A large-scale investigation of grip strength, cardiorespiratory fitness, and lung function as predictors of dementia — and the proteomic and neuroimaging pathways mediating this relationship.
Each measure independently predicted dementia risk in fully adjusted Cox proportional hazards models.
Higher grip strength was inversely associated with all-cause dementia. The largest single PAF among all three fitness measures.
View associations →Maximal workload predicted dementia risk through both direct neural pathways and protein-mediated mechanisms.
View associations →FEV₁ predicted dementia risk and mediated its effect through structural brain changes, particularly hippocampal volume.
View associations →The study identifies a chain of evidence from physical fitness through circulating proteins and brain structure to dementia risk.
Cox regression linking fitness to dementia subtypes. Interactive forest plots, stratified heatmaps, dose-response curves, and survival curves.
Proteomic mediation through 2,918 plasma proteins and neuroimaging pathways via 1,430 brain MRI features from UK Biobank imaging.
Personalized 5- and 10-year dementia risk using Elastic Net Cox model trained on 51,517 participants. Compare to age- and sex-matched peers.
Study background, design, population, and key methodological considerations for this UK Biobank cohort analysis.