| Key points |
Does the association between depression and dementia persist, whether depression is diagnosed at early, middle, or late life? Findings In this population-based cohort study of more than 1.4 million adult Danish citizens followed from 1977 to 2018, the risk of dementia more than doubled for both men and women with diagnosed depression and was higher for men than for women; The risk of dementia persisted regardless of whether depression was diagnosed at an early, middle, or late age. Meaning that the risk of dementia associated with a depression diagnosis was higher for men than for women; The persistent association between dementia and depression diagnosed in early and middle age suggests that depression may increase the risk of dementia. Importance Depressive symptoms in late life are associated with later diagnosis of dementia and may be an early symptom or response to preclinical illness. Assessing associations with depression in early and midlife will help clarify whether depression influences dementia risk. Aim To examine the associations of early, middle, and late depression with incident dementia. |
| Design, environment and participants |
This was a nationwide population-based cohort study conducted from April 2020 to March 2023. Participants included Danish citizens from the general population with diagnoses of depression who were matched by sex and year of birth to people without a diagnosis of depression. depression.
Participants were followed from 1977 to 2018. Individuals followed for less than 1 year, those younger than 18 years, or those with baseline dementia were excluded from analyses.
Exposure to depression was defined using International Classification of Diseases (ICD) diagnosis codes within the Danish National Patient Registry (DNPR) and the Danish Central Psychiatric Research Registry (DPCRR).
| Main results and measures |
Incident dementia was defined using ICD diagnosis codes within the DPCRR and DNPR. Cox proportional hazards regression was used to examine associations between depression and dementia adjusting for education, income, cardiovascular disease, chronic obstructive pulmonary disease, diabetes, anxiety disorders, stress disorders, substance use disorders and bipolar disorder. Analyzes were stratified by age at depression diagnosis, years since index date, and sex.
| Results |
There were 246,499 people (median [IQR] age, 50.8 [34.7-70.7] years; 159,421 women [64.7%]) with diagnosed depression and 1,190,302 people (median [IQR] age , 50.4 [34.6-70.0] years; 768,876 women [64.6%]) without depression.
Approximately two-thirds of those diagnosed with depression were diagnosed before the age of 60 (684,974 [67.7%]).
The risk of dementia among those diagnosed with depression was 2.41 times higher than that of the comparison cohort (95% CI, 2.35-2.47). This association persisted when the time elapsed since the index date was greater than 20 to 39 years (hazard ratio [HR], 1.79; 95% CI, 1.58-2.04) and among those diagnosed with depression in the early, middle or late life (18-44 years: HR, 3.08; 95% CI, 2.64-3.58; 45-59 years: HR, 2.95; 95% CI, 2.75 -3.17; ≥60 years: HR, 2.31; 95% CI, 2.25-2.38).
| Conclusions and relevance |
The results suggest that the risk of dementia more than doubled for both men and women diagnosed with depression.
The persistent association between dementia and depression diagnosed in the first and middle years of life suggests that depression may increase the risk of dementia.
| Discussion |
This cohort study examined the association of early, middle and late-life depression with subsequent dementia in Denmark. The findings support our hypothesis that the associations persist regardless of time since depression diagnosis or age at which depression was diagnosed.
The overall danger of dementia for people with depression was more than double that of the comparison cohort. This association persisted when the time elapsed since the index date was greater than 20 years and when depression was diagnosed early, mid-life, or late. Therefore, our results suggest that depression is not only an early symptom of dementia, but also that depression is associated with an increased risk of dementia.
In our analyses, the risk of dementia more than doubled in both men and women diagnosed with depression, although the risk of dementia was higher in men.
One possible explanation for this finding is that men are less likely to seek medical care than women. Depressive symptoms among men may therefore reflect more severe illness at diagnosis, increasing the apparent risk of depression-associated dementia compared with the relative risk for women.
Alternatively, differential mechanisms may mediate the association between depression and dementia among men, such as health behaviors, exposure to endogenous sex hormones, or comorbid medical conditions. Ultimately, this finding warrants further examination in alternative settings where direct measures of depressive symptoms and time-dependent measures of potential mediating variables are available.
The increased risk of dementia associated with a diagnosis of depression raises the intriguing question of whether effective treatment of depression could modify dementia risk. Although findings were similar between those who were and were not treated with an antidepressant within 6 months of their depression diagnosis, our analysis does not consider the duration or effectiveness of treatment, nor were we able to identify individuals who received behavioral therapy. .
In our analysis of disease severity, recurrent inpatient hospitalizations were associated with an increased risk of dementia.
Together, these results may motivate ongoing research focused on the complex and time-varying association between treatment and dementia, particularly when direct measures of disease burden and depression severity are available.
Finally, we found a persistent, although attenuated, association between depression and dementia among those with underlying anxiety disorder or substance use disorder. We were unable to examine effect modification by personality disorders, suicide attempts, bipolar disorder, or stress disorders (including post-traumatic stress disorder) due to the small number of dementia diagnoses within these strata.
Several psychiatric disorders have previously been associated with dementia, the implications of co-occurring psychiatric diagnoses for dementia risk are an important topic for future research.
