Submitted:
14 April 2026
Posted:
16 April 2026
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Abstract
Background: There is a critical need for effective therapeutics for Alzheimer’s. Personalized, precision medicine approaches represent a potentially effective strategy, and proof-of-concept trials have provided supportive data. Objective: To determine whether a precision medicine approach to Alzheimer’s at the mild cognitive impairment or early dementia stage is effective in a randomized controlled clinical trial. Methods: Seventy-three patients with mild cognitive impairment or early dementia were evaluated for biochemical, microbiological, genetic, epigenetic, and imaging parameters associated with cognitive decline, then assigned randomly to a precision medicine approach or standard of care treatment. Results: Statistically significant effects of the precision medicine approach were observed for overall neurocognitive functioning (d=1.12; 95% CI, 0.56-1.66; p<0.001), memory (d=0.94; 95% CI, 0.40-1.46; p<0.001), executive function (d=0.89; 95% CI, 0.35-1.43; p=0.001), processing speed (d=0.67; 95% CI, 0.14-1.19; p=0.012), self-reported cognitive symptom severity (d=-1.05; 95% CI, -1.60, -0.49, p<0.001), and partner-reported cognitive symptom severity (d=1.26; 95% CI, 0.70-1.81; p<0.001), with MoCA scores showing a trend to improvement (p=0.154). Furthermore, overall health was enhanced, with improvements in blood pressure, body mass index, glycemic index, lipid profiles, and methylation status. Treatment effect size on overall cognitive function exceeded previous trials, being 2-3 times larger than effects of lifestyle interventions and 4-7-times larger than those of anti-amyloid therapies. Conclusion: A personalized, precision medicine approach represents an effective treatment for patients with mild cognitive impairment or early-stage dementia. This treatment improves cognition and overall health rather than simply retarding decline, without significant negative side effects such as brain edema, microhemorrhage, or atrophy.
