Browsing by Author "Duffy, Joseph R."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Lewy Body Disease is a Contributor to Logopenic Progressive Aphasia Phenotype
    (Wiley, 2021) Buciuc, Marina; Whitwell, Jennifer L.; Kasanuki, Koji; Graff-Radford, Jonathan; Machulda, Mary M.; Duffy, Joseph R.; Strand, Edythe A.; Lowe, Val J.; Graff-Radford, Neill R.; Rush, Beth K.; Franczak, Malgorzata B.; Flanagan, Margaret E.; Baker, Matthew C.; Rademakers, Rosa; Ross, Owen A.; Ghetti, Bernardino F.; Parisi, Joseph E.; Raghunathan, Aditya; Reichard, R. Ross; Bigio, Eileen H.; Dickson, Dennis W.; Josephs, Keith A.; Pathology and Laboratory Medicine, School of Medicine
    Objective: The objective of this study was to describe clinical features, [18 F]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) metabolism and digital pathology in patients with logopenic progressive aphasia (LPA) and pathologic diagnosis of diffuse Lewy body disease (DLBD) and compare to patients with LPA with other pathologies, as well as patients with classical features of probable dementia with Lewy bodies (pDLB). Methods: This is a clinicopathologic case-control study of 45 patients, including 20 prospectively recruited patients with LPA among whom 6 were diagnosed with LPA-DLBD. We analyzed clinical features and compared FDG-PET metabolism in LPA-DLBD to an independent group of patients with clinical pDLB and regional α-synuclein burden on digital pathology to a second independent group of autopsied patients with DLBD pathology and antemortem pDLB (DLB-DLBD). Results: All patients with LPA-DLBD were men. Neurological, speech, and neuropsychological characteristics were similar across LPA-DLBD, LPA-Alzheimer's disease (LPA-AD), and LPA-frontotemporal lobar degeneration (LPA-FTLD). Genetic screening of AD, DLBD, and FTLD linked genes were negative with the exception of APOE ε4 allele present in 83% of LPA-DLBD patients. Seventy-five percent of the patients with LPA-DLBD showed a parietal-dominant pattern of hy pometabolism; LPA-FTLD - temporal-dominant pattern, whereas LPA-AD showed heterogeneous patterns of hypometabolism. LPA-DLBD had more asymmetrical hypometabolism affecting frontal lobes, with relatively spared occipital lobe in the nondominantly affected hemisphere, compared to pDLB. LPA-DLBD had minimal atrophy on gross brain examination, higher cortical Lewy body counts, and higher α-synuclein burden in the middle frontal and inferior parietal cortices compared to DLB-DLBD. Interpretation: Whereas AD is the most frequent underlying pathology of LPA, DLBD can also be present and may contribute to the LPA phenotype possibly due to α-synuclein-associated functional impairment of the dominant parietal lobe.
  • Thumbnail Image
    Item
    Neuropsychological Profiles of Patients with Progressive Apraxia of Speech and Aphasia
    (Cambridge University Press, 2022) Polsinelli, Angelina J.; Machulda, Mary M.; Martin, Peter R.; Duffy, Joseph R.; Clark, Heather M.; Butts, Alissa M.; Botha, Hugo; Lowe, Val J.; Whitwell, Jennifer L.; Josephs, Keith A.; Utiansk, Rene L.; Neurology, School of Medicine
    Objective: To characterize and compare the neuropsychological profiles of patients with primary progressive apraxia of speech (PPAOS) and apraxia of speech with progressive agrammatic aphasia (AOS-PAA). Method: Thirty-nine patients with PPAOS and 49 patients with AOS-PAA underwent formal neurological, speech, language, and neuropsychological evaluations. Cognitive domains assessed included immediate and delayed episodic memory (Wechsler Memory Scale-Third edition; Logical Memory; Visual Reproduction; Rey Auditory Verbal Learning Test), processing speed (Trail Making Test A), executive functioning (Trail Making Test B; Delis-Kaplan Executive Functioning Scale - Sorting), and visuospatial ability (Rey-Osterrieth Complex Figure copy). Results: The PPAOS patients were cognitively average or higher in the domains of immediate and delayed episodic memory, processing speed, executive functioning, and visuospatial ability. Patients with AOS-PAA performed more poorly on tests of immediate and delayed episodic memory and executive functioning compared to those with PPAOS. For every 1 unit increase in aphasia severity (e.g. mild to moderate), performance declined by 1/3 to 1/2 a standard deviation depending on cognitive domain. The degree of decline was stronger within the more verbally mediated domains, but was also notable in less verbally mediated domains. Conclusion: The study provides neuropsychological evidence further supporting the distinction of PPAOS from primary progressive aphasia and should be used to inform future diagnostic criteria. More immediately, it informs prognostication and treatment planning.