beans and nuts, both of which are thought to protect against AD risk, is associated with lower population level sCJD incidence. Conclusion: This study suggests that factors that protect against other neurodegenerative diseases might offer protection from sCJD. The low marginal burden of including protective factors in sCJD questionnaires offers a chance to better understand sCJD at little additional cost.

Introduction:Few robust studies have analyzed association between cognitive tests and the marital status of Mild Cognitive Impairment (MCI) group with ADNI dataset. To test the hypothesis that Rey Auditory Verbal Learning test (RAVLT) cognition performance with marital status is associated with greater odds of MCI group than either RAVLT independently, we used TADPOLE data to evaluate cross-sectional associations between RAVLT performance in immediate response, learning, forgetting, and perception of forgetting with marital status and MCI. Methods: Subjects with MCI and Normal Cognition were included. Logistic regression models indicate associations between four RAVLT subgroups (low and high performance of immediate response, immediate response with learning, performance of immediate response with learning and forgetting, performance of immediate response with learning, forgetting and perception of forgetting) and MCI group. Models adjust for age, sex, race, marital status, ethnicity, education, APOE4 genotype, hippocampus, whole-brain, ventricles and ICV. Results: The sample (n=6560) had a mean age of 77 / 67 years, 44% were female, 58% in MCI group. Only all RAVLT subgroups test with age 61 to 70(OR 0.26, 95% CI 0.15-0.45), age 71 or older(OR 0.07, 95% CI,0.04-0.12), race:black/african american(OR 0.13, 95% CI 0.03-0.52)race:more than one(OR 0.05, 95% CI 0.01-0.24), marital status:never married(OR 0.2, 95% CI 0.12-0.34). Conclusion: Studies are needed to evaluate other cognitive test with missing data within TADPOLE dataset as modifiable risk factor for MCI.

According to the World Health Organization (WHO), dementia is the seventh leading reason of death among all illnesses and one of the leading causes of disability among the world’s elderly people. Day by day the number of Alzheimer’s patients is raising. Considering the increasing rate and the dangers, Alzheimer’s disease should be diagnosed carefully. Machine learning is a potential technique for Alzheimer’s diagnosis but general users do not trust machine learning models due to the black-box nature. Even, some of those models do not provide the best performance because of using only neuroimaging data. To solve these issues, this paper proposes a novel explainable Alzheimer’s disease prediction model using a multimodal dataset. This approach performs a data-level fusion using clinical data, Freesurfer MRI segmentation data, and psychological data. For Alzheimer’s disease vs cognitively normal prediction, the random forest classifier provides 100% accuracy. Furthermore, Alzheimer’s disease and non-Alzheimer’s dementia should be classified properly because their symptoms are similar. To the best of our knowledge, we are the first to present a three-class classification on Alzheimer’s disease vs cognitively normal vs non-Alzheimer’s dementia and achieved 99.86% accuracy using an ensemble model. Besides, a novel Alzheimer’s patient management architecture is also proposed in this work..

Prion diseases are progressive and irreversible neurodegenerative disorders with a low incidence (1.5–2 cases per million per year). Genetic (10-15%), acquired (anecdotal) and sporadic (85%) forms of the disease have been described. The clinical spectrum of prion diseases is very varied, although the most common symptoms are rapidly progressive dementia, cerebellar ataxia and myoclonus. Mean life expectancy from the onset of symptoms is 6 months. There are currently diagnostic criteria based on clinical phenotype as well as neuroimaging biomarkers (magnetic resonance imaging), neurophysiological tests (electroencephalogram and polysomnogram) and cerebrospinal fluid biomarkers (14-3-3 protein and real-time quaking induced conversion (RT-QuIC)). The sensitivity and specificity of some of these tests (electroencephalogram and 14-3-3 protein) is under debate and the applicability of other tests such as RT-QuIC is not universal. However, the usefulness of these biomarkers beyond the most frequent prion disease, sporadic Creutzfeldt-Jakob disease, remains unclear. Therefore, research is being carried out on new, more efficient cerebrospinal fluid biomarkers (total tau, ratio total tau/phosphorylated tau and neurofilament light chain) and potential blood biomarkers (neurofilament light chain among others) to try to universalize access to early diagnosis in the case of prion diseases.

As a result of an increasing population of aged people in sub-Saharan Africa, dementia is predicted to surge up to 90% by 2030. This review is set to assess the prevalence of dementia, for 65+ aged population in sub-Saharan states and particularly in Tanzania. Subsequently, the review will identify the possible risks factors – age, gender, level of education, cardiovascular problems, diabetes and mild cognitive impairment – and will lay out the challenges of reducing the dementia burden in Tanzania. Additionally, the review explores the current approaches in solving dementia disorders, including a general view of the public understanding of dementia. Also, the review recognises the gaps in government funding to mental health, a barrier to service access and the need for further research on Alzheimer’s and other dementias. Lastly, the review links the sustainable development goals (SDGs) addressed and appreciate the impact of the coronavirus pandemic on the fight against dementia.

Donepezil (DPZ) is an acetylcholinesterase inhibitor used for the clinical treatment of mild cognitive impairment. However, DPZ has been reported to have adverse effects, including abnormal cardiac rhythm, insomnia, vomiting, and muscle cramps. However, the existence of these effects in subjects without Dementia is unknown. In this study, we use zebrafish to conduct a deeper analysis of the potential adverse effects of DPZ on the short-term memory and behaviors of normal zebrafish by performing multiple behavioral and biochemical assays. Adult zebrafish were exposed to 1 ppm and 2.5 ppm of DPZ. From the results, DPZ caused a slight improvement in the short-term memory of zebrafish and induced significant elevation in aggressiveness, while the novel tank and shoaling tests revealed anxiolytic-like behavior to be caused by DPZ. Furthermore, zebrafish circadian locomotor activity displayed a higher reduction of locomotion and abnormal movement orientation in both low- and high-dose groups, compared to the control group. Biomarker assays revealed that these alterations were associated with an elevation of oxytocin and a reduction of cortisol levels in the brain. Moreover, the significant increases of reactive oxygen species (ROS) and malondialdehyde (MDA) levels in muscle tissue suggest DPZ exposure induced muscle tissue oxidative stress and muscle weakness, which may underlie the locomotor activity impairment. In conclusion, we show, for the first time, that the chronic waterborne exposure of DPZ can severely induce adverse effects on normal zebrafish in a dose-dependent manner. These unexpected adverse effects on behavioral alteration should be carefully addressed in future studies considering DPZ conducted on zebrafish or other animals.

Canadians overwhelmingly do not want to live in long-term-care (LTC) facilities when they age; yet many end up there for lack of homecare, because family caregivers burn out, or because they and their professional advisors are unaware of alternatives to institutions. Not only is institutional dementia care problem-driven, it segregates disabled people, thereby abrogating human rights. Because systemic ageism and ableism cloud elder care, institutions remain the default option for Canadians with dementia. Yet, decades of deinstitutionalization enabled younger disabled Canadians to live in the community with supports. Why not elders? We describe a plethora of noninstitutional dementia-care alternatives. We then present a roadmap for considering all relevant care options in service plans, one that incorporates supported decision-making by people with dementia. We propose a paradigm shift in how Canada serves its elder citizens—not just the current generation, but those to come, including ourselves.

Dementia is recognized as a disability under the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD). People with disabilities like dementia have the right to access specialized health and social care services, including interventions that support independence and community participation. Cognitive Stimulation Therapy (CST) is an evidence-based psychosocial intervention that improves cognition, communication, confidence and quality of life for people living with dementia (PLwD), but an implementation gap means that CST is often not available. We recruited trained CST practitioners (n=62; 91.9% female) to a mixed methods study to examine facilitators and barriers to the implementation of CST in Ireland. Statistical analysis showed that 54.8% of practitioners had run CST following training; ratings of intervention efficacy predicted the likelihood of running CST groups (p=0.006); and seeing the benefits of CST first-hand predicted that practitioners would run a greater number of CST groups (p=0.01). Thematic analysis of qualitative data identified three key themes of ‘resources’, ‘awareness and education’, and ‘acceptability of CST’. Overall, the results show that while CST is acceptable and deemed highly effective, resources and staffing often impede implementation. The results are discussed in the context of prioritising the rights of people with disabilities and recommendations are made around improving access to evidence-based supports.

In a world filled with uncertainties, Ebb&Flow emerged as a story of convergence, intertwining dementia research, caregiving, and artistic exploration into a tripartite creative knowledge exchange. This study delves into the complexities of uncertainty in dementia care and research through a collaborative project involving artists, researchers, carers, and individuals with lived experience of dementia. Initiated by the Trellis:Arbor program, Ebb&Flow sought to co-created a human space addressing the multifaceted nature of uncertainty. The sea, with its unpredictable nature, served as a guiding metaphor for the project, reflecting the unpredictability of dementia and life. Over three months, through paintings, writings, and digital mediums, participants documented the changing emotions, challenges, and discoveries they encountered daily. The project fostered an environment where uncertainties were openly discussed, building supportive and resilient communities through participatory co-creation and methodological exchange. Key activities included a digital logbook, allowing participants to document and share their experiences of uncertainty, and the creation of the Ebb&Flow card deck—a compilation of personal stories and insights that serve as a legacy of shared experiences. Each card facilitated dialogue, understanding, and connection, bridging gaps between those affected by dementia and the broader community. The project culminated in a final exhibition and sharing event, where participants, researchers, and the public celebrated the journey's outcomes through stories and artworks. Throughout this journey, we observed that embracing uncertainty and fostering empathy through creative collaboration profoundly impacted participants, enhancing empathy and resilience. This project underscores the transformative potential of integrating artistic practices with scientific research to address the emotional and psychological burdens of dementia and research environments. Ebb&Flow demonstrates that even in the face of the unknown, a united community can find strength, solace, and understanding, highlighting the power and beauty of unity in exploring and expressing the multifaceted experiences of dementia and life.

(1) Background: The study of microbiome is being crucial for his role in major systemic diseases, in particular the oral and gut microbiota. In the last years the study of microorganism correlated for example with neurodegenerative disease is increasing the prospective of a possible link between gut microbiota and brain. Here we report a new case report about a patient evaluated genetically firstly for dementia and late-onset dyskinesia, and then tested with 16S metagenomics sequencing. (2) Methods: Starting from buccal swab, we extracted bacterial DNA and then we performed a NGS metagenomics sequencing based on the amplification of hypervariable regions of the 16S in bacteria. (3) Results: The sequencing revealed the presence of Spirochaetes Phylum, a pathogenic bacterium generally known to be able to migrate to the Central Nervous System and not only. (4) Conclusions: Oral infections as our results shows could be possible contributing factors to various neurodegenerative conditions.

Over the years there has been an increase in the development of assistive technologies (AT’s). The implementation and scaling of AT’s at care organizations remains challenging. Moreover, to date, it has been underexplored during which stages of dementia these technologies can be best implemented. Previous work has developed an infographic providing guidance on when best to introduce AT’s for people with dementia. Although this infographic is relevant, it was based solely on the experience of the authors during various national and international projects. However, over the years a wide spread of studies has been conducted in the field of dementia on the use and implementation of technology for PwD. Therefore, in this paper we will revise the current infographic based on the insight gained from existing literature and complement these by interviews with expert on the implementation of care technology

Cognitive impairment in patients with Parkinson’s disease (PD), which may occur in various severities, represents one of the commonest and most disabling non-motor manifestations during the course of the disease, causing a negative impact on patients’ quality of life. Eventually, it becomes a burden for the family members and/or the caregivers of patients, as it progresses to PD dementia. Current pharmacological treatments for cognitive impairment in PD exhibit partial efficacy, while novel effective therapeutic strategies are required. Accumulating preclinical and clinical evidence shows that several agents may provide beneficial effects on patients with PD and cognitive impairment, including ceftriaxone, ambroxol, intranasal insulin, nilotinib, atomoxetine, mevidalen, blarcamesine, prasinezumab, SYN120, ENT-01, NYX-458, GRF6021, fosgonimeton, INT-777, Neuropeptide S, silibinin, osmotin, cordycepin, huperzine A, fibroblast growth factor 21, Poloxamer 188, ginsenoside Rb1, thioredoxin-1, tangeretin, istradefylline, and Eugenia uniflora. Potential underlying mechanisms include the inhibition of a-synuclein aggregation, improvement of mitochondrial function, regulation of synaptic plasticity, impact on gut-brain axis, modulation of neuroinflammation, upregulation of neurotrophic factors, as well as cholinergic, dopaminergic, serotoninergic and norepinephrine neurotransmission. In this overview, we aim to cover the clinical aspects of PD associated cognitive impairment, highlighting recent evidence on emerging treatment approaches that are currently under investigation at a preclinical and clinical level.

