Depressive symptoms imputed across the life course are associated with cognitive impairment and cognitive decline

Willa D. Brenowitz, Adina Zeki Al Hazzouri, Eric Vittinghoff, Sherita H. Golden, Annette L. Fitzpatrick, Kristine Yaffe

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1379-1389
Number of pages11
JournalJournal of Alzheimer's Disease
Issue number3
StatePublished - 2021


  • Cognitive impairment
  • dementia
  • depression
  • imputation
  • life course

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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