Objective: To assess the validity of a patient/caregiver-reported scale for assessing functional disability in 4R tauopathies.

Background: 4R tauopathies (4RT) including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and non-fluent variant primary progressive aphasia (nfvPPA) manifest a wide range of overlapping motor, behavioral, language and cognitive clinical phenotypes. No available clinical rating scale is capable of evaluating the functional impact of these complex disorders, particularly in the context of disease modifying treatment trials directed at common pathogenic mechanisms.

Method: The CBFS was initially developed for CBD given the broad clinical heterogeneity associated with this pathology, overlapping other 4RT syndromes. The scale is composed of 12 Motor, 13 Language/Cognitive/Behavioral and 6 Other Non-Motor Experiences of Daily Living questions.  Baseline data for 38 healthy controls and 68 CBD (CBS), 65 PSP-Richardson’s Syndrome (PSP-RS), 15 nfvPPA, 14 unspecified Atypical Parkinsonism and 18 MSA patients from the North American, 4R Tauopathy Neuroimaging Initiative (4RTNI) or the UK PROgressive Supranuclear Palsy CorTico-Basal Syndrome MSA Longitudinal (PROSPECT) Study.  Internal consistency was examined using Cronbach’s α and criterion validity was examined by correlation with UPDRS, PSP Rating Scale, SEADL, FTLD-Clinical Dementia Rating Scale sum of boxes (FTLD-CDRsb), MoCA and Neuropsychiatric Inventory Questionnaire (NPI-Q) scores.  Two week test retest reliability was examined in 25 participants.

Results: Diagnostic groups were similar in age (69.0±8.9 years), gender distribution (female, 52.2%) and education (15.6±2.5 years).   Internal consistency was excellent (Cronbach’s α=0.94).  CBFS scores were strongly correlated (p≤ 0.001) with PSPRS (r=0.77), followed by SEADL (rho=0.74), UPDRS (r=0.70), FTLD-CDRsb (r=0.63), MoCA (r=0.43) and NPI-Q (r=0.42).  CBFS score was elevated in all patient groups as compared to controls (p<0.001).  CBFS score was lower in nfvPPA as compared to PSP-RS (p=0.004).  Test retest reliability was high (ICC =0.965).

Conclusion: The CBFS has excellent clinimetric properties and captures disability correlated with motor, cognitive and psychiatric impairment. If sensitive to longitudinal change, this may be an ideal endpoint for clinical trials.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/initial-validation-of-the-cortical-basal-ganglia-functional-scale-cbfs-in-two-international-multicenter-cohorts-4rtni-and-prospect/