Qualitative Deficits in Verbal Fluency in Parkinson’s Disease with Mild Cognitive Impairment: A Clinical and Neuroimaging Study

Article type: Research Article

Authors: Hamada, Tomoya^{a; b} | Higashiyama, Yuichi^{a; *} | Saito, Asami^a | Morihara, Keisuke^a | Landin-Romero, Ramon^{d; e; f} | Okamoto, Mitsuo^a | Kimura, Katsuo^c | Miyaji, Yousuke^a | Joki, Hideto^a | Kishida, Hitaru^c | Doi, Hiroshi^a | Ueda, Naohisa^c | Takeuchi, Hideyuki^a | Tanaka, Fumiaki^{a; *}

Affiliations: [a] Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan | [b] Department of Speech-Language-Hearing Therapy, Japan Welfare Education College, Shinjuku-ku, Tokyo, Japan | [c] Department of Neurology, Yokohama City University Medical Center Hospital, Yokohama, Kanagawa, Japan | [d] The University of Sydney, School of Psychology, Sydney, NSW, Australia | [e] The University of Sydney, Brain & Mind Centre, Sydney, NSW, Australia | [f] Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, NSW, Australia

Correspondence: [*] Correspondence to: Yuichi Higashiyama, MD, PhD, and Fumiaki Tanaka, MD, PhD, Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan. Tel.: +81 45 787 2725; E-mails: higashiy@yokohama-cu.ac.jp, ftanaka@yokohama-cu.ac.jp

Abstract: Background:Mild cognitive impairment (MCI) in Parkinson’s disease (PD) is considered a risk factor for PD with dementia (PDD). Verbal fluency tasks are widely used to assess executive function in PDD. However, in cases of PD with MCI (PD-MCI), the relative diagnostic accuracy of different qualitative verbal fluency measures and their related neural mechanisms remain unknown. Objective:This study aimed to investigate the relative diagnostic accuracy of qualitative (clustering and switching) verbal fluency strategies and their correlates with functional imaging in PD-MCI. Methods:Forty-five patients with PD (26 with MCI and 19 without MCI) and 25 healthy controls underwent comprehensive neurocognitive testing and resting-state functional magnetic resonance imaging. MCI in patients with PD was diagnosed according to established clinical criteria. The diagnostic accuracy of verbal fluency measures was determined via receiver operating characteristic analysis. Changes in brain functional connectivity between groups and across clinical measures were assessed using seed-to-voxel analyses. Results:Patients with PD-MCI generated fewer words and switched less frequently in semantic and phonemic fluency tasks compared to other groups. Switching in semantic fluency showed high diagnostic accuracy for PD-MCI and was associated with reduced functional connectivity in the salience network. Conclusion:Our results indicate that reduced switching in semantic fluency tasks is a sensitive and specific marker for PD-MCI. Qualitative verbal fluency deficits and salience network dysfunction represent early clinical changes observed in PD-MCI.

Keywords: Brain connectivity, mild cognitive impairment, Parkinson’s disease, salience network, verbal fluency

DOI: 10.3233/JPD-202473

Journal: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2005-2016, 2021