Depression at any stage of life (early, middle, or late) increases the risk of developing dementia, according to study findings published in JAMA Neurology.

Research suggests that late-life depression correlates with subsequent diagnosis of dementia. Therefore, depressive symptoms may be an early harbinger of dementia, potentially denoting preclinical disease processes.

Researchers from Denmark and the United States collaborated to assess whether early-life and middle-life depression also correlated with dementia risk in similar ways to late-life depressive symptoms. They conducted a nationwide, population-based, cohort study from April 2020 to March 2023, obtaining data from 2 Danish registries — the Danish National Patient Registry and Danish Psychiatric Central Research Register — between 1977 and 2018. Eligible participants included those older than age 18 years, those with at least a 1-year follow-up, and those without baseline dementia.

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The researchers used the International Classification of Diseases (ICD) diagnosis codes to select 246,499 individuals (64.7% women; median age, 50.8 years) who developed depression and 1,190,302 age- and sex-matched individuals without depression for cohort comparison (64.6% women; median age, 50.4). The median follow-up period was 7.89 years for individuals with a depression diagnosis and 9.04 years for individuals without a depression diagnosis.

The researchers subdivided the study participants into 3 life-stage groups with the early-life stage between the ages of 18 and 44 years, middle-life stage between the ages of 44 and 59 years, and the late-life stage from age 60 years and older.  

Of the 246,499 individuals with depression, around 67.7% obtained a diagnosis of depression before age 60 years. Approximately 109,396 (44.4%) received a diagnosis of depression during the early-life stage.

Among the 246,499 individuals diagnosed with depression, 14,000 (5.7%) received a diagnosis of dementia. In contrast, 38,652 (3.2%) out of 1,190,302 individuals in the cohort without depression were diagnosed with dementia.

Based on these numbers, the researchers calculated a 13.6% risk for dementia (95% CI, 13.0-14.2) among the participants with depression and a 11.5% risk for dementia (95% CI, 11.3-11.8) among the participants without depression. The overall risk difference totaled 2.09% (95% CI, 0.81-3.37) with a 2.41-fold increased hazard of dementia demonstrated by individuals with depression (95% CI, 2.35-2.47).

The researchers noted that this risk for dementia persisted regardless of length of time elapsed from onset of depressive symptoms, even when that time was greater than 20 to 39 years (hazard ratio [HR], 1.79; 95% CI, 1.58-2.04). They also observed that risk for dementia was still associated with depression regardless of whether depressive symptoms began in early- (HR, 3.08; 95% CI, 2.64-3.58), middle- (HR, 2.95; 95% CI, 2.75-3.17), or late-life (HR, 2.31; 95% CI, 2.25-2.38) stages (all P values <.001).

Compared with sex-matched individuals without depression, the risk of developing dementia was higher among men with depression (HR, 2.98; 95% CI, 2.84-3.12) than women with depression (HR, 2.21; 95% CI, 2.15-2.27).

“Results suggest that the risk of dementia was more than doubled for both men and women with diagnosed depression,” the researchers wrote. “The persistent association between dementia and depression diagnosed in early and middle life suggests that depression may increase dementia risk,” they proposed.

The results of the study are not generalizable outside of the Danish population.

Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see original source for full list of disclosures.


Elser H, Horváth-Puhó E, Gradus JL, et al. Association of early-, middle-, and late-life depression with incident dementia in a Danish cohortJAMA Neurol. Published online July 24, 2023. doi:10.1001/jamaneurol.2023.2309

This article originally appeared on Neurology Advisor