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Associations Between Walking Pace, APOE-ε4 Genotype, and Brain Health in Middle-Aged to Older Adults.
Medicine & Science in Sports & Exercise ( IF 4.1 ) Pub Date : 2025-01-09 , DOI: 10.1249/mss.0000000000003646
Daniel H Aslan,M Katherine Sayre,Pradyumna K Bharadwaj,Madeline Ally,Silvio Maltagliati,Mark H C Lai,Rand R Wilcox,Yann C Klimentidis,Gene E Alexander,David A Raichlen

Poor physical function and possession of the e4 allele of the apolipoprotein E (APOE) gene are each associated with increased dementia risk, but it is unclear how these exposures interact to influence brain health. Purpose: To investigate whether self-reported walking pace (a marker of physical function) and the presence of APOE-ε4 allele interact to modify brain health outcomes. Methods: We used data from a prospective cohort study of middle-aged to older adults from the UK Biobank who self-reported walking pace (slow or steady-to-brisk), and who were initially free of dementia (n = 415,110). Incident all-cause dementia was obtained from hospital and death registry records, and structural brain volumes (right and left hippocampus volumes, total gray matter volume, and volume of white matter hyperintensities) were measured from a subset of participants (n = 33,113). Cox proportional hazard models and generalized linear models were used to assess associations between exposures and outcomes. Results: Slow walking pace and the presence of APOE-ε4 allele were associated with increased dementia risk [HR = 1.79 (1.66,1.93), p < 0.001; HR = 3.06 (2.90,3.23), p < 0.001, respectively], and there was an interaction between these associations, indicating that the association of walking pace with dementia risk is modified by APOE-ε4 status [(reference group: HRSteady-Brisk/APOE-ε4- = 1); HRSlow/APOE-ε4- = 2.03(1.84,2.25), p < 0.001; HRSteady-Brisk/APOE-ε4+ = 3.21(3.02,3.41), p < 0.001; HRSlow/APOE-ε4+ = 4.99 (4.48,5.58), p < 0.001]. Slow self-reported walking pace was associated with worse brain volume outcomes and these associations were not modified by APOE-ε4 genotype. Conclusions: These results suggest walking pace and APOE-ε4 status independently influence brain volume outcomes, but both factors independently and jointly contribute to increased dementia risk. Individuals with both risk factors (slow walking pace and APOE-ε4 allele) show the strongest associations with dementia risk.

中文翻译:


中老年人步行速度、APOE-ε4 基因型和大脑健康之间的关联。



身体机能差和拥有载脂蛋白E(APOE)基因的e4等位基因都与痴呆风险增加有关,但目前尚不清楚这些暴露如何相互作用以影响大脑健康。目的:研究自我报告的步行速度 (身体机能的标志物) 和 APOE-ε4 等位基因的存在是否相互作用以改变大脑健康结果。方法:我们使用了来自英国生物银行的中老年人的前瞻性队列研究的数据,这些人自我报告了步行速度(缓慢或稳定到轻快),并且最初没有痴呆 (n = 415,110)。从医院和死亡登记记录中获得全因痴呆事件,并从参与者子集 (n = 33,113) 测量结构脑体积 (左右海马体积、总灰质体积和白质高信号体积)。使用 Cox 比例风险模型和广义线性模型来评估暴露与结果之间的关联。结果: 慢走速度和 APOE-ε4 等位基因的存在与痴呆风险增加相关 [HR = 1.79 (1.66,1.93),p < 0.001;HR = 3.06 (2.90,3.23),p < 0.001,分别为],并且这些关联之间存在交互作用,表明步行配速与痴呆风险的关联受 APOE-ε4 状态的修饰 [(参考组:HRSteady-Brisk/APOE-ε4- = 1);HRSlow/APOE-ε4- = 2.03(1.84,2.25),p < 0.001;HRSteady-Brisk/APOE-ε4+ = 3.21(3.02,3.41),p < 0.001;HRSlow/APOE-ε4+ = 4.99 (4.48,5.58),p < 0.001]。自我报告的缓慢步行速度与较差的脑容量结局相关,并且这些关联未被 APOE-ε4 基因型改变。 结论: 这些结果表明步行速度和 APOE-ε4 状态独立影响脑容量结果,但这两个因素独立且共同导致痴呆风险增加。具有两种风险因素 (慢走速度和 APOE-ε4 等位基因) 的个体与痴呆风险的相关性最强。
更新日期:2025-01-09
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