Depressive Symptoms Imputed Across the Life Course Are Associated with Cognitive Impairment and Cognitive Decline

Article type: Research Article

Authors: Brenowitz, Willa D.^{a; b; *} | Zeki Al Hazzouri, Adina^c | Vittinghoff, Eric^b | Golden, Sherita H.^d | Fitzpatrick, Annette L.^e | Yaffe, Kristine^{a; b; f; g}

Affiliations: [a] Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, University of California San Francisco, CA, USA | [b] Department of Epidemiology and Biostatistics, University of California San Francisco, CA, USA | [c] Department of Epidemiology, Mailman School of Public Health, Columbia University, NY, USA | [d] Department of Medicine Johns Hopkins University School of Medicine and Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA | [e] Departments of Family Medicine, Epidemiology, and Global Health, School of Public Health, University of Washington, WA, USA | [f] Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, CA, USA | [g] San Francisco VA Health Care System, San Francisco, CA, USA

Correspondence: [*] Correspondence to: Willa Brenowitz, PhD, MPH, Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, 4150 Clement Street, San Francisco, CA 94158, USA. Tel.: +1 451 221 4810 / Ex23476; Fax: +1 415 514 8150; E-mail: willa.brenowitz@ucsf.edu.

Abstract: Background:Depressive symptoms may increase risk for dementia, but findings are controversial because late-life depression may be a prodromal dementia symptom. Life course data on depression and dementia risk may clarify this association; however, data is limited. Objective:To impute adult depressive symptoms trajectories across adult life stages and estimate the association with cognitive impairment and decline. Methods:Using a pooled study of 4 prospective cohorts (ages 20–89), we imputed adult life course depressive symptoms trajectories based on Center for Epidemiologic Studies Depression Scale-10 (CESD-10) and calculated time-weighted averages for early adulthood (ages 20–49), mid-life (ages 50–69), and late-life (ages 70–89) for 6,122 older participants. Adjusted pooled logistic and mixed-effects models estimated associations of imputed depressive symptoms with two cognitive outcomes: cognitive impairment defined by established criteria and a composite cognitive score. Results:In separate models, elevated depressive symptoms in each life stage were associated with cognitive outcomes: early adulthood OR for cognitive impairment = 1.59 (95%CI: 1.35,1.87); mid-life OR = 1.94 (95%CI:1.16, 3.26); and late-life OR = 1.77 (95%CI:1.42, 2.21). When adjusted for depressive symptoms in the other life-stages, elevated depressive symptoms in early adulthood (OR = 1.73; 95%CI: 1.42,2.11) and late-life (OR = 1.43; 95%CI: 1.08,1.89) remained associated with cognitive impairment and were also associated with faster rates of cognitive decline (p < 0.05). Conclusion:Imputing depressive symptom trajectories from pooled cohorts may help expand data across the life course. Our findings suggest early adulthood depressive symptoms may be a risk factor for cognitive impairment independent of mid- or late-life depressive symptoms.

Keywords: Cognitive impairment, dementia, depression, imputation, life course

DOI: 10.3233/JAD-210588

Journal: Journal of Alzheimer's Disease, vol. 83, no. 3, pp. 1379-1389, 2021