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January 12, 2026
2 min read
Key takeaways:
- Certain depressive symptoms during midlife, like a loss of confidence, increased the risk for dementia more than others.
- These data could “open new opportunities for early prevention,” a researcher said.
Certain depressive symptoms experienced during midlife were tied to a greater risk for dementia, with some increasing the risk by around 50%, according to recently published data.
The results “show that dementia risk is linked to a handful of depressive symptoms rather than depression as a whole,” study lead author Philipp Frank, PhD, from the University College London in the U.K., said in a press release. “This symptom-level approach gives us a much clearer picture of who may be more vulnerable decades before dementia develops.”
Data derived from: Frank P, et al. Lancet Psychiatry. 2025;doi:10.1016/S2215-0366(25)00331-1.
Frank and colleagues explained that dementia is “highly comorbid” but “the role of midlife depression in dementia pathology remains poorly understood.”
“Few studies have sufficiently long follow-up periods to track participants from midlife into later life, and among those that have such follow-up periods, findings have been mixed,” they wrote.
In the current analysis, the researchers assessed the data of 5,811 adults (71.7% men, 92.2% white) aged 45 to 69 years who participated in the U.K. Whitehall II study.
From April 24, 1997, to Jan. 8, 1999, participants — then free of dementia — completed a questionnaire covering 30 depressive symptoms.
Participants’ health statuses were then followed for 25 years, with dementia diagnoses recorded until 2023, the release said.
Of the cohort, 10.1% developed dementia.
Frank and colleagues found that six depressive symptoms in particular increased the risk for dementia, including:
- “losing confidence in myself” (HR = 1.51; 95% CI, 1.16-1.96);
- “not able to face up to problems” (HR = 1.49; 95% CI, 1.09-2.04);
- “nervous and strung-up all the time” (HR = 1.34; 95% CI, 1.03-1.72);
- “difficulties concentrating” (HR = 1.29; 95% CI, 1.01-1.65);
- “not satisfied with the way tasks are carried out” (HR = 1.33; 95% CI, 1.05-1.69); and
- “not feeling warmth and affection for others” (HR = 1.44; 95% CI, 1.06-1.95).
These symptoms “fully accounted” for the link between midlife depression and dementia risk among adults aged younger than 60 years, and were independent of dementia risk factors like lifestyle factors, cardiometabolic conditions and apolipoprotein E epsilon 4 status, the researchers reported.
Frank and colleagues acknowledged the mechanisms behind these specific symptoms “remain unclear.”
They explained that the six depressive symptoms were consistently tied to established risk factors for dementia, including physical inactivity and hearing loss, at baseline, which suggests behavioral and reserve-related mechanisms might be at play.
“However, given that the symptom-dementia associations persisted after adjustment for these factors, these symptoms might also represent independent midlife risk factors for dementia,” they wrote.
Although there were study limitations, such as a lower proportion of women vs. men and limited statistical power to examine sex differences, Frank said these “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,” he said in the release.
Study co-author Gill Livingston, MD, PhD, from the University College London, underscored that the study “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,” he said in the press release.
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