Story highlights People who were depressed in midlife were 20% more likely to develop dementia

Patients who received a depression diagnosis later in life were at even greater risk

Timing of the depression seemed to predict which type of dementia an individual would get

People who have symptoms of depression in middle age may be at increased risk of dementia decades later, a new study suggests.

Using medical records, researchers tracked more than 13,000 people in a large northern California health plan from roughly their 40s and 50s into their 80s. Compared to people who had never been depressed, those who experienced symptoms of depression in middle age -- but not later in life -- were about 20% more likely to go on to develop dementia.

Those who received a depression diagnosis later in life only were at even greater risk. That group had about a 70% increased risk of dementia compared to their depression-free peers, according to the study, which was published this week in the Archives of General Psychiatry.

In a first, the researchers also found that the timing of the depression seemed to predict which type of dementia an individual would develop. Late-life depression was linked with Alzheimer's disease, while mid-life depression was mostly connected with a related condition known as vascular dementia.

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Although Alzheimer's disease and vascular dementia share many of the same outward symptoms, they're associated with different processes in the brain. In Alzheimer's, memory loss and other symptoms are believed to be caused by protein deposits that interfere with brain function. Vascular dementia, on the other hand, appears to occur when blood flow to certain areas of the brain is interrupted, such as during strokes and so-called mini-strokes.

The study participants were 3.5 times more likely to develop vascular dementia if they'd experienced depression symptoms in both middle age and later in life, which suggests that "recurring depression over the life course seems to be triggering vascular changes that puts [people] at risk for vascular dementia," says lead author Deborah E. Barnes, Ph.D., an associate professor of psychiatry at the University of California, San Francisco.

By contrast, depression that appears for the first time in old age may simply be an early symptom of Alzheimer's rather than a stand-alone condition, Barnes says.

Dr. Charles Nemeroff, chair of psychiatry at the University of Miami Miller School of Medicine, says there is already "quite a bit of evidence" that depression is a risk factor for dementia. However, this study is among the largest to show a link between the two conditions, says Nemeroff, who was not involved with the research.

Previous studies have not distinguished between depression in middle age and depression later in life, making it difficult to determine if depression is a risk factor for dementia or an early symptom, Barnes says. "The question has been, 'Is depression a true risk factor for depression?'" she says.

The findings do suggest that depression tends to precede vascular dementia, but the study does have a number of limitations that prevent the authors from concluding that depression directly causes dementia.

For most of the participants, mid-life depression was assessed using a single question on a single questionnaire, and the researchers had no information on whether an individual had been depressed as a young adult or adolescent.

In addition, the dementia diagnoses were based only on symptoms and medical history, not brain imaging or spinal fluid measurements. The latter techniques are more reliable, especially since the distinction between Alzheimer's and vascular dementia isn't always clear-cut.

Finally, the authors didn't explore whether genetic risk for Alzheimer's disease may have played a role, Nemeroff says.

But perhaps the biggest unanswered question is whether treating depression in middle age would have had any effect on dementia risk. The study didn't include any data on whether the depressed participants received treatment, or what type of treatment.

That question is "really important," Nemeroff says. "We'd really like to know: If depression [were] aggressively treated with psychotherapy or antidepressants, could you stave off dementia?"