Previous studies have shown that reduced sleep duration,sleep fragmentation,and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling.At the same time,blood-br...Previous studies have shown that reduced sleep duration,sleep fragmentation,and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling.At the same time,blood-brain barrier disruption is considered an early biomarker of Alzheimer's disease.However,currently no report has examined how changes in orexin signaling relate to changes in the blood-brain barrier of patients who have Alzheimer's disease with sleep insufficiency.This cross-sectional study included 50 patients with Alzheimer's disease who received treatment in 2019 at Beijing Tiantan Hospital.Patients were divided into two groups:those with insufficient sleep(sleep duration≤6 hours,n=19,age 61.58±8.54 years,10 men)and those with normal sleep durations(sleep duration>6 hours,n=31,age 63.19±10.09 years,18 men).Demographic variables were collected to evaluate cognitive function,neuropsychiatric symptoms,and activities of daily living.The levels of orexin,its receptor proteins,and several blood-brain barrier factors were measured in cerebrospinal fluid.Sleep insufficiency was associated with impaired overall cognitive function that spanned multiple cognitive domains.Furthermore,levels of orexin and its receptors were upregulated in the cerebrospinal fluid,and the blood–brain barrier was destroyed.Both these events precipitated each other and accelerated the progression of Alzheimer's disease.These findings describe the clinical characteristics and potential mechanism underlying Alzheimer's disease accompanied by sleep deprivation.Inhibiting the upregulation of elements within the orexin system or preventing the breakdown of the blood-brain barrier could thus be targets for treating Alzheimer's disease.展开更多
Parkinson’s disease (PD) is the second most common neurodegenerative disease. Its most prominent pathological features are the loss of dopaminergic neurons in the substantia nigra pars compacta and the deposition of ...Parkinson’s disease (PD) is the second most common neurodegenerative disease. Its most prominent pathological features are the loss of dopaminergic neurons in the substantia nigra pars compacta and the deposition of intraneuronal inclusions named Lewy bodies. Currently, the pathophysiological mechanisms of PD are not fully understood. Growing evidence suggests that insulin resistance, diabetes and PD share similar pathological processes. This raises the possibility that defective insulin signaling pathways contribute to the occurrence and development of PD. In this article, we firstly reviewed the evidence of insulin resistance from epidemiology, PD patients and animal models. We also explained the insulin signal pathways in central nervous system. We then showed the evidence that insulin resistance participates in the pathogenesis of PD via protein aggregation, mitochondrial dysfunction, neural inflammation and cognitive impairment. Finally, we introduced four categories of drugs that facilitate insulin signaling and their effects on neurodegeneration in PD.展开更多
Mild cognitive impairment （MCI） is common in patients with Parkinson＇s disease （PD）, yet the underlying neural mechanisms of this disease state remain unclear. We investigated alterations in the spontaneous brain...Mild cognitive impairment （MCI） is common in patients with Parkinson＇s disease （PD）, yet the underlying neural mechanisms of this disease state remain unclear. We investigated alterations in the spontaneous brain activity of PD patients with MCI （PD-MCI） relative to cognitively normal PD patients （PD-CN） and healthy control （HC） subjects. In this work, 13 PD-MCI patients, 16 PD-CN patients, and 16 HC subjects completed resting state functional MRI. Spontaneous brain activity was measured by calculating amplitude of low frequency fluctuation （ALFF） values across the whole brain. Between-group differences and correlations between ALFF values and cognitive test scores were analyzed. ALFF values decreased in the right superior temporal gyrus and increased in the left middle temporal gyrus and left superior frontal gyms of PD-MCI patients compared with PD-CN patients. In the PD-MCI group, ALFF values in the left middle temporal gyrus were negatively correlated with Montreal Cognitive Assessment and vocabulary test scores, and the ALFF values in the left superior frontal gyms were negatively correlated with vocabulary test scores. Our study demonstrates that PD-MCI is associated with abnormal spontaneous brain activity in the temporal and frontal lobes. These findings inform the underlying neural mechanism of cognitive impairment in PD.展开更多
