Clinical Manifestations

Alzheimers Dement. 2023 Dec;19 Suppl 18:e079020. doi: 10.1002/alz.079020.

ABSTRACT

BACKGROUND: It is unclear whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) represent the two ends of a clinical continuum or exist as distinct syndromic entities with specific pathologic/prognostic correlates. We aimed to characterize the main clinical features along the spectrum of progressive non-fluent speech-language disorders (nf-SLD) and explore the existence of data-driven symptom clusters with etiological/prognostic value.

METHOD: We included 98 participants presenting with progressive motor speech impairment and/or agrammatism, of which 43 had an autopsy-confirmed neuropathological diagnosis. Speech pathologists rated motor speech features indicative of dysarthria and AOS. Quantitative measures of expressive/receptive agrammatism were obtained and compared with healthy controls. Baseline and longitudinal disease severity was assessed with the Clinical Dementia Rating sum-of-boxes (CDR-SB). We explored the clustering tendency of the data to form robust symptom clusters and used principal component analysis to extract data-driven clinical components. The longitudinal CDR-SB change was estimated with linear mixed-effects models.

RESULT: Ninety-one participants fitted previously reported clinical profiles (69 AOS+agrammatism, 18 PPAOS and 4 PAA), while 7 remained unclassifiable and were characterized by nonfluent speech and dysarthria in the absence of apraxia of speech or agrammatism. None of the baseline clinical features discriminated between FTLD subgroups. The Hopkins statistic ruled out the existence of syndromic clusters in the whole sample. Three data-driven components explained 71% of the variance ([i]severity-agrammatism, [ii]AOS, and [iii]dysarthria). The component characterized by prominent dysarthria was more specific to patients with Progressive Supranuclear Palsy while the component characterized by severity-agrammatism predicted a faster CDR-SB increase.

CONCLUSION: Our results suggest that nf-SLD represents a clinical continuum. Splitting this continuum into different clinical phenotypes based on its major clinical features does not improve clinical-pathological correlations, stressing the need for new clinical and biological markers. The term nf-SLD could be used to group together these speech-language phenotypes strongly associated with FTLD.

PMID:39112058 | DOI:10.1002/alz.079020