Depressive symptoms mediate the association between loneliness and cognitive performance in women living with HIV: findings from the Women's Interagency HIV Study.

Loneliness is a risk factor for cognitive impairment, yet, its role in domain-specific cognitive performance and underlying mechanisms remain understudied in women living with HIV (WLWH). To assess whether depressive symptoms mediate associations between loneliness and global and domain-specific cognition, data were analyzed from 1621 WLWH participating in the Women's Interagency HIV Study, a multicenter, observational cohort conducted in the United States. Mediation analysis using linear mixed-effects models estimated average direct and indirect effects and proportion mediated, adjusting for covariates. Median age was 49 years, 75% were Black, and 25% were lonely at initial visit. Lonely WLWH had higher depressive symptoms, greater housing instability, lower employment, and higher substance use than non-lonely WLWH. In adjusted models, higher loneliness was associated with poorer global cognition, executive function, processing speed, learning, memory, and verbal fluency. Significant indirect associations through depressive symptoms were observed for global cognition, executive function, processing speed, and learning. Direct associations were attenuated after accounting for depressive symptoms, except for executive function. Interventions addressing loneliness and depression may support cognitive performance in WLWH. Findings underscore the need for additional longitudinal research to clarify the long-term cognitive consequences of loneliness in WLWH.