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.