Primary progressive apraxia of speech: Clinico-pathological associations of left-right hemispheric dominance
Carling Robinson1, Joseph Duffy1, Heather Clark1, Rene Utianski1, Mary Machulda2, Hugo Botha1, Neha Atulkumar Singh1, Nha Trang Thu Pham3, Peter Martin4, Nilufer Ertekin-Taner5, Dennis Dickson5, Val Lowe3, Jennifer Whitwell3, Keith Josephs1
1Neurology, 2Psychiatry and Psychology, 3Radiology, 4Quantitative Health Sciences, 5Department of Neuroscience, Mayo Clinic, Jacksonville, FL, Mayo Clinic
Objective:

To determine whether there are differences in in demographics, clinicopathologic-neuroimaging or survival, between left-dominant, right-dominant, and symmetric PPAOS.

Background:

Primary progressive apraxia of speech (PPAOS) is a neurodegenerative syndrome associated with neuroimaging abnormalities affecting the lateral premotor cortex (LPC) and supplementary motor area (SMA). It is unclear whether relative greater damage to premotor regions in left/right hemisphere is associated with differences in baseline and/or longitudinal features.

Design/Methods:

Fifty-one prospectively recruited PPAOS patients who completed [18F]-fluorodeoxyglucose PET scanning were classified as left-dominant, right-dominant, or symmetric, based on visual assessment of the LPC and SMA on FDG-PET by independent raters. Statistical analyses were utilized to compared baseline and longitudinal features. Kaplan-Meyer curves and Cox proportional hazards were used to evaluate survival differences across groups.

Results:

49% of PPAOS patients were identified as left-dominant, 31% as right-dominant, and 20% as symmetric. At baseline, there were no differences between groups. On longitudinal rates of clinical change, left-dominant PPAOS displayed a slower progression of Parkinsonian symptoms on the Unified Parkinson Disease Rating Scale-III (p=0.047), with a trend for slowest rates of progression in ideomotor apraxia (p=0.06) and motor speech severity (p=0.09) relative to other groups. Right-dominant PPAOS demonstrated the most rapid rates of progression of behavioral disturbances on the Frontal Behavioral Inventory (p=0.02), including disinhibition symptoms (p=0.02) and negative behaviors (p=0.05). The symmetric group had fastest worsening of dysarthria. There were no differences in survival, although a five-year increase in age at onset, but not group classification, was associated with shorter survival (Hazard Ratio = 1.32; p=0.007). Braak neurofibrillary tangle stage differed across groups (p=0.01). While not statistically significant, right-dominant PPAOS tended to have corticobasal degeneration (CBD) and left-dominant PPAOS had progressive supranuclear palsy (PSP) pathology at autopsy.

Conclusions:

Patients with PPAOS and a left-dominant pattern of hypometabolism on FDG-PET have the slowest rate of decline of clinical features.

10.1212/WNL.0000000000202410