Parkinson’s disease(PD)is a neurodegenerative disorder primarily affecting the aging population.The neurophysiological mechanisms underlying parkinsonian symptoms remain unclear.PD affects extensive neural networks a...Parkinson’s disease(PD)is a neurodegenerative disorder primarily affecting the aging population.The neurophysiological mechanisms underlying parkinsonian symptoms remain unclear.PD affects extensive neural networks and a more thorough understanding of network disruption will help bridge the gap between known pathological changes and observed clinical presentations in PD.Development of neuroimaging techniques,especially functional magnetic resonance imaging,allows for detection of the functional connectivity of neural networks in patients with PD.This review aims to provide an overview of current research involving functional network disruption in PD relating to motor and non-motor symptoms.Investigations into functional network connectivity will further our understanding of the mechanisms underlying the effectiveness of clinical interventions,such as levodopa and deep brain stimulation treatment.In addition,identification of PD-specific neural network patterns has the potential to aid in the development of a definitive diagnosis of PD.展开更多
Neurodegeneration of Parkinson’s disease(PD)starts in an insidious manner,30–50%of dopaminergic neurons have been lost in the substantia nigra before clinical diagnosis.Prodromal stage of the disease,during which th...Neurodegeneration of Parkinson’s disease(PD)starts in an insidious manner,30–50%of dopaminergic neurons have been lost in the substantia nigra before clinical diagnosis.Prodromal stage of the disease,during which the disease pathology has started but is insufficient to result in clinical manifestations,offers a valuable window for disease-modifying therapies.The most focused underlying mechanisms linking the pathological pattern and clinical characteristics of prodromal PD are the prion hypothesis of alpha-synuclein and the selective vulnerability of neurons.In this review,we consider the two potential portals,the vagus nerve and the olfactory bulb,through which abnormal alpha-synuclein can access the brain.We review the clinical,pathological and neuroimaging evidence of the parasympathetic nervous system and the olfactory system in the neurodegenerative process and using the two systems as models to discuss the internal homogeneity and heterogeneity of the prodromal stage of PD,including both the clustering and subtyping of symptoms and signs.Finally,we offer some suggestions on future directions for imaging studies in prodromal Parkinson’s disease.展开更多
基金supported by the National Key Research and Development Program of China,Nos.2016YFC1306300(to XMW),2016YFC1306000the National Key R&D Program of China-European Commission Horizon 2020,No.2017YFE0118800-779238(to YXW)+15 种基金the Notional Natural Science Foundation of Chino,Nos.81970992(to WZ),81571229(to WZ),81071015(to WZ),30770745(to WZ)Capital's Funds for Health Improvement and Research(CFH),No.2022-2-2048(to WZ)the Key Technology R&D Program of Beijing Municipal Education Commission,No.kz201610025030(to WZ)the Natural Science Foundation of Beijing,No.7082032(to WZ)the Key Project of the Natural Science Foundation of Beijing,No.4161004(to WZ)Capitol Clinical Characteristic Applicotion Research,No.Z121107001012161(to WZ)Project of Scientific and Technological Development of Traditional Chinese Medicine in Beijing,No.JJ2018-48(to WZ)High Level Technical Personnel Training Project of Beijing Health System of China,No.2009-3-26(to WZ)Excellent Personnel Training Project of Beijing,No.20071D0300400076(to WZ)Important National Science&Technology Specific Project,No.2011ZX09102-003-01(to WZ)Beijing Healthcare Research Project,No.JING-15-2(to WZ)Basic-Clinicol Research Cooperation Funding of Capitol Medical University of China,Nos.2015-JL-PT-X04(to WZ),10JL49(to WZ),14JL15(to WZ)the Natural Science Foundation of Capital Medical UniversityBeijingChina,No.PYZ2018077(to PG)Youth Research Fund of Beijing Tianton Hospital of Capital Medical University of China,Nos.2015-YQN-14(to PG),2015-YQN-15,2015-YQN-17。
文摘Previous studies have shown that reduced sleep duration,sleep fragmentation,and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling.At the same time,blood-brain barrier disruption is considered an early biomarker of Alzheimer's disease.However,currently no report has examined how changes in orexin signaling relate to changes in the blood-brain barrier of patients who have Alzheimer's disease with sleep insufficiency.This cross-sectional study included 50 patients with Alzheimer's disease who received treatment in 2019 at Beijing Tiantan Hospital.Patients were divided into two groups:those with insufficient sleep(sleep duration≤6 hours,n=19,age 61.58±8.54 years,10 men)and those with normal sleep durations(sleep duration>6 hours,n=31,age 63.19±10.09 years,18 men).Demographic variables were collected to evaluate cognitive function,neuropsychiatric symptoms,and activities of daily living.The levels of orexin,its receptor proteins,and several blood-brain barrier factors were measured in cerebrospinal fluid.Sleep insufficiency was associated with impaired overall cognitive function that spanned multiple cognitive domains.Furthermore,levels of orexin and its receptors were upregulated in the cerebrospinal fluid,and the blood–brain barrier was destroyed.Both these events precipitated each other and accelerated the progression of Alzheimer's disease.These findings describe the clinical characteristics and potential mechanism underlying Alzheimer's disease accompanied by sleep deprivation.Inhibiting the upregulation of elements within the orexin system or preventing the breakdown of the blood-brain barrier could thus be targets for treating Alzheimer's disease.
