Research Profile - It’s more than just memory

Most people find their memory starts to decline as they get older – but it takes more than just a failing memory to identify people at risk of Alzheimer's disease.

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That's why, by the time many people are diagnosed with Alzheimer's disease, much damage has already been done to their brains. And that damage isn't going to be reversed.

Dr. Sylvie Belleville of the Institut universitaire de gériatrie de Montréal wants to find a way to recognize the early signs of Alzheimer's and catch people earlier in the process. And, she says, there are good reasons for doing so.

First, even though there's no medication today that can slow the progression of the disease, there's nothing to say that this lack of a treatment is permanent. And, when a medication is developed (see the stories about Dr. Donald Weaver's and Dr. Lili-Naz Hazrati's efforts to develop such a medication in this series), the earlier people can start taking it, the more damage can be prevented. But even in the absence of a medication, there's a lot that people can do in terms of lifestyle to slow down the progression of the disease – things like physical activity and cognitive stimulation of various sorts.

The problem is, nearly everyone complains of their memory failing as they get older (though the complaints may not be entirely justified, Dr. Belleville says – studies show that changes in memory as we age are actually quite small, and tests show considerable overlap between young adults and healthy older adults in terms of memory). But how do you distinguish those who just have mild cognitive impairment from those who are showing the early signs of Alzheimer's disease?

With the help of funding from the Canadian Institutes of Health Research, Dr. Belleville has identified a series of tests that, taken together, can predict the fate of up to 80% of the older adults who take them – some of whom will remain stable with mild cognitive impairment and some whose results are consistent with the early stages of Alzheimer's disease.

Standard memory tests are part of the package, of course, with subjects asked to retell a short story that's been told to them. But so are attention tests, which involve switching back and forth from adding to subtracting numbers and test mental flexibility and executive function. And, surprisingly, Dr. Belleville says, perceptual tests are also important – such as tests where subjects are asked to assess which of two lines is longer.

"I was very surprised, because it shows that if you want to build a test sensitive and specific to Alzheimer's disease, you should not just include memory tests," she says.

Dr. Belleville is excited about her findings, mostly because of the nature of the tests.

"These are really low-cost and non-invasive procedures," she says. "They're easy for clinicians to do in their own offices."

Now Dr. Belleville has two goals. First, she wants to make sure clinicians know that this combination of tests can identify people in the very early stages of Alzheimer's disease. Once her findings are published, this will be a priority.

She also wants to combine her "low-tech" approach with higher-tech approaches such as brain imaging, to better help the 20% of people whose future isn't captured by the current set of tests. As well, she says, brain imaging will help to identify the people who suffer from vascular dementia as well as Alzheimer's disease.

"We have tended to look at the 'pure' cases," she says. "But in the real world, people have co-morbidities, like both vascular dementia and Alzheimer's."

The Study

Alzheimer's disease is a progressive disease – as it goes along, it causes increasing damage to the brain. The first signs of the disease, however, are very similar to what is found in the normal course of aging, making early diagnoses difficult. Dr. Sylvie Belleville is following people who complain to their doctors about their memories. She gives them a neuropsychological assessment and then follows them on an annual basis to see which of them go on to develop Alzheimer's disease. She then goes back to the patients' initial test results to see if there were any factors that were present early on that foreshadowed their progression. She has found that certain tests, including tests of memory, attention and perception, can together accurately predict the future for about 80% of people – whether they are simply experiencing mild cognitive impairment or whether they are experiencing the early signs of Alzheimer's disease.

"It's relatively easy to diagnose people two or three years into the disease. The difficult part is to recognize Alzheimer's early in the process."
- Dr. Sylvie Belleville, Institut universitaire de gériatrie de Montréal