To assess clinicopathological features of patients with primary progressive apraxia of speech (PPAOS) who had symptoms >10 years from onset to death and compare them to PPAOS patients with symptoms ≤10 years.

PPAOS is a neurodegenerative disorder characterized by an early, isolated speech abnormality due to impaired motor planning and programming, commonly resulting from progressive supranuclear palsy (PSP) or corticobasal degeneration pathology. We have observed that some PPAOS patients live with symptoms for >10 years. The Clinicopathological features of these long-duration patients are unclear.

We analyzed 41 PPAOS patients who were enrolled in an NIH-funded study and followed to death. Patients were divided into those with a disease duration of >10 years versus those with ≤10 years. Fisher's Exact and Mann-Whitney U tests were used to compare demographic, speech-language, pathologic, and genetic variables between groups; logistic regression was used to adjust for potential confounders, and survival analysis was done among all 67 PPAOS patients available in our data to address survivorship bias.

Eighteen PPAOS patients (44%) had a duration of >10 years. Long-duration patients were, on average, seven years younger at onset (63.2 (IQR=54.5, 72.3) vs. 70.6 (IQR=65.3, 75.7) (p=0.04)). They also had a slower decline in apraxia of speech severity over time (p=0.02) due to a slower decline of prosodic features (slow rate, syllable segmentation) (p=0.04). PSP was observed in 69% of the long-duration patients with a significant association (p=0.049) when accounted for age at onset compared to 42% of those with duration ≤10 years. The median survival rate in the younger and older disease onset group was 10.4 and 9.3 years, respectively.

Long disease duration is not uncommon in PPAOS. PPAOS patients with long disease duration are more likely to have a slower decline of apraxia of speech prosodic features- more likely due to underlying PSP pathology.