Association of Higher Levels of High-Density Lipoprotein Cholesterol in Elderly Individuals and Lower Risk of Late-Onset Alzheimer Disease

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Abstract
Dyslipidemia and late-onset Alzheimer disease (AD) are highly frequent in western societies. More than 50% of the US adult population has high cholesterol.1 About 1% of people aged 65 to 69 years develop AD, and the prevalence increases to more than 60% for people older than 95 years.2 Dyslipidemia is an established vascular risk factor, and vascular disease seems to have an important role in AD.3 It remains unclear whether dyslipidemia increases the risk of AD. There is evidence that cholesterol alters the degradation of the amyloid precursor protein and shows an effect on amyloid fibril formation, which play a major role in the pathogenesis of AD.4,5 However, other reports indicate that cholesterol depletion induces AD-type injuries in cultured hippocampal slices5 and that plasma cholesterol levels have no effect on brain HMG-CoA reductase activity.6 Observational studies relating plasma lipid levels or lipid-lowering treatment with the risk of dementia have also been inconsistent.6-31 We previously reported associations between high levels of low-density lipoprotein cholesterol (LDL-C) and decreased levels of high-density lipoprotein cholesterol (HDL-C) and vascular dementia,32 as well as low levels of total cholesterol and risk of AD,32 but no association of HDL-C, triglyceride, or LDL-C levels with AD,32 amnestic or nonamnestic mild cognitive impairment (MCI),33 or cognitive test performance over time.34 These prospective analyses were from a cohort recruited in 1992 through 1994. Our objective in the present study was to reexamine the associations of lipids with dementia in a cohort recruited in 1999 through 2001, after the start of the widespread use of lipid-lowering treatment in the 1990s following the results of a landmark clinical trial of lipid lowering.35