Refining α-synucleinopathy risk in isolated REM sleep behavior disorder patients using repeated olfactory testing.

Area of Science:

• Neurology
• Sleep Medicine
• Neurodegenerative Diseases

Background:

• Isolated REM sleep behavior disorder (iRBD) is a prodromal stage for synucleinopathies.
• Olfactory dysfunction is an early marker in synucleinopathies.
• Prognostic utility of serial olfactory testing in iRBD is not well-established.

Purpose of the Study:

• To investigate the prognostic value of repeated olfactory testing in iRBD patients.
• To predict phenoconversion to overt α-synucleinopathies using olfactory function.
• To assess the association between olfactory function changes and neurodegeneration markers.

Main Methods:

• 59 iRBD patients underwent olfactory testing (University of Pennsylvania Smell Identification Test) at baseline and 2-year follow-up.
• Patients were categorized into persistent hyposmia, persistent normosmia, or unstable olfactory function groups.
• Longitudinal assessment of clinical, cognitive, and DAT-SPECT parameters.

Main Results:

• Persistent hyposmia (62.7%) was linked to higher age, worse DAT-SPECT, and increased MDS-UPDRS III progression.
• Persistent normosmia (18.6%) showed no significant neurodegeneration and a 0% phenoconversion rate.
• Phenoconversion occurred in 20.3% of patients, primarily in the persistent hyposmia and unstable olfactory groups. Repeated hyposmia significantly increased phenoconversion risk.

Conclusions:

• Serial olfactory testing enhances risk stratification in iRBD patients.
• Persistent normosmia indicates a lower risk of phenoconversion.
• Persistent hyposmia predicts neurodegeneration, making serial olfactory tests a cost-effective tool for identifying high-risk individuals for clinical trials.