Comparison of clinical rating scales in genetic frontotemporal dementia within the GENFI cohort. Issue 2 (5th August 2021)

• Record Type: Journal Article
• Authors: Peakman, Georgia; Russell, Lucy L; Convery, Rhian S; Nicholas, Jennifer M; Van Swieten, John C; Jiskoot, Lize C; Moreno, Fermin; Sanchez-Valle, Raquel; Laforce, Robert; Graff, Caroline; Masellis, Mario; Tartaglia, Maria Carmela; Rowe, James B; Borroni, Barbara; Finger, Elizabeth; Synofzik, Matthis; Galimberti, Daniela; Vandenberghe, Rik; de Mendonça, Alexandre; Butler, Chris R; Gerhard, Alex; Ducharme, Simon; Le Ber, Isabelle; Tagliavini, Fabrizio; Santana, Isabel; Pasquier, Florence; Levin, Johannes; Danek, Adrian; Otto, Markus; Sorbi, Sandro; Rohrer, Jonathan D;
• Other Names: author non-byline.; Afonso Sónia author non-byline.; Almeida Maria Rosario author non-byline.; Anderl-Straub Sarah author non-byline.; Andersson Christin author non-byline.; Antonell Anna author non-byline.; Archetti Silvana author non-byline.; Arighi Andrea author non-byline.; Balasa Mircea author non-byline.; Barandiaran Myriam author non-byline.; Bargalló Nuria author non-byline.; Bartha Robart author non-byline.; Bender Benjamin author non-byline.; Benussi Alberto author non-byline.; Bertoux Maxime author non-byline.; Bertrand Anne author non-byline.; Bessi Valentina author non-byline.; Black Sandra author non-byline.; Bocchetta Martina author non-byline.; Borrego-Ecija Sergi author non-byline.; Bras Jose author non-byline.; Brice Alexis author non-byline.; Bruffaerts Rose author non-byline.; Camuzat Agnès author non-byline.; Cañada Marta author non-byline.; Cantoni Valentina author non-byline.; Caroppo Paola author non-byline.; Cash David author non-byline.; Castelo-Branco Miguel author non-byline.; Colliot Olivier author non-byline.; Cope Thomas author non-byline.; Deramecourt Vincent author non-byline.; Arriba María de author non-byline.; Fede Giuseppe Di author non-byline.; Díez Alina author non-byline.; Duro Diana author non-byline.; Fenoglio Chiara author non-byline.; Ferrari Camilla author non-byline.; Ferreira Catarina B author non-byline.; Fox Nick author non-byline.; Freedman Morris author non-byline.; Fumagalli Giorgio author non-byline.; Funkiewiez Aurélie author non-byline.; Gabilondo Alazne author non-byline.; Gasparotti Roberto author non-byline.; Gauthier Serge author non-byline.; Gazzina Stefano author non-byline.; Giaccone Giorgio author non-byline.; Gorostidi Ana author non-byline.; Greaves Caroline author non-byline.; Guerreiro Rita author non-byline.; Heller Carolin author non-byline.; Hoegen Tobias author non-byline.; Indakoetxea Begoña author non-byline.; Jelic Vesna author non-byline.; Karnath Hans-Otto author non-byline.; Keren Ron author non-byline.; Langheinrich Tobias author non-byline.; Lebouvier Thibaud author non-byline.; Leitão Maria João author non-byline.; Lladó Albert author non-byline.; Lombardi Gemma author non-byline.; Loosli Sandra author non-byline.; Maruta Carolina author non-byline.; Mead Simon author non-byline.; Meeter Lieke author non-byline.; Miltenberger Gabriel author non-byline.; Minkelen Rick van author non-byline.; Mitchell Sara author non-byline.; Moore Katrina author non-byline.; Nacmias Benedetta author non-byline.; Nelson Annabel author non-byline.; Öijerstedt Linn author non-byline.; Olives Jaume author non-byline.; Ourselin Sebastien author non-byline.; Padovani Alessandro author non-byline.; Panman Jessica author non-byline.; Papma Janne M author non-byline.; Pijnenburg Yolande author non-byline.; Polito Cristina author non-byline.; Premi Enrico author non-byline.; Prioni Sara author non-byline.; Prix Catharina author non-byline.; Rademakers Rosa author non-byline.; Redaelli Veronica author non-byline.; Rinaldi Daisy author non-byline.; Rittman Tim author non-byline.; Rogaeva Ekaterina author non-byline.; Rollin Adeline author non-byline.; Rosa-Neto Pedro author non-byline.; Rossi Giacomina author non-byline.; Rossor Martin author non-byline.; Santiago Beatriz author non-byline.; Saracino Dario author non-byline.; Sayah Sabrina author non-byline.; Scarpini Elio author non-byline.; Schönecker