Clinicopathologic and Neuroimaging Correlations of Nonverbal Oral Apraxia in Patients with Neurodegenerative Disease

Neurology Medicine Basic Medical Sciences Medical Imaging
Nonverbal Oral Apraxia Neurodegenerative Disease Clinicopathologic Neuroimaging Progressive Supranuclear Palsy Corticobasal Degeneration

Nonverbal Oral Apraxia in Patients with Neurodegenerative Diseases: Clinical-Pathological and Neuroimaging Correlations

Research Background

Nonverbal Oral Apraxia (NVOA) is a condition characterized by the inability to plan, sequence, and execute voluntary oral-facial movements without muscle weakness. NVOA was first identified in stroke patients, presenting as an impairment in the ability to perform voluntary oral-facial movements due to disrupted procedural planning and sequencing abilities. However, it remains unclear whether NVOA is associated with specific pathological, clinical, or neuroimaging findings in the context of neurodegenerative diseases. This study aims to evaluate the clinical-pathological and neuroimaging correlations of NVOA.

Authors and Publication Information

This paper is authored by Danna P. Garcia-Guaqueta, MD, Hugo Botha, MB, CHB, Rene L. Utianski, PhD, Joseph R. Duffy, PhD, Heather Clark, PhD, Gabriela Meade, PhD, Mary M. Machulda, PhD, Dennis W. Dickson, MD, Nha Trang Thu Pham, BS, Jennifer L. Whitwell, PhD, and Keith A. Josephs, MD, MST, MSc. The authors are affiliated with the Department of Neurology, the Department of Psychiatry and Psychology, the Department of Neuroscience (Neuropathology), and the Department of Radiology at Mayo Clinic. The paper is published in the 2024 volume 103 of the journal “Neurology,” issue e209717. The corresponding author is Dr. Josephs, whose contact email is josephs.keith@mayo.edu.

Research Methods

The study employs a retrospective analysis, screening all autopsied patients from the Neurodegenerative Research Group (NRG) database who had been assessed using the NVOA evaluation tool. A total of 104 patients were included in the study, with 63 developing NVOA. SPM12 software was used to evaluate the patterns of gray matter loss in NVOA and non-NVOA patients, adjusting for age and gender as covariates.

  1. Patient Selection and Setting: The study screened autopsied patients from the NRG database, identifying 104 patients who had undergone NVOA assessment. These patients were included in the study between July 6, 2010, and May 18, 2023.

  2. Clinical Assessment: All patients completed a series of multidisciplinary assessments during each visit, including the Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), and the Unified Parkinson’s Disease Rating Scale sponsored by the Movement Disorder Society (MDS-UPDRS III).

  3. NVOA Identification: Speech-language pathologists performed speech-language evaluations, assessing spontaneous conversation and structured speech tasks, as well as NVOA performance, using the NVOA evaluation tool for screening and confirmation. A score of ≤29 points was used as the cutoff to confirm the presence and severity of NVOA.

  4. Pathological Methods: Histopathological examinations of all cases were performed by a certified neuropathologist (D.W.D.) at Mayo Clinic, with pathological diagnoses based on published pathological standards.

  5. Neuroimaging Analysis: All patients underwent standardized 3T MRI protocol scans, including T1-weighted MPRAGE sequences, during each visit. Voxel-based morphometry using SPM12 was used to evaluate gray matter volume loss patterns in NVOA versus non-NVOA patients.

  6. Statistical Analysis: Kruskal-Wallis tests and Fisher’s exact tests were used to analyze baseline clinical diagnoses, follow-up times, and other variables. Statistical analyses were performed using Bluesky Statistics software, with significance set at p<0.05.

Research Results

  1. Patient Characteristics: A total of 104 patients participated in this study, with 57.7% male and 42.3% female. Among the 63 NVOA patients, the most common initial diagnoses were Primary Progressive Apraxia of Speech (PPAOS) and Nonfluent Variant Primary Progressive Aphasia (NFVPPA); whereas in non-NVOA patients, the most common diagnoses were Progressive Supranuclear Palsy (PSP) and Logopenic Progressive Aphasia (LPA).

  2. Clinical Diagnosis and Pathological Correlation: In NVOA patients, PSP and Corticobasal Degeneration (CBD) were the most common pathological findings, while in non-NVOA patients, PSP and Alzheimer’s Disease (AD) were more prevalent. Further analysis indicated that specific pathological findings (such as CBD and FTLD-TDP) were associated with more severe NVOA.

  3. Neuroimaging Findings: NVOA patients exhibited greater gray matter volume loss in the left premotor cortex, motor cortex, and cingulate cortex, suggesting that these regions may play a significant role in the development of NVOA.

Conclusion and Value

This study demonstrates that NVOA is common across various neurodegenerative diseases, primarily manifesting as damage to specific brain regions rather than being linked to specific pathologies. NVOA is most strongly associated with PSP and CBD pathologies, but other pathological findings can also lead to the development of NVOA. Clinically, the presence of NVOA can be used to predict disease progression and severity, providing valuable references for clinical diagnosis and treatment.

The study’s highlight is its use of large-scale data and autopsy results to deeply analyze the correlations between NVOA and different neurodegenerative diseases, enriching the clinical and pathological knowledge of NVOA and offering significant reference value for future research and clinical practice.