Associations of social isolation and its subdomains with cognition and cerebrospinal fluid amyloid pathologies in non-demented adults: The CABLE study.

BackgroundSocial isolation is increasingly recognized as a modifiable risk factor for cognitive impairment. However, the associations with Alzheimer's disease (AD)-related cerebrospinal fluid (CSF) biomarkers remain unexplored.ObjectiveTo evaluate the relationships between social isolation, cognition, and CSF biomarkers and how these are influenced by other factors.MethodsIn this cross-sectional study, 957 non-demented adults from the Chinese Alzheimer's Biomarker and LifestyLE (CABLE) study (mean age: 64.19 years; 46% male) were included. Multiple linear regression models were used to analyze the associations of social isolation and its subdomains (social networks, marital status, and social activities) with cognition and CSF biomarkers after adjustment for age, gender, education, and APOE ɛ4 allele status. Interactive, stratified, and sensitivity analyses were further conducted.ResultsSocial isolation was significantly associated with worse cognitive performance, including lower MMSE (β=-0.09, PFDR=0.008) and MoCA scores (β=-0.11, PFDR=0.002). Social isolation was also associated with CSF amyloid pathology, including decreased Aβ42 (β=-0.14, PFDR=0.004), decreased Aβ40 (β=-0.16, PFDR<0.001), and increased T-tau/Aβ42 ratio (β=0.12, PFDR=0.016) levels. Specifically, smaller social networks were correlated with poorer cognition and decreased CSF Aβ42 and Aβ40 levels, while being without a spouse was associated with decreased CSF Aβ42 and Aβ40 levels and increased P-tau/Aβ42 and T-tau/Aβ42 ratios. Associations were primarily observed among males and APOE ε4 non-carriers in subgroup analyses. Sensitivity analyses confirmed the robustness of our findings.ConclusionsSocial isolation, particularly smaller social networks and being without a spouse, is associated with worse cognitive performance and early CSF amyloid-related biomarkers levels in non-demented adults.