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updated 7/21/2010 5:33:50 PM ET 2010-07-21T21:33:50

As if depression wasn't bad enough on its own, new research suggests older adults with depressive symptoms are at increased risk of developing Alzheimer's disease.

Alzheimer's is a fatal brain disorder marked by memory loss and an inability to function in daily life. Researchers have long known that depression and Alzheimer's disease are linked, but it wasn't clear whether depression was a risk factor for Alzheimer's or a symptom of the disease.

Now, two studies published in the July 6 issue of the journal Neurology conclude that depression is indeed separate from Alzheimer's and that depressive symptoms can raise the risk of dementia by 50 percent.

The studies didn't address the question of why depression might contribute to later cognitive decline. One theory, said study author Robert Wilson, a neuropsychologist at Rush University Medical Center in Chicago, is that depression fundamentally alters the brain.

"There may be some actual structural changes associated with depression that render depressed individuals, by the time they reach old age, a little bit more vulnerable" to dementia, Wilson told LiveScience.

Story: If you're depressed, the world really looks gray

Risk factor or symptom?
Alzheimer's is caused by protein plaques and tangles that build up in and around nerve cells in the brain, causing cell death. Exactly why the plaques and tangles form is a mystery, but previous brain-anatomy studies suggested depression isn't to blame, Wilson said.

To Wilson, it seemed likely that depression was a risk factor for dementia, not a symptom of the disease. To test the theory, he and his colleagues analyzed data on older adults from Chicago's South Side who had undergone evaluation for depression and Alzheimer's every three years. About 350 of these individuals were diagnosed with dementia, which is most commonly caused by Alzheimer's.

By comparing the participants' self-reported depression ratings and dementia diagnoses, the researchers found "virtually no change" in depressive symptoms seven years prior to the dementia diagnosis and   three years after it, Wilson said. Interviews with family members and caregivers confirmed that observable signs of depression also held steady.

The results suggest depression is not an inevitable symptom of Alzheimer's, Wilson said.

"It's not to say that people with Alzheimer's never have depression," he said. "We think they're as likely to have depression as they were before the disease."

Depression and dementia are linked, however. The second study, headed by epidemiologist Jane Saczynski of the University of Massachusetts Medical School, used data from the famous Framingham Heart Study to track depression and dementia in 949 people over 17 years.

At the beginning of the study, none of the participants had any dementia symptoms; by the end, 136 had developed Alzheimer's and 28 had other dementias. Of those who had depressive symptoms at the beginning of the study, 21.6 percent later developed dementia, compared with 16.6 percent of non-depressed individuals. After controlling for factors like smoking and genetics, the researchers found that depression raised the risk of later dementia by 50 percent.

The long time frame makes it less likely that the participants already had dementia-related damage at the beginning of the study, Saczynski said. And because the depression showed up so much earlier than the dementia, the study, like Wilson's, supports the notion of depression as a dementia risk factor, not a symptom.

Dementia by a thousand cuts
Exactly how a mood disorder like depression can contribute to Alzheimer's disease isn't known, but the effect is probably cumulative.

One theory, Saczynski said, is that depression weakens the body's defenses against dementia by affecting the brain's blood supply. Cardiovascular disease (another risk factor for Alzheimer's) and depression are often clinically linked, Saczynski said, perhaps because of reduced blood flow to the brain. These vascular changes might render the brain more vulnerable to Alzheimer's-related damage.

Another possibility is that the chronic stress of depression changes the brain's structure. Studies on animals find that the brains of mice and rats kept in stressful conditions show changes in areas associated with memory and learning.

Something similar seems to happen in humans. One study, published in May in the journal Archives of General Psychiatry and co-authored by Rush University's Wilson, revealed that Catholic nuns and priests who scored high on anxiety and depression measures had different brains than other clergy did. The nerve cells in the depressed group's hippocampi brain areas associated with memory and emotion were shorter and less branched-out than normal nerve cells. The researchers didn't link these brain changes to Alzheimer's, but the findings suggest depression "takes a toll," Wilson said. Blunting the vulnerability
If depression is a risk factor for Alzheimer's disease, it is just one of many. Family history is another, as is the presence of a gene called ApoE4. Lifestyle factors like diet, exercise and cognitive engagement may also contribute, although a National Institutes of Health panel determined in May that the evidence for these factors is not yet strong enough to warrant recommendations for Alzheimer's prevention. In the case of depression, these lifestyle factors could make a difference. Exercise and diet might combat vascular disease linked to depression, Saczynski said. And, Wilson said, stressed mice and rats that exercise, take antidepressants and eat well show fewer brain changes than those that don't. "Diet and exercise seem to lessen the impact," Wilson said. "So if we're on the right track here, there do seem to be tools that can blunt the vulnerability."

 

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