Neuroimaging evidence of glymphatic system dysfunction in possible REM sleep behavior disorder and Parkinson’s disease

Su, Xiaoli; Guo, Tao; Wang, Zhiyun; Fang, Yi; Gu, Luyan; Cao, Lanxiao; Yang, Wenyi; Gao, Ting; Song, Zhe; Tian, Jun; Yin, Xinzhen; Guan, Xiaojun; Zhou, Cheng; Wu, Jingjing; Bai, Xueqin; Liu, Xiaocao; Zhao, Guohua; Zhang, Minming; Pu, Jiali; Zhang, Baorong

doi:10.1038/s41531-022-00316-9

Cited by 50 publications

(25 citation statements)

References 65 publications

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“…In patients with CSVD, Zhang et al [12] showed the consistency of the ALPS index with clearance rate of the contrast agent. Si et al [13] also confirmed a decrease of ALPS index in patients with Parkinson's disease and possible idiopathic rapid eye movement sleep behavior disorder. These results show that the ALPS index might represent the function of interstitial fluid clearance along perivascular spaces and provide evidence for the application of this method.…”

Section: Discussionmentioning

confidence: 88%

“…Glymphatic dysfunction could disturb brain homeostasis and result in multiple neurological diseases, such as Alzheimer's disease (AD), subarachnoid hemorrhage and CSVD [7][8][9]. Recently, the improvement of non-invasive neuroimaging approaches in rodents [10] and humans [11][12][13] has advanced the field of evaluating glymphatic function in vivo. In particular, the method of diffusion tensor image analysis along the perivascular space (DTI-ALPS) has shown its simplicity and effectiveness in assessing glymphatic dysfunction in multiple neurological disorders [11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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Glymphatic dysfunction correlates with severity of small vessel disease and cognitive impairment in cerebral amyloid angiopathy

et al. 2022

Euro J of Neurology

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Background and purpose: Cerebral amyloid angiopathy (CAA) is characterized by β-amyloid deposition in cortical and leptomeningeal arterioles, which might result from glymphatic dysfunction. The aim was to explore glymphatic function in CAA using the non-invasive diffusion tensor image analysis along the perivascular space method.Methods: Sixty-three patients with CAA were prospectively recruited together with seventy age-and sex-matched normal controls. The Mini-Mental State Examination and Montreal Cognitive Assessment were applied to screen global cognitive status. Magnetic resonance imaging scans were conducted to calculate the index for diffusivity along the perivascular space (ALPS index), and linear regression models were used to assess its relationships with cerebral small vessel disease (CSVD) markers, cognitive status and blood biomarkers. Cox proportional hazard models were applied to explore the role of the baseline ALPS index in disease recurrence. Results:Patients with CAA exhibited a lower ALPS index than controls globally (p < 0.001).In addition, a lower ALPS index was related to more enlarged perivascular space in basal ganglia (p = 0.026), more lacunes (p < 0.001), higher white matter hyperintensity Fazekas score (p = 0.049), elevated total magnetic resonance imaging burden of CSVD (p = 0.034) and lower Mini-Mental State Examination (p = 0.001) as well as Montreal Cognitive Assessment (p < 0.001) in CAA. During a median follow-up of 4.1 years, a higher ALPS index was associated with lower disease recurrence (p = 0.022). The ALPS index was also negatively correlated with serum soluble intercellular adhesion molecule-1, neurofilament light and chitinase-3-like protein 1 in CAA. Conclusions: Patients with CAA showed impaired glymphatic function. The ALPS index was significantly related to CSVD severity, cognitive impairment and disease recurrence in CAA.

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Glymphatic dysfunction correlates with severity of small vessel disease and cognitive impairment in cerebral amyloid angiopathy

et al. 2022

Euro J of Neurology

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“…In a follow-up study, they assessed the correlation between the ALPS index and the progression of PD. Interesting observational research by Si et al (2022) demonstrated a sequential decrease in the ALPS index from prodromal PD to clinical PD [ 127 ]. Further, the ALPS index was related to disease severity in patients with sleep behavior disorders and patients with PD [ 127 ].…”

