Depression as a Risk Factor for Alzheimer’s Disease: A Systematic Review of Longitudinal Meta-Analyses

Alzheimer’s disease (AD) is the most frequent cause of dementia, linked to morbidity and mortality among elderly patients. Recently, several clinical studies suggested that depression is a potential risk factor for cognitive decline and AD. A review of meta-analyses was performed, calculating pooled odds ratios to estimate the risk of AD in people with a prior diagnosis (or clinically significant symptoms) of depression. A total of six meta-analyses which represented 28 individual studies were analyzed. A significant association between depression and AD was found (OR = 1.54, 95% CI [1.02–2.31]; p = 0.038). The results showed that heterogeneity across studies was substantial. We found a significant positive effect size for clinical measures of depression, but not for symptomatic rating scales, in the association of depression with risk of AD. The type of rating scale used to assess depression and the cut-off criteria selected also moderated the relationship between depression and AD risk. We found that studies that used clinically significant criteria for diagnosis of depression had more consistent and significant results than studies that used symptomatic scales.
This study was supported by Grants from the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness, Madrid, Spain (grants 94/1562, 97/1321E, 98/0103, 01/0255, 03/0815, 06/0617, 12/02254, 16/00896, PI/19/01874, G03/128) and from the Fondo Europeo de Desarrollo Regional (FEDER) of the European Union “Una manera de hacer Europa” (Project number PI16/00896) and Gobierno de Aragón (grant B15_17R). BO’s work is supported by the Miguel Servet program (CP20/00040), funded by the Instituto de Salud Carlos III and co-funded by the European Union (ERDF/ESF, “Investing in your future”). This study was partially supported by FEDER funds and the Spanish Ministry of Economy and Competitiveness (Projects ECO2016-76567-C4-2-R and PID2019-104263RB-C44), the Regional Government of “Castilla y León”, Spain (Project BU329U14 and BU071G19), the Regional Government of “Castilla y León”, and FEDER funds (Project BU062U16).