Depression often precedes the onset of dementia. A recent study offers a good picture of this relationship, though the reasons behind it are not yet clear.

When American and Danish researchers analyzed more than 40 years of data from over 1,400,000 adults to look at the association between depression with dementia, they found the connection persisted regardless of when depression was diagnosed — whether early, mid or late in life. They also reported that the association between depression and dementia risk was stronger in men than women.

Depression is associated with poor health outcomes and negatively affects people’s quality of life. For this reason, people diagnosed with depression should always be helped to manage their symptoms, even if that doesn’t reduce their dementia risk, Holly Elser, lead author on the study, told TheDoctor. “The treatment of depression is very important for improving quality of life for those who currently have symptoms,” she said.

Depression late in life may be associated with an increase in dementia risk that is two to five times the risk in non-depressed people.

The findings are based on data from 246,499 adults previously diagnosed with depression and were compared to approximately 1,200,000 people without depression. Participants were enrolled in the Danish National Patient Registry. About 66 percent of those with depression were diagnosed before age 60. The risk of dementia in those with depression was twice that of people in the control group.

Researchers continue to debate how depression increases dementia risk, and a number of factors are likely at work. Depressive symptoms may develop in response to cognitive decline, what researchers consider reverse causality. Depression may also be an early symptom of dementia, a theory supported by study findings that late-life depression is associated with a two- to five-times increase in dementia risk.

Depression also causes fluctuations in key levels of neurotransmitters in the brain, such as noradrenaline and serotonin, which may increase the risk of dementia. “In other words, the effect of depression on dementia risk is mediated chemically or biologically” said Elser, a resident in neurology at the Hospital of the University of Pennsylvania. A genetic predisposition or neurologic factors may also be at work in both depression and dementia, she added.

Finally, depression often leads to lifestyle changes that could increase the risk of dementia later on. For example, people with depression are less physically active and less socially connected, two factors that can also increase dementia risk. “There is a need for future studies that examine the mechanisms that underlie this association,” said Elser, adding that it is important to remember that these factors are not mutually exclusive and can coexist.

Going forward, Elser hopes to investigate how the treatment of depression changes the relationship between depression and dementia risk.

The study is published in JAMA Neurology.