Abstract

Statins are investigational therapies for preventing or treating Alzheimer's disease (AD) and mild cognitive impairment (MCI). Hippocampal atrophy is a characteristic feature of MCI and AD. This study analyzed cross-sectional data from 246 nondemented elderly subjects to test the effect of lipid lowering agent (LLA) therapy on cognition and brain magnetic resonance imaging (MRI) measures of white matter lesions and hippocampal volume. The study also compared rates of hippocampal volume change over two and four years in a smaller subset. At baseline, LLA users were younger, better educated, more likely to be male, and had higher cognitive scores. Cognitive performance also varied by age and gender, and MRI measures varied by age. After adjusting for these differences, the effect of LLA use on baseline cognition, baseline hippocampal volume, and baseline white matter lesion scores was not significant. The effect of LLA use on hippocampal volume loss at two-year and four-year follow-ups was also not significant. This study is the first to examine statin effects on brain atrophy measured by MRI. In this cohort, statin use was not associated with rate of change of hippocampal volume. While the study was limited by a relatively small number of statin users, the findings seem consistent with three prior randomized trials that found no cognitive benefits for statins in nondemented subjects. Prospective studies in both nondemented and AD subjects may provide more conclusive answers.

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