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Verbal fluency discrepancies as a marker of the prehippocampal stages of Alzheimer’s disease.

Lookup NU author(s): Dr Laura WrightORCiD


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Objective: Prior to episodic memory decline, a lengthy preclinical phase of AD exists which may be partially characterised by the build-up of tau pathology within extrahippocampal structures. Semantic memory, also impaired in AD, has been linked to degradation within these earliest affected areas. This study aims to assess the utility of verbal fluency decline discrepancies in highlighting these early pathological changes in AD. Methods: Whole-brain voxel-based morphometry was used to assess the neural correlates of semantic memory function in three patient groups; two groups of mild cognitive impairment (MCI) patients split into mildly (n = 58) and moderately (n = 53) affected and an AD dementia group (n = 69). Discrepancies between the relative levels of decline on the semantic category fluency task and non-semantic letter fluency task were calculated for each participant and included in a regression model measuring the relationship between semantic memory and whole-brain grey matter volume. Results: Patients at all disease stages demonstrated significantly greater declines in category relative to letter fluency. Discrepancy scores in mild MCI correlated strongly with the structural integrity of the anterior medial temporal lobes. In dementia patients, this relationship spread posteriorly to temporo-occipital regions. Conclusions: Semantic memory tasks may prove useful indicators of even the earliest stages of medial temporal damage in AD. Furthermore, posterior shifts in correlation with increasing disease severity suggests potential functional reorganisation in the presence of significant medial temporal atrophy. Such findings may serve to inform future imaging protocols, facilitating earlier diagnosis and disease differentiation.

Publication metadata

Author(s): Wright LM, De Marco M, Venneri A

Publication type: Article

Publication status: Published

Journal: Neuropsychology

Year: 2022

Pages: epub ahead of print

Acceptance date: 02/04/2018

ISSN (print): 0894-4105

ISSN (electronic): 1931-1559

Publisher: American Psychological Association


DOI: 10.1037/neu0000836


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