April 7, 2008 — A history of depression, especially if it occurs early in life, boosts your risk of getting Alzheimer’s disease, according to a new study.

But depression does not seem to increase during the early stages of Alzheimer’s disease, according to another new study, refuting the idea that the Alzheimer’s causes the depression, as some claim.

Together, the two studies contribute some answers to the ongoing debate about depression and Alzheimer’s disease — and whether depression triggers the Alzheimer’s disease, the Alzheimer’s disease triggers the depression, or yet another risk factor leads to both. Up to 50% of Alzheimer’s patients also report depression.

The new research strengthens advice to take depression seriously and get treatment, says Gary Kennedy, MD, director of geriatric psychiatry at Montefiore Medical Center, New York, N.Y. “You want to get over it as quickly and completely as possible,” says Kennedy, who reviewed the studies for WebMD.

Depression and Alzheimer’s: Role of History Study

To look at the link between depression and Alzheimer’s disease, researchers from Erasmus Medical Center in the Netherlands assessed 503 men and women, aged 60 to 90 at the study start and free of dementia. All were participants in the Rotterdam Scan Study, an ongoing research effort to look at chronic diseases in the elderly.

Participants reported any history of depression and noted if it occurred before or after age 60. They also reported any symptoms of depression at the study start.

Researchers also performed three-dimensional MRI scans to look at the volume of two brain areas — the hippocampus and the amygdala, two areas that some experts say shrink in those with depression. They wanted to see if they could document that suspected association.

After a six-year follow-up, 33 people developed dementia; 134 of the participants had a history of depression (88 early onset, 46 late).

If the depression occurred before age 60, the researchers report, the risk of getting Alzheimer’s disease later was nearly four times as great as for those who did not have a history of depression. If the depression occurred after age 60, the risk was about 2.5 times greater than the risk for the depression-free.

Depression at the start of the study was not associated with an increased risk for Alzheimer’s disease.

The researchers then looked at who had depression and who did not, and compared the sizes of their hippocampus and amygdala. They found no association between the sizes of those brain areas and depression, refuting the idea that the shrinkage in the brain contributes to the Alzheimer’s disease.

“Our findings definitely do not support the notion that depression leads to loss of hippocampus and amygdala cells which then leads to Alzheimer’s,” says Monique M.B. Breteler, MD, PhD, professor of neuroepidemiology at Erasmus University and the study’s lead author, in an email interview.

Yet a third factor, she says, could be causing both depression and Alzheimer’s, and more research is needed to find out exactly what.

The study is published in Neurology.

Depression and Alzheimer’s Early Stages Study

In the second study, researchers from Rush University Medical Center, Chicago, looked at participants’ state of mind during the very early stages of Alzheimer’s disease and whether they tended to become more depressed.

Some experts have suggested depression is not a true risk factor but a consequence of the disease. If that is true, depression would likely increase as a person develops dementia.

For up to 13 years, researchers followed 917 participants of the Religious Orders Study, which launched in 1994 and includes Catholic nuns, priests, and monks. All were free of dementia at the study start and all agreed to donate their brains for autopsy at death so researchers can discover more information about Alzheimer’s disease and other problems.

They were given annual exams, including tests of memory and other cognitive skills. During the follow-up, 190 developed Alzheimer’s disease. Those with more depression at the beginning were found more likely to get it. But their depression didn’t increase in the early stages.

“We found absolutely no evidence that depressive symptoms increased during that period [of early Alzheimer’s],'” says Robert S. Wilson, PhD, professor of neurological sciences and behavioral sciences at Rush University Medical Center, Chicago, and the lead author.

“Even though it sort of makes sense that you would get depressed when you are losing cognition, it doesn’t seem to be happening.”

The research, he tells WebMD, “goes against the idea that depressive symptoms are a consequence not a risk factor of Alzheimer’s disease.”

The study is published in the Archives of General Psychiatry.

Second Opinions and Take-Home Message

The association found between depression and Alzheimer’s risk was much stronger for early-onset depression than later onset, according to other experts. The risk between late onset depression and Alzheimer’s was not statistically significant.

“People who have early-onset depression were found at an increased risk of Alzheimer’s disease,” says Wilson, the author of the study on depression during Alzheimer’s early stages. “For those with late-onset depression, the results are not as conclusive.”

The most conservative thing to say is that depression is a risk factor, more prominent with younger onset but also possibly operative at later ages as well,” says David Knopman, MD, a neurologist at Mayo Clinic, Rochester, Minn., and an associate editor of Neurology.

While more research is needed to figure out the depression-Alzheimer’s link, the results do suggest some practical advice, says Kennedy.

“If depression doubles or triples your risk, you want to make sure your depression is treated as aggressively as possible,” he says. Whether that means medication, psychotherapy, exercise, or other means, he says, the point is to treat the depression effectively.

While some older people think depression is a natural part of aging, it is not, Kennedy says. Aggressive treatment of the depression is recommended, he says, at any age.