A new study published in The Lancet Psychiatry identifies six specific depressive symptoms that, when experienced in midlife, are linked to a substantially higher risk of developing dementia later in life, with symptoms associated with nearly a 50 per cent increase in risk. These symptoms range from losing your self-confidence and not feeling warmth or affection for others to feeling stressed all the time and finding it difficult to concentrate.
"A distinct set of midlife depressive symptoms was associated with an increased risk of dementia, suggesting that these symptoms might be early markers of underlying neurodegenerative processes," according to the study.
The findings are significant as dementia is one of the fastest-growing public health challenges in the world today, and despite decades of research, scientists are still unable to pinpoint a single cause of dementia.
What is Dementia?
Dementia is not one particular disease, but "a group of symptoms affecting memory, thinking and social abilities," and can be caused by many diseases. These symptoms can affect daily life—from quality of life to productivity. While Alzheimer's and dementia are used interchangeably to refer to memory loss in older adults, they are distinct. Alzheimer's is the most common disease that causes dementia in adults.
Second, though memory loss is a common symptom associated with dementia, not all memory loss is dementia, and dementia is not just memory loss. It is "an ongoing decline of brain functioning," and is "not a natural part of ageing." It affects more than just memory loss, and affects " the way you speak, think, feel and behave."
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In 2021, an estimated 57 million people globally were living with dementia, a broad term used to describe progressive neurological conditions that impair memory, thinking, behaviour, and the ability to carry out everyday activities. Evidence suggests that the condition develops over many years, shaped by a complex mix of genetic susceptibility, environmental exposures, lifestyle factors, and long-term health conditions.
One such condition is depression, particularly when it occurs during midlife. Depression affects approximately 332 million people worldwide and is especially common among working-age adults, often driven by chronic stress, long working hours, financial insecurity, and social pressures. Growing evidence suggests that the effects of depression may extend far beyond mental health, with implications for long-term brain health.
What are the six identified depression symptoms?
The findings come from a large prospective, observational cohort study based on the UK Whitehall II study, a long-running research project launched in 1985 to examine how social, psychological, and biological factors influence long-term health.
For this analysis, researchers focused on participants who were 35 to 55 years old at the time of enrolment and had complete data on depressive symptoms, along with successful linkage to national health records. Individuals who already had dementia at baseline were excluded from the analysis.
The baseline assessment for this study took place between 1997 and 1999, when participants underwent a clinical examination and completed the 30-item General Health Questionnaire (GHQ-30), a validated screening tool used to identify clinically significant psychological distress in the general population.
A GHQ-30 score of five or higher was used to define threshold-level depression. Participants were then followed for up to 25 years, with incident dementia identified through linkage to UK National Health Service hospital records, the Mental Health Services Data Set, and national mortality records, covering the period from April 1997 to March 2023.
When researchers analysed individual depressive symptoms rather than depression as a single diagnosis, six specific symptoms emerged as robust predictors of increased dementia risk in later life. These were - “Losing confidence in myself, not able to face up to problems, not feeling warmth and affection for others, nervous and strung-up all the time, not satisfied with the way tasks are carried out and difficulties concentrating.” Each of these symptoms was independently associated with a higher risk of dementia, even after adjusting for age, sex, ethnicity, and genetic risk factors.
At the study’s conclusion, researchers found that participants who reported five or more depressive symptoms in midlife had a 27 per cent higher risk of developing dementia compared with those who reported fewer symptoms. However, this elevated risk was not evenly distributed across all symptoms. Instead, the majority of the association between midlife depression and later dementia was driven by the six specific symptoms identified in the analysis. Among participants younger than 60 years at baseline, these six symptoms fully accounted for the link between depression and dementia risk.
“The 27 per cent 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 the 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,” he added.
Why confidence and coping ability may signal higher dementia risk
A deeper analysis of the findings revealed that not all depressive symptoms carried the same level of risk. Of the six symptoms identified, loss of self-confidence and difficulty coping with problems emerged as the strongest predictors, each linked to about a 50 per cent increase in dementia risk later in life. Researchers say these two symptoms appear to be particularly informative indicators of long-term brain health vulnerability.
