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The association of depression with subsequent dementia diagnosis: A Swedish nationwide cohort study from 1964 to 2016.

ABSTRACT: BACKGROUND:Depression is associated with an increased risk of dementia. However, short follow-up times and lack of adjustment for familial factors in previous studies could influence this association. The purpose of the present study was to investigate the association between depression and subsequent dementia, while controlling for familial factors and with a follow-up of over 35 years. METHODS AND FINDINGS:Two cohorts were formed from all individuals aged 50 years or older living in Sweden as of 31 December 2005 (n = 3,341,010). The Swedish National Patient Register was searched from 1964 through 2016 to identify diagnosis of depression and dementia. In the first cohort, individuals diagnosed with depression (n = 119,386) were matched 1:1 with controls without depression diagnosis. The second cohort was a sibling cohort (n = 50,644) consisting of same-sex full sibling pairs with discordant depression status. In the population matched cohort study, a total of 9,802 individuals were diagnosed with dementia during a mean follow-up time of 10.41 (range 0-35) years (5.5% of those diagnosed with depression and 2.6% of those without depression diagnosis (adjusted odds ratio [aOR] 2.47, 95% CI 2.35-2.58; p < 0.001), with a stronger association for vascular dementia (aOR 2.68, 95% CI 2.44-2.95; p < 0.001) than for Alzheimer disease (aOR 1.79, 95% CI 1.68-1.92; p < 0.001). The association with dementia diagnosis was strongest in the first 6 months after depression diagnosis (aOR 15.20, 95% CI 11.85-19.50; p < 0.001), then decreased rapidly but persisted over follow-up of more than 20 years (aOR 1.58, 95% CI 1.27-1.98; p < 0.001). Also in the sibling cohort, the association was strongest in the first 6 months (aOR 20.85, 95% CI 9.63-45.12; p < 0.001), then decreased rapidly but persisted over follow-up of more than 20 years (aOR 2.33, 95% CI 1.32-4.11; p < 0.001). The adjusted models included sex, age at baseline, citizenship, civil status, household income, and diagnoses at baseline. The main limitation of the study methodology is the use of observational data; hence, the associations found are not proof of causal effects. CONCLUSIONS:Depression is associated with increased odds of dementia, even more than 20 years after diagnosis of depression, and the association remains after adjustment for familial factors. Further research is needed to investigate whether successful prevention and treatment of depression decrease the risk of dementia.

SUBMITTER: Holmquist S

PROVIDER: S-EPMC6952081 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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The association of depression with subsequent dementia diagnosis: A Swedish nationwide cohort study from 1964 to 2016.

Holmquist Sofie S Nordström Anna A Nordström Peter P

PLoS medicine 20200109 1

<h4>Background</h4>Depression is associated with an increased risk of dementia. However, short follow-up times and lack of adjustment for familial factors in previous studies could influence this association. The purpose of the present study was to investigate the association between depression and subsequent dementia, while controlling for familial factors and with a follow-up of over 35 years.<h4>Methods and findings</h4>Two cohorts were formed from all individuals aged 50 years or older livin ...[more]

