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

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.