PT  - JOURNAL ARTICLE
AU  - Beydoun, May A.
AU  - Beydoun, Hind A.
AU  - Fanelli-Kuczmarski, Marie T.
AU  - Weiss, Jordan
AU  - Hossain, Sharmin
AU  - Canas, Jose Atilio
AU  - Evans, Michele Kim
AU  - Zonderman, Alan B.
TI  - Association of Serum Antioxidant Vitamins and Carotenoids With Incident Alzheimer Disease and All-Cause Dementia Among US Adults
AID  - 10.1212/WNL.0000000000200289
DP  - 2022 May 24
TA  - Neurology
PG  - e2150--e2162
VI  - 98
IP  - 21
4099  - http://n.neurology.org/content/98/21/e2150.short
4100  - http://n.neurology.org/content/98/21/e2150.full
SO  - Neurology2022 May 24; 98
AB  - 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.1995 HEI=Healthy Eating Index, 1995 version; AD=Alzheimer disease; BMI=body mass index; CMS=Centers for Medicare & Medicaid Services; CPT4=Common Procedural Terminology; DHA=docosahexaenoic acid; HMO=Health Maintenance Organization; HR=hazard ratio; ICD-9=International Classification of Diseases, 9th revision; ICD-10=International Classification of Diseases, 10th revision; IRB=institutional review board; MAR=mean adequacy ratio; MEC=mobile examination center; NDI=National Death Index; NH=Non-Hispanic; NHANES III=Third National Health and Nutrition Examination Survey; PIR=poverty income ratio; ROS=reactive oxygen species; SES=socioeconomic status