Cognitively Impaired Subjects with Normal Total Cholesterol Using Lipophilic Statins Undergo Accelerated Decline in Regions Associated with Dementia and Those Regions are Predictive of Further Decline Over the Subsequent Two‐Year Period in a Multi‐Center Longitudinal Study

• Published in: Alzheimer's & dementia Vol. 19; no. S24
• Main Authors: Padmanabham, Prasanna S., Liu, Stephen S., Silverman, Daniel H.
• Format: Journal Article
• Language: English
• Published: 01.12.2023
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.083085

Background We recently reported that lipophilic statins, known to penetrate the blood‐brain barrier, were associated with accelerated decline in cortical regions known to decline in early Alzheimer’s Disease, in subjects with early Mild Cognitive Impairment (eMCI) having normal cholesterol levels. We now report the predictive value of the pattern of regional metabolism in forecasting severity of decline over the subsequent two years. Method Subjects were drawn from a consecutive series enrolled in the Alzheimer’s Disease Neuroimaging Initiative, identifying 70 with eMCI 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. FDG‐PET scans acquired at baseline and two years later were compared for each group, and rates of regional metabolic decline were determined. Result In direct statistical comparisons on a voxel‐by‐voxel basis, subjects on lipophilic statins (LS) underwent significantly greater decline in posterior cingulate (PCC) and right parietotemporal cortex (rPTC) compared to those not on statins (p<0·0005). Moreover, baseline rPTC metabolism was positively correlated with magnitude of left inferior parietal metabolism two years later in LS subjects (p = 0.008), but not in nonS subjects (p = 0.95). Conversely, baseline parietal metabolism was not correlated with subsequent rPTC metabolism in either group of subjects. In addition, based on regional network analysis, LS subjects had greater functional connectivity in the medial temporal regions. Conclusion Subjects with eMCI and normal range cholesterol levels taking lipophilic statins suffered faster metabolic decline of brain regions affected by early Alzheimer’s disease, and baseline activity in those regions predicted further decline over the subsequent two years in associative cortex. Moreover, the pattern of functional connectivity with medial temporal regions was altered in subjects on these statins.