Dementia is a rising public health concern. Feeding and nutritional problems increase as the disease progresses, affecting clinical course and caregiver burden. While some guidelines advise against percutaneous endoscopic gastrostomy (PEG) and tube feeding in advanced dementia, conflicting evidence exists. This study aims evaluating nutritional status and the influence of PEG-feeding on outcome and evolution of nutritional/progonosis markers of patients with severe dementia (PWSD) who underwent gastrostomy for nutritional support. We conducted a 16-year rectrospective study on 100 PEG-fed PWSD with strong familiar support. We evaluated survival PEG-feeding period, safety, and objective nutritional/progonosis data at the gastrostomy day and after 3 months: Body Mass Index (BMI), Mid Upper Arm Circumference, Tricipital Skinfold, Mid-Arm Muscle Circumference, albumin, transferrin, total cholesterol and hemoglobin. Most patients presented low values in these nutritional/progonosis parameters. No major life-threatening PEG complications were reported. The mean survival time after gastrostomy was 27.9 months (median of 17 months). Female sex, BMI recovery at 3 months, and higher baseline hemoglobin levels were associated with a reduced risk of death and increased survival time. The study concluded that, in carefully selected PWSD with strong familiar support, PEG feeding can improve nutritional status and have a positive impact on survival.

Background: Assessment and management of pain in elderly people with cognitive impairment is particularly challenging. Physiological changes due to aging as well as comorbidities and polypharmacy are responsible for a complex clinical approach. Concomitantly, in cognitive impairment, including advanced dementia, changes in central nervous system along with changes in the peripheral nervous system due to aging have a significant impact in pain perception. Often clinicians decide to prescribe opioids in order to relief pain, also without a clear indication. Aim: This review aims to investigate the effect of opioids in elderly patients with cognitive impairment. Methods: A literature search of PubMed/Medline, Scopus, and Cochrane databases was conducted using keyword searches to generate lists of articles which were screened for relevance by title and abstract to give a final list of articles for full-text review. Further articles were identified by snowballing from the reference lists of the full-text articles. Results: This review discuss the complex physiological and pharmacological changes in elderly as well as the neurological changes that affect pain perception in this population. Additionally, it focuses on cognitive impairment and pain in Alzheimer’s disease and other dementias, the pain assessment in the elderly with cognitive impairment as well as the safety of opioid use in elderly. Information regarding opioid prescription in nursing homes as well as recorded indications for opioids use, type and dosing of opioid and compliance of treatment in advanced dementia are also provided. Conclusions: Opioid prescription in elderly population with cognitive impairment is particularly complex. All healthcare professionals involved in the care of such patients, need to be aware of the challenges and strive to ensure analgesic use is guided by appropriate and accurate pain assessment.

Neuroprotective strategies for stroke remain inadequate. Nanoliposomes comprised of phos-phatidylcholine, cholesterol and monosialogangliosides (NL) induced an antioxidant protective response in endothelial cells exposed to amyloid insults. We tested the hypotheses that NL will preserve SH-SY5Y neuroblastoma cell viability following hypoxic injury and will reduce injury in mice following middle cerebral artery occlusion (MCAO). Neuroblastoma were exposed to 20-hour physoxic (5% oxygen) or hypoxic (1% oxygen) condition without or with NL (100 or 300 µg/mL). Viability was measured using calcein-AM fluorescence and SH-SY5Y gene expression of antioxidant proteins heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1) and superoxide dismutase 1 (SOD1) were measured by quantitative polymerase chain reaction. C57BL/6J mice were treated with saline (N=8) or NL (10000 ug/mL, N=7) while undergoing 60-minute MCAO followed by reperfusion. Day 2 post-injury neurologic impairment score and infarction size were compared. Neuroblastoma showed reduced viability following hypoxia that was reversed by NL. NL increased gene expression of HO-1, NQO1 and SOD1 versus controls. NL-treated mice showed reduced neurologic impairment and brain infarct size (18.8±2% versus 27.3±2.3%, p=0.017) versus controls. NL reduced stroke injury in mice subjected to MCAO likely through induction of an antioxidant stress response. NL is a candidate novel agent for stroke.

Background and Aims: Screening and assessment of cognitive changes in adults with Intellectual Disabilities, mainly Down Syndrome (DS), is crucial to offer appropriate services to their needs. We present a systematic review of the existing instruments assessing dementia, aiming to support researchers and clinicians’ best practice. Methods: Searches were carried out in the databases Web of Science; PubMed; PsycINFO in March 2019 and updated in May 2020. Studies were selected and examined if they: (1) focused on assessing age-related cognitive changes in person with ID; (2) included adults and/or older adults; (3) included scales and batteries for cognitive assessment. Results: Forty-eight cross-sectional studies and twenty-six longitudinal studies were selected representing a total sample of 5,851 participants (4,089 DS and 1,801 with other ID). In those studies, we found 38 scales, questionnaires, and inventories, and 14 batteries for assessing cognitive and behavioural changes in adults with DS and other ID. Conclusion: The most used instrument completed by an informant or carer was the Dementia Questionnaire for Learning Disabilities (DLD), and its previous versions. We discuss the strengths and limitations of the instruments and outline recommendations for future use.

Subjective Cognitive Decline (SCD) is a possible earliest detectable sign of dementia, but we do not know what mental processes lead to elevated concern. We summarize the previous literature on the biomarkers and functional neuroanatomy of SCD. To extend the current most-popular theory of SCD, compensatory hyperactivition, we introduce a new model: breakdown of homeostasis in the prediction error minimization system. A cognitive prediction error is a discrepancy between an implicit cognitive predictions and the corresponding outcome. Experiencing frequent prediction errors may be a primary source of elevated subjective concern. Our homeostasis breakdown model explains the progression both from normal cognition to SCD and from SCD to advanced dementia stages.

Mild cognitive impairment (MCI) and mild dementia are a clinically relevant health problem in the elderly and Alzheimer's disease being the most common neurodegenerative disorder. Furthermore, MCI and mild dementia are characterized by a deterioration of cognitive function and their diagnosis is mainly based on cognitive examination and, the prognosis of the disease seems to be an essential reason for the diagnosis, because there is a high risk of cognitive decline in the two syndromes. This review describes the effectiveness of Ginkgo biloba (EGb761®) leaf extract for the treatment of dementia syndrome and EGb761® combination therapy with other medications for symptomatic dementia. Tebonin® is a drug of plant origin based on the active ingredient “Ginkgo biloba”. This drug has shown encouraging results, improving cognitive function, neuropsychiatric disorders and consequent reduction of caregiver stress and maintenance of autonomy in patients with age-related cognitive decline, MCI and mild dementia. Nowadays, there is little evidence to support the efficacy of EGb761® combination therapy with anti-dementia drugs and, therefore, more evidence is needed to evaluate the role of EGb761® in mixed therapy.

Growing evidence suggests that abnormal diurnal blood pressure rhythms may be associated with many adverse health outcomes including increased risk of cognitive impairment and dementia. This study evaluates methodological aspects of research on bidirectional associations between ambulatory blood pressure monitoring (ABPM) patterns and cognitive function. By examining the 28 recent studies included in a recent systematic review on association between ABPM patterns with cognitive function and risk of dementia, our review revealed several significant limitations in the current studies of ABPM and cognition in terms of study design, sample characteristics, ABPM protocol, cognitive assessment, and data analysis. The major concerns include lack of diversity in study populations with underrepresentation of Blacks and Latinos, a predominant focus on Alzheimer's disease or all-cause dementia without distinguishing other dementia subtypes, different and not standardized measures of cognition or dementia, the prevalent use of 24-hour monitoring without considering the adaption effect, inconsistent definitions of dipping status, and ignorance of individual differences in timings of daily activities such as bed and awakening times. In addition, confounding variables such as class, dose, and timing of antihypertensive medication are inadequately controlled or considered. Additionally, longitudinal studies were scarce examining the bidirectional relationship between ABPM patterns and cognitive decline over time. Collectively, these deficiencies undermine the reliability and generalizability of current findings. Addressing these methodological challenges is crucial for more comprehensive understanding of diurnal blood pressure rhythms in diverse populations and for developing an evidence-based guideline of ambulatory monitoring and control of blood pressure across the sleep-wake cycle to prevent cognitive decline and dementia.

Alzheimer’s disease (AD), the leading cause of dementia (50-70%), is a multifactorial neurodegenerative disorder characterized by progressive cognitive decline and significant neuropathological changes, including β-amyloid plaques and neurofibrillary tangles. This review synthesizes current understanding of the complex interplays that contribute to the pathogenesis of AD, while exploring the mechanisms underlying the formation of β-amyloid plaques and neurofibrillary tangles, with a focus on the amyloidogenic and non-amyloidogenic pathways, Tau protein hyperphosphorylation, and the resultant neurotoxicity. Furthermore, the study delves into mitochondrial dysfunction and oxidative stress as critical contributors to neuronal degeneration, highlighting the mitochondrial cascade hypothesis and its implications in both early (EOAD) and late-onset AD (LOAD). The study emphasizes the irreversible nature of the disease’s progression, detailing the pathological transformations from the preclinical to the severe stage, where lesions disseminate throughout the entire cortex.

This systematic review provides a comprehensive neuropsychological analysis of psychotic spectrum disorders, including schizophrenia, bipolar disorder, and depression. It explores cognitive impairments in memory, attention, and executive function, and the relation between brain abnormalities and these deficits. The paper emphasizes the use of neuropsychological tests in diagnosis and early psychosis management, while also discussing interventions, the impact of dementia on psychosis, and the neurobiological patterns associated with these conditions. Additionally, it underlines the importance of childhood trauma in the development of psychosis and examines the effects of substance abuse and brain injury. Neuropsychological evaluations and targeted therapies are highlighted as crucial for the understanding, diagnosis, and treatment of psychotic disorders. The research further includes evidence of neurocognitive dysfunction in individuals with a high risk of psychosis and emphasizes the advanced brain aging in schizophrenia and bipolar disorder. The necessity of comprehensive clinical evaluations and targeted therapies for cognitive impairments is underscored throughout the research. The potential effects of dementia on individuals with psychosis, neurobiological patterns, the role of childhood trauma, the impact of psychosis in dementia patients, and proposed treatments are also explored in depth. Overall, the paper underscores the integral role neuropsychological knowledge plays in understanding, diagnosing, managing, and treating psychotic spectrum disorders.

One of the major obstacles confronting the formulation of a mechanistic understanding for Alzheimer’s disease (AD) is its immense complexity – a complexity that traverses the full structural and phenomenological spectrum, including molecular, macromolecular, cellular, neurological and behavioural processes. This complexity is reflected by the equally complex diversity of risk factors associated with AD. However, more than merely mirroring disease complexity, risk factors also provide fundamental insights into the aetiology and pathogenesis of AD as a neurodegenerative disorder since they are central to disease initiation and subsequent propagation. Based on a systematic literature assessment, this review has identified 30 risk factors for AD and then extended the analysis to further identify neuroinflammation as a unifying mechanism present in all 30 risk factors. Although other mechanisms (e.g. vasculopathy) were present in multiple risk factors, dysfunction of the neuroimmune-neuroinflammation axis was uniquely central to all 30 identified risk factors. Though the nature of the neuroinflammatory involvement varied, activation of microglia and the release of pro-inflammatory cytokines was a common pathway shared by all risk factors. This observation provides further evidence for the importance of immunopathic mechanisms in the aetiopathogenesis of AD.

