Global aging and changing family structures necessitate identifying modifiable factors for cognitive health. While social isolation is a known risk, the protective role of specific living arrangements and their interplay with neurobiology is unclear.

This study aimed to: (1) examine the longitudinal association between living arrangements and cognitive function in older adults, and (2) investigate the potential moderating roles of plasma Alzheimer’s disease (AD) biomarkers in this relationship.

Using data from the Hubei Memory and Aging Cohort Study, we followed 3,403 older adults aged 65 years and above with different living arrangements. Participants underwent standardized cognitive assessments and plasma biomarker measurements, including amyloid-beta (Abeta) 40, Abeta 42, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau) 181, and p-tau 217. Linear mixed-effects models were employed to analyze cognitive trajectories.

Compared to older adults living separately from their families, those in two specific living arrangements, living with a spouse only or in multigenerational living, demonstrated significantly better cognitive performance across multiple domains. These protective associations proved robust even after comprehensive adjustment for plasma AD biomarkers. Importantly, we found that higher plasma GFAP levels significantly attenuated the cognitive benefits conferred by favorable living arrangements. In a separate, distinct pathway, higher plasma Abeta40 levels were independently associated with better-preserved language function over time.

Favorable living arrangements may benefit cognitive health through pathways independent of typical AD pathology. Incorporating living arrangements and plasma biomarkers, particularly GFAP, could enhance risk assessment and targeted interventions for cognitive decline in older adults.