Hippocampal perfusion predicts impending neurodegeneration in REM sleep behavior disorder

Abstract

Objectives: Patients with idiopathic REM sleep behavior disorder (IRBD) are at risk for developing Parkinson disease (PD) and dementia with Lewy bodies (DLB). We aimed to identify functional brain imaging patterns predicting the emergence of PD and DLB in patients with IRBD, using SPECT with (99m)Tc-ethylene cysteinate dimer (ECD).

Methods: Twenty patients with IRBD were scanned at baseline during wakefulness using (99m)Tc-ECD SPECT. After a follow-up of 3 years on average, patients were divided into 2 groups according to whether or not they developed defined neurodegenerative disease (PD, DLB). SPECT data analysis comparing regional cerebral blood flow (rCBF) between groups assessed whether specific brain perfusion patterns were associated with subsequent clinical evolution. Regression analysis between rCBF and clinical markers of neurodegeneration (motor, color vision, olfaction) looked for neural structures involved in this process.

Results: Of the 20 patients with IRBD recruited for this study, 10 converted to PD or DLB during the follow-up. rCBF at baseline was increased in the hippocampus of patients who would later convert compared with those who would not (p < 0.05 corrected). Hippocampal perfusion was correlated with motor and color vision scores across all IRBD patients.

Conclusions: (99m)Tc-ECD SPECT identifies patients with IRBD at risk for conversion to other neurodegenerative disorders such as PD or DLB; disease progression in IRBD is predicted by abnormal perfusion in the hippocampus at baseline. Perfusion within this structure is correlated with clinical markers of neurodegeneration, further suggesting its involvement in the development of presumed synucleinopathies.

Figure 1. Hippocampal hyperperfusion in RBDEv compared with RBDSt

(Upper panels) Brain perfusion increases at baseline in patients with idiopathic REM sleep behavior disorder who would convert to neurodegenerative disease (RBDEv), compared with those who would not (RBDSt), were located in the hippocampus. The panels show the peak hyperperfusion, centered on the left hippocampus, and represented on sagittal, coronal, and transverse sections (from left to right panels) (p^corr < 0.05). The level of section is indicated on the top of each panel (x, y, and z coordinates, in mm). The color scale indicates the range of t values for this contrast. (Lower panel) Plot of the adjusted rCBF responses (arbitrary units) in the left hippocampus (x = −30 mm, y = −30 mm, z = −14 mm) showing the distinct distribution in RBDEv and RBDSt patients. Each circle represents 1 subject. Horizontal bars represent mean values. RBDEv = REM sleep behavior disorder with clinical evolution; RBDSt = state of isolated REM sleep behavior disorder; rCBF = regional cerebral blood flow.

Figure 2. Correlation between motor scores (UPDRS-III) and rCBF in patients with IRBD

Brain perfusion in the right hippocampus is positively correlated at baseline with UPDRS-III scores across IRBD patients (p^corr < 0.05). (Left) The 2 panels show the location of this positive correlation in the right hippocampus, on sagittal and coronal sections (from top to bottom), respectively. The level of section is indicated on the top of each panel (x and y coordinates, in mm). The color scale indicates the range of t values. (Right) Plot of the adjusted rCBF responses (arbitrary units) in the right hippocampus (x = 36 mm, y = −14 mm, z = −18 mm) in relation to UPDRS-III scores: rCBF increases when UPDRS-III is higher. Each circle represents 1 subject. The blue line is the linear regression. IRBD = idiopathic REM sleep behavior disorder; rCBF = regional cerebral blood flow; UPDRS = Unified Parkinson Disease Rating Scale.

Figure 3. Correlation between color vision scores (FM-100) and rCBF in patients with IRBD

Brain perfusion in the left hippocampus is positively correlated at baseline with FM-100 scores across IRBD patients (p^corr < 0.05). (Left) The 2 panels show the location of this positive correlation in the left hippocampus, on sagittal and coronal sections (from top to bottom), respectively. The level of section is indicated on the top of each panel (x and y coordinates, in mm). The color scale indicates the range of t values. (Right) Plot of the adjusted rCBF responses (arbitrary units) in the left hippocampus (x = −32 mm, y = −10 mm, z = −16 mm) in relation to FM-100 scores (adjusted for age and sex, in %): rCBF increases when FM-100 is higher. Each circle represents 1 subject. The blue line is the linear regression. FM = Farnsworth-Munsell; IRBD = idiopathic REM sleep behavior disorder; rCBF = regional cerebral blood flow.