Long-term cumulative depressive symptom burden and risk of cognitive decline and dementia among very old women

Adina Zeki Al Hazzouri, Eric Vittinghoff, Amy Byers, Ken Covinsky, Dan Blazer, Susan Diem, Kristine E. Ensrud, Kristine Yaffe

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54 Scopus citations


Background.Depressive symptoms and cognitive outcomes are strongly interrelated. Despite that rates of depressive symptoms fluctuate during late life, little is known about the impact of long-term cumulative depressive symptom burden on cognitive decline and dementia in older adults. This study examines the association of nearly 20 years of cumulative depressive symptoms with cognitive outcomes in a cohort of older women.Methods.We assessed depressive symptoms in 7,240 women using the Geriatric Depression scale (GDS) at serial visits. We used a Poisson model with random slopes to estimate GDS trajectories for each participant from baseline to death or end of follow-up, and then characterized depressive symptom burden by quartile of the area under the curve. We assessed cognitive outcomes using repeated measures of the Mini-Mental State Examination (MMSE) and Trails B score over 20 years, Year-20 neuropsychological test battery, and adjudicated dementia and mild cognitive impairment (MCI).Results.Adjusting for potential confounders, compared with women in the lowest quartile of cumulative depressive symptoms burden, women in the highest quartile had 21% more MMSE errors over time (95% CI = 17%, 26%), 20% worse Trails B score over time (95% CI = 17%, 23%), worse scores on most of the Year-20 cognitive tests, and a twofold greater likelihood of developing dementia or MCI (95% CI = 1.48, 3.11).Conclusions.Long-term cumulative depressive symptom burden was associated with cognitive decline and risk of dementia or MCI. Older adults with a history of depression should be closely monitored for recurrent episodes or unresolved depressive symptoms as well as any cognitive deficits.

Original languageEnglish (US)
Pages (from-to)595-601
Number of pages7
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume69 A
Issue number5
StatePublished - May 2014

Bibliographical note

Funding Information:
Funding This work was supported by the National Institute of Mental Health (R01 MH086498); National Institute on Aging (K24 AG031155); and Alzheimer’s Association (IIRG-08-88872). Dr. Z.A.H. is supported by the American Heart Association/American Stroke Association/American Brain Foundation Lawrence M. Brass, M.D. Stroke Research Postdoctoral Fellowship. The Study of Osteoporotic Fractures was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute on Aging (Public Health Service grants: 2 R01 AG027574-22A1, R01 AG005407, R01AG027576-22, 2 R01 AG005394-22A1, AG05407, AG05394, AR35582, AR35583, AR35584, AG026720, R01 AG18037, and R01 AG028144-01A1).


  • Alzheimer's
  • Cognition
  • Depression


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