Association of Statin Use with Dementia Risk Among Older Adults in Japan: A Nested Case-Control Study Using the LIFE Study

Article type: Research Article

Authors: Ge, Sanyu^a | Kitamura, Tetsuhisa^{a; *} | Zha, Ling^a | Komatsu, Masayo^a | Komukai, Sho^b | Murata, Fumiko^c | Maeda, Megumi^c | Gon, Yasufumi^d | Kimura, Yasuyoshi^d | Kiyohara, Kosuke^e | Sobue, Tomotaka^a | Fukuda, Haruhisa^c

Affiliations: [a] Division of Environmental Medicine and Population Sciences, Department of Social Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan | [b] Biomedical Statistics, Department of Integrated Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan | [c] Department of Health Care Administration and Management, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan | [d] Department of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan | [e] Department of Food Science, Faculty of Home Economics, Otsuma Women’s University, Tokyo, Japan

Correspondence: [*] Correspondence to: Tetsuhisa Kitamura, MD, MSc, DrPH, Division of Environmental Medicine and Population Sciences, Department of Social Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. Tel.: +81 6 6879 3922; Fax: +81 6 6879 3923; E-mail: lucky_unatan@yahoo.co.jp.

Abstract: Background:Previous studies have shown a possible association between statin use and a decreased risk of dementia, but the association has not been sufficiently established, especially in the super-aging society of Japan. Objective:This study aimed to determine the association between statin use and the risk of dementia among Japanese participants aged> =65 years old. Methods:Data from the Longevity Improvement and Fair Evidence (LIFE) Study were utilized, including medical and long-term care (LTC) claim data from 17 municipalities between April 2014 and December 2020. A nested case-control study was conducted with one case matched to five controls based on age, sex, municipality, and year of cohort entry. We used a conditional logistic regression model to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs). Results:This study included 57,302 cases and 283,525 controls, with 59.7% of the participants being woman. After adjusting for potential confounders, statin use was associated with a lower risk of dementia (OR, 0.70; 95% CI: 0.68–0.73) and Alzheimer’s disease (OR: 0.66; 95% CI: 0.63–0.69). Compared with non-users, the ORs of dementia were as follows: 1.42 (1.34–1.50) for 1–30 total standardized daily dose (TSDD), 0.91 (0.85–0.98) for 31–90 TSDD, 0.63 (0.58–0.69) for 91–180 TSDD, and 0.33 (0.31–0.36) for >180 TSDD in dose-analysis. Conclusions:Statin use is associated with a reduced risk of dementia and Alzheimer’s disease among older Japanese adults. A low cumulative statin dose is associated with an increased risk of dementia, whereas a high cumulative statin dose is a protective factor against dementia.

Keywords: Alzheimer’s disease, dementia, Japanese older adults, LIFE study, statin

DOI: 10.3233/JAD-240113

Journal: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2024