Depression as a prognostic factor for conversion from mild cognitive impairment to all-cause dementia and Alzheimer's disease: a systematic review and meta-analysis of longitudinal studies

Background Mild cognitive impairment (MCI) is a transitional stage between normal aging and dementia, with annual conversion rates to Alzheimer's disease (AD) or all-cause dementia estimated at 10%−15%. The role of depression as a prognostic factor for dementia progression remains unclear. This systematic review and meta-analysis aimed to clarify the association between depression and risk of conversion from MCI to AD and all-cause dementia. Methods We conducted a systematic review and meta-analysis of longitudinal cohort studies following PRISMA 2020 guidelines. PubMed, PsycINFO, Web of Science, and Scopus were searched. Eligible studies included adults with MCI, depression assessed by clinical diagnosis or validated scales, and reported hazard ratios (HRs) for progression to dementia. Random-effects meta-analyses were performed for unadjusted and adjusted HRs. Risk of bias was assessed using the Newcastle–Ottawa Scale, and certainty of evidence was evaluated with GRADE. Results Seventeen studies were included, with follow-up ranging from 6 months to 12 years. In unadjusted analyses, baseline depression was associated with increased risk of progression overall (HR 1.66, 95% CI 1.22–2.26); however, heterogeneity across studies was high ( I 2 = 99.1%), limiting confidence in the pooled estimate. The association was significant for progression to AD (HR 1.57, 95% CI 1.15–2.15 ; I 2 = 99.4%), but not for all-cause dementia (HR 1.95, 95% CI 0.85–4.48; I 2 = 90%). In adjusted analyses, depression remained associated with increased progression risk overall (HR 1.21, 95% CI 1.05–1.39), with high heterogeneity ( I 2 = 99.8%). The association was statistically significant for all-cause dementia (HR 1.24, 95% CI 1.01–1.52; I 2 = 78.8%), but not for AD (HR 1.18, 95% CI 0.95–1.47; I 2 = 99.8%). Sensitivity analyses confirmed robustness of findings, and publication bias was not detected. Certainty of evidence was rated very low due to heterogeneity. Conclusion Depression appears to be associated with an increased risk of progression from MCI to dementia; however, the very high heterogeneity and very low certainty of evidence substantially limit confidence in the magnitude and consistency of this association. These findings highlight the importance of depression screening and management in MCI populations. Integrating mental health care into cognitive disorder clinics may improve patient outcomes and potentially delay dementia onset. Systematic Review registration identifier: CRD420261308245.