Alzheimer patients who scored well on memory tests – show unique compensatory brain activity

Study is first link ’compensatory prefrontal network’ to better performance on memory tests

A group of Canadian researchers has found the most direct evidence to date that people with early-stage Alzheimer Disease can engage additional areas in the brain to perform successfully on memory tests.

Led by Dr. Cheryl Grady, a senior scientist with The Rotman Research Institute at Baycrest Centre for Geriatric Care, the study is published in the February 1, 2003 issue of the Journal of Neuroscience.

Alzheimer’s is a progressive, degenerative disease that affects an individual’s ability to think, remember, understand and make decisions. People with early-stage Alzheimer’s begin to experience problems with their episodic and semantic memory. Semantic refers to the accumulation of general world knowledge gained over a lifetime (for example, names of countries, famous people, major historical events). Episodic refers to events that one experiences throughout his/her life (for example, having visited the dentist yesterday, or graduating from college back in 1950).

While previous neuroimaging studies have confirmed that individuals in the early stages of the disease show ’increased’ activity in the brain’s prefrontal regions when performing cognitive tests (compared with healthy age-matched controls), Dr. Grady and her team of investigators have found the first direct link between this compensatory brain activity and successful performance on semantic and episodic memory tests.

“We found that patients who were able to recruit the prefrontal cortex of the brain ’to a greater degree’ than other patients, performed more accurately on memory tests,” says Dr. Grady, who is also Professor in Psychiatry and Psychology at the University of Toronto.

While she cautioned that this compensatory effect does not last forever and diminishes as the disease progresses, she hopes her team’s findings will inspire further research. “The development of compensatory responses in relation to early cognitive changes in Alzheimer’s is an area in need of more investigation,” she says. “The goal, until more definitive preventive treatment is found, is to develop more effective treatments that extend this compensatory effect and delay the degenerative effects of Alzheimer’s for longer periods.”

In the study, 12 healthy older adults and 11 older patients with probable early-stage Alzheimer’s participated in a series of semantic and episodic memory tasks that were flashed on a computer screen. All of the Alzheimer’s patients were taking medication for their cognitive impairment. Participants’ brain activity was monitored using positron emission tomography (PET), which measures blood flow to various regions of the brain.

In the semantic exercise, a word or object appeared on either the right or left side of the screen, and a visual noise pattern appeared on the other side. Participants were instructed to make a living/non-living decision about each object or word by pressing the left mouse button if the object/word represented something living, and the right button if it were non-living. During the episodic recognition task, objects or words were presented on either side of the screen — one new stimulus and one that was seen previously during the semantic task. Participants pressed the button corresponding to the side of the screen on which the ’old’ item was presented. All trials lasted four seconds, with a one-second interval blank screen.

Overall, Alzheimer’s patients performed less accurately on the semantic and episodic tasks compared to the normal, healthy controls. However, the range of scores was quite large in the Alzheimer group, with some performing poorly and others performing within the normal range. For those patients who did better on the memory tasks, researchers found that their prefrontal network activity was more expansive compared to the error-prone patients. This additional activity was happening in the right frontal and temporoparietal areas. It was a unique neural pattern not found in the normal, healthy controls either.

The study was funded by the Canadian Institutes of Health Research and the Alzheimer Society of Canada. The research team included Dr. Sandra Black, Head of Neurology and senior scientist at Sunnybrook and Women’s College Health Sciences Centre, as well as other scientists with The Rotman Research Institute at Baycrest Centre for Geriatric Care. Dr. Black is also a senior scientist at the Rotman. Baycrest is fully affiliated with the University of Toronto.

Dr. Cheryl Grady is internationally-recognized for her research which uses brain imaging to explore the functional changes that occur in aging and how these relate to changes in behaviour. In previous research, she has identified similar compensatory activity going on in the frontal regions of healthy older adults as they performed memory and recognition tests alongside younger adults. As brains age, do they find ways to compensate for cognitive decline? The answer, says Dr. Grady, could have exciting implications for memory rehabilitation.