Cerebrovascular and brain morphologic correlates of mild cognitive impairment in the national heart, lung, and blood institute twin study

Objective: To evaluate the relative risk (RR) of mild cognitive impairment (MCI) associated with cerebrovascular risk factors and cerebrovascular-related brain changes. Design: Mild cognitive impairment was determined for the subjects of the prospective National Heart, Lung, and Blood Institute Twin Study. Quantitative measures of brain, white matter hyperintensity, cerebral infarction, apolipoprotein E genotype, and psychometric testing were obtained. Results: Subjects with MCI were older (73.5 +/-3.0 vs 72.1 +/-2.8 years), consumed less alcohol (3.7 +/-5.8 vs 7.0 +/- 10.7 drinks per week), had greater white matter hyperintensity volumes (0.56%+/-0.82% vs 0.25%+/-0.34% of cranial volume), and had an increased prevalence of apolipoprotein E4 genotype (31.4% vs 19.2%) than normal subjects. White matter hyperintensity and the presence of the apolipoprotein E4 genotype were associated with a significantly increased risk for MCI. When all subjects were included in the analysis, alcohol consumption was associated with a reduced risk for MCI (RR=0.93, P<.05). When subjects with a history of symptomatic cerebrovascular disease were excluded from the analysis, elevated midlife diastolic blood pressure was associated with an increased risk for MCI (RR=1.70, P<.05). Conclusions: Elevated midlife blood pressures, and the resulting increased white matter hyperintensities, increase the risk for MCI in a group of community-dwelling older men to at least the same degree as apolipoprotein E4 genotype. Given the common occurrence of elevations in midlife blood pressure, early and effective treatment may be warranted to prevent late-life brain abnormalities and MCI. Moreover, since many individuals with MCI progress to clinical dementia, longitudinal evaluations of this cohort will be important.