Association of Serum Antioxidant Vitamins and Carotenoids With Incident Alzheimer Disease and All-Cause Dementia Among US Adults

May A. Beydoun, PhD, MPH, Hind A. Beydoun, PhD, MPH, Marie T. Fanelli-Kuczmarski, PhD, Jordan Weiss, PhD, Sharmin Hossain, PhD, Jose Atilio Canas, MD, Michele Kim Evans, MD, and Alan B. Zonderman, PhD

Abstract
Background and Objectives
Serum antioxidant vitamins and carotenoids may protect against neurodegeneration with age. We examined associations of these nutritional biomarkers with incident all-cause and Alzheimer disease (AD) dementia among US middle-aged and older adults.
Methods
Using data from the third National Health and Nutrition Examination Surveys (1988–1994), linked with Centers for Medicare & Medicaid follow-up data, we tested associations and interactions of serum vitamins A, C, and E and total and individual serum carotenoids and interactions with incident AD and all-cause dementia. Cox proportional hazards regression models were conducted.
Results
After ≤26 years follow-up (mean 16–17 years, 7,283 participants aged 45–90 years at baseline), serum lutein+zeaxanthin was associated with reduced risk of all-cause dementia (65+ age group), even in the lifestyle-adjusted model (per SD: hazard ratio [HR] 0.93, 95% CI 0.87–0.99; p = 0.037), but attenuated in comparison with a socioeconomic status (SES)– adjusted model (HR 0.92, 95% CI 0.86–0.93; p = 0.013). An inverse relationship was detected between serum β-cryptoxanthin (per SD increase) and all-cause dementia (45+ and 65+) for age- and sex-adjusted models (HR 0.86, 95% CI 0.80–0.93; p < 0.001 for 45+; HR 0.86, 95% CI 0.80–0.93; p = 0.001 for 65+), a relationship remaining strong in SES-adjusted models (HR 0.89, 95% CI 0.82–0.96; p = 0.006 for 45+; HR 0.88, 95% CI 0.81–0.96; p = 0.007 for 65+), but
attenuated in subsequent models. Antagonistic interactions indicate putative protective effects of 1 carotenoid may be observed at lower levels other carotenoids or antioxidant vitamin.
Discussion
Incident all-cause dementia was inversely associated with serum lutein+zeaxanthin and β-cryptoxanthin levels. Further studies with time-dependent exposures and randomized trials are needed to test neuroprotective effects of supplementing the diet with select carotenoids.
Classification of Evidence
This study provides Class II evidence that incident all-cause dementia was inversely associated with serum lutein+zeaxanthin and β-cryptoxanthin levels.

Beydoun et al 2022, doi:10.1212/WNL.0000000000200289