In advanced Parkinson’s disease (PD), and especially in PD related dementia (PDD), psychotic symptoms are common. One of the manifestations of psychosis in PD is delusional misidentification syndrome, a phenomenon in which the patient believes the identity of a person, object or location has been duplicated or altered. Our patient, a 75-year-old female, was diagnosed with idiopathic Parkinson’s disease at the age of 68. Recently, her cognition deteriorated and she developed the believe that she lived in a replica of her real home. The delusion resolved completely with rivastigmine patches. Also visual hallucinations improved on treatment. This suggests that the dysfunctional connections were likely to be cholinergic.

Frontotemporal dementia (FTD) is the second most common form of presenile dementia; however, its diagnosis has been poorly investigated. Previous attempts to diagnose FTD using quantitative electroencephalography (qEEG) have yielded inconsistent results in both spectral and functional connectivity analyses. This study aimed to introduce an accurate qEEG marker that could be used to diagnose FTD and other neurological abnormalities. We used open-access electroencephalography data from OpenNeuro to investigate the power ratio between the frontal and temporal lobes in the resting state of 23 patients with FTD and 29 healthy controls. Spectral data were extracted using a Fast Fourier Transform in the delta (1–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (13–32 Hz), and gamma (32–45 Hz) bands. We found that the spectral power ratio between the frontal and temporal lobes is a promising qEEG marker of FTD. Frontal/temporal (F/T) theta/alpha, alpha/theta, al-pha/gamma, and gamma/alpha showed a consistently high discrimination score for the diagnosis of FTD for different parameters and referencing methods. The study findings can serve as reference for future research focused on diagnosing FTD and other neurological anomalies.

Background: No studies have examined whether interactions between the apolipoprotein E4 (ApoE4) allele and peripheral biomarkers, hypertension, and type 2 diabetes mellitus (T2DM) may impact the neurocognitive, behavioral and social dysfunctions in amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). Aims: To clinically define and biologically validate a subgroup of aMCI subjects that take up an intermediate position between controls and AD patients. Methods: In 61 healthy controls, 60 subjects with aMCI, and 60 AD patients we measured the features of aMCI/AD using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). A composite BIORISK score was computed using the ApoE4 allele, serum folate, albumin, white blood cells, fasting blood glucose (FBG), atherogenic index of plasma (AIP), T2DM and hypertension. Results: Clustering and nearest neighbour analyses were unable to validate the aMCI subgroup. We constructed two z unit-based composite scores, the first indicating overall burden of cognitive, social, and behavioural deterioration (OBD), and a second reflecting the interactions between ApoE4, all other biomarkers, hypertension and T2DM (BIORISK). We found that 40.2% of the variance in the OBD score was explained by BIORISK, ApoE4, age and education. The OBD index was used to construct three subgroups (normal, medium, and high OBD) with the medium group (n=45) showing mild cognitive dysfunctions (MCD) in memory, language, orientation, and ADL. People with MCD show OBD and BIORISK scores that are significantly different from controls and AD.Conclusions: Petersen’s aMCI criteria cannot be validated and should be replaced by the more restrictive, biologically validated MCD class.

Background: The Apolipoprotein E4 (ApoE4) genotype is strongly associated with Alzheimer’s disease (AD), although the presence of the ApoE4 allele alone is not sufficient to explain AD. The pathophysiology of amnestic mild cognitive impairment (aMCI) remains unclear. This study aims to examine associations between peripheral blood biomarkers coupled with ApoE4 and episodic and semantic memory. Methods: The CERAD battery was completed and various biomarkers were assayed in 60 subjects with aMCI, 60 with AD and 62 healthy controls. Results: Deficits in semantic and episodic memory were significantly predicted by anion gap and bicarbonate, albumin and glucose coupled with Apo E4. Furthermore, these peripheral biomarkers interacted with ApoE to predict greater memory impairments. Conclusions: Peripheral blood biomarkers may interact with pathways related to ApoE4 to predict greater semantic and episodic memory impairments, thus contributing to the pathophysiology of aMCI and AD. Our data suggest that the transition from aMCI to AD could at least in some cases be associated with significant interactions between ApoE4 and those peripheral blood biomarkers.

Background: In recent years, the integration of robotic systems into various aspects of daily life has become increasingly common. As these technologies continue to advance, ensuring user-friendly interfaces and seamless interactions becomes more essential. For social robots to genuinely provide lasting value to humans, a favourable user experience (UX) emerges as an essential prerequisite. Aim: This article aimed to evaluate the usability of the MINI robot, highlighting its strengths and areas for improvement based on user feedback and performance. Method: In a controlled lab setting, a mixed-method qualitative study was conducted with ten individuals aged 65 and above diagnosed with mild dementia (MD) and mild cognitive impairment (MCI). Participants engaged in individual MINI robot interaction sessions, completing cognitive tasks as per written instructions. Video and audio recordings documented interactions, while post-session System Usability Scale (SUS) questionnaires quantified usability perception. Ethical guidelines were followed, ensuring informed consent, and the data underwent qualitative and quantitative analyses, contributing insights into the MINI robot's usability for this demographic. Results: The study addresses the ongoing challenges that tasks present, especially for MD individuals, emphasizing the importance of user support. Most tasks require both verbal and physical interactions, indicating that MD individuals face challenges when switching response methods within subtasks. These complexities originate from the selection and use of response methods, including difficulties with voice recognition, tablet touch, and tactile sensors. These challenges persist across tasks, with individuals with MD struggling to comprehend task instructions and provide correct answers and individuals with MCI struggling to use response devices, often due to the limitations of the robot's speech recognition. Technical shortcomings have been identified. The results of the System Usability Scale (SUS) indicate positive perceptions, although there are lower ratings for instructor assistance and pre-use learning. The average SUS score of 68.3 places device usability in the "good" category. Conclusion: Our study examines the usability of the MINI robot, revealing strengths in quick learning, simple system and operation, and integration of features while also highlighting areas for improvement. Careful design and modifications are essential for meaningful engagement with people with dementia. The robot could better benefit people with MD and MCI if clear, detailed instructions and instructor assistance are available.

Dementia, primarily caused by neurodegenerative diseases like Alzheimer’s disease (AD), affects millions worldwide, making detection and monitoring crucial. To enable these tasks, we propose encoding in-text pauses and filler words (i.e., “uh” and “um”) in text-based language models, and thoroughly evaluate their effect in performance. Additionally, we suggest using contrastive learning to improve performance in a multi-task framework. Our results demonstrated the effectiveness of our approaches in enhancing the model’s performance, achieving 87% accuracy and an 86% F1-score. Compared to the state-of-the-art, our approach has similar performance despite having significantly fewer parameters. This highlights the importance of pause and filler word encoding on the detection of dementia.

Eating and drinking difficulties are common in dementia, but little is known about the experiences of ethnic minority groups managing these difficulties at home. We undertook qualitative semi-structured interviews, exploring the meaning of food, the impact of dementia on eating and drinking and carers’ experiences of support. Interviews were audio-recorded and transcribed verbatim. We interviewed 17 carers and people with dementia from ethnic minority backgrounds, using reflexive thematic analysis to analyse data. Food/drink had strong links to identity, culture and emotions. Providing culturally familiar foods, celebrating traditional festivals and supporting previous food-related roles promoted reminiscence, which encouraged people with dementia to eat and drink, as did social interactions. However, these strategies sometimes led to distress in those with more advanced dementia. Food choices were also influenced by carer strain, generational differences and the impact of health conditions. Despite a strong sense of duty to care for relatives at home, there was low awareness of community support services. Carers expressed a need for culturally tailored support for managing dementia-related eating and drinking difficulties at home. Healthcare professionals must provide contextually relevant advice to carers, being mindful of how cultural backgrounds can affect dietary choices.

Background: The psychomotor agitation of the BPSD is one of the common issues in aged care facilities, leading to the poor functional and medical consequences. Psychotropic interventions are the preferable choice of treatment. But which medication should be the prescribers first preference? This review aims to compare pharmacological interventions for psychomotor agitation, judging them according to their effectuality and justifiability profiles. This is to be achieved by retrieving information from RCTs and systematic reviews. Objectives: This review evaluates evidence from RCTs, systematic reviews, and meta-analyses of BPSD patients who had taken agitation treatments. Assessing the efficacy of antidepressants and antipsychotic treatments when compared to each other for the purpose of improving agitation outcomes. Methods: This narrative review includes RCTs and retrospective studies that were comparing one or more active ingredient medications with another or with a placebo, along with sys-tematic reviews comparing antidepressants with antipsychotics such as quetiapine, olanzapine, and risperidone. Studies extracted by searching accessing databases, such as PubMed, OVID, and Cochrane with restrictions of date from 2000 to 2021 and English language. Quality of evidence: The quality of systematic reviews was judged against AMSTAR score, and RCTs were judged according to CONSORT checklist for RCT protocols. Conclusion: There are still few studies of serotonin targeting treatment of agitation in BPSD. The SSRIs such as citalopram were associated with a reduction in symptoms of agitation, and lower risk of adverse effects compared to antipsychotics. This review also illustrates brexpiprazole as a target of multimodal neurotransmitters such as dopamine, serotonin, and norepinephrine; and dextromethorphan, OR dextromethorphan associated with bupropion or quinidine as a blockade of NMDA receptors. The outcome of this review suggests that further studies involving more dementia/Alzheimer’s participants should be conducted. Future studies are required also to assess the long-term safety and efficacy of SSRI, brexpiprazole, dextromethorphan treatments for agitation in BPSD.

Aim: This research is aimed at examining the cost-effectiveness of olanzapine versus risperidone in dementia patients with behavioural and psychological symptoms in Thailand. Methods: An existing Markov model based on a critical review through the comprehensive literature search and a justification for the most appropriate model for a Thai setting was adapted to simulate the disease progression of patients with dementia with behavioural disturbances until their need for full-time care (FTC). The time to the FTC state was estimated by a predictive equation developed by Rive et al. (2010). The model was conducted to assess the expected costs and outcomes associated with olanzapine compared with risperidone for Thai patients with BPSD aged 60 years and above. This model performed over a five-year time horizon with a one-month cycle length based on a societal perspective. The incremental cost-effectiveness ratio was used as the estimated outcome. Sensitivity analyses were also conducted to demonstrate the robustness of the results. Results: Over 5 years, olanzapine was found to be a cost-effective therapeutic option for the treatment of behaviourally disturbed patients with dementia compared with risperidone, in Thailand from a societal perspective (ICER < THB 160,000). The model underwent extensive sensitivity analyses, which also confirmed that olanzapine was the dominant strategy following the base-case findings. Conclusions: By comparison with risperidone, the model suggests that olanzapine can be regarded as a cost-effective therapeutic strategy for the management of patients with behavioural and psychological symptoms in Thailand.

Amnestic mild cognitive impairment (aMCI) is a condition characterized by mild deficits in episodic and semantic memory and learning. The conversion rate of aMCI to Alzheimer disease (AD) is significantly higher in aMCI than in the general population. The aim of this study is to examine whether aMCI is a valid diagnostic category or whether aMCI comprises different subgroups based on cognitive functions. We recruited 60 aMCI patients, 60 with AD and 61 healthy controls who completed neuropsychological tests of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD-NP) and biomarkers including serum anion gap (AGAP). Principal component analysis, support vector machine and Soft Independent Modeling of Class Analogy (SIMCA) showed that AD patients and controls were highly significantly discrimanted from each other, while patients with aMCI overlap considerably with normal controls. SIMCA showed that 68.3% of the aMCI patients were assigned to the control class (named: aMCI-HC), 15% to AD (aMCI-AD), while 16.6% did not belong to either class (aMCI-strangers). aMCI-HC subjects showed sings of very mild cognitive decline and impaired recall. aMCI-strangers showed signs of mild cognitive impairment with impaired fluency and naming. aMCI-AD cases showed a cognitive profile reminiscent of AD an increased AGAP levels. In conclusion, our SIMCA model may classify subjects afforded a clinical diagnosis of aMCI according to Petersen’s criteria into three clinically relevant subgroups and help in the early detection of AD by identifying aMCI patients at risk to develop AD and those that have an AD prodrome.

