April 29, 2008

The fear and anxiety that accompanies a diagnosis of Alzheimer’s disease can understandably cause patients to become depressed. But a growing body of evidence suggests that a pattern of depression, even decades earlier, may up the risk for developing Alzheimer’s.

Two new studies shed light on the link between depression and early Alzheimer’s. The first suggests that a history of depression, particularly when it occurs before age 60, increases the risk for Alzheimer’s disease. However, changes in brain regions related to memory did not appear to play a role. The second study also showed that depression appears to be a risk factor for Alzheimer’s, but that symptoms of depression do not intensify in the years immediately before a diagnosis is made.

Researchers speculate that in some people, Alzheimer’s could be a long process that begins many years before the actual onset of memory loss, showing up as symptoms of depression. Alternatively, it is possible that depression may in some way prove “toxic” to the brain.

Understanding the link between depression and Alzheimer’s is important, as more than five million Americans are affected by Alzheimer’s. Millions more, both young and old, are affected by depression. Furthermore, researchers estimate that about half of those with Alzheimer’s disease also suffer from depression which, unlike Alzheimer’s, is a more treatable disease.

Brain Changes

In the first study, reported in the medical journal Neurology, researchers showed that people who have had depression are more likely to develop Alzheimer’s disease than people who have never had depression. The study involved 486 people ages 60 to 90 who were mentally intact and free of dementia. Of those, 134 people had experienced at least one episode of depression that prompted them to seek medical advice.

The participants were followed for an average of six years. During that time 33 people developed Alzheimer’s disease. People who had experienced depression were 2.5 times more likely to develop Alzheimer’s disease than people who had never had depression. The risk was even higher for those whose depression occurred before the age of 60; they were nearly four times more likely to develop Alzheimer’s than those with no depression.

“We don’t know yet whether depression contributes to the development of Alzheimer’s disease or whether another unknown factor causes both depression and dementia,” said study author Dr. Monique M.B. Breteler, M.D., Ph.D., with the Erasmus University Medical Center in Rotterdam, the Netherlands.  “We’ll need to do more studies to understand the relationship between depression and dementia.”

One theory is that high levels of stress hormones in depression leads to loss of cells in two areas of the brain critical for memory and emotions, the hippocampus and the amygdala, which then contributes to Alzheimer’s disease. But this study found no difference in the size of these two brain areas between people with depression and people who had never had depression.

The Dutch study also assessed whether the participants had symptoms of depression at the start of the study. But those with depressive symptoms at the start of the study were not more likely to develop Alzheimer’s than those with no depression at the start of the study.

Worsening Depression?

The second study, published in the Archives of General Psychiatry, found that symptoms of depression did not intensify in the years preceding a diagnosis of Alzheimer’s disease. The findings suggest that depression is not a consequence of developing Alzheimer’s disease. If that were the case, then feelings of sadness, apathy or hopelessness would be expected to increase during the early stages of the illness.

In the study, part of the large and ongoing Religious Orders Study, researchers at Rush University Medical Center in Chicago studied 917 older Catholic nuns, priests and monks. None had serious memory problems at the start of the study, beginning in 1994. Participants had a yearly clinical evaluation that included a neurological examination and tests of thinking, learning and memory. They also completed a 10-item scale assessing their symptoms of depression.

At the start of the study, 53.6 percent of participants had no symptoms of depression, 23.9 percent reported one symptom, 9.7 percent reported two, 6.1 percent reported three and 6.8 percent reported four or more. During follow-up, 190 individuals developed Alzheimer’s disease. Those men and women with more symptoms of depression at the beginning of the study were more likely to develop Alzheimer’s disease.

However, “those who developed Alzheimer’s disease showed no increase in depressive symptoms before the diagnosis was made, and this finding was not modified by age, sex, education, memory complaints, vascular burden or personality,” the authors write. “Among those without cognitive impairment at baseline, depressive symptoms did not increase in those who subsequently developed mild cognitive impairment.”

Depression symptoms may be associated with changes in the brain that reduce its resistance to dementia, the authors write. “Understanding the mechanisms linking depressive symptoms with dementia could suggest novel approaches to delaying dementia onset because animal research suggests diverse means by which the adverse effects of chronic stress may be modified.”

Symptoms of Depression

The findings are important, because up to half of patients with Alzheimer’s disease also have depression. Some 40 percent of those over 85 are affected by the disease, and millions more aging Americans are expected to be diagnosed with Alzheimer’s in the coming decades. Depression can take a serious toll on patients and caregivers alike.

Symptoms of depression are many and varied. They may include:

* Feeling sad, apathetic, or hopeless for weeks to months on end.

* Loss of interest in daily activities, especially ones that used to bring pleasure.

* Poor appetite and weight loss; or increased appetite and excessive weight gain.

* Troubled sleep, waking up repeatedly during the night, or an increased need for sleep.

* Feeling anxious or agitated.

* Trouble thinking or an inability to concentrate.

* Focusing on non-serious physical complaints.

Anyone with symptoms of depression should seek medical help for their condition, whether they have Alzheimer’s disease or not. If you experience one or more of these symptoms, or other unusual changes in mood or behavior, consult your physician. Medications and therapeutic counseling are available that can provide relief.

By www.ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

M.J. Geerlings, Ph.D., T. den Heijer, M.D., Ph.D., P.J. Koudstall, M.D., Ph.D., et al: “History of Depression, Depressive Symptoms, and Medial Temporal Lobe Atrophy and the Risk of Alzheimer’s Disease.” Neurology, Volume 70, April 2008, pages 1258-1264.

Robert S. Wilson, Ph.D., Steven E. Arnold, M.D., Todd L. Beck, M.S., et al: “Change in Depressive Symptoms During the Prodromal Phase of Alzheimer Disease.” Archives of General Psychiatry, Volume 65, Number 4, April 2008, pages 439-446.