Lipophilic Statins in Subjects with early Mild Cognitive Impairment and Low Serum Cholesterol: Association with Long‐Term Cerebral Metabolic and Cognitive Decline in a Prospective Longitudinal Multi‐Center Study

Abstract

AbstractBackgroundWe recently reported that lipophilic statins, known to penetrate the blood‐brain barrier, were associated with accelerated decline in regional cerebral metabolism in subjects with early Mild Cognitive Impairment (eMCI) who had relatively low serum cholesterol levels (J Nucl Med. 2021;62:Suppl 1). In this study, we expand upon our past results by studying the relationship between metabolic decline in lipophilic statin users and their decline in neuropsychological test scores.MethodsSubjects with eMCI were drawn from a consecutive series enrolled in the Alzheimer's Disease Neuroimaging Initiative, identifying 70 having serum cholesterol levels below the 206 mg/dl median of non‐statin users and with clear histories of time‐frames of prescriptions and types of statins used – 41 taking lipophilic statins throughout the 2‐year follow‐up period (LS), and 29 demographically similar non‐statin users (nonS). FDG‐PET scans acquired at baseline and 2 years later were compared for each group, and standardized Volume of Interest (sVOI) methods were used to calculate rates of regional metabolic decline. Correlations between changes in regional metabolism and changes in neuropsychological test scores were assessed by linear regression.ResultsThe strongest association occurred between declining metabolism in the left parietotemporal cortex (PTC) and declining function, as indexed by the Functional Activities Questionnaire (FAQ), which was highly significant among LS users (p=0.0004), but not among nonS subjects (p=0.56). Decline of left PTC was also a significant correlate of decline in LS memory performance (p= 0.001), but not nonS (p = 0.11). Both the left posterior cingulate and right PTC declines correlated with LS MMSE decline (p = 0.01 for both), while that metabolic decline was again uncorrelated for nonS subjects.ConclusionSubjects with eMCI with low serum cholesterol levels , who nevertheless were persistently prescribed lipophilic statins over two years, underwent accelerated metabolic decline in the brain regions most significantly hypometabolic in patients with Alzheimer's disease that was in turn significantly correlated with decline in key measures of both function and cognition, in a manner specific to statin use.