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

Background Social 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. Objective To evaluate the relationships between social isolation, cognition, and CSF biomarkers and how these are influenced by other factors. Methods In 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. Results Social 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 Aβ 42 ( β =-0.14, PFDR =0.004), decreased Aβ 40 ( β =-0.16, PFDR <0.001), and increased T-tau/Aβ 42 ratio ( β =0.12, PFDR =0.016) levels. Specifically, smaller social networks were correlated with poorer cognition and decreased CSF Aβ 42 and Aβ 40 levels, while being without a spouse was associated with decreased CSF Aβ 42 and Aβ 40 levels and increased P-tau/Aβ 42 and T-tau/Aβ 42 ratios. Associations were primarily observed among males and APOE ε4 non-carriers in subgroup analyses. Sensitivity analyses confirmed the robustness of our findings. Conclusions Social 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.