P4-345: A vitamin/nutriceutical formulation that delays cognitive decline and improves behavioral symptoms in Alzheimer's disease

Background: Nutritional supplementation may delay or reduce the progression of Alzheimer's disease (AD). Preclinical studies with mouse models of of age-related neurodegeneration led us to develop a Nutriceutical Formulation (NF) consisting of 6 over-the-counter vitamins and nutriceuticals, that buffers multiple facets of AD, including (1) reducing presenilin expression, gamma-secretase activity, Abeta generation and tau phosphorylation, (2) buffering homocysteine and Abeta-induced oxidative damage, (3) reducing aggression, (4) increasing acetylcholine production and improving/maintaining cognitive performance. Methods: Based on these published preclinical findings, we considered that a combinatorial approach may also be effective in cognition and behavioral symptoms of AD. We therefore conducted multiple clinical trials. Results: In a year-long, open-label trial with NF with mild to moderate AD patients. Cognitive performance (Dementia Rating Scale, Clock-drawing) significantly improved within 3-6 months. Caregivers reported maintenance of daily performance and improved mood (ADCS-Activities of Daily Living and NeuroPsychiatric Inventory). A placebo-controlled study with moderate to late-stage AD indicates delayed cognitive decline and maintenance of daily activities. A multi-site trial with >90 individuals aged 45-73 without dementia indicated that NF statistically improved executive function (Trails B-A) vs. placebo within 3 months, which increased further at 6 months. The placebo group demonstrated identical improvement in a 3-month open-label extension. Following NF withdrawal, participants returned to baseline; statistically-significant improvement was restored once NF was individuals resumed. A second open-label trial with 35 nondemented participants demonstrated statistical improvement within 3 months. No serious adverse events were reported. Conclusions: NF may provide a low-cost, over-the-counter neuroprotectant that can maintain neuronal health prior to dementia, and delay the decline associated with AD. Since NF boosts acetylcholine production, it may be an effective supplement for current pharmaceutical approaches for AD.