Progressive Aphasia Severity Scale: Baseline and longitudinal measures in PPA and relationship to quantitative imaging biomarkers

Abstract

Primary Progressive Aphasia (PPA) is a heterogeneous clinical syndrome characterized by deterioration of speech/language abilities. Efficacious treatments are lacking, partly due to the need for standardized methods to monitor symptom progression. To address this, we developed the Progressive Aphasia Severity Scale (PASS) to rate presence and severity of impairment in ten domains of language. In addition, sensitive and specific imaging biomarkers will likely be crucial as inclusion/exclusion criteria and for measuring the potential effects of putative disease-modifying interventions. We are working on both types of measures to determine their utility for longitudinal studies. “MsoNormal” > Patients with PPA were rated at baseline and longitudinal follow-up using the PASS and underwent performance-based language testing and MRI scans that were processed for cortical thickness measures. We demonstrated a linear relationship between change in PASS Sum-of-Boxes and overall PPA-signature rate of atrophy (r = 0.3), with some patients progressing much more rapidly than others. Correlations were present between PASS fluency and WAB fluency (r = −0.92) and BDAE grammar (r = −0.94), PASS syntax/grammar and WAB fluency (r = −0.81) and BDAE grammar (r = −0.82), and PASS word comprehension and CSB word-picture matching (r = −0.87). The NACC UDS Global Language measure correlated with WAB fluency (r = −0.59) and BDAE grammar (r = −0.66) but not CSB. Inter-rater reliability (between neurologist and speech pathologist) of PASS ratings was high with ICC > 0.9 for fluency (0.99), grammar/syntax (0.99), word comprehension (0.91), and global CDR language (1.0). The PASS Sum-of-Boxes measure was more sensitive to the degree of clinical change than was the NACC UDS Global Language measure. These preliminary findings suggest that these novel clinical and imaging measures will likely cross-validate each other and demonstrate potential utility for clinical trials. The degree of impairment reflected by PASS scores was closely related to specific performance deficits, supporting the validity of the scale. The PASS Sum-of-Boxes measure was a more sensitive measure of clinical impairment and change over time than the existing global measure, supporting its value. Further work is in progress to assess the relationships between longitudinal change in PASS and longitudinal change in language test performance measures.