Comparing the accuracy and neuroanatomical correlates of the UPSIT-40 and the Sniffin’ Sticks test in REM sleep behavior disorder

Abstract

A B S T R A C TBackground: Olfactory impairment increases the risk of developing neurodegenerative diseases in patients with idiopathic REM sleep behavior disorder (IRBD). Knowing the test properties of distinct olfactory measures could contribute to their selection for clinical or research purposes. Objective: To compare the accuracy in distinguishing IRBD patients from controls with the University of Pennsylvania Smell Identification Test (UPSIT-40) and Sniffin' Sticks Extended test, and to assess the gray-matter volume correlates of these tests. Method: Twenty-one patients with IRBD and 27 healthy controls were assessed using both olfactory tests. Independent logistic regressions were computed with diagnosis as a dependent variable and olfactory measures as predictive variables. Receiver operating characteristic curves were computed for each olfactory subtest. Diagnostic accuracy for IRBD was calculated according to the resulting optimal cut-off score. Structural MRI data, acquired with a 3T scanner, were analyzed with voxel-based morphometry. Results: Patients differed from controls in all olfactory measures. The Sniffin-Identification correctly classified 89.1% of cases; the UPSIT-40, 85.4%; the Sniffin-Discrimination, 82.6%; the Sniffin-Total, 81.8%; and the Sniffin-Threshold, 77.3%. Respective AUROC, optimal cut-off, sensitivity, and specificity for each test were: 0.902, ≤26, 85.7%, and 85.2% for the UPSIT-40; 0.884, ≤29, 89.5%, and 76.0% for the Sniffin-Total; 0.922, ≤11, 90.5%, and 88.0% for the Sniffin-Identification; 0.739, ≤4, 73.7%, and 76.0% for the Sniffin-Threshold; and 0.838, ≤11, 85.7%, and 76.0% for the Sniffin-Discrimination. UPSIT-40 scores correlated with gray-matter volumes in orbitofrontal regions in anosmic patients. Conclusions: UPSIT-40 and Sniffin' Identification showed similar discrimination accuracy, but only the UPSIT-40 showed structural correlates (p ≤ .05 FDR-corrected). dementia with Lewy bodies (DLB), Parkinson's disease (PD), or multiple system atrophy [2,3]. In this setting, IRBD has been described as the strongest and most specific clinical predictor of neurodegenerative disease available [4]. Therefore, there is a growing interest in finding clinical biomarkers of neurodegeneration in this prodromal disorder.Since olfactory loss has also been recognized as a premotor symptom of PD [5,6], it has been widely studied as a possible biomarker of neurodegeneration in IRBD [7]. In this sense, olfactory impairment in RBD has been reported in 35.7-97.0% of patients compared with

Cortical gray matter progression in idiopathic REM sleep behavior disorder and its relation to cognitive decline

“…Despite we found executive dysfunction compared to HC, no decline was found across time, which might be explained by the fact that the current neuropsychological assessment did not evaluate specifically orbitofrontal functions. On the other hand, orbitofrontal regions have also been associated with olfactory dysfunction in IRBD ( Campabadal et al, 2019a , Pereira et al, 2019 ) and PD ( Ibarretxe-Bilbao et al, 2010 ). Nonetheless, despite finding olfactory identification deficits in IRBD relative to healthy controls, our results did not show decline over the disease course.…”

“…To date, there is a considerable amount of neuroimaging research showing structural ( Campabadal et al, 2019b , De Marzi et al, 2016 , Ehrminger et al, 2016 , Ellmore et al, 2010 , Hanyu et al, 2012 , Ohlhauser et al, 2019 , Park et al, 2018 , Pereira et al, 2019 , Pyatigorskaya et al, 2017 , Rahayel et al, 2015 , Rahayel et al, 2018a , Rahayel et al, 2018b , Scherfler et al, 2011 , Unger et al, 2010 ) and functional ( Byun et al, 2020 , Campabadal et al, 2020 , Dayan and Browner, 2017 , Ellmore et al, 2013 , Park et al, 2018 , Rolinski et al, 2016 ) abnormalities in IRBD patients using MRI. Most importantly, owing to all these works, there is strong evidence that brain changes relate to cognitive impairment ( Byun et al, 2020 , Campabadal et al, 2020 , Pereira et al, 2019 , Rahayel et al, 2018b , Vendette et al, 2012 ) and olfactory loss ( Campabadal et al, 2019a , Pereira et al, 2019 , Rahayel et al, 2018b , Vendette et al, 2011 ). Nevertheless, few researchers have investigated how the disease progression affects brain structure and function, and how these changes are associated with cognitive decline.…”

Extending the Spectrum of Nonmotor Symptoms with Olfaction in Premotor Huntington’s Disease: A Pilot Study

“…Furthermore, there are preceding studies assessing olfaction in premanifest HD mutation carriers by using the UPSIT, which did not show significant impairment in HD carriers, whereas manifest HD patients showed impaired odor identification progressive with disease course [4,5,17]. This difference could be due to a higher sensitivity and specificity of the Sniffin' stick test, which has been demonstrated in patients with REM sleep behavior disorders [15] as well as in children [18] possibly due to a decreased number of test items and/or a decreased olfactory fatigue.…”

“…Most studies on odor identification use either the disposable UPSIT or the reusable Sniffin' sticks test battery [13]. The most common used test in Europe is the Sniffin' Sticks identification subtest, as it is easy-to-use, inexpen- sive, and a handy tool in clinical routine and has been performed to screen for olfactory dysfunction in patients with parkinsonism [14], REM sleep behavior disorders [15], and multiple sclerosis [16].…”

Actigraphic Screening for Rapid Eye Movement Sleep Behavior Disorder

“…Furthermore, olfactory dysfunction can have a substantial predictive value for the early conversion of IRBD to PD or DLB. Olfactory function can be assessed by Sniffin’ Sticks test, mainly showing impaired odor identification 23 and UPSIT-40, which both correlate with RBD status and UPSIT-40 scores correlated also to atrophy of grey matter in olfactory regions as measured by MRI voxel-based morphometry 24 . The most common manifestation of autonomic dysfunction in RBD and PD subjects is constipation.…”