“This finding is striking because it shows that some symptoms carry far more information about dementia risk than others,” Philipp Frank said. “These symptoms appear to be particularly important early markers of long-term dementia risk, long before a dementia diagnosis is made.”
Frank explained that focusing on specific symptoms may also help clarify why earlier research on depression and dementia has produced inconsistent results. “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,” he said.
According to Frank, the results suggest a shift in how clinicians approach depression in midlife. Rather than relying solely on broad diagnostic categories, the findings may encourage more meaningful, symptom-focused conversations in clinical settings. “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, the study found that several commonly reported depressive symptoms were not associated with an increased risk of dementia. “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,” Frank noted. “Rather, the symptoms linked to dementia risk included loss of confidence, reduced ability to cope with problems, impaired social connections, and persistent nervousness.”
By narrowing the focus to these specific experiences, researchers believe the findings could support earlier and more targeted intervention strategies. “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,” Frank added.
Limitations of the study
The authors caution that the findings should be interpreted in light of several important limitations. First, the study was observational in nature, which means it cannot establish a direct cause-and-effect relationship between depressive symptoms and dementia. As the researchers noted, “our study was based on observational data, precluding the possibility of inferring causation.” In addition, people with lived experience were not involved in the design or reporting of the study.
Another limitation relates to how depression was assessed. Depressive symptoms were measured using a self-reported questionnaire, the 30-item General Health Questionnaire, which may not fully capture the breadth, severity, or clinical complexity of depression. The authors acknowledged that “our depression measure was based on self-report and limited to 30 items,” adding that future studies should use more comprehensive, clinically validated assessments across multiple timepoints to better understand symptom trajectories and the effects of long-term or recurrent depression.
Dementia diagnoses were identified through hospital records, mortality data, and the Mental Health Services Data Set, which may miss milder or undiagnosed cases. Coding practices vary, and records often default to unspecified dementia without specialist assessment or biomarker confirmation. The authors noted that under-recognition is common, though diagnosis rates have improved.
Despite these challenges, the researchers believe the limitations likely did not bias the results, as they would affect participants with and without depressive symptoms similarly. Sensitivity analyses, including those restricted to ICD-10–diagnosed cases and later follow-up years, supported this interpretation.
The authors also acknowledged possible indication bias, where individuals with depressive symptoms might be more likely to receive a dementia diagnosis. However, this would mainly affect those with threshold-level depression, not participants with only one or two specific symptoms, who drove much of the observed association.
Questions around generalisability also remain. Dementia incidence rates in the Whitehall II cohort were lower than those typically seen in the general population, reflecting the healthier occupational profile of civil servants and the under-ascertainment of dementia in electronic health records - a phenomenon known as the “healthy worker effect.” While this may lead to an underestimation of absolute dementia risk, previous research suggests it is unlikely to substantially distort associations between risk factors and disease.
In addition, the study sample included fewer women than men, limiting the ability to examine sex-specific differences in the relationship between depressive symptoms and dementia. The authors emphasised that “further research is needed to establish whether our findings can be replicated in other study populations, including minority ethnic populations, and across different countries and settings.”
Despite these limitations, experts note that focusing on individual depressive symptoms rather than treating depression as a single, uniform condition can provide greater clinical insight. Symptom-level approaches “add value beyond traditional approaches that conceptualise depression as a single, uniform entity, obscuring clinically and biologically meaningful heterogeneity,” the study highlights.
If these findings are replicated, they “could help clinicians distinguish between middle-aged patients whose depression reflects an elevated dementia risk and those whose symptoms are more likely due to other causes, supporting clinical evaluation and more tailored treatments.” This perspective underscores the importance of nuanced assessment in improving early identification and intervention strategies for dementia risk.
This story is done in collaboration with First Check, which is the health journalism vertical of DataLEADS.
