Abstract

Late-life depression (LLD), mild cognitive impairment (MCI), and dementia are clinically distinct yet interrelated disease constructs, wherein LLD can be a prodrome, risk factor, comorbidity, or consequence of MCI and dementia. There is considerable prevalence of depression in those with MCI or dementia, and vice versa, with maximum evidence in Alzheimer's disease. These intersections often form one of the most confusing aspects of psychogeriatric practice, leading to under-detection and mismanagement of depression, thus leading to incomplete recovery in most cases. This article focuses on this clinical ambiguity in daily practice, reviews the clinico-investigative pointers for the LLD–dementia intersection, and puts forward clinical and research recommendations in view of the available evidence. Although there is conflicting evidence regarding the cause–effect relationship between LLD, MCI, and dementia, it is likely that these constructs share some common pathological processes and are often associated with each other within a longitudinal clinical continuum. This is a linear yet complex bidirectional association: either the comorbid depression exaggerates preexisting cognitive deficits or chronic persistent depression eventually leads to major neurocognitive disorders, not to mention depression as a part of behavioral and psychological symptoms of dementia, which often impairs quality of life and psychosocial morbidity. Thus, a comprehensive approach, including tailored history, neuropsychiatric examination, and relevant investigations, is necessary for assessing the differentials, with a sound clinical understanding being vital to the process. Depression, if suspected, must be treated adequately with longitudinal neuropsychological reviews. Future research warrants elucidating precision biomarkers unique to these clinicopathological entities.

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