This article proposes the use of intranasal rifampin as a means to improve protein homeostasis and disaggregate misfolded proteins in the age-related neurodegenerative proteinopathies. Alzheimer’s disease, Parkinson’s disease, multi-system atrophy, Lewy body dementia, frontotemporal dementia, amyotrophic lateral sclerosis and Huntington’s disease are all, at the core, proteinopathies. Although these diseases varying greatly in the specific disease-associated proteins, anatomic sites of the abnormal protein deposition and clinical presentations, what they have in common is disruption of normal “housekeeping” functions related to protein homeostasis, proteostasis. The prospect of pharmacologically augmenting autophagic capacity with a known drug repurposed to improve proteostasis is attractive; to accomplish these ends with an inexpensive drug with relative ease of delivery adds to the attractiveness. Rifampin can be delivered to the brain via the intranasal route. Rifampin has been used for decades primarily against mycobacterial infection; it has been given with intravenous, oral, intrathecal and topical routes including as eyedrops and nasal spray. Rifampin disaggregates toxic oligomers in vitro; given intranasally, rifampin improves memory and clears pathologic proteins in animal models of the proteinopathies. Rifampin acts as both a gatekeeper and a housekeeper against the abnormal proteins of these diseases. This article suggests the merit of a clinical trial with intranasal rifampin to boost protein homeostasis in the most common age-related neurodegenerative proteinopathy, Alzheimer’s disease. The primary outcome of such a trial is change in risk of Alzheimer’s pathology as measured by plasma-based amyloid peptide 42/40 testing pretreatment and follow-up testing after 6 months of intranasal rifampin.

Forensic hospitals throughout the country house individuals with severe mental illness and history of criminal violations. Insomnia affects 67.4% of hospitalized patients with chronic neuropsychiatric disorders, indicating that these conditions may hijack human somnogenic pathways. Conversely, somnolence is a common adverse effect of many antipsychotic drugs, further highlighting a common etiopathogenesis. The role of dysfunctional mitochondria in psychopathology is well-established, however, the association of these organelles with sleep physiology is novel. Indeed, reducing neuronal oxidative stress by importing mitochondria from astrocytes, may be the purpose of human slumber. This model may explain mitochondrial dysfunction during anesthesia as well as in the rare genetic disease, fatal familial insomnia. In this narrative review, we focus on the salience network of the brain, a common denominator for insomnia, neuropsychiatric and neurodegenerative disorders. We also discuss mitochondria-protecting strategies, including membrane lipid replacement, natural and synthetic phenazine and phenothiazine derivatives.

This study uses explainable artificial intelligence to analyze major predictors of poor self-rated health, dementia and their comorbidity, which include various aspects of social support. Data came from the Korean Longitudinal Study of Ageing (2016-2018), with 5527 participants aged 56 or more. The dependent variables were: (1) poor self-rated health (SRH) with 5 categories (very good, good, middle, poor, very poor); (2) dementia (no, yes); and (3) their comorbidity with 4 categories (SRH very good, good or middle, dementia no; SRH very good, good or middle, dementia yes; SRH poor or very poor, dementia no; SRH poor or very poor, dementia yes). The 49 demographic, socioeconomic and health-related predictors were included. The accuracy and area under the receiver operating characteristic curve (AUC) were compared for logistic regression and the random forest. Logistic regression and the random forest registered similar AUCs with the range of 0.80-0.87. Based on random forest variable importance, 18 out of top-20 predictors were identical for SRH, dementia and their comorbidity: previous SRH, life satisfaction - health, age, body mass index, income, chronic diseases, life satisfaction - economic, life satisfaction - overall, grandchildren alive, friendship meeting, brothers/sisters alive, class identity, children alive, social activity - friendship, education, children in weekly contact, religion and drinker. However, some variations were found among the three dependent variables, i.e., previous SRH for comorbidity (1st) and SRH (1st) compared to dementia (11th), grandchildren alive for SRH (6th) and dementia (4th) compared to comorbidity (9th), chronic diseases for comorbidity (6th) compared to SRH (10th) and dementia (10th). In terms of Shapley Additive Explanation (SHAP) values, the probability of dementia is expected to decrease by 5.57% in case a predictor grandchildren alive is included to the model. This study highlights the importance of social support for the prediction of poor self-rated health, dementia and their comorbidity. Specifically, the promotion of family support and friendship activity for elders would be vital for the prevention and management of their self-rated health and dementia.

Background: dementia is a significant health issue worldwide. Mild cognitive impairment (MCI) can transform into dementia over time. General practitioners may be the first to notice the cognitive deficit, so they may need a screening test in the event of suspicion, which they must be able to use under great time pressure. We examined the usability of the Hungarian Test Your Memory (TYM-Hun) self-administered dementia test in general practice, and with the results of the received tests, we tried to draw conclusions regarding the population. Methods: In the four Hungarian cities with medical universities, general practitioners filled out 368 questionnaires with their clients over 50 years of age. Results: the total scores of the test showed a significant correlation with education and the type of occupation, while a significant negative correlation with age. We found the clock drawing test and recall indicates cognitive decline the earliest. Based on the TYM-Hun results, the prevalence levels for MCI and dementia are slightly higher in Hungary than globally. Conclusion: the test can sensitively indicate MCI and early-stage dementia as a screening test, and two of its subtests can raise the possibility of cognitive impairment at an earlier age than the others.

Bright morning light (BML) entrains the body clock, modulates circadian rhythm, and improves sleep-wake disturbances. However, its impact on the autonomic nervous system (ANS) at night remains unclear. Hence, we investigated the effects of BML exposure on activities of the parasympathetic nervous system (PSNS) and sympathetic nervous system (SNS) at night. This non-randomized controlled pilot study included participants ≥60 years, diagnosed with a type of dementia or cognitive disorder. We excluded participants with pacemakers. The treatment group received 2500 lx BML, whereas the control group received approximately 200 lx of general lighting. We measured the heart rate variability to quantify ANS activity. The treatment group displayed significantly increased high-frequency (HF) power (Roy's largest root=2.44; P<.01) and insignificantly decreased normalized low-frequency (LF%) power. The corresponding low-frequency/high-frequency ratio (LF/HF), insignificant decrease, and cognitive function were correlated with PSNS activity (Roy's largest root=3.92; P<.01), which is effective for moderate dementia. BML exposure reduced SNS activity and enhanced PSNS activity at night, which consequently affected cognitive function. Furthermore, the light washout intervention markedly increased SNS activity at night. BML therapy may be a useful clinical tool for alleviating the deterioration of cognitive function.

Psychotherapy is one of the evidence-based clinical interventions for the treatment of depression in older adults with dementia. Randomized Controlled Trials are often the first methodological choice to gain evidence, yet they are not applicable to a wide range of humanistic psychotherapies. Amongst all, the efficacy of the Gestalt therapy (GT) is under-investigated. The purpose of this paper is to present a research protocol aiming to assess the effects of a GT-based intervention on people with dementia (PWD) and the indirect influence on their family carers. The study implements the Single-Case Experimental Design with Time-Series Analysis that will be carried out in Italy and Mexico. Ten people in each country, who received a diagnosis of dementia and present depressive symptoms, will be recruited. Eight or more GT sessions will be provided whose fidelity will be assessed by the GT Fidelity Scale. Quantitative outcome measures are foreseen for monitoring participants’ depression, anxiety, quality of life, carers’ burden, and the caregiving dyad mutuality, at baseline and follow-up. The advantages and limitations of the research design are considered. If GT will result effective in the treatment of depression in PWD, it could enrich the range of evidence-based interventions provided by healthcare services.

Multicomponent training is recommended for people with dementia living in long-term care homes. Nevertheless, evidence is limited and people with severe dementia are often excluded from trials. Hence, the aim of this study was to investigate (1) the feasibility and (2) the requirements regarding a multicomponent training for people with moderate to severe dementia. The study was conducted as an uncontrolled single arm pilot study with a mixed methods approach. 15 nursing home residents with a mean age of 82 years (range: 75-90 years; female: 64%) with moderate to severe dementia received 16 weeks of multicomponent training. Feasibility and requirements of the training were assessed by a standardized observation protocol. Eleven participants regularly attended the intervention. The highest active participation was observed during gait exercises (64%), the lowest during strength exercises (33%). It was supportive if exercises were task-specific or related to everyday life. This study confirms that a multicomponent training for the target group is (1) feasible and well accepted. To enhance active participation (2) individual instructions and the implementation of exercises related to everyday life is required. The effectiveness of the adapted training should be tested in future randomized controlled trials.

Background: This study aimed to assess the dementia literacy (DL) level of community-dwelling adults in the four cities (Hong Kong, Guangzhou, Macau and Zhuhai) of the Greater Bay Area of China and to determine the preferred mass media for receiving dementia information. Methods: A multi-city cross-sectional study with 788 community-dwelling adults completed the survey. Dementia literacy was indirectly measured by two validated scales, 30-item Alzhiemer’s Disease Knowledge Scale (ADKS) and 20-item Dementia Attitudes Scale (DAS). When the ADKS total score was <15 and DAS total score was <70, it was considered as ‘inadequate dementia literacy’. Participants were also asked to indicate whether they would like to receive dementia information via digital media or traditional media. Chi-square tests and logistic regressions were undertaken. Results: About one-third of the participants had inadequate dementia literacy. Those with young age or secondary education preferred to get dementia information from social media. But people living in public housing would like to get information from government or hospital websites. Middle-aged participants inclined to learn dementia from television or radio. Conclusion: It is worthy to conduct territory-wide public education in dementia and develop strategies according to their preferences in the types of mass media.

Research into the causes of neurotoxicity in Alzheimer’s Dementia (AD) has focused on neurofibrillary tangles and beta amyloid (Aβ) plaques. This paper proposes the heterodox theory that these hallmarks of AD are the visible effects, not direct causes of neuronal necrosis. Rather AD results from a combination of age-induced, disproportional decline in physiological support for aerobic metabolism, and dysregulation of the sleep cycle processes. The hypothesis is that the decimation of neurons in AD results from a combination of neurotoxicity and increased apoptosis caused by: 1. direct damage from toxic waste products of anaerobic glycolysis due to a progressive decline in the capacity of neurons to perform oxidative phosphorylation (OXPHOS) and an increased reliance on anaerobic glycolysis to meet metabolic needs; 2. impaired cellular repair and effluent release due to dysregulation of non-rapid eye movement (NREM) sleep allowing damage to cell membranes and synaptic junctions to accumulate inducing a chronic inflammatory response; 3. indirect damage from products produced by inflammatory reaction to toxic metabolites; 4. neuronal apoptosis from the AβPP-mediated pathway due to the age-induced decline of growth hormone (GH), GH-releasing hormone (GHRH) and insulin-like growth factor (IGF).

