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

Article type: Research Article

Authors: Hickey, Martha^a | Hueg, Trine K.^{b; c} | Priskorn, Lærke^{b; c} | Uldbjerg, Cecilie S.^{b; c} | Beck, Astrid L.^{b; c} | Anstey, Kaarin J.^{d; e} | Lim, Youn-Hee^{f; g; 1} | Bräuner, Elvira V.^{b; c; 1; *}

Affiliations: [a] Department of Obstetrics and Gynaecology, University of Melbourne and the Royal Women’s Hospital, Melbourne, Australia | [b] Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark | [c] International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and ChildHealth (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark | [d] UNSW Ageing Futures Institute, University of New South Wales, Sydney, Australia | [e] Neuroscience Research Australia, Sydney, Australia | [f] Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark | [g] Seoul National University Medical Research Center, Seoul, Republic of Korea

Correspondence: [*] Correspondence to: Elvira Bräuner, PhD, Senior Scientist (Reproductive Epidemiology), Juliane Marie Center, Department of Growth and Reproduction, Section 5064, Capital Region of Denmark, Rigshospitalet, Faculty of Health Sciences, Copenhagen University, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. Tel.: +45 3545 0820; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:Depression and dementia confer substantial global health burdens, particularly in women. Understanding the association between depression and dementia may inform new targets for prevention and/or early intervention. Objective:To investigate the association between depression in mid- and later-life and dementia (all-cause, Alzheimer’s disease (AD) or vascular dementia (VaD)) in women. Methods:A prospective study design. Nurses were followed from age 60 years or entry into the cohort, whichever came last, until date of dementia, death, emigration, or end of follow-up, whichever came first. Cox regression models with age as the underlying timeline were used to estimate the associations between time-varying depression and incident dementia. Results:The study included 25,651 female Danish nurses (≥45 years) participating in the Danish Nurse Cohort. During an average of 23 years of follow-up, 1,232 (4.8%) nurses developed dementia and 8,086 (31.5%) were identified with at least two episodes of treated depression. In adjusted analyses, nurses with depression were at a statistically significant 5.23-fold higher risk of all-cause dementia (aHR 5.23:95% CI, 4.64–5.91) compared to those with no history of depression. The differential effects of depression were greater for VaD (aHR 7.96:95% CI, 5.26–12.0) than AD (aHR 4.64:95% CI, 3.97–5.42). Later life depression (>60 years) (aHR 5.85:95% CI, 5.17–6.64) and recurrent depression (aHR 3.51:95% CI, 2.67–4.61) elevated dementia risk. Severe depression tripled the risk of all cause dementia (aHR 3.14:95% CI, 2.62–3.76). Conclusion:Both later life and severe depression substantially increase dementia risk in women, particularly VaD.

Keywords: Alzheimer’s disease, dementia, depression, prospective cohort study, women

DOI: 10.3233/JAD-230091

Journal: Journal of Alzheimer's Disease, vol. 93, no. 2, pp. 779-789, 2023