Depression and Dementia: Timing Matters More Than We Thought

Temporal dynamics in the association between depression and dementia: an umbrella review and meta-analysis

Jacob Brain^a,b,n jacob.brain@nottingham.ac.uk ∙ Maha Alshahrani^c,d,e,f,n ∙ Aysegul Humeyra Kafadar^a ∙ Eugene YH. Tang^g ∙ Elissa Burton^c,h ∙ Leanne Greeneⁱ ∙ et al.

A 2025 umbrella review and meta-analysis has delivered new insights into the complex relationship between depression and the risk of developing dementia. By synthesizing data from over 3 million participants across 25 high-quality studies, the researchers found that depression significantly increases the risk of dementia, but the timing of depression onset plays a crucial role.

📌 Key Findings:

• Late-life depression (≥65 years) nearly doubles the risk of developing dementia (HR 1.95).

• Midlife depression also significantly increases dementia risk, though to a lesser extent (HR 1.56).

• The risk was more pronounced in studies with shorter follow-up durations, supporting the idea that late-life depression may sometimes be an early sign of neurodegeneration.

• Substantial variability existed across studies, partly due to differences in how depression was defined and measured (clinical diagnosis vs. self-report).

🔍 Why it matters:This is the first large-scale synthesis to directly examine how the timing of depression influences dementia risk. The findings highlight that depression may act both as a prodrome (early symptom) of dementia and as an independent, modifiable risk factor—underscoring the importance of early detection and treatment.

🧠 Clinical and public health implications:

• Screening for depression in both midlife and older adults should be part of routine dementia prevention strategies.

• Integrated mental health care, especially in primary care and geriatric settings, could help reduce the global dementia burden.

• Future research should focus on whether treating depression reduces dementia risk, especially when combined with lifestyle interventions.

📖 Citation: Brain J. et al. (2025). Temporal dynamics in the association between depression and dementia: an umbrella review and meta-analysis.

https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00198-1/fulltext