Multimodal lifestyle engagement patterns support cognitive stability beyond neuropathological burden

Background: Modifiable lifestyle behaviors account for a large proportion of dementia risk. However, the combined contributions of multidomain lifestyle patterns to cognitive aging are poorly understood, as most studies have examined individual lifestyle behaviors in isolation and without neuropathological characterization. This study examined data-driven patterns of lifestyle behaviors across multiple domains among older adults and tested their associations with disease-specific neuropathological burden and cognitive decline.

Methods: Participants included 2059 older adults enrolled in the longitudinal Memory and Aging Project (MAP) at the Rush Alzheimer's Disease Center; none of whom had dementia at baseline (73% no cognitive impairment (NCI), 27% mild cognitive impairment [MCI]). All participants completed cognitive testing annually. Lifestyle factors were measured during at least one visit and included (1) actigraphy-measured physical activity, as well as self-reported (2) sleep quality, (3) life space, (4) cognitive activities, (5) social activities, and (6) social network. A subset of participants (n = 791) had autopsy data for which burden of Alzheimer's disease (AD), cerebrovascular disease (CVD), Lewy body disease, and hippocampal sclerosis/TDP-43 was measured. Latent profile analysis across all 2059 participants identified distinct subgroups (i.e., classes) of lifestyle patterns. Linear mixed-effects models examined relationships between lifestyle classes and global cognitive trajectories, with and without covarying for all neuropathologies. Classes were also compared on rates of incident MCI/dementia.

Results: Five classes were identified: Class 1_{Low Life Space} (lowest lifestyle engagement), Class 2_PA (high physical activity), Class 3_{Low Avg} (low to average lifestyle engagement), Class 4_Balanced (high average lifestyle engagement), and Class 5_Social (large social network). Classes 4_Balanced and 5_Social had the lowest AD burden, and Class 2_PA had the lowest CVD burden. Classes 2-5 had significantly less steep global cognitive decline compared to Class 1_{Low Life Space}, with comparable effect sizes before and after covarying for neuropathological burden. Classes 4_Balanced and 5_Social exhibited the lowest rates of incident MCI/dementia.

Conclusions: Lifestyle behavior patterns among older adults account for differential rates of cognitive decline and clinical progression. Those with at least average engagement across all lifestyle domains exhibit greater cognitive stability after adjustment for neuropathology, highlighting the importance of engagement in multiple healthy lifestyle behaviors for later life cognitive health.