因果发现识别英国生物库中体力活动与痴呆风险之间的通路
Causal discovery identifies pathways linking physical activity to dementia risk in the UK BioBank
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中文总结 AI 辅助
本研究通过LLM引导的因果发现与中介分析，在英国生物库老年人中识别出体力活动降低痴呆风险的多条通路，其中抑郁为核心中介路径，占比15.1%。
中文摘要 AI 辅助
体力活动（PA）始终与较低的痴呆风险相关，但将PA与痴呆预防联系起来的机制仍未被完全理解。在此，我们整合了大型语言模型（LLM）引导的因果发现与中介分析，在来自英国生物库的42,293名年龄60岁及以上的老年人中，系统识别连接客观测量的中等至剧烈体力活动（MVPA）与痴呆风险的路径。在行为、心理、功能和临床领域，因果发现一致识别出通过抑郁、功能能力、吸烟行为、高血压、心血管疾病、慢性肾脏疾病和脑损伤将较高MVPA与较低痴呆风险联系起来的相互关联路径。链式中介分析进一步将抑郁确定为核心路径，占MVPA与痴呆风险总体关联的15.1%。按性别分层分析揭示了不同的机制模式，女性主要表现为代谢和功能路径，而男性则表现出涉及吸烟和心血管疾病的行为和心脏代谢级联。总之，这些发现表明，PA与痴呆之间的保护性关联是通过相互关联的行为、心理和心脏代谢过程而非单一途径介导的。抑郁作为一个突出且可能可修改的路径出现，突显了将PA促进与心理健康和心血管风险管理相结合的痴呆预防策略的机会。
英文摘要
Physical Activity (PA) is consistently associated with lower risk of dementia, yet the mechanism linking PA to dementia prevention remain incomopletely understood. Here, we integrate large language model (LLM)-guided causal discovery with mediation analysis in 42,293 older adults aged 60 years or older from the UK Biobank to systematically identify pathways connecting objectively measured moderate-to-vigorous physical activity (MVPA) to dementia risk. Across behavioral, psychological, functional, and clinical domains, causal discovery consistently identified interconnected pathways linking higher MVPA to lower dementia risk through depression, functional capacity, smoking behavior, hypertension, cardiovascular disease, chronic kidney disease, and brain injury. Chain mediation analyses further identified depression as a central pathway, accounting for 15.1% of the overall association between MVPA and dementia risk. Sex-stratified analyses revealed distinct mechanistic patterns, with females exhibiting predominantly metabolic and functional pathways, while males showed behavioral and cardiometabolic cascades involving smoking and cardiovascular disease. Together, these findings suggest that the protective association between PA and dementia is mediated through interconnected behavioral, psychological, and cardiometabolic processes rather than a single pathway. Depression emerged as a prominent and potentially modifiable pathway, highlighting opportunities for integrating dementia prevention strategies that combine PA promotion with mental health and cardiovascular risk management.
发表机构
- University of Florida（佛罗里达大学）
- Norman Fixel Institute for Neurological Diseases（诺曼·菲克塞尔神经系统疾病研究所）
- McKnight Brain Institute（麦克奈特脑研究所）
机构由 AI 辅助整理，请以论文原文为准。