Alzheimer’s disease (AD) is the most widespread neurodegenerative disorder. Recently, it was found that mucus extract from Cornu aspersum have beneficial effects on memory and cognitive processes in a rat scopolamine model of AD. The present study elucidated mechanisms of action of standardized mucus snail extract (SE) enriched with fraction above 20 kDa on Alzheimer-type dementia in rats. Using proteomic analysis on two-dimensional polyacrylamide gel electrophoresis (2D–PAGE) on rat cortex extracts we compared protein expression in both groups: the first group treated intraperitoneally with scopolamine (Sco, 2 mg/kg, 11 days) and the second (Sco + SE) group treated intraperitoneally with Sco (Sco, 2 mg/kg) and protected by SE (0.5 ml/100 g bw) applied daily orally for 11 days. Brain cortex was separated and the expression of various proteins related to memory and cognitive functions were identified. We found that the expression of Ubiquitin carboxyl-terminal hydrolase isozyme L1, Calbindin, Vacuolar ATP synthase catalytic subunit A, Tropomyosin beta chain, 14-3-3 zeta/delta, Kinesin-1 heavy chain and Stathmin-4 significantly differs in SE-protected rats as compared to non-treated dement animals, and these brain proteins might be potential therapeutic targets for Alzheimer’s type dementia treatment.

Detecting and evaluating pain in people with cognitive impairment, especially dementia, is a challenge. Their ability to accurately report pain and comprehend related questions decreases the reliability of their self-report. This has contributed to the fact that pain is underdiagnosed and undertreated in this population, which can lead to involuntary ageism. The design and assessment of this training capsule under the context of the European COST-Action TD1005 responds to the need for education and training in "Pain Assessment In Cognitive Impairment, especially dementia" and the development of the internationally agreed observational PAIC15 scale. The 3-hour capsule, intended for healthcare workers and caregivers, consists of theoretical-practical levels: 1) basic concepts and challenges in pain in aging, cognitive impairment/dementia, 2) available scales and PAIC15, 3) video presentation of clinical cases illustrating a 3×2 matrix of situations (rest, transfer and experimental pain) and stages of disease (mild and moderate). The objectives focused on training the ability to observe, detect, and assess the signs of pain using PAIC15 and its feasibility. The pre-post analysis in a Master educational setting showed agreement with the results obtained in the Spanish national survey on 1) scarce knowledge of observational tools and their use, and 2) uncertainty in the identification of signs of pain and feasibility in moderate/severe scenarios. The capsule improved the ability to identify and evaluate the pain items, especially facial expressions, and their confidence on observational tools. Debriefings highlighted the relevance of observational scales in dementia and the gain obtained using the new observational instrument.

Considering the multifaceted nature of neurodegenerative diseases like dementia and the neces-sity for interprofessional knowledge, this research extends its scope to encompass professionals with diverse levels of training and experience in dementia care. A need analysis for the project “My INdividual Digital EDucation.RUHR” (MINDED.RUHR) is conducted to develop an au-tomatized recommender system for individual learning content using AI. In this sub-study, the aim was to reveal didactic specialties, knowledge gaps and structural challenges of further edu-cation in dementia care of different health professions and to derive learning preference personae. Eight focus group interviews among nine health professions and up to six participants (n = 34) each took place to survey distinct didactic experiences and learning needs. The results reflect various learning preferences, with a propensity to multimedia, practical and interactive tasks. Health professions are used to digital education but show aversions against certain e-learning formats. The derived learning preference personae constitute profound blueprints for a us-er-centred digital education design process, aiming to establish personalized and representative further education in dementia care applicable to various individual preferences and structural workplace challenges of healthcare professions.

TAU is the main disease driver in Alzheimer’s and many other sporadic and genetic tauopathies. TAU is differently spliced, the role of individual splice-isoforms unclear. Murine Mapt-KO mice are healthy, and protected from Alzheimer’s, but no such case has been reported in humans. Using gnomad database, we here demonstrate that the only isoform expressed during fetal human brain development is intolerant to mutation, while other brain and peripheral nervous system TAU isoforms are dispensable. With TAU targeted therapies for Alzheimer’s and other tauopathies on the rise, we caution that TAU is essential human brain development.

Better understanding of the quality of life among nursing home residents with dementia is im-portant for developing interventions. The objectives of this cross-sectional study were to examine factors associated with poor health-related quality of life in older adults with dementia living in nursing homes in Hanoi, Vietnam. In-person interviews were conducted with 140 adults 60 years and older with dementia and information about their quality of life was obtained using the Quality of Life in Alzheimer’s Disease scale (QOL-AD). A number of sociodemographic and clinical factors associated with poor health-related quality of life (lowest tertile) were assessed through the results of physical tests, interviews with nursing home staff, and review of medical records. The average age of the study sample was 78.3 years, 65% were women, and their av-erage QOL-AD total score was 27.3 (SD = 4.4). Malnutrition, total dependence in activities of daily living, and urinary incontinence were associated with poor quality of life after controlling for multiple potentially confounding factors. Our findings show that Vietnamese nursing home residents with dementia have a moderate quality of life and interventions based on comprehen-sive geriatric assessment remain needed to modify risk factors associated with poor health-related quality of life.

The blood–brain barrier (BBB) plays pivotal roles in synaptic and neuronal functioning by sealing the space between adjacent microvascular endothelial cells. BBB breakdown is present in patients with mild cognitive impairment (MCI) or Alzheimer disease (AD). Claudin-5 (CLDN-5) is a tetra-spanning protein essential for sealing the intercellular space between adjacent endothelial cells in the BBB. In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility by using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). Plasma levels of phosphorylated tau (pTau181), a biomarker of pathological tau, were elevated in patients with MCI or AD (2.86 and 4.20 pg/mL, respectively) compared with control subjects (1.81 pg/mL). In patients with MCI or AD, plasma levels of CLDN-5—but not pTau181—decreased with age, suggesting some age-dependent BBB changes in MCI and AD. These findings suggest that plasma CLDN-5 may a potential biochemical marker for the diagnosis of MCI and AD.

Synaptic zinc ions (Zn2+) play an important role in the development of vascular dementia (VD) and Parkinson’s disease (PD). In this article, based on our study and many others, we review the mo-lecular pathways by which Zn2+ causes neurotoxicity. Zn2+ influences calcium homeostasis, energy production pathway, production of reactive oxygen species, endoplasmic reticulum stress pathway, and activated protein kinase/c-Jun amino terminal kinase (SAPK/JNK) pathway and consequently exerts neurotoxicity. Furthermore, we searched various crops for substances that protect neurones from neurotoxicity caused by Zn2+ and clarified that carnosine (β-alanylhistidine) may be a therapeutic drug for VD and PD. Here, we also review the molecular mechanisms underlying the role of carnosine as an endogenous protector and its protective effect against Zn2+-induced cyto-toxicity and discuss prospects for future neurodegenerative diseases therapeutic applications of this dipeptide.

Alzheimer's disease is a neurological illness that worsens gradually. It is known as the most frequent cause of dementia. Moreover, Alzheimer's disease is a general term for memory loss and other cognitive impairments severe enough to disrupt daily life. The disease often grows in middle-aged and elderly people with the gradual loss of cognitive ability. Since the diagnosis of the illness is time consuming, a novel machine learning approach is proposed in this research to diagnose Alzheimer's levels based on Magnetic Resonance Imaging (MRI). More specifically, to provide distinct information for classification we have implemented the proposed method on a native MRI scans dataset containing three MRI channels; namely T1, T2, and, T2 tirm, which are shown in red, blue and green, respectively. The five middle layers of these three types of MRI scans are combined to form five RGB layers. In addition, we use a Convolutional Neural Network to classify each composed layer, and the final disease type is predicted using majority voting. finally, the F1-Score has been used to assess method performance, indicated that 92% of predictions of the proposed model were accurate.

ackground: This study aimed to examine the effects of a woodworking program on psychosocial health in older adults who had mild cognitive impairment (MCI) or mild dementia (MD) in Korea. Setting: The study was carried out in a dementia center in Seoul in Korea. Population: A total of 61 participants who had MCI or MD were allocated into two groups: the experimental group (EG, n = 35) and the control group (CG, n = 26). Methods: This study was carried out using a nonequivalent control group pre-test–post-test design. The EG participated in the woodworking program a total of 10 times for 120 min per session twice a week for 5 weeks, and the CG did not participate in the woodworking program. Both groups completed the same survey before and after the intervention. In the survey, demographic characteristics, psychological health (life satisfaction, depression, self-efficacy, and resilience), and social health (social isolation and social support) were measured. Results: In the within-group comparison, there was no significant difference between any factors of the CG before and after the intervention. In contrast, the EG had a significant improvement before and after the woodworking program. Participants in the EG with MCI and MD significantly improved their social support (p < 0.05). Psychological factors (life satisfaction, depression, and self-efficacy) were positively changed, although not significantly. Conclusions: The woodworking program promoted psychosocial health, such as life satisfaction, resilience, and social support, among older adults with mild cognitive impairment and mild dementia.

Several recent epidemiological studies attempted to identify risk factors for Alzheimer's disease. Age, family history, genetic factors (APOE genotype, Down syndrome), physical activity, and a low level of schooling are significant risk factors. In this review, we summarize the known psychosocial risk factors for the development of Alzheimer's disease in Down syndrome patients and their association with neuroanatomical changes in the brains of people with Down syndrome. We completed a comprehensive review of the literature on PubMed, Google Scholar, and Web of Science about psychosocial risk factors for Alzheimer's disease, for Alzheimer's disease in Down syndrome, and Alzheimer's disease in Down syndrome and their association with neuroanatomical changes in the brains of people with Down syndrome. Alzheimer's disease causes early pathological changes in Down syndrome patients, especially in the hippocampus and corpus callosum. The field needs more data about the neuroanatomical changes during childhood, how they change with increasing age, and the presence or absence of psychosocial risk factors. Further neuroimaging and psychosocial assessment-focused research is needed to understand the mechanisms leading to Alzheimer's disease at an early age and create more sensitive and relevant clinical, memory, and reasoning assessments for people with Down syndrome.

The purpose of this study is to explore the effects of dual-task training, including cognitive tasks, on cognitive and bodily functioning and β-amyloid levels in Alzheimer's dementia patients. The subjects were 34 inpatients diagnosed with Alzheimer's dementia at a nursing hospital located in Gyeongsansi, South Korea. The patients were randomly divided into a dual-task group (n = 16) and a single-task group (n = 18). The dual-task group performed cognitive tasks at the same time as exercising tasks, while the single-task group performed only exercise tasks. Each group was trained for 30 minutes three times a week for eight weeks. The Mini-Mental State Examination was used to measure the patients’ cognitive function. Static and dynamic balance were measured to evaluate bodily functioning. Static balance was measured using Biorescue, while dynamic balance was measured using the Berg Balance Scale. Blood analysis was performed to measure levels of β-amyloid, which is known to cause Alzheimer's dementia. Both groups exhibited statistically significant improvements in gait function after the training (p < .05). The dual-task group exhibited statistically significant differences in cognitive function, static and dynamic balance function, and β-amyloid levels after training (p < .05). A significant difference was observed between the two groups (p < .05). Dual-task activities were found to be effective in improving cognitive and bodily functioning and reducing β-amyloid levels in Alzheimer's dementia patients. Therefore, dual-task training is thought to be an effective method of treating and preventing Alzheimer's dementia.

As the number of older adults with dementia increases, early diagnosis and intervention are crucially important. The purpose of this study was to conduct dementia screening on older adults to determine whether there are differences in daily activities of living, depression, loneliness, social support, and life satisfaction between older adults at high-risk for dementia compared with low-risk older adults. We hypothesized a negative relationship between high-risk older adults and these factors. This study also hypothesized a moderating effect for social support on the relationship between daily living activities and life satisfaction. This study used a cross-sectional design with survey data. Participants were recruited at 15 public community health centers in South Korea. A total of 609 older adults (male 208, female 401) living in the community were screened for early dementia, and 113 participants (18.9 %) were assigned to the high-risk group. As hypothesized, participants in the high-risk group showed significantly more negative results ​​in terms of activities of daily living, depression, loneliness, social support, and life satisfaction compared with participants in the low-risk group. The findings of this study provide a theoretical basis for the importance of early screening for dementia and policies for effective dementia prevention.

