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
Background:Deep brain stimulation(DBS)of the nucleus basalis of Meynert(NBM)has shown potential for the treatment of mild-to-moderate Alzheimer’s disease(AD).However,there is little evidence of whether NBM-DBS can im...Background:Deep brain stimulation(DBS)of the nucleus basalis of Meynert(NBM)has shown potential for the treatment of mild-to-moderate Alzheimer’s disease(AD).However,there is little evidence of whether NBM-DBS can improve cognitive functioning in patients with advanced AD.In addition,the mechanisms underlying the modulation of brain networks remain unclear.This study was aimed to assess the cognitive function and the resting-state connectivity following NBM-DBS in patients with advanced AD.Methods:Eight patients with advanced AD underwent bilateral NBM-DBS and were followed up for 12 months.Clinical outcomes were assessed by neuropsychological examinations using the Mini-Mental State Examination(MMSE)and Alzheimer’s Disease Assessment Scale.Resting-state functional magnetic resonance imaging and positron emis-sion tomography data were also collected.Results:The cognitive functioning of AD patients did not change from baseline to the 12-month follow-up.Interestingly,the MMSE score indicated clinical efficacy at 1 month of follow-up.At this time point,the connectivity between the hippocampal network and frontoparietal network tended to increase in the DBS-on state compared to the DBS-off state.Additionally,the increased functional connectivity between the parahippocampal gyrus(PHG)and the parietal cortex was associated with cognitive improvement.Further dynamic functional network analysis showed that NBM-DBS increased the proportion of the PHG-related connections,which was related to improved cognitive performance.Conclusion:The results indicated that NBM-DBS improves short-term cognitive performance in patients with advanced AD,which may be related to the modulation of multi-network connectivity patterns,and the hippocampus plays an important role within these networks.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the National Natural Science Foundation of China(61761166004 and 81830033).
文摘Background:Deep brain stimulation(DBS)of the nucleus basalis of Meynert(NBM)has shown potential for the treatment of mild-to-moderate Alzheimer’s disease(AD).However,there is little evidence of whether NBM-DBS can improve cognitive functioning in patients with advanced AD.In addition,the mechanisms underlying the modulation of brain networks remain unclear.This study was aimed to assess the cognitive function and the resting-state connectivity following NBM-DBS in patients with advanced AD.Methods:Eight patients with advanced AD underwent bilateral NBM-DBS and were followed up for 12 months.Clinical outcomes were assessed by neuropsychological examinations using the Mini-Mental State Examination(MMSE)and Alzheimer’s Disease Assessment Scale.Resting-state functional magnetic resonance imaging and positron emis-sion tomography data were also collected.Results:The cognitive functioning of AD patients did not change from baseline to the 12-month follow-up.Interestingly,the MMSE score indicated clinical efficacy at 1 month of follow-up.At this time point,the connectivity between the hippocampal network and frontoparietal network tended to increase in the DBS-on state compared to the DBS-off state.Additionally,the increased functional connectivity between the parahippocampal gyrus(PHG)and the parietal cortex was associated with cognitive improvement.Further dynamic functional network analysis showed that NBM-DBS increased the proportion of the PHG-related connections,which was related to improved cognitive performance.Conclusion:The results indicated that NBM-DBS improves short-term cognitive performance in patients with advanced AD,which may be related to the modulation of multi-network connectivity patterns,and the hippocampus plays an important role within these networks.
