Abstract
BACKGROUND: Primary progressive apraxia of speech is a neurodegenerative disorder characterized by early, isolated speech impairment due to impairment of motor speech planning and programming. Patients with PPAOS have varying disease durations from the estimated onset of the first symptom to death. Clinicopathological and neuroimaging features related to disease duration are unknown for PPAOS. We determine whether clinical, neuroimaging, or pathological features are associated with disease duration in primary progressive apraxia of speech (PPAOS). METHODS: We analyzed data from 41 PPAOS participants who were enrolled and longitudinally followed to death in NIH-funded studies over 15 years. Demographic, clinical, and genetic features were abstracted. Brain volumes of cortical, subcortical, and brainstem regions were calculated. Regional tau lesion count (burden) was assessed histologically. Spearman rank correlations were performed between disease duration and variables of interest, followed by multiple regression analyses. RESULTS: Disease duration did not correlate with any baseline demographic, clinical, or pathologic features. Shorter disease duration correlated with a faster rate of behavioral change and of apraxia of speech severity over time, smaller baseline volumes of the superior frontal lobe and supplementary motor cortex, and higher tau burden in the locus ceruleus (ρ = -0.5, p = 0.03). Multiple regression analysis identified rate of behavioral change and volume loss in the superior frontal lobe as key clinical and neuroimaging variables, respectively. CONCLUSION: In patients with PPAOS, we found shorter disease duration to be related to behavioral dyscontrol and involvement of the frontal lobe, as well as a higher burden of 4-repeat tau lesions in the locus ceruleus.