Purpose: This paper extends previous works to include the role of therapeutic gardens in the healing environment as an intervention for bettering the clinical outcomes of Alzheimer’s and dementia patients, the positive impact of healing gardens and the innovative application of technologies with nature, for promoting cognitive rehabilitation in this particular patient population.Methods: Using ISI Web of Science, PubMed, ProQuest Central, MEDLIN, Scopus and Google Scholar, a relevant literature search on the positive health implications of therapeutic gardens on Alzheimer’s and dementia patients’ in the healthcare milieu was conducted.Results: Health implication of therapeutic gardens on Alzheimer’s and dementia patients’ spans across physical, social, psychological and cognitive effects. Virtual reality (VR) technologies offer positive cognitive outcomes to Alzheimer's disease (AD) and dementia patients.Conclusion: Therapeutic gardens should be extended for speedier recovery of other patient populations. Future directions in the design of healthcare gardens with a focus on patient experience are inferred.

Identifying effective and accessible interventions for family caregivers of persons with dementia (PWD) is crucial as the prevalence of dementia increases in Asia. This study investigated the efficacy of a telephone-intervention on reduction of caregiver burden, depressive and anxiety symptoms among family caregivers (FC) of PWD in Malaysia. A single-blinded randomized controlled trial was carried out with 121 FCs of PWD selected from memory or psychiatry clinics in three tertiary hospitals in Malaysia who were randomly allocated into intervention or control group. The intervention group received the psychoeducational intervention delivered by a healthcare staff via telephone for 10 sessions over 12 weeks. The outcome of the intervention was measured by the Malay version of the Zarit Burden Interview and the Hospital Anxiety and Depression Scale at baseline and post-intervention. Intention-to-treat analysis shows that caregiver burden, anxiety symptoms, and psychological distress among FCs in the intervention group decreased by 7.57 units (p&lt;0.001), 2.46 units (p&lt;0.001) and 2.98 units (p=0.011) respectively at post-intervention, compared to the differences from baseline to post-intervention in the control group. Policies aimed at integrating the telephone-intervention into memory/psychiatry clinics in Malaysia may help FCs of PWD to reduce their caregiver burden and stress while caring for a family member with dementia.

Background/Objectives: Rehabilitation helps reduce disability in dementia. The Australian National Dementia Action Plan identifies a gap in clear treatment pathways post-diagnosis, affecting the quality of life for those with dementia. This study assessed the impact of a one-day dementia training course and follow-up on GPs' and practice nurses' knowledge, attitudes, and confidence regarding dementia rehabilitation. Methods: The training, led by two experienced GPs and an academic physiotherapist, covered dementia diagnosis, allied health roles, care planning, and referrals. The follow-up involved applying the learnt material and completing a reflective task. Three longitudinal surveys (Dementia Knowledge Assessment Scale - DKAS, General Practitioners’ Attitudes and Confidence towards Dementia Survey - GPACS-D, and Dementia Rehabilitation Scale) and Likert-scale statements were conducted pre-course, post-course, and at 4-month follow-up, alongside a focus group. Descriptive and regression analyses were applied to survey data, and content analysis was used for focus group data. Results: Seventeen participants (14 GPs, 3 nurses) completed the pre-post course survey, with eight (6 GPs, 2 nurses) participating in follow-up and focus group discussions. Post-course, DKAS scores increased by 12.1%, GPACS-D by 10.1%, and the dementia rehabilitation scale by 9.4%. Likert-scale statements improved by 8-79%. At the four-month follow-up, there was a slight, non-significant decline in most measures. Focus groups highlighted the training’s impacts, useful components, barriers, and suggestions for improvement. Conclusion: Training GPs and practice nurses in dementia rehabilitation enhances knowledge, awareness, and confidence. Ongoing efforts are needed to sustain benefits and address referral barriers for better access to dementia rehabilitation services.

Background: Monogenic Alzheimer's disease (AD) has severe health and socioeconomic repercussions. Its rarest cause are presenilin 2 (PSEN2) gene mutations. We present two new cases with presumed PSEN2-AD, with unusual clinical and neuroimaging findings in order to provide more information on the pathophysiology and semiology of these patients. Methods: Women aged 69 and 62 years at clinical onset, marked by prominent behavioral and language dysfunction, progressing to severe dementia within three years. Neuroimaging, laboratory study, genetic testing. In addition, a systematic review of the PSEN2-AD were performed. Results: Neuroimaging revealed pronounced frontal white matter hyperintensities (WMH) and frontotemporal atrophy/hypometabolism. The genetic study unveiled PSEN2 variants: c.772G>A (p.Ala258Thr) and c.1073-2_1073-1del. Both cerebrospinal fluid (CSF) and experimental blood biomarkers shouldered AD etiology. Conclusions: Prominent behavioral and language dysfunction suggesting frontotemporal dementia (FTD) may be underestimated in the literature as a clinical picture in PSEN2 mutations. Thus, it may be reasonable to include PSEN2 in genetic panels when suspecting FTDL. PSEN2 mutations may cause striking WMH, arguably related with myelin disruption induced by amyloid accumulation.

We propose that a dietary reduction of Lipopolysaccharide (LPS) could reduce risk and slow the progression of cognitive decline and Alzheimer’s disease. LPS is a component of the highly inflammatory cell membrane of Gram-negative bacteria. The highest dietary sources of LPS are processed meat and dairy products, which can sharply raise plasma LPS within one to two hours. The LPS in these foods is packaged into chylomicrons, which enter the bloodstream. Smaller amounts of LPS from colonic microbiota do not account for the sharp postprandial increase of plasma LPS. Once in the bloodstream, LPS can trigger the release of inflammatory cytokines within three hours. LPS can increase cytokines via LPS binding protein and cluster of differentiation-14, triggering toll-like receptor-4, and activating nuclear factor kappa-B. Nuclear factor kappa-B can increase cytokine levels, including interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha. LPS and inflammatory cytokines are higher in Alzheimer’s disease, both in plasma and in the central nervous system. These cytokines can enter the brain via active transport and induce microglial activation and inflammatory damage in the brain, including loss of synapses and neurons. Elevated brain inflammation from dietary LPS can contribute to cognitive impairment and increased risk of dementia.

The genetic bases of Alzheimer's disease (AD) and frontotemporal dementia (FTD) have been comprehensively studied, which is not the case for atypical cases not classified into these diagnoses. In the present study, we aim to contribute to the molecular understanding of the development of non-AD and non-FTD dementia by surveying rare pathogenic variants. The analysis was performed on 91 patients, the DNA samples of which were pooled and then subjected to whole exome sequencing. Among detected variants two are rare pathogenic and show significant difference in frequency between the analyzed pool and gnomAD Bulgarian control exomes. The rs373478202, G&gt;T, B9D1 variant, most likely present in heterozygous state; is causative for the autosomal recessive ciliopathy- Joubert syndrome, which involves specific CNS malformation. The rs148918985, C&gt;T, ASS1 variant leads to arginosuccinate enzyme deficiency and in compound heterozygosity with other rare pathogenic variant detected in the same gene causes the late-onset form of citrullinemia type I. This disorder causes high ammonia levels, which can lead to cerebral dysfunction. In conclusion, the detected rare pathogenic variants suggest that, in certain cases, the development of non-AD and non-FTD dementia can be mediated by structural alterations in neuronal cilia or by hyperammoniemia.

There are two generic approaches to curing any medical condition. The first treats every patient for all of the known possible causes that contribute to pathogenesis; the second individualizes potentially curative therapy by identifying in each separate patient only those components of pathogenesis that are actually operative, and treating those. This article adopts the second approach for formulating a cure of Alzheimer’s dementia (AD). Components of AD’s pathogenesis are, in alphabetical order: circadian rhythm disturbances, depression, diabetes and insulin resistance, dyslipidemia, hypertension, inflammation, metabolic syndrome, mitochondrial dysfunction, nutritional deficiencies, TGF-β deficiency, underweight, vascular abnormalities, and Wnt/β-catenin deficiency. For each component, data are described that show the degree by which its prevalence is more in the patients with mild cognitive impairment (MCI) who did not revert to having normal cognition than in those who did, because the former group is the pool of patients from among which future AD may develop. Addressing only those components that are present in a particular individual, is potentially a curative strategy. Published data indicate that curative therapy requires that the number of such components to address should be ≥3. Although structural brain changes cannot be directly addressed, the impaired neural tracts result from many of the reversible causal elements, so correcting them will benefit those tract

Dementia education and training for workforce development is becoming increasingly important in bridging knowledge gaps among health and social care practitioners in the UK and internationally. Dementia Education for Workforce Excellence (DEWE) was developed during the COVID-19 pandemic blending both synchronous and asynchronous instruction and delivered across three different contexts: care homes, home care, and nurse education within the UK and India. This study aimed to evaluate DEWE using mixed methods with online survey data analyzed descriptively and interview data analyzed thematically. Integration of survey and interview data aimed toward a comprehensive evaluation of this novel approach for dementia workforce development. Thirty-four social care practitioners and nurse educators completed the online survey demonstrating high-level learner satisfaction; learning gains; behavioral change, and motivation to share new knowledge. Four key themes developed from the analysis of interviews (n=9) around participants’ pursuit of new knowledge; delivery modes in DEWE; learning gains and impact of DEWE; and adaptations for future program implementation. Findings suggest DEWE is an innovative resource that promotes person- and relationship-centered dementia care across all stages of one’s dementia journey. Cultural adaptations are recommended for international delivery to ensure contextual alignment and maximum impact.

Intermediate CAG expansions in the gene ataxin-2 (ATXN2) are a known risk factor for ALS, but little is known about their role in FTD risk. Moreover, their contribution to the risk and phenotype of patients might vary in populations with different genetic background. The aim of this study was to assess the relationship of intermediate CAG expansions in ATXN2 with the risk and phenotype of ALS and FTD in the Spanish population. Repeat-Primed PCR was performed in 620 ALS and 137 FTD patients in three referral centers of Spain to determine the exact number of CAG repeats. In our cohort, ≥27 CAG repeats in ATXN2 was associated with a higher risk of developing ALS (odds ratio [OR] = 2.666 [1.471-4.882]; p = 0.0013), but not FTD (odds ratio [OR] = 1.446 [0.558-3.574]; p = 0.44). Moreover, ALS patients with ≥27 CAG repeats in ATXN2 showed shorter survival rate compared to those with &lt;27 repeats (hazard ratio [HR] 1.74 [1.18, 2.56], p = 0.005), more frequent limb onset (odds ratio [OR] = 2.34 [1.093-4.936]; p = 0.028), as well as family history of ALS (odds ratio [OR] = 2.538 [1.375-4.634]; p = 0.002). Intermediate CAG expansions of ≥27 repeats in ATXN2 are associated with ALS risk, but not with FTD, in the Spanish population. ALS patients carrying an intermediate expansion in ATXN2 show more frequent limb onset, but worse prognosis than those without expansions. In patients carrying C9orf72 expansions, the intermediate ATXN2 expansion might increase the penetrance and modify the phenotype.

Sporadic Alzheimer’s disease (AD) derives from an interplay among environmental factors and genetic variants, while epigenetic modifications have been expected to affect the onset and progression of its complex etiopathology. Heterozygous carriers of the apolipoprotein E gene (APOE)4 allele have a 4-fold increased risk of developing AD, while APOE 4/4-carriers have a 12-fold increased risk in comparison with the APOE 3-carriers. The main longevity factor is the homozygous APOE ε3/ε3 genotype. In the present narrative review article, we summarized and described the role of APOE epigenetics in aging and AD pathophysiology. It is not fully understood how APOE variants may increase or decrease AD risk, but this gene is known to affect amyloid- and tau-mediated neurodegeneration directly or indirectly, also by affecting lipid metabolism and inflammation. For sporadic AD, epigenetic regulatory mechanisms may control and influence APOE expression in response to external insults. Diet, a major environmental factor, has been significant associated with physical exercise, cognitive function, and the methylation level of several cytosine-phosphate-guanine (CpG) dinucleotides sites of APOE.

