Kim Seung Ae, Shin Daeun, Ham Hongki, Kim Yeshin, Gu Yuna, Kim Hee Jin, Na Duk L, Zetterberg Henrik, Blennow Kaj, Seo Sang Won, Jang Hyemin
Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
Seoul National University College of Medicine, Seoul, South Korea.
JAMA Netw Open. 2025 Mar 3;8(3):e250096. doi: 10.1001/jamanetworkopen.2025.0096.
Physical activity (PA) is a nonpharmacological intervention for dementia prevention. The association between PA and Alzheimer disease (AD) plasma biomarkers remains underexplored.
To investigate the associations among PA; plasma biomarkers, including β-amyloid 42/40 (Aβ42/40), phosphorylated-tau217 (ptau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL); and cognition.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included participants with and without cognitive impairment recruited from multiple memory clinics in South Korea between May 2019 and May 2022. Data were analyzed from June to December 2024.
PA was assessed as metabolic equivalent task minutes per week using the International Physical Activity Questionnaire and categorized into quartiles from the lowest (Q1) to the highest (Q4).
Plasma Aβ42/40, ptau217, GFAP, and NfL were measured. Cognition was assessed using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating-Sum of Boxes (CDR-SB).
Among 1144 participants (mean [SD] age 70.9 [8.7] years; 744 [65.0%] female), the highest PA quartile showed significantly lower ptau217 (estimate [SE], -0.14 [0.06]; P = .01) and NfL (estimate [SE], -0.12 [0.05]; P = .01) compared with the lowest quartile. Higher PA quartiles were associated with higher MMSE scores (estimate [SE]: Q2, 0.93 [0.31]; P = .003; Q3, 0.82 [0.32]; P = .009; Q4, 0.94 [0.32]; P = .004) and lower CDR-SB scores (estimate [SE]: Q2, -0.33 [0.16]; P = .04; Q3, -0.37 [0.16]; P = .02; Q4, -0.55 [0.16]; P = .001) after adjusting for age, sex, education years, and β-amyloid uptake. In subgroup analyses according to age and cognitive status, the associations of PA and plasma biomarkers with cognition were more pronounced in the older (age ≥65 years) and cognitively impaired groups compared with the younger and cognitively unimpaired groups.
These findings suggest that PA may help delay cognitive decline by modulating neurodegeneration and AD-specific tau pathologies. However, the cross-sectional design limits causal inference, and longitudinal studies are needed to confirm and clarify these associations.
身体活动（PA）是预防痴呆症的一种非药物干预措施。PA与阿尔茨海默病（AD）血浆生物标志物之间的关联仍未得到充分研究。
探讨PA、血浆生物标志物（包括β-淀粉样蛋白42/40[Aβ42/40]、磷酸化tau217[ptau217]、胶质纤维酸性蛋白[GFAP]和神经丝轻链[NfL]）与认知之间的关联。
设计、设置和参与者：这项横断面研究纳入了2019年5月至2022年5月期间从韩国多个记忆诊所招募的有和没有认知障碍的参与者。2024年6月至12月对数据进行了分析。
使用国际身体活动问卷将PA评估为每周代谢当量任务分钟数，并分为从最低（Q1）到最高（Q4）的四分位数。
测量血浆Aβ42/40、ptau217、GFAP和NfL。使用简易精神状态检查表（MMSE）和临床痴呆评定量表总和（CDR-SB）评估认知。
在1144名参与者中（平均[标准差]年龄70.9[8.7]岁；744名[65.0%]为女性），与最低四分位数相比，PA最高四分位数的ptau217（估计值[标准误]，-0.14[0.06]；P = 0.01）和NfL（估计值[标准误]，-0.12[0.05]；P = 0.01）显著更低。在调整年龄、性别、受教育年限和β-淀粉样蛋白摄取后，较高的PA四分位数与较高的MMSE评分（估计值[标准误]：Q2，0.93[0.31]；P = 0.003；Q3，0.82[0.32]；P = 0.009；Q4，0.94[0.32]；P = 0.004）和较低的CDR-SB评分（估计值[标准误]：Q2，-0.33[0.16]；P = 0.04；Q3，-0.37[0.16]；P = 0.02；Q4，-0.55[0.16]；P = 0.001）相关。在根据年龄和认知状态进行的亚组分析中，与年轻和认知未受损组相比，PA和血浆生物标志物与认知之间的关联在老年（年龄≥65岁）和认知受损组中更为明显。
这些发现表明，PA可能通过调节神经退行性变和AD特异性tau病理来帮助延缓认知衰退。然而，横断面设计限制了因果推断，需要进行纵向研究来证实和阐明这些关联。
