Background: Vitamin E includes eight natural antioxidant compounds (four tocopherols and four tocotrienols), but α-tocopherol has been the main focus of investigation in studies of cognitive impairment and Alzheimer's disease.
Objective: To investigate the association between serum levels of tocopherols and tocotrienols, markers of vitamin E oxidative/nitrosative damage (α-tocopherylquinone, 5-nitro-γ-tocopherol) and incidence of cognitive impairment in a population-based study.
Design: A sample of 140 non-cognitively impaired elderly subjects derived from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study was followed-up for 8years to detect cognitive impairment, defined as development of mild cognitive impairment (MCI) or Alzheimer's dementia. The association between baseline serum vitamin E and cognitive impairment was analyzed with multiple logistic regression after adjusting for several confounders.
Results: The risk of cognitive impairment was lower in subjects in the middle tertile of the γ-tocopherol/cholesterol ratio than in those in the lowest tertile: the multiadjusted odds ratio (OR) with 95% confidence interval (CI) was 0.27 (0.10-0.78). Higher incidence of cognitive impairment was found in the middle [OR (95% CI): 3.41 (1.29-9.06)] and highest [OR (95% CI): 2.89 (1.05-7.97)] tertiles of the 5-NO2-γ-tocopherol/γ-tocopherol ratio. Analyses of absolute serum levels of vitamin E showed lower risk of cognitive impairment in subjects with higher levels of γ-tocopherol, β-tocotrienol, and total tocotrienols.
Conclusions: Elevated levels of tocopherol and tocotrienol forms are associated with reduced risk of cognitive impairment in older adults. The association is modulated by concurrent cholesterol concentration. Various vitamin E forms might play a role in cognitive impairment, and their evaluation can provide a more accurate measure of vitamin E status in humans.
Keywords: 5-NO(2)-γ-tocopherol; 5-nitro-γ-tocopherol; AD; APOE; Alzheimer's disease; Apolipoprotein E; BMI; Body mass index; CAIDE; CDR; CERAD; CI; CNS; CV; Cardiovascular Risk Factors, Aging, and Dementia study; Central nervous system; Clinical Dementia Rating Scale; Coefficient of variation; Cognitive impairment; Confidence interval; Consortium to Establish a Registry for Alzheimer's Disease; DSM-IV; Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; HDL; HPLC; High Performance Liquid Chromatography; High-density lipoprotein; LDL; Low-density lipoprotein; MCI; MMSE; MRI; Magnetic resonance imaging; Mini-Mental State Examination; NINCDS-ADRDA; NS; National Institute of Neurologic and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association; Nitrosative stress; OR; OS; Odds ratio; Oxidative stress; Oxidative/nitrosative stress; RNS; Reactive nitrogen species; SD; Standard deviation; Tocopherol; Tocotrienol; Vitamin E; mild cognitive impairment; α-Tocopherylquinone; αTQ.