基金grants of the National Key R&D Program of China (2016YFC1306000)National Natural Science Foundation of China (81870994).
文摘Parkinson’s disease (PD) is the second most common neurodegenerative disease. Its most prominent pathological features are the loss of dopaminergic neurons in the substantia nigra pars compacta and the deposition of intraneuronal inclusions named Lewy bodies. Currently, the pathophysiological mechanisms of PD are not fully understood. Growing evidence suggests that insulin resistance, diabetes and PD share similar pathological processes. This raises the possibility that defective insulin signaling pathways contribute to the occurrence and development of PD. In this article, we firstly reviewed the evidence of insulin resistance from epidemiology, PD patients and animal models. We also explained the insulin signal pathways in central nervous system. We then showed the evidence that insulin resistance participates in the pathogenesis of PD via protein aggregation, mitochondrial dysfunction, neural inflammation and cognitive impairment. Finally, we introduced four categories of drugs that facilitate insulin signaling and their effects on neurodegeneration in PD.
基金supported by the National Natural Science Foundation of China(81271429 and 81571228)
文摘Mild cognitive impairment （MCI） is common in patients with Parkinson＇s disease （PD）, yet the underlying neural mechanisms of this disease state remain unclear. We investigated alterations in the spontaneous brain activity of PD patients with MCI （PD-MCI） relative to cognitively normal PD patients （PD-CN） and healthy control （HC） subjects. In this work, 13 PD-MCI patients, 16 PD-CN patients, and 16 HC subjects completed resting state functional MRI. Spontaneous brain activity was measured by calculating amplitude of low frequency fluctuation （ALFF） values across the whole brain. Between-group differences and correlations between ALFF values and cognitive test scores were analyzed. ALFF values decreased in the right superior temporal gyrus and increased in the left middle temporal gyrus and left superior frontal gyms of PD-MCI patients compared with PD-CN patients. In the PD-MCI group, ALFF values in the left middle temporal gyrus were negatively correlated with Montreal Cognitive Assessment and vocabulary test scores, and the ALFF values in the left superior frontal gyms were negatively correlated with vocabulary test scores. Our study demonstrates that PD-MCI is associated with abnormal spontaneous brain activity in the temporal and frontal lobes. These findings inform the underlying neural mechanism of cognitive impairment in PD.
文摘Parkinson’s disease(PD)is a neurodegenerative disorder primarily affecting the aging population.The neurophysiological mechanisms underlying parkinsonian symptoms remain unclear.PD affects extensive neural networks and a more thorough understanding of network disruption will help bridge the gap between known pathological changes and observed clinical presentations in PD.Development of neuroimaging techniques,especially functional magnetic resonance imaging,allows for detection of the functional connectivity of neural networks in patients with PD.This review aims to provide an overview of current research involving functional network disruption in PD relating to motor and non-motor symptoms.Investigations into functional network connectivity will further our understanding of the mechanisms underlying the effectiveness of clinical interventions,such as levodopa and deep brain stimulation treatment.In addition,identification of PD-specific neural network patterns has the potential to aid in the development of a definitive diagnosis of PD.
文摘Neurodegeneration of Parkinson’s disease(PD)starts in an insidious manner,30–50%of dopaminergic neurons have been lost in the substantia nigra before clinical diagnosis.Prodromal stage of the disease,during which the disease pathology has started but is insufficient to result in clinical manifestations,offers a valuable window for disease-modifying therapies.The most focused underlying mechanisms linking the pathological pattern and clinical characteristics of prodromal PD are the prion hypothesis of alpha-synuclein and the selective vulnerability of neurons.In this review,we consider the two potential portals,the vagus nerve and the olfactory bulb,through which abnormal alpha-synuclein can access the brain.We review the clinical,pathological and neuroimaging evidence of the parasympathetic nervous system and the olfactory system in the neurodegenerative process and using the two systems as models to discuss the internal homogeneity and heterogeneity of the prodromal stage of PD,including both the clustering and subtyping of symptoms and signs.Finally,we offer some suggestions on future directions for imaging studies in prodromal Parkinson’s disease.
