Summary: A comprehensive new analysis reveals that depression significantly increases the risk of developing dementia, whether it begins in midlife or later in life. Researchers reviewed and re-analyzed data from dozens of studies to clarify when depression most strongly affects dementia risk.
The findings suggest late-life depression may be more than just a risk factor—it could be an early sign of dementia onset. These insights emphasize the urgent need to prioritize mental health care as a long-term strategy to protect brain health and prevent dementia.
Key Facts:
- Lifelong Risk: Depression in both midlife and later life increases dementia risk.
- Early Warning Sign: Late-life depression may signal the early stages of dementia development.
- Broad Strategy Needed: Mental health care should be central to dementia prevention efforts.
Source: University of Nottingham
A new study has found that depression is linked to an increased risk of dementia in both mid and later life.
The new research, which is published in eClinicalMedicine, was led by Jacob Brain and Maha Alshahrani from the Institute of Mental Health and School of Medicine at the University of Nottingham, University of Adelaide and the Dementia Centre of Excellence at Curtin University in Australia.
Mr Brain said: “Our study shows that depression is linked to an increased risk of dementia in both midlife and late life.
“This highlights the importance of recognising 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.”
Dementia affects over 57 million people globally. There is currently no cure, so identifying and treating the factors to reduce the risk, such as depression, is an important public health priority.
The potential links between depression and dementia are complex and may include chronic inflammation, hypothalamic-pituitary-adrenal axis dysregulation, vascular changes, alterations to neurotrophic factors and neurotransmitter imbalances. Shared genetic and behavioural related changes may also increase the risks.
Previous studies have shown that people with depression are more likely to develop dementia later in life, but there’s been a lot of debate about when depression matters most, whether it’s depression that starts in midlife – in your 40s or 50s, or depression that appears later in life – in your 60s or beyond.
This new research brings together all the existing evidence and adds new analysis to examine this timing in more detail.
“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. By clarifying this timing, our work helps guide future research, treatment, and prevention strategies,” says Mr Brain.
The team carried out an umbrella review and meta-analysis. They firstly gathered and reviewed all the best available data from systematic reviews with meta-analyses (a statistical method that combines results from multiple studies to provide a more reliable overall estimate), that had already looked at the link between depression and dementia.
They then went a step further by extracting and re-analysing data from the individual studies within those reviews, plus they added in newer studies that were missed in the earlier work.
Mr Brain adds: “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. 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.”
About this depression and dementia research news
Author: Charlotte Wall
Source: University of Nottingham
Contact: Charlotte Wall – University of Nottingham
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Temporal dynamics in the association between depression and dementia: an umbrella review and meta-analysis” by Jacob Brain et al. eClinicalMedicine
Abstract
Temporal dynamics in the association between depression and dementia: an umbrella review and meta-analysis
Background
Identifying modifiable risk factors is crucial for dementia prevention, a global health concern. Depression is considered a risk factor for dementia, but the temporal dynamics across the life course remain inconclusive. Therefore, we aimed to systematically assess the relationship between the timing of depression assessment and risk of all-cause late-life dementia.
Methods
We conducted an umbrella review and meta-analysis to assess incident dementia in individuals with non-current history of depression. PubMed and Ovid Embase, MEDLINE, and PsycInfo were searched from inception up to February 17, 2025. Systematic reviews with meta-analyses investigating the association between depression and incident late-life dementia were included.
From eligible reviews, we also extracted data from studies reporting dementia risk as hazard ratios (HRs), analysing the timing of depression measurement using random-effects models for meta-analysis. This study is registered with PROSPERO, CRD42021249706.
Findings
Of the 7763 records identified, nine reviews were eligible for inclusion of the umbrella review. One review was judged to be of moderate quality, while the others were either low (n = 3) or critically low (n = 5). For our meta-analyses, 18 studies reporting depression onset in later life (n = 901,762 participants, n = 7595 incident dementia cases) and seven studies on depression assessed during midlife (n ≥ 2,501,269 participants, n ≥ 276,929 incident dementia cases) were included.
All studies in the meta-analyses were deemed to be of good quality, with no strong evidence of publication bias. Pooled HRs indicated depression present in late-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 risk of all-cause dementia.
Interpretation
The findings suggest that depression across the life course may increase dementia risk; however, substantial heterogeneity and review quality should be considered when interpreting the strength of this evidence.
A life course approach to the treatment and prevention of depression may help reduce the burden of dementia, but this will require scaling up access to effective mental health care for vulnerable populations.
Further research is needed to clarify if the stronger late-life association reflects depression as an immediate risk factor or an early manifestation of neurodegenerative processes.
Funding
National Institute for Health and Care Research, UK Research and Innovation, and Saudi Arabian Cultural Mission.
