Effects of LDL Cholesterol and Statin Use on Verbal Learning and Memory in Older Adults at Genetic Risk for Alzheimer’s Disease

Article type: Research Article

Authors: Wroolie, Tonita^a | Roat-Shumway, Siena^a | Watson, Katie^a | Reiman, Eric^b | Rasgon, Natalie^{a; *}

Affiliations: [a] Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA | [b] Banner Alzheimer’s Institute, Stead Family Memory Center, Phoenix, AZ, USA

Correspondence: [*] Correspondence to: Natalie Rasgon, MD, PhD, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Quarry Road, Stanford, CA 94305, USA. Tel.: +1 650 724 6689; E-mail: [email protected].

Abstract: Background:The apolipoprotein epsilon 4 (APOE4) allele is a well-established genetic risk factor for Alzheimer’s disease (AD). However, there are mixed findings as to how the APOE4 allele modifies the effects of both higher low-density lipoprotein cholesterol (LDL) and statin use on cognitive functioning. Objective:This study sought to examine the effects of LDL levels and statin use on verbal learning and memory, as modified by the presence of the APOE4 allele, in a sample of cognitively unimpaired, older adults at risk for AD. Methods:Neuropsychological, LDL, statin use, and APOE4 data were extracted from an ongoing longitudinal study at the Banner Alzheimer’s Institute in Arizona. Participants were cognitively unimpaired based on Mini-Mental State Examination scores within a normal range, aged 47–75, with a family history of probable AD in at least one first-degree relative. Results:In the whole sample, higher LDL was associated with worse immediate verbal memory in APOE4 non-carriers, but did not have an effect on immediate verbal memory in APOE4 carriers. In APOE4 non-carriers, statin use was associated with better verbal learning, but did not have an effect on verbal learning in APOE4 carriers. Among women, higher LDL in APOE4 carriers was associated with worse verbal learning than in APOE4 non-carriers, and statin use in APOE4 non-carriers was associated with better verbal learning and immediate and delayed verbal memory but worse performances on these tasks in APOE4 carriers. Conclusion:LDL and statin use may have differential effects on verbal learning and/or memory depending on genetic risk for AD. Women appear to be particularly vulnerable to statin use depending on their APOE4 status.

Keywords: APOE4 , at risk for alzheimer’s disease, immediate and delayed verbal memory, LDL cholesterol, statins, verbal learning

DOI: 10.3233/JAD-191090

Journal: Journal of Alzheimer's Disease, vol. 75, no. 3, pp. 903-910, 2020