Study on the Incidence of Primary Progressive Apraxia of Speech and Primary Progressive Aphasia in Olmsted County (2011-2022)

Background and Study Objectives

Primary Progressive Aphasia (PPA) and Primary Progressive Apraxia of Speech (PPAOS) are rare neurodegenerative diseases that respectively lead to the degeneration of language abilities and speech planning and programming. Despite these diseases significantly impacting patients’ social and occupational lives, their epidemiological characteristics have not been formally assessed. Therefore, this study aims to evaluate the incidence of these diseases in Olmsted County, Minnesota, USA, from 2011 to 2022, and to characterize the clinical, radiological, and pathological features of these patients.

Study Source

This study was authored by Dr. Pierpaolo Turcano, Dr. Jennifer L. Whitwell, Dr. Joseph R. Duffy, Dr. Mary M. Machulda, Ming Aidan Mullan, Dr. Keith A. Josephs, and Dr. Rodolfo Savica. The authors are affiliated with various departments at the Mayo Clinic in Rochester, MN, including Neurology, Radiology, and Psychology. The paper was published in the journal Neurology in 2024 and is available as open access.

Research Methods

Case Confirmation

All participants were recruited by the Neurodegenerative Disease Research Team at the Mayo Clinic and prospectively followed under NIH funding from January 1, 2011, to December 31, 2022. These patients were residents of Olmsted County and diagnosed by experienced behavioral neurologists. Patients meeting specific criteria were classified as having PPA and PPAOS.

Data Collection and Evaluation

The study subjects included all adult patients diagnosed with PPA or PPAOS within the specified time frame. PPA patients were further divided into three variants: Non-Fluent/Agrammatic Variant PPA (NFvPPA), Logopenic Variant PPA (LVPPA), and Semantic Variant PPA (SVPPA). Additionally, patients underwent multimodal neuroimaging examinations, including 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), brain MRIs, and detailed speech and language assessments.

Research Process and Experimental Methods

1. Neuropsychological Assessment and Speech Evaluation

   • The overall cognitive abilities and language impairments of the patients were assessed using the Montreal Cognitive Assessment (MoCA) and other cognitive testing tools.
   • The Western Aphasia Battery-Revised (WAB-R) was used to evaluate the patients’ overall language abilities, and the severity of apraxia of speech was assessed using the Apraxia of Speech Rating Scale and Motor Speech Disorder Severity Scale.

2. Radiological Imaging Assessment

   • Various imaging techniques were used to examine metabolic changes and structural alterations in different brain regions. For example, FDG-PET images were used to identify patterns of metabolic reduction in specific cortical areas to help differentiate between different PPA variants and PPAOS.

3. Pathological Assessment

   • Post-mortem brain pathological examinations were conducted to confirm pathological diagnoses and assess neuronal degeneration.

Data Analysis and Results

1. Incidence Analysis A total of 10 patients were confirmed during the study period, including 8 PPA patients and 2 PPAOS patients. The median age at symptom onset was 70 years, and the median age at diagnosis was 72 years. The study showed that the overall incidence of PPA and PPAOS was 0.70 per 100,000 person-years (95% confidence interval: 0.34-1.29), with an incidence of 0.14 per 100,000 person-years (95% confidence interval: 0.02-0.55) for PPAOS patients, and 0.56 per 100,000 person-years (95% confidence interval: 0.24-1.10) for PPA patients.

2. Incidence of Different Variants

   • NFvPPA: 0.14 per 100,000 person-years (95% confidence interval: 0.02-0.55)
   • LVPPA: 0.21 per 100,000 person-years (95% confidence interval: 0.04-0.61)
   • SVPPA: 0.21 per 100,000 person-years (95% confidence interval: 0.04-0.61)

3. Clinical and Imaging Evaluation Results

   • Most patients exhibited mild cognitive impairment in the early stages, confirmed through a series of tests on cognitive processing speed, executive function, and visuospatial function.
   • MRI and FDG-PET imaging showed that NFvPPA patients typically exhibited metabolic reduction in the dominant posterior inferior frontal gyrus; SVPPA patients had metabolic reduction in the anterior temporal lobe; LVPPA patients primarily exhibited metabolic reduction in the left lateral temporoparietal region; and PPAOS patients showed metabolic reduction in the left precentral gyrus and supplementary motor area.

4. Disease Progression and Prognosis

   • The disease course of PPA and PPAOS patients showed more extensive neurodegenerative changes over time. Some PPAOS patients developed parkinsonism, vertical gaze palsy, and stereotyped behaviors during the disease course.
   • Pathological studies indicated that most patients exhibited 4-repeat tauopathy consistent with progressive supranuclear palsy (PSP).

Study Conclusions and Significance

PPA and PPAOS are relatively rare but clinically significant neurodegenerative diseases. This study systematically evaluated the incidence of these diseases in a specific region and time frame for the first time, filling the gap in epidemiological research and revealing differences in clinical presentation, imaging features, and pathological diagnosis among different disease variants. These findings not only help the medical community better understand the pathological mechanisms of PPA and PPAOS but also provide valuable information for clinical diagnosis and treatment.

Highlights and Further Research

The highlights of this study include its revelation of significant differences in the incidence, clinical features, imaging characteristics, and pathological diagnosis of PPA and its variants, as well as PPAOS. The study also suggests that future epidemiological research on these diseases should involve larger cohort studies to further explore their etiological mechanisms and treatment approaches.

Through detailed clinical assessment and systematic data analysis, this study provides new insights into understanding PPA and PPAOS, while also calling on health policymakers to pay attention to the early diagnosis and management of these rare diseases.