Primary Progressive Aphasia in the Network of French Alzheimer Plan Memory Centers

Article type: Research Article

Authors: Magnin, Eloi^{a; *} | Démonet, Jean-François^b | Wallon, David^c | Dumurgier, Julien^{d; e} | Troussière, Anne-Cécile^f | Jager, Alain^g | Duron, Emmanuelle^h | Gabelle, Audreyⁱ | de la Sayette, Vincent^j | Volpe-Gillot, Lisette^k | Tio, Gregory^a | Evain, Sarah^l | Boutoleau-Bretonnière, Claire^l | Enderle, Adeline^f | Mouton-Liger, François^{d; e; m} | Robert, Philippeⁿ | Hannequin, Didier^c | Pasquier, Florence^f | Hugon, Jacques^{d; e; m} | Paquet, Claire^{d; e; m} | on behalf of ePLM collaborators¹

Affiliations: [a] Centre Mémoire de Ressources et de Recherche (CMRR), Hôpital Universitaire de Besançon, Besançon, France | [b] Centre Leenaards de la Mémoire, CHUV, Lausanne, Suisse | [c] Service de Neurologie, Hôpital universitaire de Rouen, et INSERM UMR1079, Université de Rouen, Rouen, France | [d] Centre Mémoire de Ressources et de Recherche (CMRR), Paris Nord Ile de France, APHP, Paris, France | [e] INSERM U942, Paris, France | [f] Inserm 1171, Univ. Lille, CHU Lille, Distalz, CMRR, CNR-MAJ, F-59000 Lille, France | [g] Centre de Neurologie, 6 place Luxembourg, Thionville, France | [h] Centre Mémoire de Ressources et de Recherche Paris Sud, Hôpital Broca APHP, Université Paris V, Paris, France | [i] Centre Mémoire de Ressources et de Recherche (CMRR) de Montpellier, Hôpital Gui de Chauliac, Centre Hospitalo-Universitaire Montpellier et INSERM U1040, hôpital Saint Eloi, Montpellier, France | [j] Centre Mémoire de Ressources (CMRR) de Caen, Hôpital Universitaire de Caen, Caen, France | [k] Consultation Mémoire, Groupe Hôpitalier Saint-Joseph, Paris, France | [l] Centre mémoire de ressources et de recherche, Service de Neurologie, CHU Nantes, Nantes, France | [m] Unité d’Histologie et de Biologie du Vieillissement, APHP, Paris, France | [n] Centre Mémoire de Ressources et de Recherche/EA COBTEK, CHU, Université de Nice, Nice, France

Correspondence: [*] Correspondence to: Eloi Magnin, MD, PhD, Department of Neurology, CHU, Boulevard Fleming, 25000 Besançon, France. Tel.: +33 381668098; Fax: +33 381668740; E-mail: eloi.magnin@laposte.net.

Note: [1] ePLM collaborators: Sylvain Lehmann, Luc Buée, Susanna Schraen, Frederic Blanc, Stephanie Bombois, Olivier Bousiges, Dominique Campion, Benjamin Cretin, Constance Delaby, Barbara Jung, Jean-Louis Laplanche, Mathilde Sauvée, Carole Miguet-Alfonsi, Katell Peoc’h, Nathalie Philippi, Muriel Quillard-Muraine, Bernard Sablonnière, Jacques Touchon, Olivier Vercruysse.

Abstract: Background: Few demographical data about primary progressive aphasia (PPA) are available, and most knowledge regarding PPA is based on tertiary centers’ results. Objective: Our aims were to describe demographical characteristics of the PPA population in a large sample of PPA patients from the network of French Alzheimer plan memory centers (Sample 1), and to describe the stratification of cerebrospinal fluid (CSF) biomarkers in two different samples of PPA patients (Samples 2 and 3). Methods: All registered PPA patients in the French Alzheimer’s disease (AD) databank (Sample 1: n = 2,035) and a subsample (Sample 2: n = 65) derived from a multicentric prospective cohort with CSF biomarker analysis were analyzed. A multicentric retrospective cohort from language expert tertiary centers (Sample 3: n = 97) with CSF biomarker analysis was added. Sample 3 was added to replicate the CSF results of the Sample 2 and to evaluate repartition of AD pathology in the three variant of PPA according to the latest classification. Results: Non-Fluent/Agrammatic, Logopenic, and Unclassifiable PPA patients (NF/A-Logo-Unclass PPA) were older and more frequent than Semantic PPA patients (2.2 versus 0.8/100,000 inhabitants; p < 0.00001). Male predominance occurred after the age of 80 (p < 0.00001). A higher level of education was observed in the PPA population compared to a typical amnesic AD group. No demographical significant difference between PPA due to AD and not due to AD was observed. The Logopenic variant was most frequent with 85% of AD CSF biomarker profiles (35% in NF/A PPA; 20% in Semantic PPA). Conclusion: PPA occurs also in an elderly population, especially in male patients over 80. CSF biomarkers are useful to stratify PPA. The epidemiology of PPA should be further investigated to confirm gender and cognitive reserve role in PPA to better understand the factors and mechanisms leading to this language-predominant deficit during neurodegenerative diseases.

Keywords: Alzheimer’s disease, cerebrospinal fluid biomarkers, epidemiology, frontotemporal dementia, gender, primary progressive aphasia

DOI: 10.3233/JAD-160536

Journal: Journal of Alzheimer's Disease, vol. 54, no. 4, pp. 1459-1471, 2016