Semantic Fluency Deficits and Associated Brain Activity in Parkinson’s Disease Patients With Mild Cognitive Impairment

Abstract Parkinson’s disease (PD) patients with poor verbal fluency have an increased risk of developing dementia. This study examines the neural mechanisms underpinning semantic fluency deficits in PD patients with mild cognitive impairment (PD-MCI) compared to patients without MCI (PD-NC) and healthy controls (HC). Thirty-seven (37) PD patients completed a cognitive assessment battery to identify MCI (13 PD-MCI). Gender- and age-matched 20 HC also participated. Participants were scanned (3T Siemens PRISMA) whilst performing semantic fluency, semantic switching, and automatic speech tasks. The number of responses, error rate, and fMRI data for semantic generation and semantic switching were analyzed. Participants also completed a series of verbal fluency tests outside the scanner, including letter fluency. Patients with PD-MCI performed significantly worse than PD-NC and HC during semantic fluency and semantic switching tasks. Patients with PD-MCI showed greater activity in the right angular gyrus compared to PD-NC and HC during semantic switching. Increased right angular activity correlated with worse verbal fluency performance outside the scanner. Our study showed that PD-MCI patients perform more poorly on semantic fluency than either PD-NC or HC groups. Increased right angular gyrus activity in patients with PD-MCI during semantic switching suggests early compensatory mechanisms predicting the risk of future dementia in PD.