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Semantic Decision-Making Corrupted in MCI, AD


Patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) are consistently slower and less accurate than healthy control persons in making semantic decisions in response to stimuli with words and images, new research shows.
Brady Kirchberg and colleagues at Hofstra North Shore–Long Island Jewish School of Medicine, Manhasset, New York, found that both MCI and AD groups were not only less accurate and slower than healthy control participants in making semantic decisions in response to word stimuli but also that the deficit worsened as the sizes of the objects being compared became more similar.
When line drawings were used as stimuli, the size of the drawings themselves had an undue influence upon semantic knowledge judgments in the 2 groups, investigators add.
Performance on the semantic distance task was also a "strong and significant" predictor of everyday functional capacity.
Dr. Terry Goldberg
"When MCI/AD patients have to make decisions about the size of real-world objects, they are less accurate than controls, and that gets amplified when they have to make fine-grained decisions about the size of these things in the real world," Terry Goldberg, PhD, who was the principle investigator of the study, toldMedscape Medical News.
"So making these size distinctions becomes increasingly more difficult for patients with MCI and AD, and we think it's because semantic knowledge gets corrupted with advancing disease, especially disease in the temporal lobe."
The study was published in the December issue of the American Journal of Psychiatry.
Semantic Processing
For the study, investigators studied semantic processing in 25 patients with amnestic MCI; 27 with mild to moderate AD; and 70 healthy control participants.
To do so, they used a novel paradigm that does not require overt word retrieval but rather capitalizes on "distance effects" in the semantic system.
Semantic memory was then assessed using a semantic distance task in which participants had to judge which of 2 entities, presented as images or words, was larger in the real world.
Semantic distance was also manipulated by adjusting the disparity in real-world size between the 2 entities that were being compared.
Images were also presented either as "congruent," in which the image of the larger real-world object was larger than the image of the smaller object, or "incongruent," in which the image of the smaller object was larger than the image of the larger object.
In addition to their main findings, investigators observed that the MCI/AD groups each had disproportionately more difficulty than control participants when making accurate responses in comparisons involving small semantic distances.
The same 2 groups were also disproportionately slower in making responses to contrasts involving small semantic distances.
Collapsing across image congruency conditions, the MCI/AD groups also demonstrated steeper declines in performance as they went from easier to harder small-distance conditions.
Across this task, performance declined 8 percentage points for healthy control participants, 11 percentage points for the MCI group, and 12 percentage points for the AD group.
Critically, investigators add, abnormalities in semantic processing were related to compromises in everyday functional competence as measured by the UCSD Performance-Based Skills Assessment tool.
"You could say these people had a word finding problem — they knew the answers, they just couldn't find the word, but this was nonverbal, so it's not that people can't come up with the word," Dr. Goldberg said.
"So this reflects loss of knowledge — they once had knowledge, but because of disease, the neurons become less functional, and they die. At the same time, we showed this kind of processing impairment compromises how a person does in terms of everyday function, so these problems impact on daily function for the worse."
The "Incongruent Condition"
In an accompanying editorial, David Salmon, PhD, University of California, San Diego, pointed out that the image effect observed between the 3 groups in the study was largely driven by the incongruent condition.
In the incongruent condition, "patients with mild cognitive impairment performed similarly to healthy subjects in tasks with large semantic distances and similarly to Alzheimer's disease patients in tasks with the more semantically demanding small distances."
Nevertheless, the deficits in semantic memory shown in this study "add confidence to the growing perception that subtle decline in this cognitive domain occurs in patient with amnestic mild cognitive impairment," Dr. Salmon observed.
He also suggested that decrements in semantic memory as seen in MCI patients in this study suggest that loss of semantic knowledge may be an important reason for this decline, insofar as early loss of semantic knowledge may contribute to a decline in judgment.
The study was funded by the Feinstein Institute for Medical Research and the Litwin-Zucker Center for Research in Alzheimer's Disease and Memory Disorders. Dr. Goldberg received an investigator-initiated grant from Pfizer/Eisai.

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