Sonja author non-byline.; Seelaar Harro author non-byline.; Semler Elisa author non-byline.; Shafei Rachelle author non-byline.; Shoesmith Christen author non-byline.; Swift Imogen author non-byline.; Tábuas-Pereira Miguel author non-byline.; Tainta Mikel author non-byline.; Taipa Ricardo author non-byline.; Tang-Wai David author non-byline.; Thomas David L author non-byline.; Thompson Paul author non-byline.; Thonberg Hakan author non-byline.; Timberlake Carolyn author non-byline.; Tiraboschi Pietro author non-byline.; Todd Emily author non-byline.; Damme Philip Van author non-byline.; Vandenbulcke Mathieu author non-byline.; Veldsman Michele author non-byline.; Verdelho Ana author non-byline.; Villanua Jorge author non-byline.; Warren Jason author non-byline.; Wilke Carlo author non-byline.; Woollacott Ione author non-byline.; Wlasich Elisabeth author non-byline.; Zetterberg Henrik author non-byline.; Zulaica Miren author non-byline.;
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 93:Issue 2(2022)
• Page Start: 158
• Page End: 168
• Publication Date: 2021-08-05
• Subjects: frontotemporal dementia; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2021-326868
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Background: Therapeutic trials are now underway in genetic forms of frontotemporal dementia (FTD) but clinical outcome measures are limited. The two most commonly used measures, the Clinical Dementia Rating (CDR)+National Alzheimer's Disease Coordinating Center (NACC) Frontotemporal Lobar Degeneration (FTLD) and the FTD Rating Scale (FRS), have yet to be compared in detail in the genetic forms of FTD. Methods: The CDR+NACC FTLD and FRS were assessed cross-sectionally in 725 consecutively recruited participants from the Genetic FTD Initiative: 457 mutation carriers (77 microtubule-associated protein tau ( MAPT), 187 GRN, 193 C9orf72 ) and 268 family members without mutations (non-carrier control group). 231 mutation carriers (51 MAPT, 92 GRN, 88 C9orf72 ) and 145 non-carriers had available longitudinal data at a follow-up time point. Results: Cross-sectionally, the mean FRS score was lower in all genetic groups compared with controls: GRN mutation carriers mean 83.4 (SD 27.0), MAPT mutation carriers 78.2 (28.8), C9orf72 mutation carriers 71.0 (34.0), controls 96.2 (7.7), p<0.001 for all comparisons, while the mean CDR+NACC FTLD Sum of Boxes was significantly higher in all genetic groups: GRN mutation carriers mean 2.6 (5.2), MAPT mutation carriers 3.2 (5.6), C9orf72 mutation carriers 4.2 (6.2), controls 0.2 (0.6), p<0.001 for all comparisons. Mean FRS score decreased and CDR+NACC FTLD Sum of Boxes increased with increasing disease severity within each individual genetic group. FRS and CDR+NACC FTLD Sum of Boxes scores were strongly negatively correlated across all mutation carriers (rs =−0.77, p<0.001) and within each genetic group (rs =−0.67 to −0.81, p<0.001 in each group). Nonetheless, discrepancies in disease staging were seen between the scales, and with each scale and clinician-judged symptomatic status. Longitudinally, annualised change in both FRS and CDR+NACC FTLD Sum of Boxes scores initially increased with disease severity level before decreasing in those with the most severe disease: controls −0.1 (6.0) for FRS, −0.1 (0.4) for CDR+NACC FTLD Sum of Boxes, asymptomatic mutation carriers −0.5 (8.2), 0.2 (0.9), prodromal disease −2.3 (9.9), 0.6 (2.7), mild disease −10.2 (18.6), 3.0 (4.1), moderate disease −9.6 (16.6), 4.4 (4.0), severe disease −2.7 (8.3), 1.7 (3.3). Sample sizes were calculated for a trial of prodromal mutation carriers: over 180 participants per arm would be needed to detect a moderate sized effect (30%) for both outcome measures, with sample sizes lower for the FRS. Conclusions: Both the FRS and CDR+NACC FTLD measure disease severity in genetic FTD mutation carriers throughout the timeline of their disease, although the FRS may be preferable as an outcome measure. However, neither address a number of key symptoms in the FTD spectrum, for example, motor and neuropsychiatric deficits, which future scales will need to incorporate.