UCSF-led study shows depressive symptoms increase risk for cognitive impairment
The researchers used innovative statistical methods to predict average trajectories of depressive symptoms for approximately 15,000 participants ages 20 to 89, divided into three life stages: older, midlife and young adulthood. They then applied these predicted trajectories and found that in a group of approximately 6,000 older participants, the odds of cognitive impairment were 73 percent higher for those estimated to have elevated depressive symptoms in early adulthood, and 43 percent higher for those estimated to have elevated depressive symptoms in later life.
These results were adjusted for depressive symptoms in other life stages and for differences in age, sex, race, educational attainment, body mass index, history of diabetes and smoking status. For depressive symptoms in midlife, the researchers found an association with cognitive impairment, but this was discounted when they adjusted for depression in other life stages.
Excess Stress Hormones May Damage Ability to Make New Memories
“Several mechanisms explain how depression might increase dementia risk,” said first author Willa Brenowitz, PhD, MPH, of the UCSF Department of Psychiatry and Behavioral Sciences and the Weill Institute for Neurosciences. “Among them is that hyperactivity of the central stress response system increases production of the stress hormones glucocorticoids, leading to damage of the hippocampus, the part of the brain essential for forming, organizing and storing new memories.”
Other studies have linked depression with atrophy of the hippocampus, and one study has shown faster rates of volume loss in women, she said.
In estimating the depressive symptoms across each life stage, researchers pooled data from younger participants with data from the approximately 6,000 older participants and predicted average trajectories. These participants, whose average age was 72 at the start of the study and lived at home, had been enrolled by the Health Aging and Body Composition Study and the Cardiovascular Health Study. They were followed annually or semi-annually for up to 11 years.
U-Shaped Curve Adds Credence to Predicted Trajectories
While assumed values were used, the authors stated, no longitudinal studies have been completed across the life course. “Imputed depressive symptom trajectories fit a U-shaped curve, similar to age-related trends in other research,” they noted.
Participants were screened for depression using a tool called the CESD-10, a 10-item questionnaire assessing symptoms in the past week. Moderate or high depressive symptoms were found in 13 percent of young adults, 26 percent of midlife adults and 34 percent of older participants.
Some 1,277 participants were diagnosed with cognitive impairment following neuropsychological testing, evidence of global decline, documented use of a dementia medication or hospitalization with dementia as a primary or secondary diagnosis.
“Generally, we found that the greater the depressive symptoms, the lower the cognition and the faster the rates of decline,” said Brenowitz, who is also affiliated with the UCSF Department of Epidemiology and Biostatistics. “Older adults estimated to have moderate or high depressive symptoms in early adulthood were found to experience a drop in cognition over 10 years.”
With up to 20 percent of the population suffering from depression during their lifetime, it’s important to recognize its role in cognitive aging, said senior author Kristine Yaffe, MD, of the UCSF departments of Psychiatry and Behavioral Sciences, and Epidemiology and Biostatistics. “Future work will be needed to confirm these findings, but in the meantime, we should screen and treat depression for many reasons.”
The co-authors include Eric Vittinghoff, PhD, from UCSF; Adina Zeki Al Hazzouri, PhD, from Columbia University; Sherita H. Golden, MD, from Johns Hopkins University School of Medicine; and Annette L. Fitzpatrick, PhD, from University of Washington.
NOTES FOR EDITORS
Full study: "Depressive Symptoms Imputed Across the Life Course Are Associated with Cognitive Impairment and Cognitive Decline” by Willa D. Brenowitz, Adina Zeki Al Hazzouri, Eric Vittinghoff, Sherita H. Golden, Annette L. Fitzpatrick, and Kristine Yaffe (DOI: 10.3233/JAD-210588), published in the Journal of Alzheimer’s Disease, Volume 83, Issue 3 (September 2021). The article is available online at: content.iospress.com/articles/journal-of-alzheimers-disease/jad210588.
Funding: National Institutes of Health and National Institute on Aging (1RF1AG054443).
The media contact is Suzanne Leigh, UC San Francisco (firstname.lastname@example.org or +1 415) 680-5133).
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About the Journal of Alzheimer's Disease
The Journal of Alzheimer’s Disease (JAD) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment, and psychology of Alzheimer’s disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease, and clinical trial outcomes. JAD has a Journal Impact Factor of 4.472 according to Journal Citation Reports (Clarivate, 2021). The journal is published by IOS Press. j-alz.com
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