Functional Neural Correlates of Semantic Fluency Task Performance in Mild Cognitive Impairment and Alzheimer’s Disease: An FDG-PET Study

Article type: Research Article

Authors: Ahn, Hyejin^a | Yi, Dahyun^{b; *; 1} | Chu, Kyungjin^c | Joung, Haejung^d | Lee, Younghwa^d | Jung, Gijung^a | Sung, Kiyoung^e | Han, Dongkyun^f | Lee, Jun Ho^g | Byun, Min Soo^h | Lee, Dong Young^{a; i; j; *; 1}

Affiliations: [a] Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea | [b] Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea | [c] Korea Counseling Center for Fertility and Depression, National Medical Center, Seoul, Republic of Korea | [d] Interdisciplinary Program of Cognitive Science, Seoul National University, Seoul, Republic of Korea | [e] Department of Psychiatry, Nowon Eulji Medical Center, Eulji University, Seoul, Republic of Korea | [f] Jamsil Forest Neuropsychiatric Clinic, Seoul, Republic of Korea | [g] Mind Lab The Place Psychiatric Clinic, Seoul, Republic of Korea | [h] Department of Psychiatry, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea | [i] Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea | [j] Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea

Correspondence: [*] Correspondence to: Dong Young Lee, MD, PhD, Department of Neuropsychiatry, Seoul National University Hospital & Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea. Tel.: +82 2 2072 2205; Fax: +82 2 744 7241; E-mail: [email protected] and Dahyun Yi, PhD, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea. Tel.: +82 2 2072 1722; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background: Total score (TS) of semantic verbal fluency test (SVFT) is generally used to interpret results, but it is ambiguous as to specific neural functions it reflects. Different SVFT strategy scores reflecting qualitative aspects are proposed to identify specific cognitive functions to overcome limitations of using the TS. Objective: Functional neural correlates of the TS as well as the other strategy scores in subjects with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia using Fluorine-18-Fluorodeoxyglucose positron emission tomography (FDG-PET). Methods: Correlations between various SVFT scores (i.e., TS, mean cluster size, switching (SW), hard switching, cluster switching (CSW)) and cerebral glucose metabolism were explored using voxelwise whole-brain approach. Subgroup analyses were also performed based on the diagnosis and investigated the effects of disease severity on the associations. Results: Significant positive correlation between TS and cerebral glucose metabolism was found in prefrontal, parietal, cingulate, temporal cortex, and subcortical regions. Significantly increased glucose metabolism associated with the SW were found in similar but smaller regions, mainly in the fronto-parieto-temporal regions. CSW was only correlated with the caudate. In the subgroup analysis conducted to assess different contribution of clinical severity, differential associations between the strategy scores and regional glucose metabolism were found. Conclusion: SW and CSW may reflect specific language and executive functions better than the TS. The SVFT is influenced by brain dysfunction due to the progression of AD, as demonstrated by the SW with larger involvement of temporal lobe for the AD, and CSW with significant association only for the MCI.

Keywords: Alzheimer’s disease, dementia, fluorodeoxyglucose F18, mild cognitive impairment, neuropsychological tests, positron emission tomography

DOI: 10.3233/JAD-215292

Journal: Journal of Alzheimer's Disease, vol. 85, no. 4, pp. 1689-1700, 2022