Scientists have identified six specific symptoms of depression in midlife that are linked to a significantly higher risk of developing dementia more than two decades later, according to a study published in The Lancet Psychiatry. The authors suggest that this could open new doors for early prevention.
A team from the University College London (UCL) followed nearly 6,000 middle-aged adults for 25 years. The authors found that while depression in midlife has long been considered a risk factor for dementia, it is not depression as a whole that drives this link, but rather a specific cluster of six symptoms including:
- Losing confidence in yourself
- Not being able to face up to problems
- Not feeling warmth and affection for others
- Feeling nervous and strung-up all the time
- Not being satisfied with the way tasks are carried out
- Difficulties concentrating
Participants were assessed for depressive symptoms between 1997 and 1999, when they were aged between 45 and 69 and free of dementia. Their health was then tracked through national registries for 25 years, with dementia diagnoses recorded up to 2023. During that time, just over 10% developed dementia.
Those classified as depressed in midlife had a 27% higher risk of developing dementia overall, but this increased risk was driven entirely by the six specific symptoms listed above, particularly in adults under 60. Loss of self-confidence and difficulty coping with problems were each associated with roughly a 50% increased risk on their own.
The researchers believe these particular symptoms may contribute to dementia risk by reducing a person’s social engagement and exposure to mentally stimulating activities, both of which are important for maintaining the brain’s resilience as it ages.
“Our findings show that dementia risk is linked to a handful of depressive symptoms rather than depression as a whole. This symptom-level approach gives us a much clearer picture of who may be more vulnerable decades before dementia develops. Everyday symptoms that many people experience in midlife appear to carry important information about long-term brain health. Paying attention to these patterns could open new opportunities for early prevention,” said lead author Dr Philipp Frank of UCL’s Division of Psychiatry.
Notably, other common depressive symptoms, including low mood, sleep problems and suicidal thoughts, showed no meaningful link to dementia risk in the long term.
“Depression doesn’t have a single shape, symptoms vary widely and often overlap with anxiety. We found that these nuanced patterns can reveal who is at higher risk of developing neurological disorders. This brings us closer to more personalised and effective mental health treatments,” said Professor Mika Kivimäki of UCL, who leads the Whitehall II study on which the research is based.
“This is a new and important way of considering depression and dementia, and it is more evidence that depression is a wide umbrella and not necessarily one illness. There is some limited evidence that treating depression in midlife might reduce later dementia risk, but further research is needed to better understand how best to reduce dementia risk,” added Professor Gill Livingston of UCL, chair of the Lancet Commission on dementia prevention, intervention and care.
The researchers acknowledged that further studies across different populations are needed to confirm how broadly these findings apply.
“Dementia is the UK’s biggest killer and one in three people born today will go on to develop the condition. The Lancet Commission, part-funded by Alzheimer’s Society, has previously identified depression as a midlife risk for dementia. The connection between dementia and depression is complicated. It’s encouraging to see this new observational study begin to unpick how dementia and depression are interlinked. However, more research is needed to confirm whether these six symptoms also apply to women and ethnic minorities. It’s important to note that not everyone who has depression will go on to develop dementia, and people with dementia won’t necessarily develop depression,” concluded Dr Richard Oakley, Associate Director of Research and Innovation at Alzheimer’s Society.
Frank P, Singh-Manoux A, Pentti J et al. Specific midlife depressive symptoms and long-term dementia risk: a 23-year UK prospective cohort study. The Lancet Psychiatry, 2025; 13, 100-111