How loneliness and social isolation are linked to cognitive decline among older adults? A systematic review of underlying physiological and psychobehavioral mechanisms.

Despite empirical evidence linking loneliness and social isolation to cognitive decline (CD) in later life, the underlying physiological and psychobehavioral mechanisms remain unclear. We conducted a systematic review to synthesize relevant evidence. Studies examining psychobehavioral pathways required mediation analyses, whereas studies on physiological pathways were included when mediation was examined or when outcomes are dementia-related neuropathological changes. Thirty-eight articles were included. Evidence pointed to multiple physiological mechanisms, including Alzheimer's disease pathology, brain structural differences, inflammation, cardiovascular risks, neurotrophic factors, hypothalamic-pituitary-adrenal (HPA) -axis function, gene expression, and general health, although findings were mixed. Psychobehavioral pathways, including depressive symptoms, neuroticism, lower sense of control, sleep disturbance, and lower engagement in social or leisure activities, mediated the association. This review identified mechanistic targets that may be leveraged in non-pharmacological interventions. Future intervention programs aimed at reducing social isolation and loneliness to delay CD could investigate whether they impact physiological and psychobehavioral pathways summarized here.