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

Background. Serum antioxidant vitamins and carotenoids may protect against neurodegeneration with age. We examined associations of these nutritional biomarkers with incident all-cause and AD dementia among U.S. middle-aged and older adults. Methods. Using data from the third National health and Nutrition Examination Surveys (1988-1994), linked with Centers for Medicare and Medicaid-Medicare 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 Alzheimer’s Disease (AD) and all-cause dementia. Cox proportional hazards regression models were conducted. Results. After ≤26y follow-up (mean:16-17y, n=7,283 participants aged 45-90y 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, HR=0.93, 95%CI: 0.87-0.99, p=0.037), though attenuated in comparison to a socio-economic 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 one 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.