• Federica Piras, Nerisa Banaj, Desirée E Porcari, Fabrizio Piras, and Gianfranco Spalletta.
• Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
• Minerva Med. 2021 Aug 1; 112 (4): 456-466.

AbstractCurrent investigations in pre-symptomatic dementia have suggested that depressive mood, a treatable condition, may play an important role in the development of the disorder. However, whether depression in adulthood constitute a risk factor, or a prodrome of dementia remains unclear. A major implication in such dispute is the analytic framework used to identify putative risk factors. Indeed, if evaluated in the years immediately prior to dementia diagnosis the association between depression and dementia may reflect depressive symptoms as a prodrome of yet-undiagnosed dementia. Unfortunately, long term prospective cohort investigations, reaching back into the preclinical phase of dementia are sparse. Here, we have surveyed high-quality evidence (systematic reviews and meta-analyses) on the association between depressive symptoms and increased odds of dementia. Meta-analytic findings are also presented and discussed regarding depression as a prodromal stage of dementia, or a consequence of underlying neurodegenerative processes. Additionally, the potential confounding effect of several variables on the risk association between depression and dementia, an aspect hardly investigated, is discussed. While early onset late-life depression - defined as starting before 60 years of age - increases the odds of developing dementia in predisposed subjects, late-onset depression appears to be a prodrome and a clear accelerating factor for cognitive deterioration. Since it is increasingly important to consider the potential of preemptive approaches to decrease the impact of dementia, evidence on potentially effective preventive strategies targeting depression as a risk factor, and next steps in further research are presented as concluding remarks.

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