Learning slows physical progression of Alzheimer's disease

Study suggests keeping brain active may have significant therapeutic value

Irvine, Calif. -- Learning appears to slow the development of two brain lesions that are the hallmarks of Alzheimer's disease, scientists at UC Irvine have discovered. The finding suggests that the elderly, by keeping their minds active, can help delay the onset of this degenerative disease.

This study with genetically modified mice is the first to show that short but repeated learning sessions can slow a process known for causing the protein beta amyloid to clump in the brain and form plaques, which disrupt communication between cells and lead to symptoms of Alzheimer's disease.

Learning also was found to slow the buildup of hyperphosphorylated-tau, a protein in the brain that can lead to the development of tangles, the other signature lesion of the disease. Scientists say these findings have large implications for the understanding and treatment of Alzheimer's disease, as it is already known that highly educated individuals are less likely to develop the disease than people with less education.

"This study shows learning can delay the progression of Alzheimer's neuropathology in mice genetically engineered to develop this insidious disorder, and learning also delays the cognitive decline," said Frank LaFerla, professor of neurobiology and behavior and co-author of the study. "These remarkable findings suggest stimulating the mind with activities such as reading books or completing crossword puzzles may help delay and/or prevent Alzheimer's disease in senior citizens."

The study appears in the Jan. 24 issue of the Journal of Neuroscience.

LaFerla; James McGaugh, research professor of neurobiology and behavior; and postdoctoral researchers Kim Green and Lauren Billings studied hundreds of mice between two and 18 months of age that were bred to develop the plaques and tangles characteristic of the disease. Mice in one group were allowed to "learn" by swimming in a round tank of water until they found a submerged platform on which to stand. These mice received training four times a day for one week at two, six, nine, 12, 15 and 18 months of age, and were evaluated at each session for learning and memory abilities. Other groups of untrained mice were allowed to swim in the tank for just one session before their learning and memory skills were tested and their brains examined for plaques and tangles.

Mice up to 12 months of age that learned on previous occasions had fewer plaques and tangles in their brains, and they learned and remembered the location of the escape platform much better than mice not previously allowed to learn. At the 12-month point, the mice that had learned developed levels of beta amyloid and hyperphosphorylated-tau that were 60 percent less than the mice that had not learned; but, by 15 months of age, the mice that had learned deteriorated and were identical both physically and cognitively to the mice that had not learned.

"We were surprised this mild learning had such big effects at reducing Alzheimer's disease pathology and cognitive decline, but the effects were not strong enough to overcome later and more severe pathology," Green said. "We are now investigating if more frequent and vigorous learning will have bigger and longer benefits to Alzheimer's disease."

LaFerla and other colleagues developed the transgenic mice used in this study. These mice, bred to develop the brain lesions associated with Alzheimer's, now are used by scientists worldwide to study the disease.

Alzheimer's is a progressive neurodegenerative disorder that affects more than 4.5 million adults in the United States. With an aging population, that number could approach 20 million by 2050. Alzheimer's is the third-leading cause of death, behind cancer and heart disease. Five percent of people older than 65 have Alzheimer's, and up to one-half of people are affected by age 80.