Association Between Amyloid Accumulation and Sleep in Patients With Idiopathic REM Sleep Behavior Disorder

Abstract

Background and Objectives: Amyloid-beta protein may lead to sleep disturbance and eventually develop cognitive impairment. Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a predictor of neurodegeneration, yet there have been limited studies evaluating the relationship between cognitive decline and amyloid accumulation in iRBD patients. The aim of this study is to investigate the clinical and sleep characteristics of iRBD patients and its association with amyloid deposition.Methods: We enroll 23 iRBD patients (mean age, 65.8 years; male, 73.9%), and their mean history of clinically suspected RBD was 6.5 years. All underwent 18F-flutemetamol amyloid PET completed polysomnography (PSG) and questionnaires. Patients were classified into two groups according to amyloid deposition as amyloid positive and negative. Clinical and sleep parameters were compared between groups and were correlated with amyloid deposition, calculated as a standardized uptake value ratio (SUVR).Results: Four patients (17.4%) were revealed to be amyloid positive, and they showed increased percentage of wake after sleep onset (WASO), stage N1, and stage N2 sleep and worse on the Stroop Word Color Test compared to amyloid negative patients. Global SUVR was correlated with total sleep time, sleep efficiency, WASO, and N1 sleep, and these sleep parameters were associated with a part of default mode network of brains such as orbitofrontal, dorsolateral pre-frontal, and left temporal areas.Conclusion: iRBD patients with amyloid deposition have worse sleep quality than patients without amyloid. Relationship between fragmented sleep and amyloid deposition in the default mode network may be crucial to elucidate the disease progress of iRBD.

Neuroimaging of rapid eye movement sleep behavior disorder and its relation to Parkinson's disease

“…Lee et al (2020) measured the cortical amyloid beta levels using the [ 18 F]Flutemetamol PET tracer in a group of 23 iRBD patients and found that four patients were positive for amyloid and also showed elevated percentage of wake after sleep onset (WASO) compared to 19 amyloid negative patients. Global radioligand uptake also correlated with total sleep time, sleep efficiency, WASO, and N1 sleep (Lee et al, 2020). These sleep quality measurements are typically associated with brain regions involved in the default mode network, including the orbitofrontal, dorsolateral prefrontal, and left temporal cortices (Lee et al, 2020).…”

“…Global radioligand uptake also correlated with total sleep time, sleep efficiency, WASO, and N1 sleep (Lee et al, 2020). These sleep quality measurements are typically associated with brain regions involved in the default mode network, including the orbitofrontal, dorsolateral prefrontal, and left temporal cortices (Lee et al, 2020).…”

“…There is a sparsity of studies that examined the role of beta amyloid deposition in iRBD pathology. Lee et al (2020) measured the cortical amyloid beta levels using the [ 18 F]Flutemetamol PET tracer in a group of 23 iRBD patients and found that four patients were positive for amyloid and also showed elevated percentage of wake after sleep onset (WASO) compared to 19 amyloid negative patients. Global radioligand uptake also correlated with total sleep time, sleep efficiency, WASO, and N1 sleep (Lee et al, 2020).…”

Plasma biomarkers of neurodegeneration in patients with Parkinson’s disease and dementia with Lewy bodies and at-risk individuals of Lewy body disease in the NaT-PROBE cohort

“…These results are consistent with those reported in previous studies, namely, that the rate of positive amyloid PET in patients with idiopathic RBD was similar to that in cognitively normal individuals. [35][36][37] Although these findings indicate that AD-related plasma biomarkers become detectable after the manifestation of motor/cognitive symptoms in LBD, comorbid AD neuropathology may subsist at an undetectable level in the prodromal phase and influence disease progression. Therefore, further longitudinal data analysis must elucidate the role of AD-related plasma biomarkers on motor function and non-motor symptoms in high-risk individuals.…”

Deep learning signature of brain [18F]FDG PET associated with cognitive outcome of rapid eye movement sleep behavior disorder

“…A [ 11 C]donepezil PET study showed more widely reduced cortical acetylcholinesterase activity in iRBD patients with cognitive impairment 21 . Moreover, an amyloid PET study showed that 17.4% of patients with iRBD show positive cerebral amyloid deposit 22 . In addition, recent amyloid PET studies in patients with DLB and PD dementia showed increased amyloid deposit that was associated with cognitive dysfunction, and the amyloid deposition in DLB patients was associated with striatal dopaminergic depletion 23 , 24 .…”