- In 2021, about 57 million people globally were living with dementia.
- Researchers have identified a number of risk factors for dementia including specific health conditions such as depression during midlife.
- A new study has identified six specific depressive symptoms that, when experienced in midlife, may be the drivers behind increased dementia risk later in life.
Now a new study recently published in the journal The Lancet Psychiatry has identified six specific depressive symptoms that, when experienced in midlife, may be the drivers behind increased dementia risk later in life.
For this study, researchers analyzed medical data from more than 5,800 middle-aged adult participants with an average of 55 from the Whitehall II study, which was initiated in 1985.
All study participants had depressive symptoms assessed from 1997-1999, and then had their health followed for 25 years.
At the study’s conclusion, scientists found that participants who had five or more depression symptoms in midlife had a 27% higher risk of developing dementia.
However, researchers discovered the majority of that increased risk was powered by six specific depression symptoms:
“The 27% higher risk confirms that depression in midlife is associated with dementia many years later, but on its own it doesn’t tell the full story,” Philipp Frank, PhD, senior research fellow in the Division of Psychiatry at University College London, and lead author of this study, told Medical News Today.
“What’s important is that this overall increase was not evenly distributed across all depressive symptoms. When we looked more closely, we found that the elevated risk was driven by a small subset of symptoms rather than depression as a single diagnosis,” Frank added.
When researchers analyzed their findings further, they also found that of the six depression symptoms, two of them — loss of self-confidence and difficulty coping with problems — were linked with an almost 50% increased dementia risk.
“This finding is striking because it shows that some symptoms carry far more information about dementia risk than others,” Frank said.
“These symptoms appear to be particularly important early markers of long-term dementia risk, long before a dementia diagnosis is made. This may also help explain why previous studies of depression and dementia have produced mixed results, as many have treated depression as a simple ‘yes or no’ diagnosis. Our study highlights the value of looking beyond diagnosis to specific symptom patterns.”
– Philipp Frank, PhD
Frank said that these research findings may allow clinicians to move away from broad labels and toward more meaningful conversations about specific symptoms.
“Our study shows that not everyone with depression in midlife has a higher risk of developing dementia later in life; instead, the increased risk appears to be driven by a small number of specific symptoms,” he explained.
“Importantly, some of the most commonly seen symptoms in both our study and routine clinical practice, such as low mood or sleep disturbances, were not associated with increased dementia risk. Rather, the symptoms linked to dementia risk included loss of confidence, reduced ability to cope with problems, impaired social connections, and persistent nervousness,” Frank noted.
“Focusing on issues like confidence, coping, and social engagement opens the door to practical, supportive advice about mental and brain health, while reassuring patients that not everyone with depression is at higher risk of dementia,” he told us.
MNT had the opportunity to speak with Richard A. Bermudes, MD, FCTMSS, psychiatrist, chief medical officer at BrainsWay, and founder and president of Empathy MindCare, about this study.
Bermudes, who was not involved in the study, commented that its findings really highlights how closely mental health and brain health are connected.
“When patients talk about things like losing confidence in themselves or having trouble concentrating — two of the specific symptoms this study identified — I don’t think of those as just emotional symptoms,” he said.
“I think of them as signals that the brain itself may not be functioning at its best. This study reinforces that idea and reminds us that what’s happening in the brain in midlife can matter many years down the line. The fact that researchers followed participants for over 2 decades makes these findings particularly compelling,” Bermudes told MNT.
“To me, this study adds weight to the idea that depression symptoms may reflect changes in brain circuits, not just mood,” he continued. “Some of the symptoms they identified, like difficulty concentrating or not feeling warmth and affection for others, line up with what we know about how certain brain networks function.“
“It strengthens the case for thinking about depression through a brain-health lens and for taking a more proactive approach to supporting brain function earlier in life,” Bermudes added.
MNT also spoke with Kamal Wagle, MD, MPH, CMD, DipABLM, AGSF, a geriatric medicine specialist at Hackensack University Medical Center in New Jersey, about this research.
Wagle, who was likewise not involved in this study, commented that his initial reaction to the findings was one of optimistic caution.
“It is a step forward to move from the general association between midlife depression and dementia to identifying a specific cluster of six predictive symptoms,” Wagle told us.
“This symptom-level approach offers a much clearer picture and could allow for more targeted interventions decades before dementia might develop. The finding that symptoms like losing self-confidence and difficulty concentrating are more predictive than low mood or sleep problems is particularly striking, as it refines our understanding and could help in identifying patients who may be more vulnerable,” he noted.
“These findings solidify the potential link between mental health and dementia risk by providing a more nuanced perspective,” Wagle continued. “Instead of viewing depression as a single, uniform condition, the study suggests that specific psychological experiences in midlife carry important information about long-term brain health.”
“For the next steps, it is crucial to see this research expanded to more diverse populations to confirm how broadly these findings apply, a point acknowledged by the researchers and external commentators,” he added. “Further investigation is needed to understand if effectively treating these six specific symptoms in midlife can genuinely reduce later dementia risk.”


