Abstract
BackgroundThe efficacy of cholesterol lowering agents, specifically statins, in slowing the rate of decline of cognitive function in Alzheimer’s disease (AD) patients is not yet fully understood. Our team’s previously published paper showed that patients who used statins demonstrated no increase in cognitive decline in mild cognitive impairment when compared with nonusers. Further, AD patients on statins demonstrated a slight decreasing trend in cognitive decline. The purpose of this study is therefore to investigate the association between stain use in AD confirmed by clinical diagnosis and autopsy and the pathological burden (plaques, tangles, Braak stage). The hypothesis leading this investigation is that prolonged statin use associates with lower AD pathology at autopsy.MethodsWe queried the National Alzheimer’s Coordinating Center (NACC) database for autopsy-confirmed AD cases. Of the Uniform Data Set (UDS) participants who are deceased, 16,163 were diagnosed with dementia at their last UDS visit prior to death, and autopsy data are available for 3945 patients. These patients were then stratified into two groups based upon statin use. The two groups were then analyzed for their pathological AD burden, including total plaques, total tangles, age at death, age of onset, and Braak stage.ResultsNACC data were available for 1816 subjects with clinically and pathologically confirmed AD; 1558 were not on statins and 258 were on statins. No significant differences in age at death, age at onset, Braak stages, mean total tau, and mean total amyloid were found between the two subject groups. When statin use was analyzed by apolipoprotein E (ApoE) genotype carrier statins, the presence of ApoE4 did not influence the effects (or lack thereof) of statin use.ConclusionsProlonged statin use in pathologically confirmed AD dementia does not appear to influence the amount of burden of plaques and tangles or Braak stage. These observations were not altered by the presence of absence of ApoE4.
Highlights
The efficacy of cholesterol lowering agents, statins, in slowing the rate of decline of cognitive function in Alzheimer’s disease (AD) patients is not yet fully understood
This study was carried out to confirm the hypothesis that chronic statin use associates with less AD pathology at autopsy
Study sample All data were obtained from the Uniform Data Set (UDS), the Neuropathology Data Set, and the Researcher’s Data Dictionary—Genetic Data from the National Alzheimer’s Coordinating Center (NACC), a database funded by the National Institute on Aging (NIA); compilation of the data began in September 2015
Summary
The efficacy of cholesterol lowering agents, statins, in slowing the rate of decline of cognitive function in Alzheimer’s disease (AD) patients is not yet fully understood. The purpose of this study is to investigate the association between stain use in AD confirmed by clinical diagnosis and autopsy and the pathological burden (plaques, tangles, Braak stage). The hypothesis leading this investigation is that prolonged statin use associates with lower AD pathology at autopsy. The direct effects of plasma cholesterol and related lipoproteins on the incidence and severity of dementia and cognitive decline remain a controversial topic deserving of deeper exploration.
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