The Impact of APOE ɛ4 in Alzheimer’s Disease Differs According to Age

Article type: Research Article

Authors: Kim, Jaeho^{a; b} | Park, Seongbeom^{a; b} | Yoo, Heejin^c | Jang, Hyemin^{a; b} | Kim, Yeshin^{a; b} | Kim, Ko Woon^{a; b; d} | Jang, Young Kyoung^{a; b} | Lee, Jin San^e | Kim, Sung Tae^f | Kim, Seonwoo^g | Lee, Jong Min^h | Ki, Chang-Seokⁱ | Na, Duk L.^{a; b; j} | Seo, Sang Won^{a; b; k} | Kim, Hee Jin^{a; b; *}

Affiliations: [a] Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea | [b] Neuroscience Center, Samsung Medical Center, Seoul, Korea | [c] Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul, Korea | [d] Department of Neurology, Chonbuk National University Hospital, Chonbuk National University Medical school, JeonJu, Korea | [e] Department of Neurology, Kyung Hee University Hospital, Seoul, Korea | [f] Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea | [g] Biostatistics team, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea | [h] Department of Biomedical Engineering, Hanyang University, Seoul, Korea | [i] Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea | [j] Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea | [k] Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Korea

Correspondence: [*] Correspondence to: Hee Jin Kim, MD, PhD, Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-ku, Seoul 06351, Republic of Korea. Tel.: +82 2 2148 9794; Fax: +82 2 3410 0052; E-mail: [email protected].

Abstract: We evaluated how the impact of apolipoprotein E4 (APOE4) differs according to age in Alzheimer’s disease (AD) patients. We recruited 846 AD patients and 815 cognitively normal controls and categorized into three groups with respect to their age (<65, 65–74, and ≥75 years). We evaluated the risk of AD in APOE4 carriers and compared cortical thickness and cognitive function according to APOE4 status in each age group. At the point of this study, in young (<65 years) AD, APOE4 noncarriers had the most severe frontal and perisylvian atrophy, while in old (≥75 years) AD, APOE4 carriers had the most severe medial temporal atrophy. In AD under 75 years, APOE4 noncarriers and heterozygotes showed worse performance in language, visuospatial, and frontal function compared to homozygotes, while, in old (≥75 years) AD, APOE4 homozygotes showed worse performance in memory compared to noncarriers. As the detrimental effects of APOE4 seen in older AD patients were not found in younger AD patients, we suggest that some unrevealed factors are associated with cortical atrophy and non-amnestic cognitive dysfunction in young AD with APOE4 noncarriers.

Keywords: Apolipoprotein E4 (APOE4), Alzheimer’s disease, cognitive dysfunction, magnetic resonance imaging

DOI: 10.3233/JAD-170556

Journal: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1377-1385, 2018