New Cognitive Stress Test Can Detect Early Signs of Alzheimer’s Disease

“We could see a clear difference between people who had normal cognition and those with preclinical stages of cognitive impairment,” said David Loewenstein, Ph.D., professor of psychiatry and behavioral sciences. “The study confirmed that this test is very sensitive to early memory impairment. In addition, the results were clearly associated with the level of abnormal amyloid protein in the brain, a key risk factor for developing Alzheimer’s disease.”

Loewenstein was lead author of a recent study, “A Novel Cognitive Stress Test for the Detection of Preclinical Alzheimer’s Disease: Discriminative Properties and Relation to Amyloid Load,” published in the American Journal of Geriatric Psychiatry. Other Miller School co-authors were Rosie E. Curiel, Psy.D., assistant professor of clinical psychiatry and neuropsychology, and Elizabeth Crocco, M.D., associate professor of clinical psychiatry and Director of the Geriatric Psychiatry Training Program in the Department of Psychiatry and Behavioral Sciences. The study was supported by a $2.7 million grant from the National Institutes of Health.

The study focused on 93 older adults who took the Loewenstein-Acevedo Scales of Semantic Interference and Learning (LASSI-L), a test developed by Loewenstein and Amarilis Acevedo, Ph.D., a researcher in the Department of Psychology at Nova Southeastern University.

“Alzheimer’s patients tend to make errors in memorizing and recalling a list, such as replacing the word ‘bracelet’ with ‘necklace’ or ‘lighter’ with ‘matches,’” said Loewenstein, who has been studying semantic interference for the past 20 years. “Drawing on that finding, we created a test that deliberately challenges participants to see their susceptibility to semantic interference effects and how quickly they can recover from these effects.”

Loewenstein said LASSI-L uses controlled learning and cued recall strategies to help participants remember a list of common words for fruits, musical instruments or articles of clothing. Next, a similar list but with different words from the same three categories is presented, producing a cognitive effect called proactive semantic interference (PSI). Finally, the individual is again given the second list to measure recovery from the initial PSI effects.

“The inability to recover from PSI has been shown in previous studies to predict mild cognitive impairment,” Loewenstein added.

The test takes about 15 minutes, but can also be condensed into a two-minute screening tool in primary care clinics, Loewenstein said.

“This is a very culture-fair test,” he added, noting that the LASSI-L has already been translated into several languages and is used in Italy, Spain and Argentina, as well as in the U.S.

Loewenstein said the LASSI-L test could be used to provide a baseline to help clinicians monitor cognitive changes in older adults over time.

“We think it can also be an effective way to monitor treatment outcomes as more effective pharmacology trials for Alzheimer’s disease become more prevalent.”

LASSI-L assessments may also help researchers find appropriate participants for future clinical studies.

“Fewer subjects would be needed for clinical trials because we can identify participants with cognitive impairments and the biological underpinnings of Alzheimer’s disease before symptoms appear,” he said. “That capability to determine appropriate subjects could speed the process of developing and testing new therapies.”

Two other large-scale studies of the LASSI-L are under way, with Loewenstein as the principal investigator. These studies, which are supported by NIH grants, involve larger numbers of patients, who will be followed for several years.

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