Depression at Any Stage of Life Tied to Increased Dementia Risk

Adults with depression have more than double the risk of developing dementia and the risk persists regardless of when in life depression is diagnosed, a large population-based study shows.

That the association between depression and dementia persisted even among individuals first diagnosed with depression in early or mid-life provides “strong evidence that depression is not only an early symptom of dementia, but also that depression increases dementia risk,” study investigator Holly Elser, MD, PhD, epidemiologist and resident physician, University of Pennsylvania, Philadelphia, told Medscape Medical News.

The study was published online July 24 in JAMA Neurology.

Double the Risk

Several prior studies that have examined the relationship between depression and dementia over the life course have consistently shown depression later in life is associated with subsequent dementia.

“Late-life depression is generally thought to be an early symptom of dementia or a reaction to subclinical cognitive decline,” said Elser.

The investigators wanted to examine whether the association between depression and dementia persists even when depression is diagnosed earlier in life, which may suggest it increases the risk of dementia.

“To my knowledge, ours is the largest study on this topic to date, leveraging routinely and prospectively collected data from more than 1.4 million Danish citizens followed from 1977 to 2018,” Elser noted.

The cohort included 246,499 individuals diagnosed with depression and 1,190,302 individuals without depression. 

In both groups, the median age was around 50 years and 65% were women. Roughly two thirds (68%) of those diagnosed with depression were diagnosed before age 60 years.

In Cox proportional hazards regression models, the overall hazard of dementia was more than doubled in those diagnosed with depression (hazard ratio [HR] 2.41). The risk of dementia with depression was more pronounced for men (HR, 2.98) than women (HR, 2.21).

This association persisted even when the time elapsed from depression diagnosis was between 20 to 39 years (HR, 1.79) and whether depression was diagnosed in early life (18-44 years: HR, 3.08), mid-life (45-59 years: HR, 2.95), or late life (≥ 60 years: HR, 2.31).

It remains unclear whether effective treatment of depression modifies the risk of dementia, as the current study explored the role of antidepressants in a “very limited fashion,” Elser told Medscape Medical News.

Specifically, the researchers considered whether an individual was treated with an antidepressant within 6 months of the initial depression diagnosis and found no evidence of a difference in dementia risk between the treated and untreated groups.

“Research that explores implications of the timing and duration of treatment with antidepressants for dementia, treatment withcognitive behavioral therapy, and is able to evaluate the effectiveness of those treatments will be extremely important,” Elser said.

“An Assault on the Brain”

Reached for comment, John Showalter, MD, chief product officer at Linus Health, said one of the most “intriguing” findings of the study is that a depression diagnosis earlier in adulthood conferred a greater risk of developing vascular dementia (HR, 3.28) than dementia due to Alzheimer’s disease (HR, 1.73).

“The difference in risk for subtypes of dementia is a meaningful addition to our understanding of depression’s connection to dementia,” said Showalter, who was not involved in the study.

Also weighing in, Shaheen Lakhan, MD, PhD, a neurologist and researcher from Boston, Massachusetts, said the findings from this “far-reaching investigation leave little room for doubt — depression unleashes a devastating storm within the brain, wreaking havoc on the lives of those ensnared by its grip.”

“This massive, multi-decade, and high-data quality registry study adds another brick to the growing edifice of evidence attesting to the profound connection between psychiatric health and the very essence of brain health,” said Lakhan, who was not involved in the study.

“In a resounding declaration, this research underscores that psychiatric health should be perceived as an integral component of overall health — a paradigm shift that challenges long-standing misconceptions and stigmas surrounding mental disorders. Depression, once marginalized, now claims its rightful place on the pedestal of health concerns that must be addressed with unwavering resolve,” said Lakhan.

He noted that depression is “not just a mental battle, it’s a profound assault on the very fabric of the brain, leaving lives in turmoil and hearts in search of hope. No longer shrouded in silence, depression demands society’s attention.”

The study had no specific funding. Elser, Showalter, and Lakhan have reported no relevant financial relationships.

JAMA Neurol. Published online July 24, 2023. Abstract

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