The CBI-R detects early behavioural impairment in genetic frontotemporal dementia

Abstract

Introduction: Behavioural dysfunction is a key feature of genetic frontotemporal dementia (FTD) but validated clinical scales measuring behaviour are lacking at present.

Methods: We assessed behaviour using the revised version of the Cambridge Behavioural Inventory (CBI-R) in 733 participants from the Genetic FTD Initiative study: 466 mutation carriers (195 C9orf72, 76 MAPT, 195 GRN) and 267 non-mutation carriers (controls). All mutation carriers were stratified according to their global CDR plus NACC FTLD score into three groups: asymptomatic (CDR = 0), prodromal (CDR = 0.5) and symptomatic (CDR = 1+). Mixed-effects models adjusted for age, education, sex and family clustering were used to compare between the groups. Neuroanatomical correlates of the individual domains were assessed within each genetic group.

Results: CBI-R total scores were significantly higher in all CDR 1+ mutation carrier groups compared with controls [C9orf72 mean 70.5 (standard deviation 27.8), GRN 56.2 (33.5), MAPT 62.1 (36.9)] as well as their respective CDR 0.5 groups [C9orf72 13.5 (14.4), GRN 13.3 (13.5), MAPT 9.4 (10.4)] and CDR 0 groups [C9orf72 6.0 (7.9), GRN 3.6 (6.0), MAPT 8.5 (13.3)]. The C9orf72 and GRN 0.5 groups scored significantly higher than the controls. The greatest impairment was seen in the Motivation domain for the C9orf72 and GRN symptomatic groups, whilst in the symptomatic MAPTgroup, the highest-scoring domains were Stereotypic and Motor Behaviours and Memory and Orientation. Neural correlates of each CBI-R domain largely overlapped across the different mutation carrier groups.

Conclusions: The CBI-R detects early behavioural change in genetic FTD, suggesting that it could be a useful measure within future clinical trials.

Figure 1

Mean CBI‐R total scores in healthy controls and each genetic group stratified by global CDR plus NACC FTLD scores. Significant differences between controls and within each genetic group are starred. Differences between different genetic groups are not shown. Error bars represent the standard error of the mean.

Figure 2

Cross‐sectional CBI‐R total scores (mean with standard errors) in each genetic group by CDR plus NACC FTLD global score.

Figure 3

Mean CBI‐R scores (expressed as a percentage to allow comparison) in each of the individual 10 domains within healthy controls and each genetic group stratified by CDR plus NACC FTLD global scores. Significant differences between controls and within each genetic group are starred. Differences between different genetic groups are not shown. Error bars represent the standard error of the mean.