With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterati...With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.展开更多
Insulin,a key pleiotropic hormone,regulates metabolism through several signaling pathways in target tissues including skeletal muscle,liver,and brain.In the brain,insulin modulates learning and memory,and impaired ins...Insulin,a key pleiotropic hormone,regulates metabolism through several signaling pathways in target tissues including skeletal muscle,liver,and brain.In the brain,insulin modulates learning and memory,and impaired insulin signaling is associated with metabolic dysregulation and neurodegenerative diseases.At the receptor level,in aging and Alzheimer’s disease(AD)models,the amount of insulin receptors and their functions are decreased.Clinical and animal model studies suggest that memory improvements are due to changes in insulin levels.Furthermore,diabetes mellitus(DM)and insulin resistance are associated with age-related cognitive decline,increased levels ofβ-amyloid peptide,phosphorylation of tau protein;oxidative stress,pro-inflammatory cytokine production and dyslipidemia. Recent evidence shows that deleting brain insulin receptors leads to mildobesity and insulin resistance without influencing brain size and apoptosis development.Conversely, deleting insulin-like growth factor 1 receptor (IGF-1R) affects brain size anddevelopment, and contributes to behavior changes. Insulin is synthesized locally in the brain andis released from the neurons. Here, we reviewed proposed pathophysiological hypotheses toexplain increased risk of dementia in the presence of DM. Regardless of the exact sequence ofevents leading to neurodegeneration, there is strong evidence that mitochondrial dysfunctionplays a key role in AD and DM. A triple transgenic mouse model of AD showed mitochondrialdysfunction, oxidative stress, and loss of synaptic integrity. These alterations are comparable tothose induced in wild-type mice treated with sucrose, which is consistent with the proposal thatmitochondrial alterations are associated with DM and contribute to AD development. Alterationsin insulin/IGF-1 signaling in DM could lead to mitochondrial dysfunction and low antioxidantcapacity of the cell. Thus, insulin/IGF-1 signaling is important for increased neural processing andsystemic metabolism, and could be a specific target for therapeutic strategies to decreasealterations associated with age-related cognitive decline.展开更多
Alzheimer's disease(AD)is a neurodegenerative disease that gradually impairs cognitive functions.Recently,there has been a conceptual shift toward AD to view the disease as a continuum.Since AD is currently incura...Alzheimer's disease(AD)is a neurodegenerative disease that gradually impairs cognitive functions.Recently,there has been a conceptual shift toward AD to view the disease as a continuum.Since AD is currently incurable,effective intervention to delay or prevent pathological cognitive decline may best target the early stages of symptomatic disease,such as subjective cognitive decline(SCD),in which cognitive function remains relatively intact.Diagnostic methods for identifying AD,such as cerebrospinal fluid biomarkers and positron emission tomography,are invasive and expensive.Therefore,it is imperative to develop blood biomarkers that are sensitive,less invasive,easier to access,and more cost effective for AD diagnosis.This review aimed to summarize the current data on whether individuals with SCD differ reliably and effectively in subjective and objective performances compared to cognitively normal elderly individuals,and to find one or more convenient and accessible blood biomarkers so that researchers can identify SCD patients with preclinical AD in the population as soon as possible.Owing to the heterogeneity and complicated pathogenesis of AD,it is difficult to make reliable diagnoses using only a single blood marker.This review provides an overview of the progress achieved to date with the use of SCD blood biomarkers in patients with preclinical AD,highlighting the key areas of application and current challenges.展开更多
Epidemiological and biological evidences support a link between type 2 diabetes mellitus(DM2) and Alzheimer's disease(AD). Persons with diabetes have a higher incidence of cognitive decline and an increased risk o...Epidemiological and biological evidences support a link between type 2 diabetes mellitus(DM2) and Alzheimer's disease(AD). Persons with diabetes have a higher incidence of cognitive decline and an increased risk of developing all types of dementia. Cognitive deficits in persons with diabetes mainly affect the areas of psychomotor efficiency, attention, learning and memory, mental flexibility and speed, and executive function. The strong epidemiological association has suggested the existence of a physiopathological link. The determinants of the accelerated cognitive decline in DM2, however, are less clear. Increased cortical and subcortical atrophy have been evidenced after controlling for diabetic vascular disease and inadequate cerebral circulation. Most recent studies have focused on the role of insulin and insulin resistance as possible links between diabetes and AD. Disturbances in brain insulin signaling mechanisms may contribute to the molecular, biochemical, and histopathological lesions in AD. Hyperglycemia itself is a risk factor for cognitive dysfunction and dementia. Hypoglycemia may also have deleterious effects on cognitive function. Recurrent symptomatic and asymptomatic hypoglycemic episodes have been suggested to cause sub-clinical brain damage, and permanent cognitive impairment. Futuretrials are required to clarify the mechanistic link, to address the question whether cognitive decline may be prevented by an adequate metabolic control, and to elucidate the role of drugs that may cause hypoglycemic episodes.展开更多
