Late-life depression, mild cognitive impairment, and dementia: possible continuum?

Clinical and epidemiologic research has focused on the identification of risk factors that may be modified in predementia syndromes, at a preclinical and early clinical stage of dementing disorders, with specific attention to the role of depression. Our goal was to provide an overview of these studies and more specifically to describe the prevalence and incidence of depression in individuals with mild cognitive impairment (MCI), the possible impact of depressive symptoms on incident MCI, or its progression to dementia and the possible mechanisms behind the observed associations. Prevalence and incidence of depressive symptoms or syndromes in MCI vary as a result of different diagnostic criteria and different sampling and assessment procedures. The prevalence of depression in individuals with MCI was higher in hospital-based studies (median: 44.3%, range: 9%-83%) than in population-based studies (median: 15.7%, range: 3%-63%), reflecting different referral patterns and selection criteria. Incidence of depressive symptoms varied from 11.7 to 26.6/100 person-years in hospital-based and population-based studies. For depressed normal subjects and depressed patients with MCI, the findings on increased risk of incident MCI or its progression to dementia were conflicting. These contrasting findings suggested that the length of the follow-up period, the study design, the sample population, and methodological differences may be central for detecting an association between baseline depression and subsequent development of MCI or its progression to dementia. Assuming that MCI may be the earliest identifiable clinical stage of dementia, depressive symptoms may be an early manifestation rather than a risk factor for dementia and Alzheimer disease, arguing that the underlying neuropathological condition that causes MCI or dementia also causes depressive symptoms. In this scenario, at least in certain subsets of elderly patients, late-life depression, MCI, and dementia could represent a possible clinical continuum.