Effect of a 1-Year Nutritional Blend Supplementation on Plasma p-tau181 and GFAP Levels among Community-Dwelling Older Adults: A Secondary Analysis of the Nolan Trial

Observational studies and some randomized controlled trials have suggested that nutritional supplementation could be a possible intervention pathway to prevent cognitive decline and Alzheimer's disease (AD). As measuring amyloid-β and tau pathophysiology by positron emission tomography (PET) or cerebrospinal fluid (CSF) analyses may be perceived as complex, plasma versions of such biomarkers have emerged as more accessible alternatives with comparable capacity of predicting cognitive impairment. This study aimed to evaluate the effect of a 1-year intervention with a nutritional blend on plasma p-tau181 and glial fibrillary acidic protein (GFAP) levels in community-dwelling older adults. Effects were further assessed in exploratory analyses within sub-cohorts stratified according to p-tau status (with the third tertile considered as high: ≥15.1 pg/ mL) and to apolipoprotein E (APOE) ε4 allele status. A total of 289 participants ≥70 years (56.4% female, mean age 78.1 years, SD=4.7) of the randomized, double-blind, multicenter, placebo-controlled Nolan trial had their plasma p-tau181 assessed, and daily took either a nutritional blend (composed of thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid, cobalamin, vitamin E, vitamin C, vitamin D, choline, selenium, citrulline, eicosapentaenoic acid - EPA, and docosahexaenoic acid - DHA) or placebo for 1 year. After 1-year, both groups presented a significant increase in plasma p-tau181 and GFAP values, with no effect of the intervention (p-tau181 between-group difference: 0.27pg/mL, 95%CI: -0.95, 1.48; p=0.665; GFAP between-group difference: -3.28 pg/mL, 95%CI: -17.25, 10.69; p=0.644). P-tau-and APOE ε4-stratified analyses provided similar findings. In community-dwelling older adults, we observed an increase in plasma p-tau181 and GFAP levels that was not different between the supplementation groups after one year.