Journal of Alzheimer's Disease · May 29, 2026
Evaluation of physical functioning as a marker of brain imaging outcomes in a multiethnic community-based cohort
By Knell G, Meeker KL, Zhou Z et al.
BackgroundPhysical functioning (PF) tests are scalable screening tools for neurodegenerative risk that differ by race and ethnicity, reflecting upstream social inequities. Prior work shows that PF relates to Alzheimer's disease blood biomarkers differentially by race and ethnicity, yet it is unclear if similar associations exist with structural brain outcomes (hyperintensities and brain volumes).ObjectiveThis study evaluated associations between PF and white matter hyperintensity volume (WMH), total brain volume (TBV), and hippocampal volume (HV) and assessed heterogeneity by race and ethnicity.MethodsCognitively normal non-Hispanic Black (n = 420), non-Hispanic white (n = 917), and Hispanic (n = 828) older adults (mean [SD] age = 64.7 [8.4]) from the Healthy Aging Brain Study-Health Disparities cohort completed the Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB). Brain imaging was collected via 3 T magnetic resonance imaging (MRI). Multivariable linear models related PF to brain imaging outcomes (normalized by intracranial volume) and assessed heterogeneity by race and ethnicity.ResultsBonferroni adjusted significant (p < 0.05) associations were observed between WMH and PF (TUG: β = 0.28, 95% CI = 0.17, 0.40; SPPB:β = -0.19, 95% CI = -0.32, -0.07), TBV and PF (TUG: β = -0.50, 95% CI = -0.61, -0.40; SPPB: β = 0.30, 95% CI = 0.18, 0.42), and HV and PF (TUG: β = -0.28, 95% CI = -0.38, -0.18). Associations were generally similar across race and ethnicity groups for TBV and HV.ConclusionsPoorer PF was associated with reduced TBV and HV and greater WMH. Results support PF tests as scalable, non-invasive indicators of brain health in community-based populations.