Late-Life Physical Activities Moderate the Relationship of Amyloid-β Pathology with Neurodegeneration in Individuals Without Dementia

Article type: Research Article

Authors: Sohn, Bo Kyung^a | Byun, Min Soo^b | Yi, Dahyun^c | Jeon, So Yeon^d | Lee, Jun Ho^e | Choe, Young Min^f | Lee, Dong Woo^a | Lee, Jun-Young^{g; h} | Kim, Yu Kyeongⁱ | Sohn, Chul-Ho^j | Lee, Dong Young^{h; k; l; *} | for the KBASE Research Group

Affiliations: [a] Department of Psychiatry, Inje University Sanggye Paik Hospital, Seoul, Republic of Korea | [b] Department of Psychiatry, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea | [c] Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea | [d] Department of Psychiatry, Chungnam National University Hospital, Daejeon, Republic of Korea | [e] Department of Neuropsychiatry, National Center for Mental Health, Seoul, Republic of Korea | [f] Department of Neuropsychiatry, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Republic of Korea | [g] Department of Neuropsychiatry, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea | [h] Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea | [i] Department of Nuclear Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea | [j] Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea | [k] Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea | [l] Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, Republic of Korea

Correspondence: [*] Correspondence to: Dong Young Lee, Department of Neuropsychiatry, Seoul National University Hospital & Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea. Tel.: +82 2 2072 2205; Fax: +82 2 744 7241; E-mail: selfpsy@snu.ac.kr.

Abstract: Background:Physical activities (PA) have been suggested to reduce the risk of Alzheimer‘s disease (AD) dementia. However, information on the neuropathological links underlying the relationship is limited. Objective:We investigated the role of midlife and late-life PA with in vivo AD neuropathologies in old adults without dementia. Methods:This study included participants from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s disease (KBASE). The participants underwent comprehensive clinical and neuropsychological assessment, [11C] Pittsburgh Compound B positron emission tomography (PET), [18F] fluorodeoxyglucose PET, and magnetic resonance imaging. Using the multi-modal brain imaging data, in vivo AD pathologies including global amyloid deposition, AD-signature region cerebral glucose metabolism (AD-CM), and AD-signature region cortical thickness (AD-CT) were quantified. Both midlife and late-life PA of participants were measured using the Lifetime Total Physical Activity Questionnaire. Results:This study was performed on 260 participants without dementia (195 with normal cognitive function and 65 with mild cognitive impairment). PA of neither midlife nor late-life showed direct correspondence with any neuroimaging biomarker. However, late-life PA moderated the relationship of brain amyloid-β (Aβ) deposition with AD-CM and AD-CT. Aβ positivity had a significant negative effect on both AD-CM and AD-CT in individuals with lower late-life PA, but those with higher late-life PA did not show such results. Midlife PA did not have such a moderation effect. Conclusion:The findings suggest that physically active lifestyle in late-life, rather than that in midlife, may delay AD-associated cognitive decline by decreasing Aβ-induced neurodegenerative changes in old adults.

Keywords: Amyloid, cortical thickness, neurodegeneration, physical activity

DOI: 10.3233/JAD-215258

Journal: Journal of Alzheimer's Disease, vol. 86, no. 1, pp. 441-450, 2022