2026 American Academy of Neurology Abstract Website

Objective:

Relationships between speech, alpha-synuclein, and smell were examined in patients with SSRI-induced REM sleep behavior disorder (5-HT RBD).

Background:

It is uncertain if 5-HT RBD is, like idiopathic RBD, a syndrome synucleinopathy and a prodrome of Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB). Because speech and smell changes associated with synucleinopathy may be early PD indicators in this population.

Design/Methods:

28 patients with 5-HT RBD and 19 controls completed speech tasks, skin biopsy for alpha-synuclein, and smell testing. Speech acoustics were analyzed with the Acoustic Voice Quality Index (AVQI), smoothed cepstral peak prominence (CPP), Harmonics-to-Noise ratio (HNR), and percent creak. Relationships among speech acoustics, smell testing, and synucleinopathy were assessed with multimodal analysis, controlling for sex and age.

Results:

5-HT RBD cases demonstrated significant differences in several speech tasks compared to controls. In particular CPPs (p=0.020) was lower in glottal stop sentences, and percent creak was higher in spontaneous speech (p=0.034). Total Voiced Time was higher in easy onset (p=0.005), all voiced (p=0.033), and glottal stop (p=0.008) sentences. HNR was significantly lower in all voiced sentences (p=0.03) and in spontaneous speech (p=0.003). Controlling for group, patients with synucleinopathy had higher total voiced time (p=0.016) in easy onset sentences, lower AVQI (p=0.042) in all voiced sentences, and higher HNR in the rainbow passage (p=0.004). Total voiced time was higher in glottal stop sentences in patients with normal smell function (p=0.007).

Conclusions:

Patients with 5-HT RBD demonstrated evidence of prodromal speech differences consistent with early parkinsonism. These findings suggest that speech changes represent a signal that may precede cutaneous synuclein pathology, representing a unique early biomarker of disease progression. These findings suggest speech acoustics could be used as outcome measures in the development of disease-modifying neuroprotective therapies to prevent PD and DLB.