Two recent studies may help clinicians and researchers better predict and understand dementia of the Alzheimer's type

Sep 26 2005

Two recent studies may help clinicians and researchers better predict and understand dementia of the Alzheimer's type early in its history.

Both studies appear in the September issue of Neuropsychology, which is published by the American Psychological Association (APA). Psychologists focus on early detection in part because current medications are useful only when given very early in the course of the disease.

In the first study, psychologists Pauline Spaan, PhD, and Jeroen Raaijmakers, PhD, from the University of Amsterdam in collaboration with neurologist Cees Jonker, MD, PhD, from the Vrije Universiteit in Amsterdam analyzed the data on 119 participants in the Longitudinal Aging Study Amsterdam, a large, population-based study of older people. The researchers visited older people in their homes and gave them memory tests loaded on laptop computers. Two years later, they compared the test scores of people who went on to develop Alzheimer's with the scores of those who stayed healthy.

The researchers analyzed memory components that included episodic (what happened; what did you hear or read); semantic (vocabulary, facts); and implicit (learning without awareness of learning, "priming"). Three tests were very good at predicting who would develop Alzheimer's by two years later. Participants for whom "priming" information didn't aid memory or whose learning wasn't aided by semantic knowledge -- were significantly more likely to develop Alzheimer's.

The strongly predictive tests were, in order of their power, a Paired-Associate Learning Test, which cued participants to recall five semantically related and five semantically unrelated pairs of words; and a Perceptual Identification Task, which measured how fast participants read aloud words briefly presented on a computer screen. To test implicit memory, experimenters repeated some words to see whether "priming" took place, which would help participants read those words faster. The researchers also gave a Visual Association Test, which cued participants to recall six line drawings of common objects that had been presented earlier in an illogical interaction with another object or cue.

On the word-pair memory test, people destined to develop Alzheimer's disease didn't do any better when words were related than when they weren't. The authors think these participants may already have lost key knowledge of word attributes that normally help people to more easily remember words by means of their semantic associations. Sometimes, at-risk participants reported a vague sense that one word had something to do with another, but they couldn't say exactly what. The authors suspect they couldn't encode the word pairs at a sufficiently deep level because they'd lost the semantic knowledge that stays intact in normally aging people.

On the word-reading test, word repetition (to measure priming) didn't help high-risk participants to perform better, a sign that they weren't learning implicitly as well as the people who would stay healthy. The authors speculate that because high-risk participants drew less benefit from word repetition, they did not encode the words properly.

These tests remained sensitive to the risk of developing Alzheimer's disease even within a more homogeneous subset of the broader study population, people with mild cognitive impairment. For both the whole and subset study groups, these tests predicted future Alzheimer's diagnosis as much as two years early.

Equally important, the popular Mini Mental Status Exam (MMSE), a test mainly sensitive to episodic memory, was not as good a predictor. Although clinicians use it for quick, easy-to-administer screening, the authors found it to be "less predictive [than the tests sensitive to semantic and implicit memory]. These [MMSE and other purely episodic memory] tasks may only differentiate between pathological and normal aging when dementia has progressed to a more advanced stage."

In the second Neuropsychology study, an established psychological test has picked up early-warning signs of Alzheimer's disease. A new study in the September issue of Neuropsychology explains how the dichotic listening task, which measures how well people process information when they hear one thing in the left ear and another in the right ear, confirms that very early in the disease, people have problems with selective attention. This problem, although not as obvious as memory loss, may also explain why early-stage patients start to struggle with everyday tasks that call for processing a lot of information – such as driving.

At the Alzheimer's Disease Research Center at Washington University in St. Louis, Janet Duchek, PhD and David Balota, PhD, studied 94 participants in their early to mid-70s with healthy, very mild, or mild dementia of the Alzheimer's type. They looked for information-processing breakdowns suspected to happen early in the disease, before the appearance of language and visuospatial problems. Problems with attention, the authors say, could "underlie the difficulty with daily activities often seen in the early stages of the disease."

Duchek and Balota used a dichotic listening task, presenting information to participants via headphones. One stream of information – computer-generated speech naming three digits (such as 4, 3, 1) – went to the left ear; a different stream (such as 9, 2, 5) went to the right ear. The psychologists measured how well participants recalled the digits presented to each ear.

As predicted, people with early dementia remembered the digits presented to the right ear far better than they recalled the digits presented to the left ear. When the researchers controlled for overall recall performance, the mild dementia group recalled 21.7% more information from their right ear vs. left ear, and even the very mildly affected group recalled 11.3% more from the right ear. The control participants only recalled 5.8% more from the right vs. left.

Clearly, people with mild or very mild Alzheimer's relied more heavily on the default pathway for processing information, which for language would be the left side of the brain. In other words, these patients had a harder time switching their attention and reporting what they heard in the left ear, which sent information to the right half of the brain.

The right-ear advantage increased with dementia severity. People farther along in the disease relied even more on the dominant left-side channel; in other words, they found it even harder to override the usual path to process what went through the left ear to the right brain. The study confirms that attentional processing, like other cognitive processes, is affected early in Alzheimer's disease. Poor attentional controls can leave people falling back on familiar, "pre-programmed" information pathways. Write the authors, "One can speculate about the importance of attentional control in everyday tasks, such as driving." Their speculation is supported by prior findings that performance on dichotic listening predicts accident rates in commercial bus drivers.