Dementia Linked With Depression in Early and Middle Life

— Can better depression treatment reduce dementia risk?

A photo of a sad and thoughtful looking woman sitting on her couch.

Depression diagnosed in early, middle, or late life more than doubled the risk for subsequent dementia, a study of 1.4 million people in Denmark showed.

The overall hazard of all-cause dementia among people diagnosed with depression was 2.41 times that of their counterparts without depression (95% CI 2.35-2.47), reported Holly Elser, MD, PhD, of the Hospital of the University of Pennsylvania in Philadelphia, and co-authors.

The association persisted when the time elapsed from depression diagnosis was longer than 20 to 39 years (HR 1.79, 95% CI 1.58-2.04), the researchers wrote in JAMA Neurologyopens in a new tab or window.


The link was present in adults who were diagnosed with depression at:

  • Ages 18-44: HR 3.08
  • Ages 45-59: HR 2.95
  • Ages 60 and up: HR 2.31

Earlier studies have demonstrated links between dementia and late-life depressionopens in a new tab or window, which may be an early symptom of dementia, Elser noted.

“Our study leverages data from more than 1.4 million Danish citizens followed from 1977 onward and demonstrates that there is a persistent association of dementia with depression diagnosed in early, middle, or late life,” she told MedPage Today. “There is a clear need for future research that examines potential mechanisms that relate depression earlier in adulthood to subsequent onset of dementia.”

Those mechanisms may be connected to shared risk factors for depression and dementia that may occur early in life, Elser suggested. Depression may increase dementia risk by altering levels of key neurotransmitters or may lead to changes in health behaviors that raise dementia risk, she added.


Elser and colleagues evaluated national registry data in Denmark, following adult patients from 1977 to 2018. Participants included Danish citizens with depression diagnoses, matched by sex and birth year to people with no depression diagnosis. Both depression and dementia were defined using diagnostic codes.

People with baseline dementia were excluded. Findings were adjusted for education, income, cardiovascular disease, chronic obstructive pulmonary disease, diabetes, anxiety disorders, stress disorders, substance use disorders, and bipolar disorder.

The study included 246,499 people with diagnosed depression and 1,190,302 people without a depression diagnosis. Median baseline age was about 50, and approximately 65% were women. Most people with depression (67.7%) were diagnosed before age 60.

The most common comorbidity was cardiovascular disease, which was present in 19.8% of people with a depression diagnosis and 11.8% of the comparison cohort. Substance use disorders were the second most common comorbidity in the group with depression at 11.7%, compared with 2.6% of the comparison group.

Among people with depression, 5.7% were subsequently diagnosed with dementia over the follow-up period; in the comparison cohort, 3.2% had an eventual dementia diagnosis. There was a greater hazard for vascular dementia (HR 3.28) and a smaller hazard for Alzheimer’s disease (HR 1.73).


The overall hazard for dementia was greater for men (HR 2.98) than women (HR 2.21). Dementia risk was similar for people who were (HR 2.42) and were not (HR 2.35) prescribed an antidepressant in the 6 months before or after depression diagnosis.

Further research about the role of depression treatment is needed, Elser observed.

“Our study considered treatment with an antidepressant within 6 months of the initial depression diagnosis and found no evidence of a difference in dementia risk between the treated and untreated groups,” she said. “Research that explores implications of the timing and duration of treatment with antidepressants for dementia, as well as simultaneous treatment with cognitive behavioral therapy, will be important.”

The study had several limitations, the researchers acknowledged. Incident depression and dementia were identified by diagnostic codes and may be subject to misclassification. Variables not included in the study may have influenced results, including family history, physical activity, dietary patterns, reproductive history, or social factors.

  • Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow 


Elser had no disclosures. Co-authors reported relationships with Peabody Arnold, FDA, NIH, Amgen, and the Institute for Clinical and Economic Review, and a patent pending for use of glecaprevir/pibrentasvir to treat post-traumatic stress disorder.

Primary Source

JAMA Neurology

Source Reference: opens in a new tab or windowElser H, et al “Association of early-, middle-, and late-life depression with incident dementia in a Danish cohort” JAMA Neurol 2023; DOI: 10.1001/jamaneurol.2023.2309.