PMID: 31917808

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Project description:BackgroundAlzheimer's disease (AD) affects 50 million people worldwide. The immune system plays a major role in the pathogenesis of AD. Several retrospective analyses have reported a decreased risk of AD and other dementias in bladder cancer patients treated with immunotherapy in the form of Bacillus Calmette-Guerin (BCG) bladder instillations. We tested this hypothesis in a Swedish population-based prospective cohort of patients with non-muscle invasive bladder cancer (NMIBC).Methods and findingsWe utilized the BladderBaSe 2.0 database, which contains tumor-specific, health-related, and socio-demographic information for patients diagnosed with NMIBC between 1997 and 2019. The database also includes a matched comparison cohort sampled from the general population, consisting of individuals free from urinary tract cancer at the time of the index case's diagnosis. Five controls were randomly selected for each index case without replacement on the date of the index case's diagnosis. Our inclusion criteria identified participants diagnosed with NMIBC who had received BCG as primary treatment, along with their corresponding comparison cohort. We excluded those diagnosed with dementia before or within 6 months of NMIBC diagnosis. To compare the NMIBC cohort with their matched comparison cohort, we used a stratified Cox model, treating each case with its controls as a stratum. We identified 38,934 patients in the NMIBC cohort, with 6,496 receiving BCG after primary diagnosis (cases). AD/dementia was diagnosed during follow-up in 6.1% of cases and 7.4% of controls. Cases had a slightly lower risk of dementia than controls, with a hazard ratio (HR) of 0.88 (95% confidence interval [CI] 0.780-0.991), and a HR of 0.89 (CI 0.703-1.119) for AD. Subgroup analysis for dementia showed that age over 75 years had an HR of 0.73 (CI 0.616-0.863), and female gender had an HR of 0.73 (CI 0.552-0.971). The associations were similar for AD specifically, but not statistically significant. Similar to previous studies, we analyzed bladder cancer patients treated with and without BCG therapy. Multivariate Cox analysis indicated that those treated with BCG had a lower risk of dementia (HR 0.81, 95% CI 0.71-0.92), and an HR of 0.98 (95% CI 0.75-1.27) for AD specifically. High age was a significant risk modifier; the HR was 3.8 (CI 3.44-4.11) for dementia and 3.1 (CI 2.59-3.73) for AD. Even patients not receiving BCG had a significantly lower risk for AD than controls (HR 0.86, CI 0.77-0.96).ConclusionsThis study observed a marginally decreased risk of developing AD/dementia associated with earlier intravesical BCG treatment in NMIBC patients. This small benefit was most pronounced in those with high age and female gender. The disparity from previous highly positive studies underscores the importance of using an appropriate control cohort.

Project description:ImportanceUnderstanding of personality as an independent risk factor for serious mental illness (SMI) remains limited. Recently, overlap between the polygenic basis for specific personality traits and specific SMIs has been identified.ObjectiveTo determine the association of the adolescent personality domains of social maturity, mental energy, and emotional stability with later diagnosis of SMI.Design, setting, and participantsThis longitudinal cohort study enrolled Swedish male military conscripts aged 18 or 19 years from January 1, 1974, through December 31, 1997. The diagnosis of an SMI was extracted from the National Patient Register for all inpatient treatment episodes in Sweden from January 1, 1974, through December 31, 2011. Data were analyzed from May 3 to September 16, 2016.ExposuresSocial maturity, mental energy, and emotional stability assessed at conscription interview.Main outcomes and measuresInpatient diagnoses of bipolar disorder, schizoaffective disorder, schizophrenia, and other nonaffective psychoses occurring until December 31, 2011.ResultsOf the 1 017 691 men included in the cohort, 4310 developed bipolar disorder; 784, schizoaffective disorder; 4823, schizophrenia; and 5013, other nonaffective psychoses. After adjustment, with use of mean scores as a reference, low social maturity (hazard ratio [HR], 1.61; 95% CI, 1.48-1.74), low mental energy (HR, 1.34; 95% CI, 1.24-1.44), and low emotional stability (HR, 1.51; 95% CI, 1.40-1.63) were inversely associated with schizophrenia in a dose-dependent fashion. Other nonaffective psychoses displayed a similar pattern. Bipolar disorder was associated with high (HR, 1.21; 95% CI, 1.09-1.35) and low (HR, 1.12; 95% CI, 1.01-1.25) social maturity and low emotional stability (HR, 1.62; 95% CI, 1.46-1.78). Schizoaffective disorder was associated with low emotional stability (HR, 1.53; 95% CI, 1.26-1.85).Conclusions and relevanceEmotional stability is inversely associated with all SMI. Bipolar disorder has a unique U-shaped association with social maturity. Premorbid personality may reflect subtle changes in cerebral function, may combine with symptoms and other neurocognitive deficits to influence illness presentation, and/or may be owing to shared genetic architecture.

