Original ArticlesFunctional Connectivity is Reduced in Early-stage Primary Progressive Aphasia When Atrophy is not ProminentBonakdarpour, Borna MD*,†; Rogalski, Emily J. PhD*; Wang, Allan*; Sridhar, Jaiashre MS*; Mesulam, M.M. MD*,†; Hurley, Robert S. PhD*,†,‡Author Information *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 Supported by the Northwestern University Alzheimer Disease Center Rosenstone fellowship fund, pilot grant P30 AG13854, and NIH NIDCD K23 DC014303-01A1 (Bonakdarpour); NIH NIDCD DC008552 (Mesulam) and NIDCD DC013386 grants (Hurley). B.B., M.M.M., and R.S.H.: designed the study and wrote the manuscript. B.B., E.J.R., A.W., J.S., and R.S.H.: analyzed data. B.B. is funded by NIH K23 DC014303-01A1, and Northwestern Cognitive Neurology and Alzheimer Disease Center pilot grant (P30 AG13854). E.J.R. is funded by NIH grants R01AG045571, R03 DC013386, R01NS075075, and receives research support from the Alzheimer’s Association and the Davee Foundation. M.M.M.: is on the medical advisory council for the Association for Frontotemporal Degeneration, is funded by NIH grants P30 AG13854 and R01 DC008552 and R01AG045571, U01 AG016976 and received research support from the Alzheimer’s Association and the Davee Foundation. R.S.H.: is funded by NIH grants NIDCD DC013386 and NIDCD DC008552, and received research support from the Davee Foundation. The remaining authors declare no conflicts of interest. Reprints: Borna Bonakdarpour, MD, Northwestern University Feinberg School of Medicine, Chicago, IL 60016 (e-mail: [email protected]). Alzheimer Disease & Associated Disorders: April–June 2017 - Volume 31 - Issue 2 - p 101-106 doi: 10.1097/WAD.0000000000000193 Buy SDC Metrics Abstract 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. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.