AUTHOR=Jeon So Yeon , Byun Min Soo , Yi Dahyun , Lee Jun-Ho , Ko Kang , Sohn Bo Kyung , Lee Jun-Young , Ryu Seung-Ho , Lee Dong Woo , Shin Seoung A , Kim Yu Kyeong , Kang Koung Mi , Sohn Chul-Ho , Lee Dong Young 

TITLE=Midlife Lifestyle Activities Moderate APOE ε4 Effect on in vivo Alzheimer’s Disease Pathologies

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=12

YEAR=2020

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2020.00042

DOI=10.3389/fnagi.2020.00042

ISSN=1663-4365

ABSTRACT=<p>This study aimed to investigate whether the midlife cognitive activity and physical activity moderate the relationship between apolipoprotein Eε4 (APOE4) and <italic>in vivo</italic> Alzheimer’s disease (AD) pathologies. In total, 287 non-demented older adults (mean age 72 years) from the Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer’s disease cohort were included. Participants underwent a comprehensive clinical assessment including the evaluation for midlife CA and physical activity, [<sup>11</sup>C]-Pittsburgh-Compound-B-positron emission tomography (PET), [<sup>18</sup>F]-fluorodeoxyglucose PET, structural magnetic resonance imaging (MRI), and APOE genotyping. We used linear regression and regression-based mediated-moderation models for statistical analyses. Neither midlife cognitive activity nor physical activity moderated the effect of APOE4 on β-amyloid (Aβ) retention itself. Midlife cognitive activity significantly moderated the effect of APOE4 on hippocampal volume [<italic>B</italic> (SE) = − 627.580 (252.327), <italic>t</italic> = −2.488, <italic>p</italic> = 0.014]: APOE4 carriers had smaller hippocampal volume than non-carriers at relatively high cognitive activity state (<italic>p</italic> = 0.004), but not at relatively low cognitive activity condition (<italic>p</italic> = 0.937). Midlife physical activity significantly moderated the effect of Aβ retention, which was closely related to APOE4, on AD-signature region cerebral glucose metabolism [AD-CM; <italic>B</italic> (SE) = 0.004 (0.002), <italic>t</italic> = 2.030, <italic>p</italic> = 0.043]: higher Aβ accumulation was associated with lower AD-CM in relatively low physical activity condition (<italic>p</italic> &lt; 0.001), whereas no such association was observed in relatively high physical activity state (<italic>p</italic> = 0.791). The findings suggest that high midlife cognitive activity may accelerate hippocampal atrophy induced by APOE4, whereas high midlife physical activity may delay AD-related cerebral hypometabolism by weakening the influence of APOE4-associated Aβ retention.</p>