Social determinants of health, genetic biomarkers, and cognitive function in Chinese older adults with subjective cognitive decline and mild cognitive impairment: A cross-sectional analysis

Background Social isolation (SI) is an established risk factor for Alzheimer's disease (AD) and cognitive decline. However, its stage-specific effects across the AD continuum, particularly at subjective cognitive decline (SCD) and mild cognitive impairment (MCI) stages, remain unquantified in Chinese populations. The sex-specific effects of SI on cognitive decline remain incompletely characterized. The apolipoprotein E ( APOE ) genotype is a driver of cognitive decline and dementia. Objective To investigate social connection characteristics and gene distribution in individuals with SCD or MCI, examine their cross-sectional associations with cognitive function, and explore gender differences in SCD or MCI risk/prevention. Methods A community-based sample of 164 SCD and 84 MCI patients (July 2021–Dec 2024) was assessed. Demographic, social connectivity, APOE genotype and cognitive data were collected. Social connectivity, APOE genotype and cognitive function were compared between groups. In the overall or male and female genders, Pearson correlation analyzed associations between social connectivity and cognitive scores. Sex-stratified multivariable models tested Lubben Social Network Scale (LSNS-6)-by-sex interactions on MCI risk. Results LSNS-6 scores showed weak-to-moderate correlations with Montreal Cognitive Assessment ( r = 0.140, p = 0.027), Animal Verbal Fluency Test-Huashan (AVLT-H) delayed recall ( r = 0.129, p = 0.043), AVLT-H recognition ( r = 0.190, p = 0.003), Trail Making Test-B ( r = -0.132, p = 0.038), Boston Naming Test ( r = 0.147, p = 0.021), and Animal Verbal Fluency Test ( r = 0.148, p = 0.020). Multivariable binary logistic regression analysis revealed the association between social network and MCI risk differed by sex (OR male = 0.581; OR female = 0.746; p interaction = 0.021). Conclusions SI may exacerbate cognitive dysfunction in adults with SCD or MCI. Women leverage social connectivity into significantly greater neuroprotective gains compared to men. Trial registration ChiCTR2300073429. https://www.chictr.org.cn/bin/project/edit?pid=200381