Background and purpose: White matter hyperintensities are a common magnetic resonance imaging (MRI) observation in the elderly. They are believed to represent a subclinical form of ischemic brain damage, but the underlying pathophysiological mechanisms are still incompletely understood. We postulated that oxidative mechanisms may favor the development of these changes and therefore correlated their presence and extent with the plasma concentrations of 10 naturally occurring antioxidants.
Methods: We studied 355 clinically normal volunteers 45 to 75 years of age who were randomly selected from the official community register. A 1.5-T MRI of the brain and measurements of the plasma concentrations of antioxidants including zeaxanthin, cryptoxanthin, canthaxanthin, lycopene, alpha- and beta-carotene, retinol, gamma- and alpha-tocopherol, as well as ascorbate were performed in all study participants. White matter hyperintensities were graded as punctate, beginning confluent, and confluent abnormalities.
Results: Punctate, beginning confluent, and confluent white matter abnormalities occurred in 101 (28.5%), 44 (12.4%), and 14 (3.9%) individuals, respectively. Study participants with white matter damage were significantly older and had a higher frequency of arterial hypertension and cardiac disease but lower serum concentrations of total cholesterol. The plasma levels of lycopene and alpha-tocopherol were significantly lower in subjects with early confluent and confluent white matter hyperintensities, while individuals with punctate foci had an antioxidant status similar to those with normal MRI scans. Alpha-tocopherol was the only antioxidant that remained significantly and inversely related to the presence of beginning confluent and confluent white matter changes after adjustment for the between-group differences in age, arterial hypertension, cardiac disease, and cholesterol. The adjusted odds ratio for early confluent and confluent white matter abnormalities was 3.70 (95% CI, 1.69 to 8.10) in the lowest compared with the highest quartile of the alpha-tocopherol concentration. The odds ratio increased to 7.11 (95% CI, 1.63 to 22.84) when quintiles of the alpha-tocopherol level were compared.
Conclusions: These data do not prove a causal relation, but they provide evidence of an association between low plasma concentrations of vitamin E and a higher risk of cerebral white matter disease in elderly normal subjects.