Cognitive Impairment, Dementia and Depression in Older Adults

Depression and cognitive impairment frequently co-occur in late life and exhibit substantial clinical and biological overlap. Epidemiological evidence consistently shows that late-life depression increases the risk of mild cognitive impairment and dementia, with stronger associations observed for vascular dementia than for Alzheimer’s disease. Neurobiological studies implicate cerebrovascular pathology, neuroinflammation, hypothalamic–pituitary–adrenal axis dysregulation, and fronto-subcortical circuit dysfunction as key mechanisms linking depressive symptoms to later cognitive decline. In a subset of older adults, new-onset depression—particularly when accompanied by executive dysfunction, subjective cognitive decline, or high white-matter hyperintensity burden—may represent a prodromal manifestation of emerging neurodegenerative or vascular brain changes. Depression is also highly prevalent as part of the behavioral and psychological symptoms of dementia, occurring in 30–50% of individuals with Alzheimer’s disease and even higher proportions in dementia with Lewy bodies or frontotemporal dementia. Comorbid depression in dementia accelerates cognitive and functional decline, increases neuropsychiatric burden, and worsens quality of life for patients and caregivers. Therapeutically, antidepressants may provide modest cognitive benefits in non-demented older adults but show limited efficacy in dementia. In contrast, cholinesterase inhibitors, memantine, and multimodal non-pharmacological interventions yield small but measurable improvements in depressive or apathy-related symptoms. While anti-amyloid therapies slow cognitive deterioration in early Alzheimer’s disease, their effects on mood remain unclear. These findings underscore the need for stage-specific, integrative strategies to address the intertwined trajectories of mood and cognition in aging.