News Release
A nurse sits next to an older adult who is applying pressure to the side of his head.

PHILADELPHIA – Those diagnosed with depression—including young and middle-aged adults—were more than twice as likely to be diagnosed with dementia later in life, as compared to those without depression, according to an analysis conducted in collaboration between researchers at the Perelman School of Medicine at the University of Pennsylvania and Aarhus University in Denmark. The study marks the largest analysis of its kind with the longest follow-up time to date—with data from 1.4 million Danish citizens over nearly four decades. The findings were published this week in JAMA Neurology.

“While depression diagnosed later in life is generally thought to be an early symptom of dementia, our results suggest that a depression diagnosis at any point in adulthood increases the risk of dementia later on,”  said first author, Holly Elser, MD, PhD, a Neurology resident at Penn. “Previous studies with smaller sample sizes and shorter follow-up times have consistently illustrated the link between dementia and depression diagnosed later in life, but with our long-term analysis, we were able to precisely estimate the association between dementia and depression over an individual’s life span.”

Depression and dementia are common disorders, with depression affecting an estimated 20 million American adults, and dementia affecting an estimated 5 million adults, and that number is projected to grow to nearly 14 million by 2060. Depression is a mood disorder, characterized by feelings of hopelessness, thoughts of death, and even suicide attempts. Dementia refers to the impaired ability to remember, think, or make decisions that interferes with doing everyday activities. Alzheimer’s disease is the most common type of dementia.

Health data has been gathered routinely and prospectively for all Danish citizens since the late 1970s, and recorded for Danish National Health Registers. For this study, researchers analyzed the health records of over 1.4 million Danish citizens and identified about 246,500 individuals with a new depression diagnosis between 1980 and 2018. A comparison cohort of more than 1,190,300 individuals without depression were randomly sampled from the Danish general population. Of those with a depression diagnosis, 14,000 were subsequently diagnosed with dementia. In the comparison cohort, about 38,650 individuals were diagnosed with dementia—indicating that those previously diagnosed with depression were 2.41 times more likely to have a dementia diagnosis later in life.

The association between depression and dementia for men and women persisted regardless of whether depression was diagnosed in early, middle, or late life, although the association between depression and dementia among men was stronger. Multiple inpatient hospitalizations for depression were associated with an increased risk of dementia later in life, and the risk increased with each subsequent hospitalization. Researchers found that being prescribed an antidepressant within six months of depression diagnosis had no effect on the rate of dementia diagnosis later in life.  

The researchers acknowledge the limitations of the paper and underscore the need to further investigate the link between depression and dementia.

“It is still unclear what about depression increases the risk of a dementia diagnosis, and I hope to see further research that evaluates whether the link between depression and dementia may be biological, a result of behaviors associated with depression like social isolation and other changes in key health behaviors, or some combination of these mechanisms,” said Elser. “What’s more, since depression affects so many individuals, research that examines whether clinical practices to manage depression can reduce the risk for dementia in individuals diagnosed with depression.”

Henrik Toft Sørensen, MD, PhD, DMSc, DSc, Chair of the Department of Clinical Epidemiology at Arhaus University, and Victor W. Henderson, MD, MS, professor of Epidemiology & Population Health and of Neurology & Neurological Sciences at Stanford University, were co-senior authors on the publication.

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.

The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.

The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.

Share This Page: