Stress, depression, and risk of dementia – a cohort study in the total population between 18 and 65 years old in Region Stockholm

Background Chronic stress and depression are potential risk factors for mild cognitive impairment and dementia, including Alzheimer disease. The aim was to investigate whether any such risk is additive. Methods Cohort study including 1 362 548 people (665 997 women, 696 551 men) with records in the Region Stockholm administrative healthcare database (VAL). Exposure was a recorded ICD-10 diagnosis of chronic stress, depression, or both, recorded in 2012 or 2013. Outcome was a diagnosis of Alzheimer disease, other dementia, or mild cognitive impairment recorded from 2014 through 2022. Odds ratios with 99% confidence intervals (CI) adjusted for age, sex, neighborhood socioeconomic status, diabetes, and cardiovascular disorders were calculated. Results During the exposure period, 4 346 patients were diagnosed with chronic stress, 40 101 with depression, and 1 898 with both. The average age at baseline was around 40 years in all groups. In the fully adjusted model, the odds ratio of Alzheimer disease was 2.45 (99% CI 1.22–4.91) in patients with chronic stress, 2.32 (99% CI 1.85–2.90) in patients with depression, and 4.00 (99% CI 1.67–9.58) in patients with chronic stress and depression. The odds ratio of mild cognitive impairment was 1.87 (99% CI 1.20–2.91) in patients with chronic stress, 2.85 (99% CI 2.53–3.22) in patients with depression, and 3.87 (99% CI 2.39–6.27) in patients with both. When other dementia was analyzed, the odds ratio was significant only in patients with depression, 2.39 (99% CI 1.92–2.96). Conclusions Documented chronic stress increased the risk of mild cognitive impairment and Alzheimer disease. The same was seen with depression. The novel finding is the potential additive effect of chronic stress to depression, on risk of MCI and AD.