Protective Effects of Socioeconomic Status and Lifestyle on Amyloid- and White Matter Hyperintensity-Related Longitudinal Brain Atrophy and Cognitive Decline.

OBJECTIVE

Socioeconomic status (SES) and lifestyle activities (LA) are strongly related, and both are associated with dementia risk. We investigated the influence of SES and LA on brain atrophy and cognitive decline considering amyloid-beta (Aβ) positron emission tomography and white matter hyperintensity (WMH) load.

METHODS

We investigated 221 older adults (mean age, 67.1 ± 8.2 years) who underwent cognitive testing annually over a median follow-up period of 3.4 years. Longitudinal T1-weighted magnetic resonance imaging was available for 181 participants. Measures of SES and LA were collected using questionnaires and combined to SES and LA scores using a latent variable approach. We used linear mixed-effects models to investigate if SES and LA are independently or interactively with Aβ and WMH load associated with decline in domains language, processing speed/attention, executive function, and episodic memory. Mediation models assessed whether these associations were explained by gray matter atrophy.

RESULTS

SES and LA were associated with better cognitive performance at baseline, but were not associated with cognitive decline over time. In interaction with brain pathologies, higher LA reduced the detrimental effects of Aβ and WMH load on language decline, whereas higher SES reduced the detrimental effects of Aβ pathology on episodic memory decline. Individuals with low SES showed faster Aβ-related gray matter atrophy, which mediated the association between Aβ and episodic memory decline but not language decline.

INTERPRETATION: These results suggest that multiple resilience mechanisms underlie the protective effects of SES and LA on cognitive decline. Interventions targeting SES-related risk factors may be most effective when implemented early, before neurodegenerative changes begin. ANN NEUROL 2025;98:1222-1236.