Neuropsychological, Metabolic, and Connectivity Underpinnings of Semantic Interference Deficits Using the LASSI-L

Article type: Research Article

Authors: Valles-Salgado, María^a | Cabrera-Martín, María Nieves^b | Curiel-Cid, Rosie E.^c | Delgado-Álvarez, Alfonso^a | Delgado-Alonso, Cristina^a | Gil-Moreno, María José^a | Matías-Guiu, Jorge^a | Loewenstein, David A.^c | Matias-Guiu, Jordi A.^{a; *}

Affiliations: [a] Department of Neurology, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISSC), Universidad Complutense de Madrid, Madrid, Spain | [b] Department of Nuclear Medicine, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISSC), Universidad Complutense de Madrid, Madrid, Spain | [c] Center for Cognitive Neuroscience and Aging, Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami and Center of Aging, Miami, FL, USA

Correspondence: [*] Correspondence to: Jordi A. Matias-Guiu, Department of Neurology, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISSC), Universidad Complutense de Madrid, Profesor Martin Lagos St s/n. 28040, Madrid, Spain. E-mails: [email protected], [email protected].

Abstract: Background:LASSI-L is a novel neuropsychological test specifically designed for the early diagnosis of Alzheimer’s disease (AD) based on semantic interference. Objective:To examine the cognitive and neural underpinnings of the failure to recover from proactive semantic and retroactive semantic interference. Methods:One hundred and fifty-five patients consulting for memory loss were included. Patients underwent neuropsychological assessment, including the LASSI-L, and FDG-PET imaging. They were categorized as subjective memory complaints (SMC) (n=32), pre-mild cognitive impairment (MCI) due to AD (Pre-MCI) (n=39), MCI due to AD (MCI-AD) (n=71), and MCI without evidence of neurodegeneration (MCI-NN) (n=13). Voxel-based brain mapping and metabolic network connectivity analyses were conducted. Results:A significant group effect was found for all the LASSI-L scores. LASSI-L scores measuring failure to recover from proactive semantic interference and retroactive semantic interference were predicted by other neuropsychological tests with a precision of 64.1 and 44.8%. The LASSI-L scores were associated with brain metabolism in the bilateral precuneus, superior, middle and inferior temporal gyri, fusiform, angular, superior and inferior parietal lobule, superior, middle and inferior occipital gyri, lingual gyrus, and posterior cingulate. Connectivity analysis revealed a decrease of node degree and centrality in posterior cingulate in patients showing frPSI. Conclusion:Episodic memory dysfunction and the involvement of the medial temporal lobe, precuneus and posterior cingulate constitute the basis of the failure to recover from proactive semantic interference and retroactive semantic interference. These findings support the role of the LASSI-L in the detection, monitoring and outcome prediction during the early stages of AD.

Keywords: Alzheimer’s disease, connectivity, FDG-PET, interference, memory, mild cognitive impairment, neuropsychological assessment

DOI: 10.3233/JAD-220754

Journal: Journal of Alzheimer's Disease, vol. 90, no. 2, pp. 823-840, 2022