Dysphagia in primary progressive aphasia: Clinical predictors and neuroanatomical basis

• Published in: European journal of neurology 2024-09, Vol.31 (9), p.e16370-n/a
• Main Authors: Mazzeo, Salvatore, Mulroy, Eoin, Jiang, Jessica, Lassi, Michael, Johnson, Jeremy C. S., Hardy, Chris J. D., Rohrer, Jonathan D., Warren, Jason D., Volkmer, Anna
• Format: Article
• Language: English
• Subjects: Aged; Alzheimer dementia; Aphasia; Aphasia, Primary Progressive - complications; Aphasia, Primary Progressive - diagnostic imaging; Aphasia, Primary Progressive - pathology; Atrophy; Atrophy - pathology; Basal ganglia; Brain architecture; Case-Control Studies; Central nervous system diseases; Cognitive ability; Deglutition Disorders - etiology; Deglutition Disorders - pathology; Dementia and Cognitive Disorders; Disorders; Dysphagia; Female; Humans; Learning algorithms; Machine learning; Magnetic Resonance Imaging; Male; Middle Aged; Morphometry; Motor task performance; Movement disorders; Neurodegenerative diseases; Neuroimaging; Original; Predictive control; primary progressive aphasia; Retrospective Studies; semantic dementia; Substantia grisea; swallowing
• ISSN: 1351-5101; 1468-1331; 1468-1331
• DOI: 10.1111/ene.16370

Background and purpose Dysphagia is an important feature of neurodegenerative diseases and potentially life‐threatening in primary progressive aphasia (PPA) but remains poorly characterized in these syndromes. We hypothesized that dysphagia would be more prevalent in nonfluent/agrammatic variant (nfv)PPA than other PPA syndromes, predicted by accompanying motor features, and associated with atrophy affecting regions implicated in swallowing control. Methods In a retrospective case–control study at our tertiary referral centre, we recruited 56 patients with PPA (21 nfvPPA, 22 semantic variant [sv]PPA, 13 logopenic variant [lv]PPA). Using a pro forma based on caregiver surveys and clinical records, we documented dysphagia (present/absent) and associated, potentially predictive clinical, cognitive, and behavioural features. These were used to train a machine learning model. Patients' brain magnetic resonance imaging scans were assessed using voxel‐based morphometry and region‐of‐interest analyses comparing differential atrophy profiles associated with dysphagia presence/absence. Results Dysphagia was significantly more prevalent in nfvPPA (43% vs. 5% svPPA and no lvPPA). The machine learning model revealed a hierarchy of features predicting dysphagia in the nfvPPA group, with excellent classification accuracy (90.5%, 95% confidence interval = 77.9–100); the strongest predictor was orofacial apraxia, followed by older age, parkinsonism, more severe behavioural disturbance, and more severe cognitive impairment. Significant grey matter atrophy correlates of dysphagia in nfvPPA were identified in left middle frontal, right superior frontal, and right supramarginal gyri and right caudate. Conclusions Dysphagia is a common feature of nfvPPA, linked to underlying corticosubcortical network dysfunction. Clinicians should anticipate this symptom particularly in the context of other motor features and more severe disease.