Some elderly patients with super-sharp memory avoid tau tangle formation or have fewer tangles than are typically present in normal aging.
SAN FRANCISCO—A study of the brains of people who stay mentally sharp into their 80s and beyond challenges the notion that brain changes linked to mental decline and Alzheimer’s disease are a normal, inevitable part of aging.
In a presentation at the 239th National Meeting of the American Chemical Society, Changiz Geula, PhD, and colleagues reported on their findings of elderly people with super-sharp memory—so-called super-aged individuals—who have not experienced the formation of brain tangles. Such tangles consist of an abnormal form of the protein tau that damages and eventually kills nerve cells. Tangles increase with advancing age and peak in people with Alzheimer’s disease.
“This discovery is very exciting,” said Dr. Geula, Principal Investigator of the Northwestern University Super Aging Project and a Professor of Neuroscience at the Cognitive Neurology and Alzheimer’s Disease Center in Chicago. “It is the first study of its kind, and its implications are vast. We always assumed that the accumulation of tangles is a progressive phenomenon throughout the normal aging process. Healthy people develop moderate numbers of tangles, with the most severe cases linked to Alzheimer’s disease. But now we have evidence that some individuals are immune to tangle formation. The evidence also supports the notion that the presence of tangles may influence cognitive performance. Individuals with the fewest tangles perform at superior levels. Those with more appear to be normal for their age.”
Secrets of the Super-Aged
The findings are based on examination of the brains from nine super-aged individuals. Subjects who volunteered for the study underwent a battery of memory and other tests and agreed to donate their brains for examination after death. They are considered super-aged because of their high performance on the tests. The tests included memory exercises to evaluate their ability to recall facts after being told a story and their ability to remember a list of more than a dozen words and recall those words at a later point.
The super-aged individuals recruited for the study so far are older than 80, but they performed the memory tasks at the level of 50-year-olds. The researchers are recruiting more volunteers, with the goal of eventually including about 50 people.
Dr. Geula pointed out that previous studies tended to focus on what goes wrong with the brain as people age. Those studies found that tangles and plaques accumulate at higher levels in the brains of people with Alzheimer’s disease. Dr. Geula said that the new study is unique in its focus on what is right with the brains of older people. The investigators are seeking insight into how lifestyle, genetics, or other factors may protect super-aged individuals from the age-related memory loss that affects most other people.
Avoiding Tangle Formation
The researchers found that super-aged people appear to fall into two subgroups—those who are almost immune to tangle formation and those who have few tangles.
“One group of super-aged seems to dodge tangle formation,” Dr. Geula commented. “Their brains are virtually clean, which doesn’t happen in normal aged individuals. The other group seems to get tangles, but it’s less than or equal to the amount in the normal elderly. But for some reason, they seem to be protected against its effects.”
The next step, according to Dr. Geula, involves determining why one subgroup is immune to tangle formation and the other seems to be immune to its effects. Environment, lifestyle, and genetics may be key factors. For example, some super-aged individuals might have a genetic predisposition to being super-aged, while others may help preserve high brain function by maintaining a healthy diet or staying physically active. Others may reduce the risk of mental decline by engaging in activities that keep the brain itself active, such as reading books, doing crossword puzzles, or engaging in other mentally demanding activities.
“Ultimately, chemistry is one of the keys to understanding what makes these tangles form,” Dr. Geula said. “By understanding the specific anatomic, pathologic, genetic, and molecular characteristics of high-performing brains, we may eventually be able to protect normal brains from age-related memory loss.”
Suggested Reading
Leung E, Guo L, Bu J, et al. Microglia activation mediates fibrillar amyloid-beta toxicity in the aged primate cortex. Neurobiol Aging. 2009 Apr 4; [Epub ahead of print].