Frontal Temporal Dementia (FTD) is a neurological disorder known to have less therapeutic options. So far only a few biomarkers are available for FTD that can be used as potential comorbidity targets. To this end, in the present study we aim to identify potential biomarkers or susceptible genes for FTD that show comorbidities with diseases such as COVID-19 and Breast Cancer. Gene expression Omnibus datasets containing FTD expression profiles from African American and white ethnicity background were included in our study. In FTD samples of GSE193391 dataset, we identified 305 DEGs with 168 genes being up-regulated and 137 genes being down-regulated. We conducted comorbidity analysis for COVID-19 and Breast cancer followed by analysis of potential drug interactions, pathogenicity, analysis of genetic variants and functional enrichment analysis. Resulting genes AKT3, GFAP, ADCYAP1R1, VDAC1, and C4A showed significant transcriptomic alterations in FTD and significant comorbidity status with COVID-19 and Breast cancer. Functional pathway analysis revealed that these comorbid genes were significantly enriched in the pathways such as glioma, JAK/STAT signaling, systematic lupus erythematosus, neurodegeneration-multiple diseases and neuroactive ligand-receptor interaction. Overall, from these results, we concluded that these genes could be recommended as potential therapeutic targets for the treatment of comorbidities in FTD.

Depression is estimated to be a leading contributor to the global mental health-related burden. The determinants of this huge prevalence lie in the fact that depressive symptoms may be comorbid in a wide variety of disorders, thus complicating and exacerbating their clinical pictures. This makes the treatment of depressive symptoms even more difficult since many pharmacological and pharmacokinetic interactions should be considered by physicians approaching the therapy. Hence, depression still represents a challenge for both psychiatrists and the other clinicians, in terms of its high rates of relapse and resistance despite well-established protocols. It is also complicated by the well-known latency in its complete response to current antidepressant treatments. In this context, the search for new strategies in antidepressant treatment is mandatory; even including revising the use of “old” pharmacotherapies by considering their specific features may help to perfecting the treatment of depression, both in its standalone psychiatric manifestation and in the framework of other clinical conditions. The results of a consensus of experts regarding the possible use of trazodone as a valuable strategy for addressing the “real world” unmet needs of depression treatment is herein reported. This is based on the unique characteristics of this drug possibly delivering a rapid antidepressant action as compared to other selective serotonin reuptake inhibitors (SSRIs) as well as on its pharmacodynamic malleability and pharmacokinetic tolerability when used in the milieu of other drugs in treating comorbid depressive symptoms.

Introduction: Periodontitis is a severe oral infection that can contribute to systemic inflammation. A large body of evidence suggests a role for systemic inflammation in the initiation of neurodegenerative disease. This systematic review synthesized data from observational studies to investigate the association between periodontitis and neuroinflammation in adults. Methods and materials: A systematic literature search of PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) was performed for studies published from the date of inception up to September 2021. Search terms for the exposure “oral disease” and outcome “dementia”, “neuroinflammation” and “cognitive decline” were used. Study selection and data extraction were independently undertaken by two reviewers. The final eligible articles were included only if the exposure is periodontitis and the outcome is cognitive impairment or dementia or a topic related to this condition, and if the study was conducted in an adult population. The quality and risk of bias were assessed by Newcastle Ottawa Scale (NOS). Qualitative synthesis was used to narratively synthesize the results. Six cohort studies, three cross-sectional studies, and two case-control studies met the inclusion criteria. These eleven studies were only narratively synthesized. Meta-analysis was not performed due to the methodological heterogeneity of the studies. Results: All the included studies show evidence of an association between periodontitis and cognitive im-pairment or dementia and Alzheimer’s disease pathology. Conclusion: Nonetheless, the mechanisms responsible for the association between periodontitis and dementia are still unclear.

Type 2 Diabetes Mellitus is being increasingly associated with dysfunction of cognition. Dementia, including vascular dementia and Alzheimer’s disease, is being recognized as comorbidities of this metabolic disorder. The progressive hallmarks of this cognitive dysfunction include mild impairment of cognition and cognitive decline. Dementia and mild impairment of cognition appear in older patients primarily. Studies on risk factors, neuropathology, and brain imaging have provided important suggestions for mechanisms that lie behind the development of dementia. It is a significant challenge to understand the disease processes related to diabetes which affect the brain and lead to dementia development. The connection between Diabetes Mellitus and dysfunction of cognition has been observed in many human and animal studies that have noted mechanisms related to Diabetes Mellitus are possibly responsible for aggravating cognitive dysfunction. This article attempts to narrate the possible association between type 2 diabetes and Dementia, reviewing studies that have noted this association in vascular dementia and Alzheimer’s disease and helping to explain the potential mechanisms behind the disease process. The Google search for ‘Diabetes Mellitus and Dementia’ was carried out. Also, the search was done using ‘Diabetes Mellitus,’ ‘Vascular Dementia,’ ‘Alzheimer’s Disease.’ The literature search was done from Google Scholar, Pubmed, Embase, ScienceDirect, and MEDLINE. Keeping in mind the increasing rate of Diabetes Mellitus, it is important to establish the type 2 diabetes effect on the brain and diseases of neurodegeneration. This narrative review aims to build awareness regarding different types of dementia and their relationship with diabetes.

Because of an often complicated and difficult-to-access care system, help-seeking for people with suspected dementia can be stressful. Difficulty in help-seeking may contribute to carer burden, in addition to other known stressors in dementia care. This study examined the relationship between perceived help-seeking difficulty and carer burden, and the barriers contributing to perceived difficulty. We interviewed 110 carers accessing a community-based dementia assessment service for suspected dementia of a family member for their perceived difficulty, delays, and barriers in help-seeking, and carers burden in terms of role strain, self-criticism, and negative emotions. Linear regression models showed that perceived help-seeking difficulty is associated with carer self-criticism, while carer role strain and negative emotions are associated with symptom severity of the person with dementia but not help-seeking difficulty. Inadequate knowledge about symptoms, service accessibility, and affordability together explained more than half of the variance in perceived help-seeking difficulty (Nagelkerke R2 = .56). Public awareness about symptoms, support in navigating service, and financial support may reduce perceived difficulty in help-seeking, which in turn may reduce carer self-criticism during the early course of illness.

Important policy developments in dementia and palliative care in nursing homes between 2010 and 2015 in Flanders, Belgium might have influenced which people die in nursing homes and how they die. We aimed to examine differences between 2010 and 2015 in the prevalence and characteristics of residents with dementia in nursing homes in Flanders, and their palliative care service use and comfort in the last week of life. We used two retrospective epidemiological studies, including 198 residents in 2010 and 183 in 2015, who died with dementia in representative samples of nursing homes in Flanders. We found a 23%-point increase in dementia prevalence (P-value<0.001), with a total of 11%-point decrease in severe to very severe cognitive impairment (P=0.04). Controlling for this difference in resident characteristics, in the last week of life, there were increases in the use of pain assessment (+20%-point; P<0.001) and assistance with eating and drinking (+10%-point; P=0.02) but no change in total comfort. The higher prevalence of dementia in nursing homes with no improvement in residents’ total comfort while dying emphasize an urgent need to better support nursing homes in improving their capacities to provide timely and high-quality palliative care services to more residents dying with dementia.

Background: Advancements in the next-generation sequencing (NGS) techniques have allowed for efficient genetic variant detection at reduced costs. Methods: We describe an ad hoc NGS-based custom designed resequencing gene panel to identify genetic variants in 8 patients with dementing disorders. Results: We found variants of TREM2 and APP genes in three patients; these have been previously identified as pathogenic or likely pathogenic and, therefore, considered as “Disease Causing”. In the remaining subjects, the pathogenicity was evaluated on the in silico analysis, according to the guidelines of the American College of Medical Genetics. In one patient, the p.R205W variant was causative of the disease, thus considered as “Possibly Disease Causing”. The variants found from the other four subjects in the CSF1R, SERPINI1, GRN, and APP genes revealed discordant in silico results and, therefore, it was not possible to assign a definitive pathogenicity. Conclusions: Notwithstanding the limitations of a customized panel, we detected some rare genetic variants with a probable disease association. The future application of NGS techniques and the further replication of these experimental data will replace the so-called “gene by gene” approach with a “panel of genes” strategy, that offers promising perspectives in the diagnosis and management of neurodegenerative disorders.

The following systematic and bibliographic review investigates the intersection between the treatment of cognitive impairments and virtual and augmented reality-based game-oriented applications. The review provides a view into the last 12 years of research. The PubMed Database served as the main source for the review. We defined a comprehensive set of investigation variables and classified three main topics: bibliography, medical, and technical. Of a total of 61 identified articles, 19 were included. The findings from these studies indicate the positive effects of using virtual and augmented reality applications to improve cognitive function and depression. There is also a gap in high-quality evidence since clinical trials have been conducted only with a few patients. Preliminary results indicate positive cognitive and physical well-being effects, but the field demands further investigation to determine the effectiveness. Future research needs to focus on larger studies and the quality of the developed applications. Further, it is important to look at scores like Quality of Living and Satisfaction in Daily Activities to create a functioning environment for the patient.

Background: Falls in older adults are prevalent and can result in an injury affecting their quality of life. Whether a fall is fatal or not, it has a high financial impact. Older adults with dementia are more likely to fall than their cognitively healthy counterparts, increasing their risk of serious injury or even death. This quality improvement project developed, implemented, and evaluated an evidence-based fall prevention bundle to reduce preventable falls in a long-term memory care unit.; Methods: The interventions that were implemented includes fall risk screening, physical exercise, vitamin D supplementation, purposeful hourly rounds, and post-fall huddles. Kurt Lewin’s force field analysis guided the project’s implementation. Nurses, healthcare providers, certified nursing assistants, restorative aides, and life enrichment staff from all shifts at a long-term memory care unit participated in the project. The participants implemented the evidence-based fall prevention bundle based on their scope of practice. They participated for 12 weeks. The frequency of falls was compared three months before, during, and after implementation. Paired t-test and independent samples t-test were used to analyze statistically significant differences between variables.; Results: Thirty staff members attended educational sessions, and 22 residents received interventions. Fall rates dropped 50% during the project's implementation but increased subsequently. The difference in the number of falls before, during, and after implementation was not statistically significant.; Conclusions: Staff working in a long-term care facility may help reduce fall rates using evidence-based interventions, but measures should be taken to sustain the initiative's implementation.

The behavioral variant of frontotemporal dementia (bvFTD) has a devastating effect on multiple domains of daily living. The purpose of this PRISMA-compliant systematic review is to summarize the most important factors associated with functional impairment in this clinical group by critically analyzing the existing literature spanning the period from 2000 to 2023. To be included in the review, the study had to investigate any kind of correlates of functional status in bvFTD patients, using a previously validated instrument of functional assessment. Out of 40 articles assessed for eligibility, 18 met the inclusion criteria. The anatomical pattern of cerebral atrophy at baseline appeared to be the strongest predictor of the rate of functional decline over time, with the frontal-dominant anatomical subtype being associated with a faster rate of functional impairment. Additionally, executive dysfunction as well as apathy appeared to contribute significantly to functional disability in bvFTD patients. A comparative examination of bvFTD in relation to other clinical subtypes of FTD and other types of dementia in general suggests that it’s the predominant atrophy of the frontal lobes along with the subsequent unique combination of cognitive and neuropsychiatric manifestations that account for the pronounced functional limitations observed in these individuals, even from the early stages of the disease.

