An international study conducted by researchers from the dementia neurobiology group at the Sant Pau Research Institute and the Memory Unit of the same hospital suggests that primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) are disorders that could be part of a clinical continuum rather than being completely distinct entities. The research, which focused on patients with progressive speech impairment and/or agrammatism, sought to identify distinct sets of symptoms that do not naturally overlap, such as PPAOS and PAA.
Dr. Ignacio Illan Gala, a researcher at the Biomedical Research Networking Center for Neurodegenerative Diseases (CIBERNED) at IR Sant Pau and lead author of the study, explains that “there are various solutions for these patients. We can, for example, provide speech therapy and interventions to try to improve patients’ speech and articulation, which may temporarily alleviate symptoms, although it will not alter the progression of these diseases.”
The study, published in the prestigious journal Brain, was conducted by specialists in speech pathology and included 98 participants, 43 of whom had a neuropathological diagnosis confirmed by autopsy. Researchers evaluated characteristics indicative of dysarthria and apraxia of speech. In addition, quantitative measures of expressive/receptive agrammatism were taken and compared with healthy controls. The severity of the disease at onset and progression was assessed using the sum of scores from the Clinical Dementia Rating (CDR-SB). Dr. Illan explains that “the diagnosis of this syndrome is general and interpretative; what is needed are objective markers that are not clinical to reach a definitive diagnosis.”
The results revealed that 93 out of 98 participants matched previously documented clinical profiles, with 75 of them diagnosed with apraxia of speech (AOS) and agrammatism, 12 with PPAOS, and 6 with PAA. However, five participants showed a different pattern, with no clear evidence of apraxia of speech or agrammatism, characterized by non-fluent speech, executive dysfunction, and dysarthria. “We are working to understand these diseases in order to identify the specific pathology causing the symptoms in each patient. Once identified, we will then propose treatments specifically targeted at that pathology,” says Dr. Illan.
Statistical analysis revealed a low tendency toward clustering in the dataset, indicating a lack of clear separation between subgroups. Only two solid subgroups were identified, differentiated by the presence of agrammatism, executive dysfunction, and overall disease severity. Furthermore, three latent clinical dimensions were identified based on the following data: severity-agrammatism, prominent presence of Apraxia of Speech (AOS), and prominent presence of dysarthria. These dimensions explained 71% of the variability observed in the patients’ symptoms.
Although none of these dimensions enabled precise prediction of neuropathology, it was observed that the intensity of agrammatism acted as an independent predictor of faster increase in CDR-SB score in all participants. Additionally, the severity of dysarthria, reduction in words per minute, and intensity of expressive/receptive agrammatism at onset also independently predicted accelerated disease progression.
In conclusion, this study suggests that PPAOS and PAA, rather than being completely distinct entities, constitute a clinical continuum. The findings highlight the need for new biological markers and consensus on updated terminology and clinical classification within the spectrum of non-fluent/agrammatic primary progressive aphasia.
Illán-Gala I, Lorca-Puls DL, Tee BL, Ezzes Z, de Leon J, Miller ZA, Rubio-Guerra S, Santos-Santos M, Gómez-Andrés D, Grinberg LT, Spina S, Kramer JH, Wauters LD, Henry ML, Boxer AL, Rosen HJ, Miller BL, Seeley WW, Mandelli ML, Gorno-Tempini ML. Clinical dimensions along the non-fluent variant primary progressive aphasia spectrum. Brain. 2023 Nov 21:awad396. doi: 10.1093/brain/awad396. Epub ahead of print. PMID: 37988272. DOI: 10.1093/brain/awad396
