Wednesday, April 6, 2011

Clinical Depression as Risk Factor for Alzheimer’s Disease


Clinical Depression and Alzheimer's disease have a lot in common and share a complex relationship. Depression -- a mental disorder caused by chemical imbalances in the brain -- can include symptoms that look like Alzheimer's, such as concentration problems, memory impairment, and difficulty making decisions. When depression looks like Alzheimer's disease or another dementia, it's often referred to as pseudodementia. It's treatable, but relapse is a significant concern. Depression and Alzheimer's disease can also occur together, where each disorder requires treatment that doesn't interfere with the treatment of the other condition. This is another complex diagnostic and treatment situation.

Traditional science admits that Depression is one of the multiple symptoms, associated with Alzheimer’s Disease (AD). However, new research data show a different causal relationship between these two disorders. Clinical depression might be a substantial risk factor for AD.

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Study from Rush University Medical Center (2008)

Investigators from Rush University Medical Center sought to determine if depressive symptoms actually contribute to the development of dementia (risk factor hypothesis) or are a consequence of the disease (reverse causality hypothesis.) The research emanates from numerous observational studies that show higher levels of depressive symptoms in old age are associated with increased incidence of Alzheimer’s disease and mild cognitive impairment.

Robert S. Wilson, PhD, a neuropsychologist at the Rush Alzheimer’s Disease Center, and colleagues examined data from the Rush Religious Orders Study, a cohort of 917 older Catholic clergy without dementia at study onset, to examine the change in depressive symptoms of Alzheimer’s disease before and after the emergence of the cognitive symptoms of the disease.

For up to 13 years, the study participants underwent annual clinical evaluations that included assessment of depressive symptoms, cognitive testing, and clinical classification of mild cognitive impairment (MCI) and Alzheimer’s disease. During the study period, 190 participants developed Alzheimer’s disease.

Consistent with earlier findings in the Rush Religious Orders Study, having more depressive symptoms at baseline was associated with increased incidence of Alzheimer’s disease and MCI.

However, the study found that those who developed Alzheimer’s disease showed no increase in depressive symptoms before clinical diagnosis. Researchers were able to observe patients during a mean of approximately four years before the onset of dementia. Additionally, researchers saw no increase in depression during the three to four years preceding the onset of MCI, which antedates the onset of dementia by several years.

“If depressive symptoms are a consequence of dementia or a reaction to declining function, depressive symptoms would likely increase at some point before dementia is clinically evident,” said Wilson. “We observed no such increase.”

The study also found that even after the diagnosis of Alzheimer’s disease was made there was no general increase in depression, but rather an increase that was confined to individuals with certain personality traits.

“Depressive symptoms may be associated with distinctive changes in the brain that somehow reduce neural reserve, which is the brain’s ability to tolerate the pathology associated with Alzheimer’s disease,” said Wilson.

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Study from University of Massachusetts Medical School (2010)

The 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.

Exactly how a mood disorder like depression can contribute to Alzheimer's disease isn't currently clear, 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.

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Study from Erasmus Medical Center (2008)

Dr. Breteler published her study in the April 2008 issue of Neurology when she worked at the Erasmus Medical Center in the city of Rotterdam in the Netherlands. During the study she followed 503 non-demented persons aged 60-90 over a period of 6 years to chart the association, if any, between depression, the development of Alzheimer’s disease and hippocompal volume. She used three-dimensional MRI scans to quantify the size of each study participant’s hippocampus. Prior to the study 88 participants developed depression before age 60 and 46 participants developed depression after age 60. None of these people showed hippocampal atrophy (i.e. shrinkage of the hippocampus) at the outset of the study.

During the course of the study 33 people developed Alzheimer’s disease. Statistical analysis showed that people with a history of early onset depression (before age 60) had a 3.76 times greater chance of developing Alzheimer’s than non-depressed participants, whereas people with late onset depression (after age 60) had an increased risk of 2.34 over non-depressed participants. People who developed depression during the study showed no increased risk of developing Alzheimer’s.

Dr. Breteler concluded that depression is clearly a predictor of Alzheimer’s disease but not necessarily a cause and it’s possible there is a single as-yet-unknown mechanism in the brain which causes both problems. Dr. Breteler said that if Dr. Wilson’s theory that depression shrinks the hippocampus before onset of Alzheimer’s was correct she would have expected to find decreased hippocampal volume in the depressed patients at the study outset, but she didn’t find this, since the study participants all had hippocampal volume within normal range. She also said that if depression causes Alzheimer’s the people who first experienced depression during the study should have higher rates of Alzheimer’s than the normal population. 

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So, who is right: Dr. Wilson and Dr. Saczynski, claiming that depression constitutes a big risk for the AD development later in life, or Dr. Breteler, who did not find this causal relationship? It is probably subject for additional research and multiple longitude studies. However, one thing is obvious. If you have depression – do not let it be. Seek for medical assistance promptly and fight with it by all available means. Not only you make your life miserable, but you also may step forward towards the greater risk of developing AD.

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