Socioeconomic, Behavioral and Clinical Characteristics and Risk of Depression and Dementia Comorbidity: A Prospective Cohort Study

Background: Depressive symptom may be a risk factor or prodrome of dementia, and the two neuropsychiatric disorders are commonly comorbid in late-life, but the patterns of depression-dementia comorbidity have not been well established. The current study aimed to investigate the associations of socioeconomic status, behavioral factors and clinical characteristics with the risk of depression-dementia comorbidity, along with how these factors modify the temporal progression of dementia after the onset of depression. Methods: Our analysis was based on data from the ongoing UK Biobank study, which included 497,533 participants (age 37-73 years) between 2006 and 2010, and thereafter followed up to 2020. Three sets of risk factors were assessed at baseline, each on a 5-point scale: socioeconomic status (Townsend deprivation index), behavioral factors (smoking, alcohol consumption, diet, physical activity) and clinical profile (obesity, hypertension, hyperglycemia, hypercholesterolemia). Electronic health records were used to assess the incidence of depression, dementia and comorbidity. Multistate models to estimate the transition-specific hazard ratios (HRs) and 95% confidence interval (CIs) of 3 risk factor scales in the transitions from a healthy state to progression of depression and subsequent comorbid dementia. Findings: During a median follow-up of 11.8 years, 23,516 (4.7%) and 6,872 (1.4%) participants separately developed depression and dementia, 1,341 (0.3%) had depression-dementia comorbidity. Adverse socioeconomic status, behavioral factors and clinical scale was strongly associated with increased risk of depression-dementia comorbidity, with highest vs. lowest group HRs of 2.40 (95% CI: 2.03-2.84), 3.43 (95% CI: 2.35-5.00) and 2.95 (95% CI: 2.06-4.22), respectively. In multistate models, adverse socioeconomic status (HR = 1.35, 95% CI: 1.11-1.65), behavioral factors (HR = 1.85, 95% CI: 1.22-2.80) and clinical scale (HR = 1.75, 95% CI: 1.15-2.66) was significantly associated with elevated risk of transition from depression to comorbid dementia. The incidence of dementia in people with depression was far more than those who were free of depression (9.16 vs. 1.04 per 1000 person-years). Of the 3 risk factor scales, behavioral factors were the strongest predictor of incident dementia whether in those with depression or not. Interpretation: Adverse socioeconomic status, behavioral factors and clinical characteristics increase the risk of depression-dementia comorbidity. Behavioral scale had the strongest association with temporal progression of dementia after the onset of depression, making it a central target for improving healthy aging. Funding: The National Natural Science Foundation of China (71910107004, 91746205). Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: All participants gave written informed consent prior data collection.UK Biobank has full ethical approval from the NHS National Research Ethics Service (16/NW/0274).