Project description:BackgroundTraumatic brain injury (TBI) has been associated with dementia. The questions of whether the risk of dementia decreases over time after TBI, whether it is similar for different TBI types, and whether it is influenced by familial aggregation are not well studied.Methods and findingsThe cohort considered for inclusion comprised all individuals in Sweden aged ≥50 years on December 31, 2005 (n = 3,329,360). Diagnoses of dementia and TBI were tracked through nationwide databases from 1964 until December 31, 2012. In a first cohort, individuals diagnosed with TBI (n = 164,334) were matched with up to two controls. A second cohort consisted of subjects diagnosed with dementia during follow-up (n = 136,233) matched with up to two controls. A third cohort consisted of 46,970 full sibling pairs with discordant TBI status. During a mean follow-up period of 15.3 (range, 0-49) years, 21,963 individuals in the first cohort (6.3% with TBI, 3.6% without TBI) were diagnosed with dementia (adjusted odds ratio [OR], 1.81; 95% confidence interval [CI], 1.75-1.86). The association was strongest in the first year after TBI (OR, 3.52; 95% CI, 3.23-3.84), but the risk remained significant >30 years (OR, 1.25; 95% CI, 1.11-1.41). Single mild TBI showed a weaker association with dementia (OR, 1.63; 95% CI, 1.57-1.70) than did more severe TBI (OR, 2.06; 95% CI, 1.95-2.19) and multiple TBIs (OR, 2.81; 95% CI, 2.51-3.15). These results were in general confirmed in the nested case-control cohort. TBI was also associated with an increased risk of dementia diagnosis in sibling pairs with discordant TBI status (OR, 1.89; 95% CI, 1.62-2.21). A main limitation of the present study is the observational design. Thus, no causal inferences can be made based on the associations found.ConclusionsThe risk of dementia diagnosis decreased over time after TBI, but it was still evident >30 years after the trauma. The association was stronger for more severe TBI and multiple TBIs, and it persisted after adjustment for familial factors.

Project description:Depression and dementia are common mental health problems and are associated in several ways. Early-life depression is associated with increased risk of later life dementia, and depression can present as a preclinical symptom or consequence of dementia. Despite the plausible relationship between these two clinical entities, the potential association between antidepressant medication and dementia has rarely been investigated. We conducted a 9-year retrospective analysis of Taiwan's National Health Insurance Research Database (NHIRD), enrolling 5819 cases who had received prescriptions of antidepressants between 2003 and 2006, and 23,276 (with ratio of 1:4) age, sex, and index date-matched controls. The hazard ratio (HR) of dementia among antidepressant users with depression was 2.42 (95% confidence interval (CI): 1.15-5.10), for those without depression was 4.05 (95% CI: 3.19-5.15), compared to antidepressant non-users respectively. Among the 6 classes of common antidepressants used in Taiwan, the adjusted HRs were 3.66 (95% CI: 2.62-5.09) for SSRIs, 4.73 (95% CI: 2.54-8.80) for SNRI, 3.26 (95% CI: 2.30-4.63) for TCAs, 6.62 (95% CI: 3.34-13.13) for TeCA, 4.94 (95% CI: 2.17-11.24) for MAOI, and 4.48 (95% CI: 3.13-6.40) for SARI. Furthermore, the multivariate analysis result showed that the adjusted HRs of cumulative defined daily doses (cDDDs) were 3.74 (95% CI: 2.91-4.82), 3.73 (95% CI: 2.39-5.80) and 5.22 (95% CI: 3.35-8.14) for those who had cDDDs of <90, 90-180 and >180 compared to those who had taken no antidepressant medication. This is a retrospective study based on secondary data, hence, we could not claim causality between antidepressant medication and dementia. However, a potential association between antidepressant and occurrence of dementia after controlling for the status of depression was observed. Lack of patients' data about smoking status and body mass index in NHIRD, which are considered related to dementia, was also a limitation in this study. In this study, we concluded that antidepressant medication is a potential risk factor for dementia, independent from any effect of depression itself.

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The association of depression with subsequent dementia diagnosis: A Swedish nationwide cohort study from 1964 to 2016.

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The association of depression with subsequent dementia diagnosis: A Swedish nationwide cohort study from 1964 to 2016.

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