Aline Mendes1, Anne Bertrand1, Foudil Lamari1, Olivier Colliot1, Alexandre Routier1, Olivier Godefroy1, Frédérique Etcharry-Bouyx1, Olivier Moreaud1, Florence Pasquier1, Philippe Couratier1, Karim Bennys1, Martine Vercelletto1, Olivier Martinaud1, Bernard Laurent1, Jérémie Pariente1, Michèle Puel1, Stéphane Epelbaum1, Serge Belliard1, Takoua Kaaouana1, Ludovic Fillon1, Marie Chupin1, Bruno Dubois1, Marc Teichmann2. 1. From the Department of Internal Medicine, Rehabilitation and Geriatrics (A.M.), Geneva University Hospitals and University of Geneva, Switzerland; Department of Neurology (A.M., S.E., B.D., M.T.), National Reference Center for PPA and Rare Dementias, Institute for Memory and Alzheimer's Disease, Pitié Salpêtrière Hospital, AP-HP, Paris; Sorbonne Universités (A.B., O.C., A.R., S.E., L.F., M.C., B.D., M.T.), UPMC University Paris 06, Inserm, CNRS, Institut du Cerveau et la Moelle, Paris; Inria Paris (A.B., O.C., A.R., S.E., T.K.), Aramis Project-Team, Paris; Departments of Neuroradiology (A.B.) and Metabolic Biochemistry (F.L.), Pitié Salpêtrière Hospital, AP-HP, Paris; Department of Neurology and Laboratory of Functional Neurosciences (EA 4559) (O.G.), University Hospital of Amiens; Department of Neurology (F.E.-B.), Memory Research and Resource Center for Alzheimer's Disease, University Hospital of Angers; Department of Psychiatry, Neurology and Rehabilitation (O. Moreaud), University Hospital of Grenoble, Memory Research and Resource Center for Alzheimer's Disease; Department of Neurology (F.P.), University Hospital of Lille; Department of Neurology (P.C.), University Hospital of Limoges; Department of Neurology (K.B.), Memory Research and Resource Center for Alzheimer's Disease, University Hospital of Montpellier; Department of Neurology (M.V.), University Hospital of Nantes; Department of Neurology (O. Martinaud), University Hospital of Rouen; Normandie University (O. Martinaud, S.B.), UNICAEN, EPHE, INSERM, U1077, Neuropsychologie et Imagerie de la Mémoire Humaine; Department of Neurology (B.L.), University Hospital of Saint-Etienne; Department of Neurology (J.P., M.P.), Pierre Paul Riquet Hospital, Toulouse; INSERM/UPS (J.P.), UMR 1214-ToNIC, Toulouse NeuroImaging Center, University of Toulouse III; and Department of Neurology (S.B.), Memory Research and Resource Center for Alzheimer's Disease, University Hospital Pontchaillou, Rennes, France. 2. From the Department of Internal Medicine, Rehabilitation and Geriatrics (A.M.), Geneva University Hospitals and University of Geneva, Switzerland; Department of Neurology (A.M., S.E., B.D., M.T.), National Reference Center for PPA and Rare Dementias, Institute for Memory and Alzheimer's Disease, Pitié Salpêtrière Hospital, AP-HP, Paris; Sorbonne Universités (A.B., O.C., A.R., S.E., L.F., M.C., B.D., M.T.), UPMC University Paris 06, Inserm, CNRS, Institut du Cerveau et la Moelle, Paris; Inria Paris (A.B., O.C., A.R., S.E., T.K.), Aramis Project-Team, Paris; Departments of Neuroradiology (A.B.) and Metabolic Biochemistry (F.L.), Pitié Salpêtrière Hospital, AP-HP, Paris; Department of Neurology and Laboratory of Functional Neurosciences (EA 4559) (O.G.), University Hospital of Amiens; Department of Neurology (F.E.-B.), Memory Research and Resource Center for Alzheimer's Disease, University Hospital of Angers; Department of Psychiatry, Neurology and Rehabilitation (O. Moreaud), University Hospital of Grenoble, Memory Research and Resource Center for Alzheimer's Disease; Department of Neurology (F.P.), University Hospital of Lille; Department of Neurology (P.C.), University Hospital of Limoges; Department of Neurology (K.B.), Memory Research and Resource Center for Alzheimer's Disease, University Hospital of Montpellier; Department of Neurology (M.V.), University Hospital of Nantes; Department of Neurology (O. Martinaud), University Hospital of Rouen; Normandie University (O. Martinaud, S.B.), UNICAEN, EPHE, INSERM, U1077, Neuropsychologie et Imagerie de la Mémoire Humaine; Department of Neurology (B.L.), University Hospital of Saint-Etienne; Department of Neurology (J.P., M.P.), Pierre Paul Riquet Hospital, Toulouse; INSERM/UPS (J.P.), UMR 1214-ToNIC, Toulouse NeuroImaging Center, University of Toulouse III; and Department of Neurology (S.B.), Memory Research and Resource Center for Alzheimer's Disease, University Hospital Pontchaillou, Rennes, France. marc.teichmann@psl.aphp.fr.
