A new study using PET scans to to examine the brains of healthy older people finds those who have been mentally stimulated all their lives, doing things like reading, writing, and playing games and puzzles, have fewer deposits of beta-amyloid, a destructive protein that is a hallmark of Alzheimer’s Disease. The researchers suggest their findings will encourage scientists to think differently about how mental stimulation affects the biology of the brain.

A team from the University of California, Berkeley led the study, and with their colleagues, write about their findings in a report published online in the Archives of Neurology on Monday. Funds for their work came partly from the National Institutes of Health and partly from the Alzheimer’s Association.

Beta-amyloid deposits are fibrils of proteins that have misfolded into fibrous sheet structures that accumulate in the brain and clog up the spaces between brain cells. They are the prime suspect in the pathology of Alzheimer’s Disease and a much pursued goal by researchers in this field is to find a way to reduce them.

Previous studies have already suggested that keeping the brain active by pursuing activities that challenge thinking skills, such as reading, writing and playing games, may help put off Alzheimer’s Disease later in life. But none has yet pointed to a link with the underlying suspected biology.

Lead author Susan Landau, a research scientist at the Helen Wills Neuroscience Institute and the Berkeley Lab, said in a statement:

“This is the first time cognitive activity level has been related to amyloid buildup in the brain.”

Dr. William Jagust, a professor with appointments at UC Berkeley’s Helen Wills Neuroscience Institute, the School of Public Health and Lawrence Berkeley National Laboratory, led the research. He said the results point us in a new direction about how lifelong mental stimulation affects the brain:

“Rather than simply providing resistance to Alzheimer’s, brain-stimulating activities may affect a primary pathological process in the disease. This suggests that cognitive therapies could have significant disease-modifying treatment benefits if applied early enough, before symptoms appear.”

Amyloid build up is also affected by genes and age (a third of the over-60s have some amyloid build up in their brains), and while we can’t do anything about those, something we can change is cognitive stimulation, such as doing more reading and writing, said the researchers.

But it seems the message about this has to go out early, before the disease sets in.

Landau said:

“Amyloid probably starts accumulating many years before symptoms appear. So it’s possible that by the time you have symptoms of Alzheimer’s, like memory problems, there is little that can be done to stop disease progression.”

The study participants were 65 healthy older adults (mean age 76), 10 patients with Alzheimer’s Disease (mean age 75) and 11 young people (the controls, mean age 25). The setting was Berkeley, California, and the period of study was from October 2005 to February 2011.

The researchers used two sources of data: one came from PET scans of the participants’ brains and the other from questionnaires where the 65 healthy older participants rated their lifelong participation (since age of 6) in mentally stimulating activities such as reading, writing, and playing games. It also asked them about exercise.

The PET scan method they used employs an imaging agent called carbon 11-labeled Pittsburgh Compound B or [11C]PiB. This compound sticks to amyloid deposits so they can then be “seen” in the PET scan. A reduced “uptake” of [11C]PiB correlates with fewer deposits.

When they analyzed the results of the PET scans with the lifelong mental activity response ratings in the questionnaires, the researchers found:

  • Greater participation in mentally stimulating activities across the lifespan (but particularly in early and middle life), was linked to reduced [11C]PiB uptake.
  • The link was found to be independent of other factors such as memory function, physical activity, self-rated memory ability, level of education and gender.
  • Ranking the older participants by amount of participation in mentally stimulating activities, the top one third had [11C]PiB uptake that was comparable to the younger controls.
  • In contrast, the [11C]PiB uptake of those in the lowest third was similar to that of the patients with Alzheimer’s Disease.
  • Although greater mentally stimulating activity was linked to more physical exercise, exercise itself was not linked to [11C] PiB uptake.

The researchers conclude:

“We report a direct association between cognitive activity and [11C]PiB uptake, suggesting that lifestyle factors found in individuals with high cognitive engagement may prevent or slow deposition of [beta]-amyloid, perhaps influencing the onset and progression of AD [Alzheimer’s Disease].”

They also point out they did not find a strong link between signs of amyloid deposit and levels of current cognitive activity.

Landau said this suggests that a “whole lifetime of engaging in these activities has a bigger effect than being cognitively active just in older age”.

However, the researchers don’t wish to downplay the importance of increasing brain activity later in life.

Jagust said “there is no downside to cognitive activity”. It can only do good, even if for reasons other than reducing amyloid deposits in the brain:

“And actually, cognitive activity late in life may well turn out to be beneficial for reducing amyloid. We just haven’t found that connection yet,” he added.

The number of Americans living with Alzheimer’s disease is rising as the baby boomer generation ages. There are around 5.4 million Americans living with Alzheimer’s, the sixth-leading killer in the US, where deaths from the disease went up by 66% between 2000 and 2008.

There is no cure for Alzheimer’s, but last week the US Health Authorities set 2025 as the deadline for coming up with an effective treatment.

Written by Catharine Paddock PhD