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

Abstract

B A C K G R O U N D : O b s e r v a t i o n a l s t u d i e s a n d s o m e 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. OBJECTIVES: 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 communitydwelling 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. METHODS: 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. RESULTS: 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-tauand APOE ε4-stratified analyses provided similar findings. CONCLUSIONS: 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.

Does Nutritional Supplementation Have a Disease-Modifying Effect on the Alzheimer’s Disease Neurodegenerative Process?

“…The Nolan Study, in turn, tested the effect of a 1-year multi-nutrient supplementation (including omega-3 PUFA, vitamin C, vitamin D, vitamin E, thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, folic acid, biotin, cobalamin, selenium, choline and citrulline) on clinical tests, imaging and blood biomarkers related to the AD pathology among a sample of 362 community-dwelling older adults living in France ( 28 , 29 ). At the end of the follow-up, supplementation could not postpone the increase in plasma p-tau181 (observed in both intervention and placebo groups) ( 29 ), and neither showed an effect on cognitive function ( 28 ). Another randomized controlled trial (RCT) found no benefits of a 16-week supplementation of combined vitamin E (800IU/day), vitamin C (500mg/day) and α-lipoic acid (ALA) (900mg/day), or coenzyme Q alone (1200mg/day) on CSF Aβ42, t-tau or p-tau181 in a sample of 66 subjects with mild to moderate AD ( 30 ).…”

“…The Nolan Study, in turn, tested the effect of a 1-year multi-nutrient supplementation (including omega-3 PUFA, vitamin C, vitamin D, vitamin E, thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, folic acid, biotin, cobalamin, selenium, choline and citrulline) on clinical tests, imaging and blood biomarkers related to the AD pathology among a sample of 362 communitydwelling older adults living in France (28,29). At the end of the follow-up, supplementation could not postpone the increase in plasma p-tau181 (observed in both intervention and placebo groups) (29), and neither showed an effect on cognitive function (28).…”

Biotin Homeostasis and Human Disorders: Recent Findings and Perspectives

“…In another recent study, the authors reported plasma p-tau181 and glial fibrillary acidic protein (GFAP) levels in community-dwelling older adults who had received supplementation with a nutritional blend including biotin (0.15 mg/day); an increase was observed in both levels, but no difference was found between subjects receiving the nutritional supplement for one year and those receiving placebo. Nevertheless, according to the authors, further investigation is necessary to clarify whether nutritional supplementation may be able to protect brain health and cognitive functions and prevent Alzheimer’s Disease by affecting tau accumulation, amyloidosis, and glial activation [ 152 ].…”