Biomarkers have the potential to aid in the study of Alzheimer’s disease (AD); unfortunately, AD biomarker values often have a high degree of overlap between healthy and AD individuals. This study investigates the potential utility of a series of novel AD biomarkers, the sixty second ¹²⁹Xe retention time, and the xenon washout parameter, based on the washout of hyperpolarized ¹²⁹Xe from the brain of AD participants following inhalation. The xenon washout parameter is influenced by cerebral perfusion, T1 relaxation of xenon, and the xenon partition coefficient, all factors influenced by AD. Participants with Alzheimer’s disease (n=4) and healthy volunteers (n=4) were imaged using hyperpolarized ¹²⁹Xe magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to determine the amount of retain xenon in the brain. At 60 sec post breath hold, AD patients retained significantly higher amounts of ¹²⁹Xe compared to healthy controls. Data was fit to a pharmacokinetic model and the xenon washout parameter was extracted. Xenon washout in white and grey matter occurs at a slower rate in Alzheimer’s participants (¹²⁹Xe half-life time of 42s and 43s, respectively) relative to controls (20s and 16s, respectively). Following larger scale clinical trials for validation, the xenon washout parameter has the potential to become a useful biomarker for the support of an AD diagnosis.

Since coffee has been shown to influence positively the metabolism of subjects with metabolic syndrome (MetS), we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high fructose diet with or without a mixture of caffeic acid (30 mg/day), trigonelline (20 mg/day), and cafestol (1 mg/day) for 12 weeks. An additional 11 rats were assigned to an acute crossover study. In the chronic experiment, nutraceuticals did not alter body weight or glycemic control but improved fed hyperinsulinemia and HOMA-IR, and plasma adiponectin levels. The impact of nutraceuticals on post-prandial glycemia tended to be more pronounced after acute administration than at the end of the chronic study. Circulating and intrahepatocellular alanine transaminase activity, assessed by hyperpolarized-¹³C NMR spectroscopy, were reduced by coffee nutraceuticals at endpoint. There was also a tendency towards lower liver triglyceride content and histological steatosis score in the intervention group. In conclusion, a mixture of coffee nutraceuticals improved insulin sensitivity and exhibited hepatoprotective effects in a rat model of MetS. Higher dosages with or without caffeine deserve to be studied in the future.