Brain Exercise Delays The Onset of Dementia

Anne Harding

A new study in Bronx seniors provides yet more evidence that keeping your brain active for fun can keep dementia at bay.

Dr. Charles B. Hall of the Albert Einstein College of Medicine in Bronx, New York, and his colleagues found that every day per week that a person engaged in one of six mentally stimulating leisure activities delayed the onset of dementia by about two months.

Hall and his colleagues had previously shown that people with more years of education who developed dementia did so later than less educated individuals. In the current study, he said, "it was the cognitive activity that mattered, not the education."

In the current study, published in Neurology, Hall and his team looked at 101 people who developed dementia. All were participating in the Bronx Aging Study, which has been following 488 people since the early 1980s.

All of the study participants, who ranged in age from 75 to 85, had reported their years of formal education at the study's outset, as well as how often each week they read, wrote, did crossword puzzles, played board or card games, participated in group discussions, or played music. A person scored 1 for each day that they did each activity. The study participants, all of whom were dementia free at the beginning of the study, underwent cognitive testing every 12 to 18 months.

The higher a person's score on the activity scale, the later the onset of accelerated mental decline, Hall and his colleagues found. For example, a person in the top 25 percent based on their activity scale, who engaged in 11 "activity days" a week, started their accelerated decline 1.29 years later, on average, than a person in the bottom 25 percent, with four activity days a week.

But once that decline began, it happened faster in people with higher activity scores.

The findings back up the idea of "cognitive reserve," Hall noted, which is the theory that education and brain exercise build extra capacity into the brain so it can better handle the damage to neurons caused by Alzheimer's disease. But once that damage reaches a certain point, a person will develop dementia.

Being more mentally active "might keep you out of a nursing home for a year or two," Hall said. "But it's not going to prevent Alzheimer's disease unfortunately, at least that's the theory, and this is evidence toward that theory." Eventually, he said, the disease "would overwhelm whatever reserve you had."

Hall and his colleagues are now investigating which of the six activities in the current study might give the most brain-preserving "bang for the buck." Studies will need to tease out whether education and later-life mental activities have effects that are independent of one another.

With what we know now, he added, engaging in these activities could help-and it certainly won't hurt. "You might get depressed from not being able to do a crossword puzzle, but there's really very little of a downside here."

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New Vaccine To Control Immune System Of Alzheimer's Sufferers

Researchers at the NYU Medical Center believe that a new vaccine can harness the immune system in Alzheimer. The vaccine can fight the pathological form of tau protein, a key protein related to Alzheimer’s disease.

The researchers created the vaccine in mice that suppresses aggregates of tau protein which otherwise amasses into dangerous tangles in the memory center of the brains of Alzheimer’s patients. The research was led by Einar Sigurdsson Ph.D., Assistant Professor of Psychiatry and Pathology at New York University School of Medicine.

The vaccine successfully slowed the deterioration of motor abilities produced by excessive amounts of tau in the central nervous system of mice, according to the study published in the August 22, 2007 issue of the Journal of Neuroscience. Dr. Sigurdsson plans to conduct follow-up studies using mice that slowly develop tangles and cognitive impairments without movement problems.

The study used mice that were genetically engineered to produce abnormal tau proteins early in life. These became entangled in several regions of the central nervous system. The resulting loss of motor coordination was significantly reduced in those immunized with a specific piece of the detrimental tau protein. By producing antibodies that could enter the brain and bind to irregular tau, the immune system prevented their harmful aggregation and associated behavioral impairments.

“This approach may have extensive therapeutic implications because you can specifically target the problematic protein,” said Dr. Sigurdsson. “Tau aggregates are inside the cell, making it especially difficult to develop a therapy to target and clear them from the cell.” Alzheimer’s disease is estimated to affect five million Americans. While treatments exist that may modestly alleviate its symptoms, none delay or prevent the onset of the disease, according to the Alzheimer’s Association.

The disease is associated with neurons in the memory center of the brain becoming choked by the buildup of two types of proteins: tau, which turns destructive when it is prone to forming fibrous tangles, and amyloid beta. Compared to extracellular amyloid plaques, tau aggregates are confined inside of brain cells, making them more difficult to reach.

“It’s likely that there’s a synergism in the pathology,” said Dr. Sigurdsson. “Amyloid pathology may cause tau pathology and tau pathology might cause more amyloid pathology. What you have is a vicious cycle. If you can target both of these proteins you’ll likely have more efficacious treatment.”

The therapeutic approach is based on using fragments of abnormal tau protein as a vaccine. These fragments are studded with phosphate groups, which are thought to promote the aggregation of tau. The antibodies generated by the vaccine are therefore likely to bind to abnormal tau and promote its breakdown. Normal tau, which would be far less affected, has such important biological functions as facilitating transport of chemicals within neurons and maintaining their structure.

In previously published studies and in ongoing work, Dr. Sigurdsson has been developing ways to target the amyloid beta peptide, the other major hallmark of Alzheimer’s disease. Those experiments employed a different but complementary approach and were performed in collaboration with NYU School of Medicine’s Thomas Wisniewski, M.D., Professor of Neurology, Pathology and Psychiatry, David Quartermain, Ph.D., Professor of Neurology and Neuroscience and Physiology and Blas Frangione, M.D., Ph.D., Professor of Pathology and Psychiatry.

The transgenic mice in the new study were predisposed to forming tau tangles early in life. Although a decline in motor abilities had progressed by eight months, the mice still remained healthy enough to walk, feed and attempt simple behavioral tasks. But the mice did not undergo thorough cognitive testing, which requires intact mobility to navigate various mazes.

The battery of behavioral tests at five and eight months of age showed that immunized mice performed better—they traveled faster during exploratory activity, exhibited better balance on a rotating rod and committed less foot-slips while traversing a narrow wooden beam. These mice were also found to have less tau protein tangles in the brain. Object-recognition test showed that immunized mice and their controls remained cognitively normal, although mental deficits were expected to appear after the maximum 8-month period allowed in the study.

The mice in the study also had tau aggregates in the hippocampus, a brain region important for cognition and memory. The vaccine cleared tangles in this region as well, suggesting the immunotherapy could improve cognition.

The antibodies raised by the vaccine must reach the brain by traversing the organ’s protective blockade, the blood brain barrier. “Normally antibodies aren’t getting into the brain in any large quantities,” said Dr. Sigurdsson. “In this animal model—and also in Alzheimer’s disease—there’s a breakdown of the blood brain barrier.

In addition, it is well established that neurons have receptors that can bind to and promote uptake of antibodies and our studies seem to indicate that sick neurons that are accumulating tau aggregates take up more antibodies than healthy neurons. The antibodies then end up at the site where they can interact with pathological tau protein in the neuron, and promote its clearance.”

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