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At the outset, Alzheimer’s disease subtly disrupts some mental abilities, leaving others intact. So, well before a person develops clear cognitive impairment, his or her performance declines slightly on a few measures. When shown on a graph, these changes cause a healthy symmetric, bell-shaped curve to shift and become asymmetrical. (Credit: iStockphoto)

aging

‘Lopsided’ test scores may predict Alzheimer’s sooner

The pattern of scores on cognitive tests may help doctors determine if an older patient’s minor memory loss is benign or a stop on the road to Alzheimer’s dementia.

If confirmed, the finding from a proof-of-concept study could allow physicians to diagnose Alzheimer’s disease far earlier.

"If we are going to have any hope of helping patients with Alzheimer’s disease, we need to do it as early as possible," says David J. Schretlen. "Once the brain deteriorates, there’s no coming back." (Credit: Martin Garrido/Flickr)
“If we are going to have any hope of helping patients with Alzheimer’s disease, we need to do it as early as possible,” says David J. Schretlen. “Once the brain deteriorates, there’s no coming back.” (Credit: Martin Garrido/Flickr)

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“If we are going to have any hope of helping patients with Alzheimer’s disease, we need to do it as early as possible,” says David J. Schretlen, professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “Once the brain deteriorates, there’s no coming back.”

A diagnosis of mild cognitive impairment markedly increases the risk that a patient will develop dementia eventually, even though that relatively minor initial decline does not seriously interfere with daily life, Schretlen says.

But physicians now have no reliable way to predict which people with mild cognitive impairment are likely to be in the 5 to 10 percent a year who progress to dementia.

Schretlen’s team analyzed records of 528 people 60 and older referred for cognitive testing as part of a dementia work-up. The results were compared with those of 135 healthy older adults who participated in a study of normal aging. Both groups had completed tests of memory, language, attention, processing speed, and drawing abilities from which 13 scores were recorded.

Varying levels of dementia

Since anyone is naturally more skilled in some areas than others, the scores of healthy adults can be represented on a graph showing a symmetrical, bell-shaped range: Most of their scores were high, a few were a bit lower, and a few were even lower.

People with such symmetrical, evenly distributed scores were not likely to develop dementia, even if those scores were relatively low. But those with clearly lopsided test score distributions on the 13 tests were already experiencing varying levels of dementia, the researchers found.

“Departures from the normal bell-shaped pattern of variability on cognitive tests might determine which people with low scores develop dementia,” says Schretlen, leader of a study published in the journal Neuropsychology.

Asymmetrical bell curve

At the outset, Alzheimer’s disease subtly disrupts some mental abilities, leaving others intact. So, well before a person develops clear cognitive impairment, his or her performance declines slightly on a few measures. When shown on a graph, these changes cause a healthy symmetric, bell-shaped curve to shift and become asymmetrical.

Since these declines can be subtle, the researchers also increased the precision of cognitive testing by accounting for the effects of age, sex, race, and education on test performance.

The challenge for doctors, is that most normal, healthy people will produce a few low scores on cognitive testing. That makes it nearly impossible to know at the outset whether a patient who reports forgetfulness and produces one or two low scores has a benign form of mild cognitive impairment or is in the earliest stage of dementia. As a result, doctors often tell such patients to return for follow-up testing in a year or two.

But if future research confirms it, this new statistical model could help doctors get the prognosis right earlier in the disease, at the first visit, and start treating patients accordingly. Doctors could use the new model to reassure patients who are not at risk of dementia, while starting interventions for those who are, Schretlen says.

Time for Alzheimer’s counseling

Because there currently are no effective medical treatments for Alzheimer’s disease, those likely headed that way could be counseled to take the good time they have to organize their affairs and do things they have always wanted to do. They also could be fast-tracked into any clinical trials of medications designed to slow the progression of dementia.

The main reason it is difficult now to tell whether older people have benign mild cognitive impairment or early stage dementia is that they have not been routinely screened for cognitive impairment, Schretlen says.

A visit to a specialist comes only after someone has noticed symptoms, and then cognitive testing is interpreted without the benefit of a baseline assessment. What would solve this problem, he says, would be for everyone over the age of 55 to get routine neurocognitive testing every five years.

The Therapeutic Cognitive Neuroscience Fund; the Benjamin and Adith Miller Family Endowment on Aging, Alzheimer’s and Autism; the William and Mary Ann Wockenfuss Research Fund Endowment; and the National Institutes of Health.

Under an agreement with Psychological Assessment Resources Inc., Schretlen is entitled to a share of royalties on sales of a test and software used in the study. The terms of this arrangement are being managed by Johns Hopkins University in accordance with its conflict-of-interest policies.

Source: Johns Hopkins University

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