Brain reserve capacity and its role in preventing clinical signs of Alzheimer's disease studied

July 22, 2002

Identifying factors that increase the reserve capacity of the brain and enable people to tolerate the pathological changes that occur in the brains of people with Alzheimer's disease offers a new and potentially powerful approach to delaying the clinical signs of the Alzheimer's and other neurodegenerative diseases, according to researchers at Rush-Presbyterian-St. Luke's Medical Center, Chicago.

Research is underway at Rush to identify the factors that increase or maintain the reserve capacity of the human brain. Researchers have known for some time that education and related lifestyle experiences affect cognitive function across the lifespan. There is also evidence that these educational experiences can reduce one's risk of developing Alzheimer's disease.

"How these lifestyle experiences actually affect the brain is unknown," according to Dr. David A. Bennett, director of the Rush Alzheimer's Disease Center. "We think that education and factors related to education may affect the way the brain responds to the abnormal proteins that accumulate in the brains of people with Alzheimer's disease. In other words, in people with similar amounts of these abnormal Alzheimer's disease protein deposits, those with more educational experiences will be less likely to have memory loss than those with less education," he explained.

The $9 million grant from the National Institute of Aging funds the "Memory and Aging Project" under the direction of Dr. Bennett. The study plans to enroll 1,200 older persons from throughout the Chicago area who agree to annual testing of cognitive and motor function and organ donation at the time of death.

"Even relatively small reductions of risk from Alzheimer's disease and other common neurological conditions will have a major public health impact for future generations," said Bennett.

"We want to understand how cognitively stimulating activities, from childhood to old age, affect brain structure," Bennett said. "Animal studies suggest that different experiences can affect the structure the brain, including the number of brain cells and the number of synapses, the connections between brain cells. The extent to which this occurs in humans is unknown. But if lifestyle affects the brain structure of humans, it is possible that education and related factors could increase neural reserve and allow the brain to tolerate pathology without manifesting memory loss and other clinical signs."

The Rush researchers believe that there is a redundancy of several cellular and subcellular components of the neural systems responsible for cognitive function, mobility and strength that are crucial for efficient performance of these systems, and that this redundancy could comprise the structural basis of neural reserve.

The researchers suggest that, whereas some risk factors will directly promote the accumulation of Alzheimer's disease pathology in these systems, other risk factors may actually maintain the structural integrity of these systems and reduce the likelihood that Alzheimer's disease pathology will express itself as memory loss and other signs of the disease.

Volunteers in the study will be recruited from Chicago area continuous care retirement centers, retirement facilities, and subsidized senior housing with a goal toward achieving a gender, racial, and ethnic composition comparable to the over-age-65 population in the United States.

"Enrolling participants representing a wide spectrum of lifetime experiences is crucial," according to Bennett. More than 200 seniors from several Chicago area facilities have participated in a pilot study for the Memory and Aging Project, which has been ongoing since 1997.

A detailed interview covering each participant's life history will be administered at the beginning of the study. Participants will subsequently undergo extensive testing of cognitive and motor function each year.

Since the pathology of Alzheimer's disease can only be documented by examining brain tissue under a microscope after death, volunteers will sign an Anatomical Gift Act donating their brains to Rush investigators at the time of death.

Researchers will look at both the pathologic markers of common diseases and several possible structural elements of neural reserve. The pathologic markers will represent the post-mortem features of Alzheimer's disease, Parkinson's disease, and cerebrovascular disease. The structural elements of neural reserve will include neurons, synapses, dendrites, and dendritic spines.

Researchers will examine how different factors are related to these two different sets of post-mortem markers, and whether the structural elements of neural reserve can reduce the extent to which pathology is expressed as clinical disease.

Medical research has made remarkable progress toward increasing life expectancy for older people," said Bennett. "Unfortunately, many people develop problems with memory, walking and weakness as they get older. Although these problems are common, they are not normal," according to Bennett, "since many older people do not develop these problems. Available information suggests that these problems may be caused by neurologic conditions that damage different parts of the nervous system, including the brain, spinal cord, nerves and muscles."
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Researchers at the University of Pennsylvania (Dr. Steven Arnold), MCP Hahnemann University (Dr. Jonathan Nissanov), and the University of British Columbia (Dr. William Honer) are also involved in the study which is currently funded through August of 2006.

Rush University Medical Center

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