Loneliness as a sex-specific risk factor for cognitive aging

Loneliness has emerged as a robust risk factor for adverse cognitive outcomes, including accelerated cognitive decline and increased dementia risk. However, accumulating evidence suggests that the cognitive consequences of loneliness may be sex-specific, with women experiencing disproportionate exposure, vulnerability, and downstream effects across the life course. This mini-review synthesizes epidemiological, psychosocial, and neurobiological evidence linking loneliness to cognitive aging in women, highlighting sex differences in prevalence, social role exposures (e.g., caregiving, widowhood), stress responsivity, and neuroendocrine and inflammatory pathways. Findings from longitudinal cohort studies are reviewed, demonstrating stronger associations between loneliness and cognitive decline in women, alongside emerging mechanistic research implicating hypothalamic-pituitary-adrenal (HPA) axis dysregulation, immune activation, and hippocampal vulnerability. Critical gaps in aging neuroscience, including limited sex-disaggregated analyses and undermeasurement of relational and social variables, require urgent attention. A sex-sensitive framework for integrating loneliness into cognitive aging research and prevention strategies, emphasizing targeted assessment and intervention approaches that reflect women's lived social contexts, holds promise for advancing precision prevention in women's brain health. Framing loneliness as a modifiable, sex-specific risk factor offers a novel avenue for precision prevention in women's cognitive aging.