Regional neuropathology distribution and verbal fluency impairments in Parkinson's disease

Background: Verbal fluency deficits are common in patients with Parkinson's disease. The association of these impairments with regional neuropathological changes is unexplored. Objectives: Determine if patients with verbal fluency impairments have greater neuropathological burden in frontal, temporal, and limbic regions and if Lewy bodies or neurofibrillary tangles were associated with verbal fluency impairments. Methods: Data was derived from the Arizona Study of Aging and Neurodegenerative Disorders. 47 individuals who completed phonemic and semantic verbal fluency tasks and met clinicopathological criteria for Parkinson's disease (with and without comorbid Alzheimer's disease) were included. Impairment on fluency tasks was defined by normative data, and the density of neuropathology in temporal, limbic, and frontal regions was compared between groups. Results: Individuals with semantic fluency impairments had greater total pathology (Lewy bodies + neurofibrillary tangles) in limbic structures (W = 320.0, p =.033, r_pb =.33), while those who had phonemic fluency impairments had increased total neuropathology in frontal (W = 364.5, p =.011, r_pb =.37), temporal (W = 356.5, p =.022, r_pb =.34), and limbic regions (W = 357.0, p =.024, r_pb =.34). Greater Lewy body density was found in those with verbal fluency impairments, though trends for greater neurofibrillary tangle density were noted as well. Conclusions: Impaired phonemic fluency was associated with higher Lewy body and tangle burden in frontal, temporal, and limbic regions, while impaired semantic fluency was associated with greater limbic pathology. Though neurofibrillary tangles trended higher in several regions in those with impaired verbal fluency, higher Lewy body density in general was associated with verbal fluency deficits. Implications for research and clinical practice are discussed.