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'SuperAgers' could hold key to Alzheimer's code

Is Alzheimer's disease really a disease that can be cured, like cancer, or is it a product of aging, like skin wrinkles and hearing loss — a form of degeneration that affects just about everybody as they get older? • Researchers have been defining Alzheimer's as a disease distinct from the aging process, says Ming Chen, a professor of molecular pharmacology and physiology at the University of South Florida. He believes this approach obscures the fact that the risk of dementia increases with age, which suggests it can only be postponed, like heart disease, but never really cured.

"To researchers, Alzheimer's disease connotes a discrete disease," said Chen. "Thus, over 90 percent of the Alzheimer's studies funded by the National Institutes of Health are on mutations, toxic amyloid, pathogens, and so on. And that is why after three decades and billions of dollars spent, more than 90,000 research papers published, and numerous great breakthroughs claimed, the condition remains a persistent enigma."

Chen is the co-author of two articles in the December issue of the Journal of Alzheimer's Disease that encourage scientists to stop searching for "silver bullets" to eradicate the disease, and focus instead on finding ways to modify the disease process through lifestyle changes and perhaps medication. That's how we deal with other age-related disorders, which are considered a normal part of aging unless they occur earlier in life, according to Chen. For example, senile hearing loss is a consequence of age, of damage to the hearing system that accumulates gradually over many years. Childhood hearing loss, in contrast, should be regarded as a disease, something that shouldn't happen to young people.

Similarly, the first case of Alzheimer's disease, diagnosed by Alois Alzheimer in 1906, involved a 51-year-old woman who developed a rapidly progressing form of dementia that Alzheimer attributed to the clumps of amyloid protein he spotted between her neurons when he examined them under the microscope after her death, and the tangles of tau protein he saw within her neurons.

Since then, Alzheimer's disease has been viewed as a single disease. But like childhood hearing loss, the dementia that this woman developed at an early age might have differed significantly from the brain degeneration that becomes increasingly common with age. For many years Alzheimer's disease was considered "presenile" dementia, a form of brain degeneration that takes place in middle age.

In recent years, however, this distinction has been lost as researchers have focused on ways to eradicate Alzheimer's pathology altogether.

But brain cells, like all other cells in the body, become more frail and vulnerable to breakdown with age, Chen says, and while this process, known as senescence, cannot be cured, diet, exercise, and certain medications may help postpone the inevitable.

"We propose that advanced aging plus risk factors best explain most senile dementia cases," Chen and his colleagues argue.

And yet, if dementia comes with age, why do some people in their 80s retain the mental acuity of people 30 years younger?

Researchers in Chicago are trying to answer that question by studying what they call "SuperAgers," a diverse group of older people whose brains appear to defy the ravages of time.

The biggest difference they've found so far in the SuperAgers involves brain shrinkage, which takes place in virtually everyone with age. Over time, neurons die, and the fatty white myelin that wraps around the brain's transmission fibers becomes thinner, leaving a brain that is smaller than it used to be.

The SuperAgers, according to Emily Rogalski, who is leading the study, show virtually no "cortical shrinkage," as she calls it. By conducting MRI scans, she and her colleagues at Northwestern University's Feinberg School of Medicine have determined that the SuperAgers show "no significant difference in cortical thickness compared to people in their 50s," Rogalski said. One part of the brain implicated in Alzheimer's disease, the anterior cingulate, was even thicker in some of the SuperAgers.

And remember those plaques and tangles that Dr. Alzheimer found in the brain of his demented patient? The brains of some SuperAgers are riddled with them, even though their cognition appears to be much better than normal for their age. Those familiar hallmarks of Alzheimer's disease, which researchers have spent so much time, energy, and money trying to eradicate, don't seem to affect the SuperAgers at all.

"Why?" Rogalski asks herself, admitting that she is perplexed by such an unexpected finding. "There has to be a reason for this."

Tom Valeo writes frequently about health matters. He can be reached at tom.valeo@gmail.com.

'SuperAgers' could hold key to Alzheimer's code 12/20/11 [Last modified: Tuesday, December 20, 2011 3:30am]
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