Effect of a multivitamin and cocoa flavanol extract on changes in neurofilament light, N-terminal tau fragment, and oligomeric amyloid-β levels in COSMOS-clinic.

BackgroundMultivitamin-multimineral (MVM) supplements and cocoa flavanols may delay cognitive aging, but underlying pathways remain unclear.ObjectiveWe examined the effect of MVM or cocoa extract (CE) supplementation on 2-year changes in three blood-based neurodegenerative biomarkers.MethodsThe COcoa Supplement and Multivitamin Outcomes Study (COSMOS) was a 2 × 2 factorial trial of a MVM (Centrum Silver) and/or CE supplement (containing 500 mg/d, including 80 mg (-)-epicatechin) among older US adults free of major cardiovascular disease and recently diagnosed cancer. The primary outcomes of this ancillary study were the 2-year change in neurofilament light chain (NfL), N-terminal tau fragment (NT1), and oligomeric amyloid-β (oAβ) levels. We examined the effect of each intervention on each biomarker in separate general linear models of response profiles.ResultsWe included 506 individuals with available NT1 or NfL levels and 498 individuals with oAβ levels. We observed no significant difference between the changes over time in either NT1 (mean difference in yearly percentage change=3.7%; 95% CI: -3% to 10.8%; p = 0.29), NfL (3.1%; 95% CI: -1.9% to 8.3%; p = 0.23), or oAβ (-8.9%; 95% CI: -23.9% to 9%; p = 0.31) for those randomized to MVM versus placebo. We observed no significant differences between changes over time for those randomized to CE versus placebo for NT1 (-0.7%; 95% CI: -7.1% to 6.1%; p = 0.83), NfL (0.5%; 95% CI: -4.4% to 5.6%; p = 0.85), or oAβ (-5.9%; 95% CI: -21.4% to 12.6%; p = 0.51).ConclusionsDaily supplementation with MVM or CE compared to placebo did not affect two-year changes in NfL, NT1, and oAβ.Clinicaltrials.gov: COSMOS (clinicaltrials.gov NCT02422745).