Association between Cholesterol Exposure and Neuropathological Findings: The ACT Study

Article type: Research Article

Authors: Bettcher, Brianne M.^{a; *} | Ard, M. Colin^b | Reed, Bruce R.^c | Benitez, Andreana^d | Simmons, Amanda^e | Larson, Eric B.^f | Sonnen, Josh A.^g | Montine, Thomas J.^h | Li, Geⁱ | Keene, C. Dirk^j | Crane, Paul K.^k | Mungas, Dan^e

Affiliations: [a] Departments of Neurosurgery and Neurology, Rocky Mountain Alzheimer’s Disease Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA | [b] Department of Neuroscience, University of California, San Diego, La Jolla, CA, USA | [c] Center for Scientific Review, National Institute of Health, Bethesda, MD, USA | [d] Department of Neurology, Medical University of South Carolina, Charleston, SC, USA | [e] Department of Neurology, University of California, Davis, CA, USA | [f] Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA | [g] Departmentof Pathology, University of Utah, Salt Lake City, UT, USA | [h] Department of Pathology, Stanford University, Stanford, CA, USA | [i] Department of Medicine, Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, WA, USA | [j] Department of Pathology, University of Washington, Seattle, WA, USA | [k] Department of Medicine, University of Washington, Seattle, WA, USA

Correspondence: [*] Correspondence to: Brianne Bettcher, PhD, Departments of Neurosurgery and Neurology, Rocky Mountain Alzheimer’s Disease Center, University of Colorado Anschutz Medical Campus, 12631 E. 17th Avenue, C307, Aurora, CO 80045, USA. Tel.: +1 720 848 7015; Fax: +1 303 724 2300; E-mail: [email protected].

Abstract: We characterized the relationship between late life cholesterol exposure and neuropathological outcomes in a community-based, older adult cohort. Adult Changes in Thought (ACT) is a cohort study that enrolls consenting, randomly selected, non-demented people aged ≥65 from a healthcare delivery system. We used late life HDL and total cholesterol lab values from Group Health computerized records, and calculated HDL and non-HDL levels. We evaluated neuropathological outcomes of Alzheimer’s disease, cerebral amyloid angiopathy, vascular brain injury, and Lewy body disease. Using linear mixed models with age and antilipemic medication as predictors, we obtained predicted cholesterol values at age 70 and 10 years prior to death for individuals with available cholesterol data in 10-year exposure windows. We used logistic regression to determine whether predicted late life cholesterol levels were associated with neuropathological outcomes controlling for age at death, APOE genotype, sex, and their interactions with cholesterol levels. 525 decedents came to autopsy by 08/2014. Of these, plasma cholesterol concentration was available for 318 (age 70, model 1) and 396 (10 years prior to death, model 2) participants. We did not find associations between late life cholesterol and Alzheimer’s disease neuropathological changes, and there were no associations between cholesterol levels and amyloid angiopathy or vascular brain injury. We observed an association between predicted non-HDL cholesterol at age 70 and Lewy body disease. Our study suggests an association between late life non-HDL cholesterol exposure and Lewy body disease. We did not observe associations between late life cholesterol levels and Braak stage or CERAD score.

Keywords: Alzheimer’s disease, epidemiology, Lewy body, lipids, neuropathology, vascular

DOI: 10.3233/JAD-161224

Journal: Journal of Alzheimer's Disease, vol. 59, no. 4, pp. 1307-1315, 2017