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Functional Connectivity is Reduced in Early-stage Primary Progressive Aphasia When Atrophy is not Prominent

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Primary progressive aphasia (PPA) is a clinical syndrome of language decline caused by neurodegenerative pathology. Although language impairments in PPA are typically localized via the morphometric assessment of atrophy, functional changes may accompany or even precede detectable structural alterations, in which case resting state functional connectivity (RSFC) could provide an alternative approach. The goal of this study was to determine whether language network RSFC is reduced in early-stage PPA when atrophy is not prominent. We identified 10 individuals with early-stage agrammatic variant of PPA with no prominent cortical thinning compared with nonaphasic controls. RSFC between 2 nodes of the language network and 2 nodes of the default mode network were compared between agrammatic variant of PPA and healthy control participants. Language network connectivity was comparable with controls among patients with milder agrammatism, but was significantly reduced in patients with more pronounced agrammatism. No group differences were observed in default mode network connectivity, demonstrating specificity of findings. In early stages of PPA when cortical atrophy is not prominent, RSFC provides an alternative method for probing the neuroanatomic substrates of language impairment. RSFC may be of particular utility in studies on early interventions for neurodegenerative disease, either to identify anatomic targets for intervention or as an outcome measure of therapeutic efficacy.
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Keywords: biomarkers; cognition; dementia; dementing disorders; functional MRI; functional neuroimaging; physiology and pharmacology; volumetric MRI

Document Type: Research Article

Affiliations: 1: Cognitive Neurology and Alzheimer’s Disease Center, Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 2: Cognitive Neurology and Alzheimer’s Disease Center 3: Cognitive Neurology and Alzheimer’s Disease Center, Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, Department of Psychology, Cleveland State University, Cleveland, OH

Publication date: April 1, 2017

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