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

Abstract

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.

Astrocytes as a Therapeutic Target in Alzheimer’s Disease–Comprehensive Review and Recent Developments

“…Treatments focused on the interference of oxidative stress in AD have been proposed as a novel therapeutic strategy, including AGE-inhibitors, increasing levels of antioxidants, stabilizing mitochondrial activity and prevention of ROS formation [ 103 , 176 ]. Likewise, a recent large-scale study (n = 7283 participants) evidenced an association between serum antioxidants levels, such as the carotenoids lutein+zeaxantin and B-cryptoxanthin, either as potential risk or protective factor in all-cause dementia, including AD [ 177 ].…”

Molecular and Cellular Interactions in Pathogenesis of Sporadic Parkinson Disease

“…They act by attenuating neurotoxin-induced memory loss and behavioral impairment, oxidative stress, and dopaminergic cell death, thus alleviating PD progression. People with very high levels of the antioxidants lutein, zeaxanthin, and beta-cryptoxanthin (carotenoids) in their blood have a much lower risk of developing dementia in old age [ 373 ]. Resveratrol is a polyphenolic compound found in grapes, it is able to cross the BBB and is water soluble.…”

Pharmaceutical and pharmacological studies of Shen Ma Yi Zhi granule for prevention of vascular dementia: A review

“…Oxidative stress and inflammation directly damage cells (Beydoun et al, 2022). Bioactive products in the setting of oxidative stress initiate the inflammatory response (Wang et al, 2007) and are known to significantly aggravate cerebral injury.…”