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Original Investigation |

Trajectories of Depressive Symptoms in Older Adults and Risk of Dementia

Allison R. Kaup, PhD1,2; Amy L. Byers, PhD, MPH1,2; Cherie Falvey, MPH2; Eleanor M. Simonsick, PhD3; Suzanne Satterfield, MD, DrPH4; Hilsa N. Ayonayon, PhD5; Stephen F. Smagula, PhD6; Susan M. Rubin, MPH5; Kristine Yaffe, MD2,7,8,9
[+] Author Affiliations
1Research Service, San Francisco Veterans Affairs Medical Center, San Francisco, California
2Department of Psychiatry, University of California, San Francisco
3Intramural Research Program, National Institute on Aging, Baltimore, Maryland
4Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis
5Department of Epidemiology and Biostatistics, University of California, San Francisco
6Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania
7Department of Neurology, University of California, San Francisco
8Department of Epidemiology and Biostatistics, University of California, San Francisco
9San Francisco Veterans Affairs Medical Center, San Francisco, California
JAMA Psychiatry. 2016;73(5):525-531. doi:10.1001/jamapsychiatry.2016.0004.
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Importance  Depression has been identified as a risk factor for dementia. However, most studies have measured depressive symptoms at only one time point, and older adults may show different patterns of depressive symptoms over time.

Objective  To investigate the association between trajectories of depressive symptoms and risk of dementia in older adults.

Design, Setting, and Participants  This was a prospective cohort investigation of black and white community-dwelling older adults in the Health, Aging, and Body Composition study. Participants were enrolled between May 1997 and June 1998 and followed up through 2001-2002. The dates of this analysis were September 2014 to December 2015. The setting was community research centers in Memphis, Tennessee, and Pittsburgh, Pennsylvania. Trajectories of depressive symptoms were assessed from baseline to year 5. Symptoms were measured with the Center for Epidemiologic Studies Depression Scale Short Form, and trajectories were calculated using latent class growth curve analysis.

Main Outcomes and Measures  Incident dementia through year 11, determined by dementia medication use, hospital records, or significant cognitive decline (≥1.5 SD race-specific decline on the Modified Mini-Mental State Examination). We examined the association between depressive symptom trajectories and dementia incidence using Cox proportional hazards regression models adjusted for demographics, health factors that differed between groups, and cognition during the depressive symptom assessment period (baseline to year 5).

Results  The analytic cohort included 2488 black and white older adults with repeated depressive symptom assessments from baseline to year 5 who were free of dementia throughout that period. Their mean (SD) age at baseline was 74.0 (2.8) years, and 53.1% (n = 1322) were female. The following 3 depressive symptom trajectories were identified: consistently minimal symptoms (62.0% [n = 1542] of participants), moderate and increasing symptoms (32.2% [n = 801] of participants), and high and increasing symptoms (5.8% [n = 145] of participants). Compared with the consistently minimal trajectory, having a high and increasing depressive symptom trajectory was associated with significantly increased risk of dementia (fully adjusted hazard ratio, 1.94; 95% CI, 1.30-2.90), while the moderate and increasing trajectory was not associated with risk of dementia after full adjustment. Sensitivity analyses indicated that the high and increasing trajectory was associated with dementia incidence, while depressive symptoms at individual time points were not.

Conclusions and Relevance  Older adults with a longitudinal pattern of high and increasing depressive symptoms are at high risk for dementia. Individuals’ trajectory of depressive symptoms may inform dementia risk more accurately than one-time assessment of depressive symptoms.

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Figure 1.
Study Design Showing the Time Line of Analysis

The time line was used to investigate the association between depressive symptom trajectories over years 1 through 5 and subsequent risk of dementia after year 5. Comorbidities and other health factor variables were assessed at year 5 to adjust models for health factors that had developed by the end of the depressive symptom assessment period. To adjust for differences in overall level of cognitive functioning and cognitive change during the depressive symptom assessment period, models were adjusted for the mean Modified Mini-Mental State Examination score over years 1 through 5 and the Modified Mini-Mental State Examination difference score (year 5 minus year 1).

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Figure 2.
Depressive Symptom Trajectories From Baseline to Year 5 Among 2488 Older Adults

Shown are results of the latent class growth curve analysis used to identify groups of individuals following a similar trajectory of depressive symptoms over time, as assessed with the Center for Epidemiologic Studies Depression Scale Short Form (CES-D-10) score at years 1, 3, 4, and 5. The 3 depressive symptom trajectories that were identified are shown with 95% CIs (gray shaded area).

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Figure 3.
Association Between Depressive Symptom Trajectory Group and Dementia-Free Survival Among 2488 Older Adults

Kaplan-Meier survival curves show dementia incidence after year 5 by depressive symptom trajectory group (P < .001 by log-rank test).

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