Clinical scale useful for measuring behavioral change in frontotemporal dementia

A validated clinical scale detected early behavioral change in frontotemporal dementia, according to study results presented at the Alzheimer’s Association International Conference.

“The behavioral variant is the most common subtype of frontotemporal dementia [FTD], and behavioral dysfunction is the key feature, so it's important that we have validated assessment scales that focus specifically on the behavioral features to measure the presence and the severity of the disease,” Annabel Nelson, BSc, of the Institute of Neurology at the University College London, said during a virtual presentation.

“There are currently several informant-based questionnaires typically used to measure the severity of the behavioral symptoms in FTD,” she continued. “We have the Neuropsychiatric inventory, which is used for many different dimensions and is not specific to FTD; the Frontotemporal Dementia Rating Scale; and the revised version of the Cambridge Behavioural Inventory [CBI-R].”

Despite the key role of behavioral dysfunction in genetic FTD, validated clinical scales that evaluate behavior are currently lacking, according to Nelson and colleagues. In the current study, they used the CBI-R to evaluate behavior among 733 participants of the Genetic FTD Initiative study. Of these participants, 466 carried mutations (195 C9orf72; 76 MAPT; 195 GRN), and 267 served as healthy controls. The researchers stratified mutation carriers based on their Clinical Dementia Rating (CDR) Dementia Staging Instrument plus National Alzheimer's Coordinating Center (NACC) frontotemporal lobar degeneration (FTLD) into asymptomatic, mildly symptomatic and fully symptomatic groups. Further, they used a mixed-effects model adjusted for age, education, sex and family clustering to compare CBI-R total scores between mutation carrier groups.

Results showed significantly higher CBI-R total scores among all fully symptomatic mutation carrier groups compared with controls (C9orf72 mean = 70.5; GRN mean = 56.2; MAPT mean = 62.1) as well as among their respective mildly symptomatic groups (C9orf72 mean = 13.5; GRN mean = 13.3; MAPT mean = 9.4) and asymptomatic groups (C9orf72 mean = 6; GRN mean = 3.6; MAPT mean = 8.5). Moreover, the researchers noted significantly higher scores among C9orf72 and GRN mildly symptomatic groups compared with controls and their respective asymptomatic groups.

Those in the C9orf72 and GRN fully symptomatic groups scored highest in motivation and memory domains, and those in the MAPT fully symptomatic group scored highest in stereotypic behavior and memory. Nelson and colleagues observed a positive correlation between CBI-R scores and CDR plus NACC FTLD Sum of Box scores among all mutation carrier groups.

“These findings suggest that the CBI-R questionnaire could be a useful marker in clinical trial settings to measure behavioral change and progression in genetic FTD,” Nelson said. “However, we need to investigate this longitudinally to consider how the CBI-R tracks behavior change over time. This will help us to understand how it might be used as a surrogate endpoint for disease-modifying therapies in genetic FTD.”