Study Finds Depression May Increase Risk of Developing Dementia

Study findings published in eClinicalMedicine demonstrate that depression during an individual’s lifespan may increase their risk of developing dementia. The authors wrote that a life course approach to the treatment and prevention of depression may help reduce individuals’ burdens of dementia; however, such efforts will require scaling up access to effective mental health care for populations who are vulnerable.¹

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To prevent dementia onset, it is crucial to identify risk factors that are considered modifiable. Although depression has previously been considered a risk factor for dementia, at the time of this study’s initiation, temporal dynamics across the life course remained inconclusive. For these reasons, the investigators sought to systematically assess the relationship between risk of all-cause late-life dementia and the timing of depression assessment.¹

The investigators conducted an umbrella review and meta-analysis to assess incident dementia in participants with a noncurrent history of depression. PubMed, Ovid Embase, MEDLINE, and PsycInfo were searched from inception up to February 17, 2025. Additionally, systematic reviews with meta-analyses investigating the association between depression and incident late-life dementia were included. From eligible reviews, the authors noted also extracting data from studies that reported dementia risk as hazard ratios (HRs), analyzing the timing of depression measurement using random-effects models for meta-analysis.¹

“We specifically focused on the timing of when depression was measured, whether it was measured in midlife or in later life, and calculated how much it increased the risk of developing dementia,” Jacob Brain, PhD, a researcher at the Institute of Mental Health and School of Medicine at the University of Nottingham, the University of Adelaide, and the Dementia Centre of Excellence at Curtin University in Australia, said in a news release. “This essentially allowed us to provide a more accurate and up-to-date picture of how depression at different life stages is linked to dementia risk.”²

Among a total of 7763 records identified, only 9 were included in the umbrella review, and 18 studies were included in the meta-analysis. In the umbrella review, only 1 review was judged to be of moderate quality, whereas the others were either low (n = 3) or critically low (n = 5). For the meta-analyses, 18 studies reporting depression onset in later life (7595 incident dementia cases amid a cumulative 901,762 participants) and 7 studies on depression assessed during midlife (n ≥ 2,501,269 participants, n ≥ 276,929 incident dementia cases) were included. The authors determined the studies in the meta-analyses were all of good quality, with no strong evidence of publication bias. Pooled HRs indicated depression that was present later in life (HR 1.95 [95% CI: 1.68–2.26]; I² = 77.5%) and midlife (HR 1.56 [95% CI: 1.12–2.18]; I² = 97.5%) significantly increased the risk of all-cause dementia.¹

“Our study shows that depression is linked to an increased risk of dementia in both midlife and late life. This highlights the importance of recognizing and treating depression across the life course, not just for mental health, but also as part of a broader strategy to protect brain health. Public health efforts need to place greater emphasis on preventative brain health, including scaling up access to effective mental health care,” said Brain.²

The authors explained that their findings contribute to the evidence supporting depression as a potentially modifiable risk factor for dementia, while also highlighting a complex temporal gradient within this association. Because of the substantial public health implications, it is imperative that depression detection and treatment efforts are scaled up, particularly in primary care settings and for older populations. By expanding access to mental health services through the integration of mental health screening and referral to treatment into routine health assessments for midlife and older adults, dementia risk can be mitigated or lessened within this population.¹

The study authors warned that substantial heterogeneity and review quality should be considered when interpreting the strength of their evidence. Additionally, they suggest that additional research is conducted to clarify whether stronger late-life association reflects depression as an immediate risk factor or an early manifestation of neurodegenerative processes.¹

“Our findings raise the possibility that depression late in life may not just be a risk factor, but it could also be an early warning sign of dementia beginning to develop," concluded Brain. "By clarifying this timing, our work helps guide future research, treatment, and prevention strategies.”²

REFERENCES

1. Brain J, Alshahrani M, Kafadar AH, et al. Temporal dynamics in the association between depression and dementia: an umbrella review and meta-analysis. eClinicalMedicine. 2025:103266. doi:10.1016/j.eclinm.2025.103266

2. University of Nottingham. Depression is linked to an increased risk of dementia in both mid and later life, finds a new study. News release. May 29, 2025. Accessed June 10, 2025. https://www.eurekalert.org/news-releases/1085443