Abstract
OBJECTIVE: To reveal the prevalence and localization of cerebral microbleeds (CMBs) in the 3 main variants of primary progressive aphasia (PPA) (logopenic, semantic, and nonfluent/agrammatic), to identify the relationship with underlying Alzheimer pathology, and to explore whether CMBs contribute to language breakdown. METHODS: We used a cross-sectional design in a multicenter cohort of 82 patients with PPA and 19 similarly aged healthy controls. MRI allowed for rating CMBs (2-dimensional gradient recalled echo T2*, susceptibility weighted imaging sequences) and white matter hyperintensities. CSF Alzheimer disease biomarker analyses available in 63 of the 82 patients provided the stratification of PPA into subgroups with patients who had or did not have probable underlying Alzheimer pathology. RESULTS: The prevalence of CMBs was higher in patients with PPA (28%) than in controls (16%). They were more prevalent in logopenic PPA (50%) than in semantic PPA (18%) and nonfluent/agrammatic PPA (17%). The localization of CMBs was mainly lobar (81%) with no difference between the PPA variants. CMBs were more frequent in PPA patients with positive than with negative CSF Alzheimer disease biomarkers (67% vs 20%). Patients with and without lobar CMBs had similar volumes of white matter hyperintensities. Language and general cognitive impairment in PPA was unrelated to CMB rates. CONCLUSIONS: CMB prevalence in PPA is higher than in healthy controls. CMBs were most prevalent in the logopenic variant, were related to underlying Alzheimer pathology, and did not affect the language/cognitive impairment. Our findings also suggest that CMB detection with MRI contributes to PPA variant diagnosis, especially of logopenic PPA, and provides an estimator of the underlying neuropathology.
OBJECTIVE: To reveal the prevalence and localization of cerebral microbleeds (CMBs) in the 3 main variants of primary progressive aphasia (PPA) (logopenic, semantic, and nonfluent/agrammatic), to identify the relationship with underlying Alzheimer pathology, and to explore whether CMBs contribute to language breakdown. METHODS: We used a cross-sectional design in a multicenter cohort of 82 patients with PPA and 19 similarly aged healthy controls. MRI allowed for rating CMBs (2-dimensional gradient recalled echo T2*, susceptibility weighted imaging sequences) and white matter hyperintensities. CSF Alzheimer disease biomarker analyses available in 63 of the 82 patients provided the stratification of PPA into subgroups with patients who had or did not have probable underlying Alzheimer pathology. RESULTS: The prevalence of CMBs was higher in patients with PPA (28%) than in controls (16%). They were more prevalent in logopenic PPA (50%) than in semantic PPA (18%) and nonfluent/agrammatic PPA (17%). The localization of CMBs was mainly lobar (81%) with no difference between the PPA variants. CMBs were more frequent in PPA patients with positive than with negative CSF Alzheimer disease biomarkers (67% vs 20%). Patients with and without lobar CMBs had similar volumes of white matter hyperintensities. Language and general cognitive impairment in PPA was unrelated to CMB rates. CONCLUSIONS:CMB prevalence in PPA is higher than in healthy controls. CMBs were most prevalent in the logopenic variant, were related to underlying Alzheimer pathology, and did not affect the language/cognitive impairment. Our findings also suggest that CMB detection with MRI contributes to PPA variant diagnosis, especially of logopenic PPA, and provides an estimator of the underlying neuropathology.
Authors: Carolyn Akers; Lealani May Y Acosta; Ciaran Considine; Daniel Claassen; Howard Kirshner; Matthew Schrag Journal: Curr Neurol Neurosci Rep Date: 2019-07-27 Impact factor: 5.081