Depression in Mid- and Later-Life and Risk of Dementia in Women: A Prospective Study within the Danish Nurses Cohort

Background Depression can be associated with increased mortality and morbidity, but no studies have investigated the specific causes of death based on autopsy reports. Autopsy studies can yield valuable and detailed information on pathological ailments or underreported conditions. This study aimed to compare autopsy-confirmed causes of death (CoD) between individuals diagnosed with major depressive disorder (MDD) and matched controls. We also analyzed subgroups within our MDD sample, including late-life depression and recurrent depression. We further investigated whether machine learning (ML) algorithms could distinguish MDD and each subgroup from controls based on their CoD. Methods We conducted a comprehensive analysis of CoD in individuals who died from nontraumatic causes. The diagnosis of lifetime MDD was ascertained based on the DSM-5 criteria using information from a structured interview with a knowledgeable informant. Eleven established ML algorithms were used to differentiate MDD individuals from controls by simultaneously analyzing different disease category groups to account for multiple tests. The McNemar test was further used to compare paired nominal data. Results The initial dataset included records of 1,102 individuals, among whom 232 (21.1%) had a lifetime diagnosis of MDD. Each MDD individual was strictly paired with a control non-psychiatric counterpart. In the MDD group, the most common CoD were circulatory (67.2%), respiratory (13.4%), digestive (6.0%), and cancer (5.6%). Despite employing a range of ML models, we could not find distinctive CoD patterns that could reliably distinguish individuals with MDD from individuals in the control group (average accuracy: 50.6%; accuracy range: 39-59%). These findings were consistent even when considering factors within the MDD group, such as late-life or recurrent MDD. When comparing groups with paired nominal tests, no differences were found for circulatory (p=0.450), respiratory (p=0.790), digestive (p=1.000), or cancer (p=0.855) CoD. Conclusions Our analysis revealed that autopsy-confirmed CoD exhibited remarkable similarity between individuals with depression and their matched controls, underscoring the existing heterogeneity in the literature. Future research should prioritize more severe manifestations of depression and larger sample sizes, particularly in the context of CoD related to cancer.

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Changes in dementia risk along with onset age of depression: A longitudinal cohort study of elderly depressed patients

Jang,

Kim,

Moon

et al. 2024

Preprint

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Background Depression in late-life is linked to an increased risk of Alzheimer's dementia (AD), with the risk potentially varying based on the onset age of depression. Previous research typically dichotomized depression onset age between 55 and 65 years; however, the specific age at which depression onset increases AD risk in older adults remains unclear. In this study, we aimed to investigate the relationship between depression onset age and AD risk and compare characteristics between different onset age groups. Methods A longitudinal cohort of 251 elderly patients diagnosed with major depressive disorder was followed for up to 22 years. Participants were categorized into four groups based on depression onset age: ≤ 54 years, 55–64, 65–74, and ≥ 75 years. Annual cognitive assessments were conducted using the Korean Mini-Mental State Examination, with further neuropsychological testing when cognitive decline was suspected. Cox proportional hazards models were used to assess AD conversion risk across groups, adjusting for covariates. Results During follow-up, 75 patients (29.88%) converted to AD. Depression onset after age 75 was significantly associated with a higher risk of AD conversion (hazard ratio [HR], 8.95; 95% confidence interval [CI], 3.41–23.48; p < 0.0001) and a shorter time to conversion compared to onset before age 55 (40.93 vs. 83.40 months). After adjusting for covariates, depression onset after age 75 remained significantly associated with AD conversion (adjusted HR, 6.07; 95% CI, 1.26–29.34; p = 0.0189). This group also had milder depressive symptoms and a higher prevalence of hypertension and cerebrovascular disease than those with depression onset before age 55. Conclusions Depression onset after age 75 is strongly associated with an increased risk of AD and a shorter time to dementia onset. Individuals with depression onset after age 75 appear more closely linked to vascular comorbidities, while those with depression onset before age 55 are characterized by severe and recurrent depressive episodes. The mechanisms leading to AD in individuals with depression may differ from those without prior depression. Trial registration: The study is registered (NCT01237275, 1994-10-14, Development of A Technique to Predict Antidepressant Responsiveness in Depressive Patients) in ClinicalTrials.gov.

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Depression in Mid- and Later-Life and Risk of Dementia in Women: A Prospective Study within the Danish Nurses Cohort

Cited by 3 publications

References 40 publications

Depression in Alzheimer’s Disease: Epidemiology, Mechanisms, and Treatment

Depression in Alzheimer’s Disease: Epidemiology, Mechanisms, and Treatment

Causes of death in individuals with lifetime major depression: a comprehensive machine learning analysis from a community-based autopsy center

Changes in dementia risk along with onset age of depression: A longitudinal cohort study of elderly depressed patients

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