DEPRESSION is associated with an increased risk of developing dementia in both midlife and later life, with the risk being nearly double for those experiencing depression in late life compared to those without.
Dementia is a major global health challenge, affecting over 57 million people worldwide, and there is currently no cure, making the identification of modifiable risk factors a public health priority. Depression has long been recognised as a potential risk factor for dementia, but the relationship is complex, involving possible mechanisms such as chronic inflammation, hormonal changes, vascular damage, and neurotransmitter imbalances. The timing of depression—whether it occurs in midlife or later life—has been a subject of debate, with some suggesting that late-life depression may be both a risk factor and an early warning sign of dementia. Understanding these temporal dynamics is essential for guiding prevention, early intervention, and public health strategies.
The research team conducted an umbrella review and meta-analysis, synthesising data from existing systematic reviews and meta-analyses, as well as re-analysing data from individual studies and incorporating newer research. After screening 7,763 records, nine reviews were included in the umbrella review, with quality ranging from moderate to critically low. For the meta-analysis, 18 studies assessed depression in later life (901,762 participants, 7,595 incident dementia cases) and seven studies assessed depression in midlife (over 2.5 million participants, at least 276,929 incident dementia cases). All meta-analysed studies were of good quality with no strong evidence of publication bias. The pooled results showed that depression in late life was associated with a hazard ratio (HR) of 1.95 (95% CI: 1.68–2.26; I² = 77.5%) for dementia, while depression in midlife was associated with an HR of 1.56 (95% CI: 1.12–2.18; I² = 97.5%), indicating a significant increase in dementia risk at both life stages.
These findings highlight the importance of recognising and treating depression across the life course as part of a broader strategy to protect brain health and reduce the risk of dementia. For clinical practice, this underscores the need for integrated mental health care that addresses depression from midlife onwards, with particular attention to older adults who may be at heightened risk. Public health efforts should prioritise accessible, effective mental health services and promote brain health through prevention and early intervention. Further research is needed to clarify whether late-life depression is a direct risk factor or an early marker of dementia, and to identify optimal approaches for reducing risk in vulnerable populations.
Reference
Brain J et al. Temporal dynamics in the association between depression and dementia: an umbrella review and meta-analysis, eClinicalMedicine. 2025;DOI:10.1016/j.eclinm.2025.103266.
