Comparison of clinical rating scales in genetic frontotemporal dementia within the GENFI cohort
Creators: name: Peakman, Georgia
name: Russell, Lucy L
name: Convery, Rhian S
name: Nicholas, Jennifer M
name: Van Swieten, John C
name: Jiskoot, Lize C
name: Moreno, Fermin
name: Sanchez-Valle, Raquel
name: Laforce, Robert
name: Graff, Caroline
name: Masellis, Mario
name: Tartaglia, Maria Carmela
name: Rowe, James B
name: Borroni, Barbara
name: Finger, Elizabeth
name: Synofzik, Matthis
name: Galimberti, Daniela
name: Vandenberghe, Rik
name: De Mendonça, Alexandre
name: Butler, Chris R
name: Gerhard, Alex
name: Ducharme, Simon
name: Le Ber, Isabelle
name: Tagliavini, Fabrizio
name: Santana, Isabel
name: Pasquier, Florence
name: Levin, Johannes
name: Danek, Adrian
name: Otto, Markus
name: Sorbi, Sandro
name: Rohrer, Jonathan D
Publisher: name: Universität Ulm
Year: 2021
Subjects: subject: DDC 150 / Psychology
subject: Frontotemporal dementia
subject: Alzheimer’s disease
subject: Alzheimerkrankheit

description: BackgroundTherapeutic 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.MethodsThe 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.ResultsCross-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&lt;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&lt;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&lt;0.001) and within each genetic group (rs=−0.67 to −0.81, p&lt;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.ConclusionsBoth 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.