Does Depression Contribute to Dementia?

by Judith Graham for The New York Times:

A large body of research has linked late-life depression to social isolation, poorer health and an increased risk of death. Now, a new study finds that depression is associated with subsequent vascular dementia and Alzheimer’s disease, conditions poised to expand dramatically with the aging population.The report, published on Wednesday in the British Journal of Psychiatry, is a meta-analysis of 23 previous studies that followed nearly 50,000 older adults over a median of five years.The researchers found that depressed older adults (defined as those over age 50) were more than twice as likely to develop vascular dementia and 65 percent more likely to develop Alzheimer's disease than similarly aged people who weren’t depressed.“We can’t say that late-life depression causes dementia, but we can say it likely contributes to it,” said Meryl Butters, an associate professor of psychiatry at the University of Pittsburgh School of Medicine and a co-author of the paper. “We think depression is toxic to the brain, and if you’re walking around with some mild brain damage, it will add to the degenerative process.”In terms of absolute risk, she said, the data suggest that 36 of every 50 older adults with late-life depression may go on to develop vascular dementia, while 31 of every 50 seniors with a history of depression may eventually be diagnosed with Alzheimer’s.Previous research has shown that a history of depression is linked to a doubling of the risk that someone will end up with Alzheimer’s disease. But this is the first analysis to demonstrate an even stronger association with vascular dementia, a condition caused by strokes or other interruptions to blood flow in the brain.That does not mean a causal relationship between depression and dementia has been established; it hasn’t. Nor is there any solid evidence yet that forestalling depression will prevent dementia.About 20 percent of people with dementia in the United States — between 500,000 and 1 million adults — are thought to have the vascular form of this condition, according to the National Institute of Neurological Disorders and Stroke. Over all, up to 5 percent of adults aged 65 and older have clinical depression; the numbers are higher among those who receive home health care or live in institutions.What biological mechanisms might account for a relationship between depression and dementia? Some evidence suggests that people who are depressed produce high levels of the hormone cortisol, which in turn has an adverse effect on the hippocampus — a part of the brain responsible for new learning and short-term memory.“We know that people who are depressed have elevated levels of cortisol, a hormone related to the stress response, and a smaller hippocampus, a brain structure critically important for memory,” said Dr. Raymond Ownby, chair of psychiatry at Nova Southeastern University’s College of Osteopathic Medicine in Fort Lauderdale, Fla., who studies the possible links between depression and dementia.Other evidence suggests that depression contributes to chronic inflammation that damages blood vessels and impedes blood flow in the brain, leading to the deterioration of neural networks.“If chronic inflammatory changes are a common feature of depression, that could predispose depressed patients to neurodegenerative changes in later life,” according to a 2007 article in Neurochemical Research.Some experts have hypothesized that depression may share genetic underpinnings with dementia, be an early signal of dementia, or serve as an emotional reaction to impaired thinking and unreliable memory. Alternately, depression may deplete a person’s cognitive reserves, bringing encroaching dementia to light earlier than otherwise would be the case.Whatever the underlying mechanism may be, the implications for older adults are clear. “If someone in later life develops depression, they should get early, aggressive treatment, and if they do so and recover, they should try to prevent recurrence,” Dr. Butters said.While there is no evidence that doing so will prevent dementia, treating depression in older adults at least improves one’s quality of life, relieving suffering and reducing other health risks, several other experts said.In the new analysis, groups of older adults were surveyed for self-reported symptoms of depression in each of the 23 studies. The fact that people with mild cognitive impairment weren’t excluded from this baseline group is a significant limitation, some experts said.“M.C.I. is an independent risk factor for Alzheimer’s disease, and people with M.C.I. often have depression and anxiety,” said Dr. David Loewenstein, a professor of psychology and behavioral sciences at the University of Miami Miller School of Medicine. “The depression reported could have been a co-morbid condition of underlying early stage disease.”Still, previous meta-analyses by researchers inChina, Australia and the United States have suggested a link between depression and Alzheimer’s disease. That the association might extend also to vascular dementia isn’t a surprise, given a large body of research connecting depression with cerebrovascular disease, experts said.Researchers are pursuing several related questions — most importantly, whether “identifying depression early and treating it adequately lower the risk of dementia,” said Deborah Barnes, associate professor of psychiatry, epidemiology and biostatics at the University of California, San Francisco.She is the author of a study of 13,535 members of Kaiser Permanente, a California-based health maintenance organization, published a year ago in JAMA Psychiatry that found that older adults were three times more likely to develop vascular dementia if they suffered from depression starting in middle age and continuing on in later life.Dr. Barnes also wrote a 2011 paper in The Lancet that estimated that almost 15 percent of Alzheimer’s disease cases in the United States are “potentially attributable to depression” and that a 10 percent reduction in depression might prevent 68,000 cases of dementia.Source: http://nyti.ms/130hxsOPicture: Getty Images