Section: The Glymphatic System In Neuroimaging Studiesmentioning

confidence: 99%

“…Interesting observational research by Si et al (2022) demonstrated a sequential decrease in the ALPS index from prodromal PD to clinical PD [ 127 ]. Further, the ALPS index was related to disease severity in patients with sleep behavior disorders and patients with PD [ 127 ]. As the authors stated, the study lacks an intervention to modify the glymphatic system, and further experimental evidence is needed to confirm that DTI-ALPS measures glymphatic function [ 127 ].…”

Section: The Glymphatic System In Neuroimaging Studiesmentioning

confidence: 99%

“…Further, the ALPS index was related to disease severity in patients with sleep behavior disorders and patients with PD [ 127 ]. As the authors stated, the study lacks an intervention to modify the glymphatic system, and further experimental evidence is needed to confirm that DTI-ALPS measures glymphatic function [ 127 ]. DTI-ALPS evaluation has also been used to study glymphatic system dysfunction in patients with hemorrhagic stroke, where DTI-ALPS index reflected disease duration [ 128 ].…”

Section: The Glymphatic System In Neuroimaging Studiesmentioning

confidence: 99%

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The Role of Glymphatic System in Alzheimer’s and Parkinson’s Disease Pathogenesis

et al. 2022

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Alzheimer’s disease (AD) is the most common cause of neurodegenerative dementia, whilst Parkinson’s disease (PD) is a neurodegenerative movement disorder. These two neurodegenerative disorders share the accumulation of toxic proteins as a pathological hallmark. The lack of definitive disease-modifying treatments for these neurogenerative diseases has led to the hypothesis of new pathogenic mechanisms to target and design new potential therapeutic approaches. The recent observation that the glymphatic system is supposed to be responsible for the movement of cerebrospinal fluid into the brain and clearance of metabolic waste has led to study its involvement in the pathogenesis of these classic proteinopathies. Aquaporin-4 (AQP4), a water channel located in the endfeet of astrocyte membrane, is considered a primary driver of the glymphatic clearance system, and defective AQP4-mediated glymphatic drainage has been linked to proteinopathies. The objective of the present review is to present the recent body of knowledge that links the glymphatic system to the pathogenesis of AD and PD disease and other lifestyle factors such as sleep deprivation and exercise that may influence glymphatic system function. We will also focus on the potential neuroimaging approaches that could identify a neuroimaging marker to detect glymphatic system changes.

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Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzheimer's disease

Huang,

Zhang,

Guo

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONAlthough glymphatic function is involved in Alzheimer's disease (AD), its potential for predicting the pathological and clinical progression of AD and its sequential association with core AD biomarkers is poorly understood.METHODSWhole‐brain glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI‐ALPS) in participants with AD dementia (n = 47), mild cognitive impairment (MCI; n = 137), and normal controls (n = 235) from the Alzheimer's Disease Neuroimaging Initiative.RESULTSALPS index was significantly lower in AD dementia than in MCI or controls. Lower ALPS index was significantly associated with faster changes in amyloid positron emission tomography (PET) burden and AD signature region of interest volume, higher risk of amyloid‐positive transition and clinical progression, and faster rates of amyloid‐ and neurodegeneration‐related cognitive decline. Furthermore, the associations of the ALPS index with cognitive decline were fully mediated by amyloid PET and brain atrophy.DISCUSSIONGlymphatic failure may precede amyloid pathology, and predicts amyloid deposition, neurodegeneration, and clinical progression in AD.Highlights The analysis along the perivascular space (ALPS) index is reduced in patients with Alzheimer's disease (AD) dementia, prodromal AD, and preclinical AD. Lower ALPS index predicted accelerated amyloid beta (Aβ) positron emission tomography (PET) burden and Aβ‐positive transition. The decrease in the ALPS index occurs before cerebrospinal fluid Aβ42 reaches the positive threshold. ALPS index predicted brain atrophy, clinical progression, and cognitive decline. Aβ PET and brain atrophy mediated the link of ALPS index with cognitive decline.

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Neuroimaging evidence of glymphatic system dysfunction in possible REM sleep behavior disorder and Parkinson’s disease

Cited by 50 publications

References 65 publications

Glymphatic dysfunction correlates with severity of small vessel disease and cognitive impairment in cerebral amyloid angiopathy

Glymphatic dysfunction correlates with severity of small vessel disease and cognitive impairment in cerebral amyloid angiopathy

The Role of Glymphatic System in Alzheimer’s and Parkinson’s Disease Pathogenesis

Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzheimer's disease

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