Protecting Your Brain with Cognitive Activity

By Cordula Dick-Muehlke, Ph.D.

The discovery in mice, and now in humans, that cognitive stimulation during early life can reduce Alzheimer’s disease (AD) pathology is just one example of how basic science at UCI MIND is leading the way toward more effective treatments, prevention strategies, and ultimately a cure for AD.

A team of UCI researchers, including Dr. Lauren Billings, Dr. Kim Green, Dr. James McGaugh, and Dr. Frank LaFerla, Director of UCI MIND, were the first to demonstrate that early and repeated practice could improve acquisition and retention of a spatial water maze task in transgenic mice programmed to develop AD, as well as reduce levels of toxic amyloid beta (Aβ) and tau proteins in the animals’ brains.

Interestingly, transgenic mice trained repeatedly, from age 2 months on, to escape a water maze (i.e., swim to and crawl onto a floating platform), were able to learn this task as well as healthy mice at 12 months old. In comparison, transgenic mice that only received training at 12 months of age had severe difficulty learning the water maze task. Upon examining the brains of the 12-month old transgenic mice, the researchers found less Aβ and tau neuropathology in the animals receiving repeated practice than those trained only once. Despite the reduction in AD pathology at 12 months, the advantage of repeated practice for both learning and retention were lost by 18 months in transgenic mice that continued to receive training. While the effects on learning and memory were transient, the finding that cognitively stimulating transgenic mice throughout life can delay both the emergence of AD neuropathology and clinical symptoms laid the groundwork for human studies.

As hoped for, Dr. Susan Landau and her colleagues at the University of Berkeley recently demonstrated that cognitive activity in early and midlife can similarly reduce Aβ deposition in humans.

Participants, including 65 cognitively normal older adults, 10 individuals with AD, and 11 young adults, (1) rated their frequency of participation in cognitively demanding activities (e.g., reading books or newspapers, writing letters or emails, playing games) currently and at ages 6, 12, 18, and 40 on a 1 (once a year or less) to 5 (every day or almost every day) point scale and (2) underwent a PET (positron emission tomography) scan using a new compound that has made it possible to image accumulation of the Aβ protein in the brain.

Greater participation in complex cognitive activities across the lifespan, but particularly in early and midlife, was associated with lower Aβ accumulation or amyloid burden in the brain. Analyses separated the healthy older adults into thirds (i.e., highest, middle, and lowest) based on their cognitive activity scores. Cognitively normal older adults with scores in the lowest tertile had significantly greater Aβ accumulation than their peers with scores falling in the middle and highest thirds. In fact, amyloid burden in the cognitively normal older adults with the lowest scores was similar to that in AD patients, with brain images resembling each other. In a related study led by Dr. Michael J. Valenzuela at the University of New South Wales, researchers also found that older adults with greater lifelong participation in complex mental activities showed less atrophy in the hippocampus, an area of the brain that important for learning, storing, and processing memories.

Clearly, ensuring brain health is a lifelong endeavor. Interesting your children and grandchildren in cognitive activities, as simple as reading and playing games, could save their brains from the devastation of Alzheimer’s disease. And, if you’re an older adult, it’s never too late to start challenging yourself cognitively. In one of many studies demonstrating the value of cognitive engagement for older adults, Dr. Charles Hall of the Albert Einstein School of Medicine found that older adults who spent the most time participating in mentally stimulating activities such as crossword puzzles, card games, reading, writing, playing music, or group discussions, developed significant cognitive problems 1.3 years later than their peers who spent the least time engaged in such activities. For suggestions on how to exercise your brain, see the sidebar on the front of this news brief.

Billings, L. M., Green, K. N., McGaugh, J. L., & LaFerla, F. M. (2007). Learning decreases Aβ and tau pathology and ameliorates behavioral decline in 3xTg-AD mice. Journal of Neuroscience, 27, 41-761.
Hall, C. B., Lipton, R. B., Sliwinski, M., Katz, M. J., Derby, C. A., & Verghese, J. (2009). Cognitive activities delay onset of memory decline in persons who develop dementia.
Landau, S. M., Marks, S. M., Mormino, E. C., Rabinovici, G. D., Oh, H., O’Neil, J P., Wilson, R. S., & Jagust, W. J. (2012). Association of lifetime cognitive engagement and low β-amyloid deposition. Archives of Neurology, published online first January 23, 2012.
Valenzuela, m. J., Sachdev, P., Wen, W., Chen, X., Broadaty, H. Lifespan mental activity predicts diminished rate of hippocampal atrophy. PLoS One, 2008, 3(7):e2598. Doi:10.1371/journal.pone.0002598

Greater participation in complex cognitive activities across the lifespan, but particularly in early and midlife, was associated with lower Aβ accumulation or amyloid burden in the brain.

Challenge Your Brain

  • Engage in mind-stimulating activities. Example: Play chess, bridge, or board games
  • Learn something new every day. Example: Look up unfamiliar words; then try to use them in conversation.

  • Find opportunities to interact with others. Example: Join a book club to stimulate your intellect and meet new people.

  • Deliberately change your routine. Example: Shop at a different grocery store than usual.

  • Test your sense of direction. Example: Take a new route to work.

  • Challenge your sense of touch. Example: Sort coins while blindfolded.

  • Switch sides. Example: Use your non-dominant hand for routine activities such as brushing your teeth.