Significance of hyposmia in isolated REM sleep behavior disorder

Objective To determine if hyposmia in isolated REM sleep behavior disorder (IRBD) predicts short-term conversion to any α-synucleinopathy and declines with time. Methods Olfaction was tested using the University of Pennsylvania Smell Identification Test (UPSIT-40) in 140 consecutive patients with polysomnography-confirmed IRBD and in 77 matched controls. Patients were followed-up during 5.6 ± 3.9 (range 0.2–13) years. Twenty-one patients underwent serial UPSIT-40 evaluations at 1–3 and 4–6 years after baseline. Results UPSIT-40 score was lower in patients than in controls (20.2 ± 6.5 vs. 28.6 ± 5.0; p < 0.001). Hyposmia (UPSIT-40 score < 19 points) occurred in 42.9% patients. Forty-three (30.7%) patients developed Parkinson disease (PD = 27), dementia with Lewy bodies (DLB = 13) and multiple system atrophy (MSA = 3). Kaplan–Meier analysis showed that hyposmics had higher risk than normosmics to develop a synucleinopathy at the short term ( p = 0.030). UPSIT-40 score was similar between patients who developed PD and DLB ( p = 0.136). Normal smell occurred in all three (100%) IRBD patients who developed MSA, 12 of 27 (44%) who developed PD, and 4 of 13 (31%) that developed DLB. Serial UPSIT-40 evaluations showed no changes with time ( p = 0.518). Conclusion In IRBD, hyposmia is a short-term risk for synucleinopathies but cannot distinguish underlying PD from DLB. Normosmia not only occurs in latent MSA but also in latent PD and DLB. In future IRBD neuroprotective trails, individuals at entry could be enriched for hyposmia, whereas serial evaluation of smell would not be useful to monitor the efficacy of a therapeutic intervention.