Study suggests depression is a risk factor for mild cognitive impairment

Tuesday, April 04, 2006

JACKSONVILLE, Fla. — In a new study, Mayo Clinic researchers found that cognitively normal, elderly people who developed depression during subsequent follow up were at increased risk of developing mild cognitive impairment (MCI). When viewed as a spectrum of cognitive functioning, MCI falls between normal brain aging and dementing illnesses, notably, Alzheimer's disease.

Investigators recruited 840 cognitively normal, elderly adults without depression and followed them for a median duration of 3.5 years. During the course of the study, 143 developed depression and were compared with the 697 who didn't. Of those with depression (defined as a score greater than or equal to six on an assessment tool called the short Geriatric Depression Scale), 13.3 percent developed MCI. Only 4.9 percent of those who weren't depressed went on to develop MCI.

Although mild depression is a risk factor for MCI, "The good news is that depression is now a modifiable risk factor," says Dr. Yonas Geda, a Mayo Clinic neuropsychiatrist and the study's lead investigator. "There are treatments. There are medications. Psychiatrists, behavioral neurologists, family physicians and internists are now trained to manage depression. Additionally, social workers and psychologists are trained to treat depression through counseling. It's not something that you helplessly watch."

In their study, published in the March 2006 issue of Archives of Neurology, researchers also examined the association between depression and a particular gene known to be a risk factor for dementia.

Everyone has two copies of the apolipoprotein E (APOE) gene. One is inherited from the father and one from the mother. People with one or two copies of the ƒÕ4 variant are at greater risk of developing dementia than people without the e4 variant. "We know that APOE e4 is a risk factor for Alzheimer's disease and one of the predictors of decline from mild cognitive impairment to Alzheimer's," Geda says. "So we asked, 'Could there be interaction between depression and APOE e4? Could they be working together to amplify the risk for MCI?'"

Geda and his colleagues found that those who developed depression and had one or two copies of the APOE e4 gene were more than twice as likely to develop MCI as those with depression who did not have a copy of the "at risk" gene. Geda says the study's major contribution is the theoretical model he and his colleagues proposed that can explain the association between depression and new onset or incident MCI. First, they suggest that in a chain of events leading to MCI, depression may precede MCI. Second, some environmental or genetic factor may lead to both depression and MCI. Third, people with declining cognitive functioning may become depressed as a reaction to their symptoms. Fourth, depression may lead to cognitive decline in people with a genetic susceptibility factor such as the APOE e4 gene.

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