Clinico-imaging features of subjects at risk of Lewy body disease in NaT-PROBE baseline analysis

Abstract

Individuals with prodromal symptoms of Lewy body disease (LBD), such as rapid eye movement sleep behavior disorder (RBD), often showed imaging defects similar to patients with Parkinson's disease and dementia with Lewy bodies. We examined dopamine transporter (DaT) single-photon-emission computed tomography (SPECT) and metaiodobenzylguanidine (MIBG) scintigraphy in 69 high-risk subjects with ≥2 prodromal symptoms (dysautonomia, hyposmia, and probable RBD) and 32 low-risk subjects without prodromal symptoms, whom were identified through a questionnaire survey of health checkup examinees. The high-risk subjects had significantly worse scores on Stroop test, line orientation test, and the Odor Stick Identification Test for Japanese than the low-risk subjects. The prevalence of abnormalities on DaT-SPECT was higher in the high-risk group than in the low-risk group (24.6% vs. 6.3%, p = 0.030). A decreased uptake on DaT-SPECT was associated with motor impairment, and MIBG scintigraphy defects were associated with hyposmia. The simultaneous evaluation of DaT-SPECT and MIBG scintigraphy may capture a wide range of individuals with prodromal LBD.

Fig. 1. Participant flowchart of this study.

We screened health checkup examinees to identify potential participants using the following questionnaires: SCOPA-AUT the Japanese version of the Scale for Outcomes in Parkinson’s disease for Autonomic Symptoms, SAOQ Self-administered Odor Question, RBDSQ REM behavior disorder screening scale, BDI-II Beck Depression Inventory-Second Edition, ESS Epworth Sleepiness Scale, and PASE Physical Activity Scale for the Elderly. We classified subjects who were ≥50 years old and had ≥2 abnormal scores in the SCOPA-AUT, SAOQ, and RBDSQ into the high-risk group. The cut-off value for identifying the high-risk group was 10 for SCOPA-AUT, 90.0% for SAOQ, and 5 for RBDSQ. Subjects who were ≥50 years old and had no abnormalities in all the questionnaires were classified into the low-risk group.

Fig. 2. Scatterplot of SBR by age for the high-risk and low-risk subjects.

SBR values of DaT-SPECT of the high-risk and low-risk subjects were plotted with lines showing the upper and lower limits of the 95% confidence interval in healthy subjects. a males; b females; c both genders. DaT dopamine transporter, SBR specific binding ratio.

Fig. 3. The correlation between DaT-SPECT SBR and clinical indices in the high-risk subjects.

Pearson’s correlation test comparing the DaT SBR and motor (a) and cognitive (b–e) functions as well as non-motor symptoms (f–h) in the participants. DaT dopamine transporter, SBR specific binding ratio, MDS-UPDRS Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale, MoCA-J the Japanese version of the Montreal Cognitive Assessment, OSIT-J the odor stick identification test for Japanese, SCOPA-AUT the Japanese version of the Scale for Outcomes in Parkinson’s disease for Autonomic Symptoms, RBDSQ RBD screening scale.

Fig. 4. The correlation between delayed MIBG H/M and clinical indices in the high-risk subjects.

Pearson’s correlation test comparing the delayed MIBG H/M ratio and motor (a) and cognitive (b–e) functions as well as non-motor symptoms (f–h) in the participants. MIBG metaiodobenzylguanidine, MDS-UPDRS Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale, MoCA-J the Japanese version of the Montreal Cognitive Assessment, OSIT-J the odor stick identification test for Japanese, SCOPA-AUT the Japanese version of the Scale for Outcomes in Parkinson’s disease for Autonomic Symptoms; RBDSQ RBD screening scale.