Alzheimer's disease (AD) is a complex disease involving multiple factors such as amyloid plaque formation, mitochondrial dysfunction, telomere length, and oxidative stress. As the disease began 20 years before the onset of clinical symptoms, treatment of AD after its onset is likely to be too late to have a significant effect. Therefore, prevention from an early stage is important. Twendee X®︎ (TwX, Oxicut®︎) is an antioxidant supplement consisting of eight ingredients. TwX has been proven to prevent dementia in patients with mild cognitive impairment (MCI) in a multicenter, randomized, double-blind, placebo-controlled, prospective intervention trial. To elucidate the mechanisms of TwX on brain and cellular function, TwX was administered in in vitro experiments and in a C57BL/6 old wild-type, and spontaneous hyperglycemia model with accelerated cognitive decline, and its effects on diabetes, brain autophagy, neurogenesis, and telomere length were evaluated in comparison with those of the non-treated groups. TwX protected mitochondria from oxidative stress with higher antioxidant capacity than a single antioxidant. TwX not only lowered blood glucose levels, but also suppressed reduction of brain neurogenesis and loss of autophagy. Telomeres in aged mice were significantly longer than those in non-TwX-treated mice. Development of dementia is based on many factors of brain function. TwX was suggested to prevent dementia not only by its antioxidant effects, but also by its effects on diabetes, brain neurogenesis, telomere deficiency, and energy production.

Genetic discoveries related to Alzheimer’s disease and other dementias have been performed using either large cohorts of affected subjects or multiple individuals from the same pedigree, therefore disregarding mutations in the context of healthy groups. Moreover, a large portion of studies so far have been performed on individuals of European ancestry, with a remarkable lack of epidemiological and genomic data from underrepresented populations. The present study aims at scanning 70 single-point mutations on the APP gene in a publicly available genetic dataset including 2.504 healthy individuals from 26 populations, and analyzing their distribution. Moreover, after gametic phase reconstruction, a pairwise comparison of the segments surrounding the mutations was performed to reveal patterns of haplotype sharing that could point to specific cross-population and cross-ancestry admixture events. Eight mutations have been detected in the worldwide dataset, with several of them being specific for a single individual, population or macroarea. Patterns of segment sharing reflect recent historical events of migration and admixture possibly linked to colonization campaigns. These observations reveal the population dynamics of the considered APP mutations in worldwide human groups, and support the development of ancestry-informed screening practices for the improvement of precision and personalized approaches to neurodegeneration and dementias.

Background and objectives: Alzheimer's disease (AD) is a progressive neurodegenerative illness, responsible for 60-70% of all dementias, affecting over 50 million people worldwide, and nearly 11 million in European countries. Several putative factors are identified in the literature as causative agents or risk factors for the development of AD. The amyloid cascade hypothesis has been the main hypothesis about the pathophysiology of AD for decades. Recent studies raised the possible role of dysbiosis in the development of AD which prevents memory loss. The amyloid-β (Aβ) deposition might be considered as an inflammatory reaction to certain molecular products arising from the altered microbiome. Based on the above observations, it has been suspected, that antibiotic consumption patterns of different antibiotic classes might be associated with the prevalence of AD in European countries. Methods: Antibiotic consumption (ECDC) for 1997-2007, 2008-2018, and as the whole 1997-2018 period, have been compared to the AD prevalence for 2018 expressed in percentage of the population and statistically analyzed by Pearson calculation. Results: A significant positive correlation has been found between the AD prevalence (2018) and the average quinolone consumption for the year 1997-2007 (p: 0.044). A similar association was not observed for the entire 22 years (1997-2018) of the average quinolone consumption, and the years 2008-18, indicating 10-20 years of time-lapse between the antibiotic exposure and the development of AD. The ratio of broad-spectrum and narrow-spectrum antibiotics (B/N) estimated in the ECDC database for the years of 2008-2018 showed a strong positive association with AD prevalence (2018) (p: 0.026) and a positive correlation tendency for the entire 22 years 1997-2018 (p: 0.063), but none for the years 1997-2007 (p: 0.241). Broad-spectrum, beta-lactamase sensitive penicillin (J01CA) consumption showed a positive (non-significant) correlation with the prevalence of AD for the years 2008-2018 (p:0.080).Discussion: Our study indicated the possible sequential role of certain classes of antibiotics in the development of dysbiosis leading to amyloid deposits of AD, which strengthen the possible role of different mediator molecules (short-chain fatty acids, lipopolysaccharides, etc.) produced by the altered microbiome in the development of AD.

Background: This paper investigates the statistical relationship between bilingualism and the Onset Age (OA) of AD and MCI across a clinical sample, consisting of 580 Alzheimer's Disease (AD) subjects and 1264 Mild Cognitive Impairment (MCI) subjects, via a statistical analysis conducted on the sample retrieved from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Method: To investigate whether bilingualism has any correlation with the OAs of AD or MCI subjects, our study leverages the full potential of the ADNI dataset, a dataset that covers both the OA and the bilingualism status of both the AD and MCI subjects. Prior to performing any meaningful statistical analysis, a regression model and a probabilistic model were developed in parallel to fill in the missing OA and bilingualism values. A simple least-square regression model that consists of an independent variable of registered age for Mini-Mental State Examination (MMSE) score was used to estimate the OA of the AD and MCI subjects in the ADNI dataset. After filling in the missing OA values, the number of subjects relevant for the statistical analysis increased from 816 (AD: 371, MCI: 445) to 1844 (AD: 580, MCI: 1264), which greatly enlarged the representation of the AD and MCI sample in the ADNI population. With increased sample size, a novel probabilistic classification model was introduced to infer an ADNI subject’s bilingualism when relevant demographic information and deterministic outcome were not readily available from the ADNI dataset. The weighted average OA for the bilinguals and the monolinguals was then computed, where the weights for the probabilistic labels were assigned based on the percentage of bilingualism in the general US population. Finally, a statistical analysis was performed to test whether any statistically significant correlation exists between the OA and the bilingualism of the AD and MCI subjects within the ADNI dataset. Findings: Our preliminary study demonstrates no significant statistical difference between the OA of the bilinguals and the monolinguals within the ADNI dataset. Thus, the monolingual speakers within the ADNI dataset do not statistically manifest earlier onset, as compared to the bilingual speakers, which is slightly inconsistent with some earlier statistical findings that bilingual speakers enjoy certain distinctive advantages, such as late onset of AD, as compared to monolingual counterparts.

The term dehumanisation refers to the ways in which a person is perceived to be less than human or treated as if they are less than human. It involves treating a person as if they are a child or infant, like an animal or non-living object, or as if they are dead, or any other way in which someone fails to be treated like a human being with an adult identity. Dehumanisation is widespread in dementia care; it is a major obstacle to person-centred care and has poor outcomes for people with dementia. This article proposes a new model of dehumanisation. The New Model presents a new way of describing dehumanisation that has been synthesised from current understanding about the phenomenon and reflects what is presently known about the subject. The model aims to summarise existing theories and models of dehumanisation and make dehumanisation theory accessible to students and trainees in healthcare. This article describes the new model, discusses existing models and theories in the literature, and explores the potential role of the new model in solutions for reducing dehumanisation in dementia care.

Dementia is a group of detrimental diseases and conditions that damage the human brain and impair mental functioning. In recent years, significant efforts have been made to develop robust computer-aided diagnostic tools, particularly AI models for detection. However, their clinical implementation remains limited. One issue identified is that despite achieving high accuracy, AI-powered predictions have relied on single features or small sets of features in limited categories, hindering their robustness and generalizability. Moreover, the accuracy alone has not been sufficient to convince medical practitioners to adopt these tools, as they require transparent and scientifically grounded diagnostic processes. This study aims to improve the transparency and reliability of AI models in predicting dementia through three key steps: 1) compare a Machine Learning (ML) model's accuracy in detecting dementia when trained on a multi-domain dataset to when trained on subsets of features, 2) evaluate additional ML models for dementia detection using the multi-domain dataset, and 3) apply Explainable AI (XAI) to elucidate the importance of specific features in ML-based predictions, thereby enhancing transparency and interpretability. We hypothesize that utilizing multi-domain data will enhance the performance of ML models. Furthermore, XAI will demonstrate that features with high influence on the model's decisions are aligned with established indicators of dementia. This study contributes to the field by constructing lightweight predictive models that deliver highly accurate performance while enhancing transparency and interpretability, advancing toward clinically applicable AI-powered diagnosis.

Background: Neurocognitive disorders (NCDs) have a variable decline in cognitive function, while loneliness was associated with cognitive impairment and increased dementia risk. In the present study, we examined the associations of loneliness with functional and cognitive status in patients with minor (mild cognitive impairment) and major NCDs (dementia). Methods: We diagnosed mild NCD (n=42) and major NCD (n=164) through DSM-5 criteria on 206 participants aged>65 years using the UCLA 3-Item Loneliness Scale (UCLA-3) to evaluate loneliness, the activities of daily living (ADL) and the instrumental activities of daily living (IADL) scales to measure functional status, and Mini-Mental State Examination (MMSE) to assess cognitive functions. Results: In a multivariate regression model, the effect of loneliness on cognitive functions was negative in major (=-1.05-p<.0001) and minor NCD (=-0.06-p<.01). In the fully-adjusted multivariate regression model (sex-age-education-multimorbidity-depressive symptoms-antidementia drug treatment), the effect of loneliness remained negative for major NCD and became positive for minor NCD (=0.09-p<.001). The effect of loneliness on IADL (=-0.26-p<.0001) and ADL (=-0.24-p<.001) showed a negative effect for major NCD across the different models, while for minor NCD, the effect was positive (IADL:=0.26-p<.0001-ADL:=0.05-p=0.01). Minor NCD displayed different levels of MMSE (=6.68-p<.001), but not ADL or IADL, compared to major NCD for the same levels of loneliness. MANOVA pill’s test suggested a statistically significant and different interactive effect of loneliness on functional and cognitive variables between minor and major NCDs. Conclusions: We confirmed the relationships between loneliness and cognitive and functional status in major NCD, observing a novel trend in minor NCD.

Background/Objectives: Vitamin D’s effect on risk health outcomes is often evaluated using prospective cohort studies. Risk ratios (RRs; e.g., hazard ratios or odds ratios) are determined for incidence for participants with baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations below or above specified values. Serum 25(OH)D concentrations vary over time, thereby diluting the effect of 25(OH)D for long follow-up periods. Inverse relationships between RR and follow-up period have been reported for all-cause mortality rate and cancer incidence rates. Here I evaluate the effect for neurological outcomes. Methods: I analyzed how follow-up period affected results from 10 cohort studies of all-cause dementia, 6 studies of Alzheimer’s disease, and 9 for cognitive impairment with respect to vitamin D deficiency. Results: For all-cause dementia, Alzheimer’s disease, and cognitive impairment, respectively, the linear regression fits are RR = 2.9 – 0.14 × years, r = 0.73, p = 0.02; RR = 2.9 – 0.14 × years, r = 0.69, p = 0.13; and RR = 1.8 – 0.066 × years, r = 0.72, p = 0.03. The regression fit to RR for the shortest follow-up period for each outcome is considered the best estimate of vitamin D deficiency’s effect on risk. Those values are approximately twice that found by averaging all RRs without considering the effect of follow-up period. Conclusions: Vitamin D’s effect on risk of neurological conditions should be determined with relatively short follow-up periods after repeated 25(OH)D measurements as warranted during follow-up.

Informal dementia home caregiving is viewed negatively and can result in caregiver depression and anxiety from burnout, potentially compromising caregiving. Solutions are unclear, as caregiving relationships are unique—caregiver creation of a graphic memoir may help to mitigate the negative dementia narrative and reduce experienced burnout. This investigation examines the writing of a graphic memoir by one informal dementia home caregiver, created with the help of a cartoon illustrator and a publisher who edited, printed, and made the graphic memoir available at the psychiatric bookstore considered the largest in North America. Mother of the illustrator and the editor and publisher of this graphic memoir, this author provides the perspective taken in this investigation. The analysis, developed by this author, represents psychoanalytic narrative research, serving as the historical method. Aided by email threads between the publisher/caregiver, publisher/printer, and publisher/bookseller, and a published interview with the dementia caregiver are answers to how writing, illustrating, and publishing the graphic memoir affected the caregiver’s narrative reconstruction and burnout. Providing an example for other informal dementia home caregivers similarly to write and illustrate a publishable graphic memoir for their positive narrative reconstruction and to help decrease their depression and anxiety from burnout is the aim.