Study Objectives: Growing evidence suggests that sleep disturbances is common in vascular dementia (VaD). The goal of the current study is to assess the disturbance in sleep pattern in patients with VaD, and compare i...Study Objectives: Growing evidence suggests that sleep disturbances is common in vascular dementia (VaD). The goal of the current study is to assess the disturbance in sleep pattern in patients with VaD, and compare it to healthy normally cognitive elderly individuals. We next studied whether there are meaningful differences in the Subjective sleep assessment: Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and sleep measurements by polysomnography (PSG) in VaD patients. Study design: Case control study. Subject and methods: Overnight PSG recordings and self-reported sleep measures were obtained from 20 healthy elderly subjects and 20 VaD patients at the sleep laboratory. Results: This study showed abnormal subjective sleep quality in all patients and revealed that the most common sleep complaints among VaD patients were: excessive daytime sleepiness (EDS), sleep disordered breathing (SDB), insomnia, restless leg syndrome (RLS), periodic limb movements (PLMS) and REM behavioral disordered (RBD) respectively. Moreover, patients spent more time in stage I sleep, but less time in slow wave sleep (SWS) and REM sleep compared to control populations, with delayed REML and less 1st REML. Also, increased sleep fragmentation;wakefulness after sleep onset (WASO) & sleep fragmentation index (SFI), increased arousal index (AI) & PLMS index were detected in VaD patients. Finally, VaD patients had significant high Apnea, Hypopnea and Respiratory Distress Index (RDI) score with high average SpO2 Desaturation. Conclusions: Sleep is significantly impaired in patients with VaD at both the objective and subjective level, which may be used as a diagnostic marker of VaD. SDB is a common feature of VaD and leads to fragmented sleep, increased nocturnal confusion, and excessive daytime sleepiness. Subjective sleep assessment questionnaire (ESS and PSQI) can be used in VaD patients when objective sleep assessment by PSG recordings is difficult to be done. The PSG study of sleep continuity, sleep architecture, and REM sleep may help in the prevention of progression of VaD.展开更多
Alzheimer’s disease affects millions of persons every year. Negative emotions such as stress and frustration have a negative impact on memory function and Alzheimer's patients experience more negative emotions th...Alzheimer’s disease affects millions of persons every year. Negative emotions such as stress and frustration have a negative impact on memory function and Alzheimer's patients experience more negative emotions than healthy adults. Non-pharmacological treatment such as immersion in virtual environments could help Alzheimer patients by reducing their negative emotions, but it has restrictions and requirements. In this work, we present three virtual reality relaxing systems in which the patients are immersed in relaxing environments. We propose to use intelligent agents in order to adapt the relaxing environment to each participant and optimize its relaxation effect. The intelligent agents track the emotions of patients using electroencephalography as input in order to adapt</span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the environments. We designed each system with different levels of intelligence in order to analyze the impact of the adaptation on the patients. Experiments were performed for each system on participants with subjective cognitive decline. Results show that these relaxing systems can reduce negative emotions and improve participants’ memory performance. The positive effects on affective state and memory persisted for a longer period of time and were generally more effective for the systems with more intelligence. We believe that the combination of </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">a </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">relaxing environment, virtual reality, intelligent agents for adapting</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the environment, and brain assessment is a promising method for helping Alzheimer’s patients.展开更多
基金supported by the Haihe Laboratory of Cell Ecosystem Innovation Foundation,No.22HHXBSS00047(to PL)Graduate Science and Technology Innovation Project of Tianjin,No.2022BKY173(to LZ)Tianjin Municipal Science and Technology Bureau Foundation,No.20201194(to PL).
文摘With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.
文摘Insulin,a key pleiotropic hormone,regulates metabolism through several signaling pathways in target tissues including skeletal muscle,liver,and brain.In the brain,insulin modulates learning and memory,and impaired insulin signaling is associated with metabolic dysregulation and neurodegenerative diseases.At the receptor level,in aging and Alzheimer’s disease(AD)models,the amount of insulin receptors and their functions are decreased.Clinical and animal model studies suggest that memory improvements are due to changes in insulin levels.Furthermore,diabetes mellitus(DM)and insulin resistance are associated with age-related cognitive decline,increased levels ofβ-amyloid peptide,phosphorylation of tau protein;oxidative stress,pro-inflammatory cytokine production and dyslipidemia. Recent evidence shows that deleting brain insulin receptors leads to mildobesity and insulin resistance without influencing brain size and apoptosis development.Conversely, deleting insulin-like growth factor 1 receptor (IGF-1R) affects brain size anddevelopment, and contributes to behavior changes. Insulin is synthesized locally in the brain andis released from the neurons. Here, we reviewed proposed pathophysiological hypotheses toexplain increased risk of dementia in the presence of DM. Regardless of the exact sequence ofevents leading to neurodegeneration, there is strong evidence that mitochondrial dysfunctionplays a key role in AD and DM. A triple transgenic mouse model of AD showed mitochondrialdysfunction, oxidative stress, and loss of synaptic integrity. These alterations are comparable tothose induced in wild-type mice treated with sucrose, which is consistent with the proposal thatmitochondrial alterations are associated with DM and contribute to AD development. Alterationsin insulin/IGF-1 signaling in DM could lead to mitochondrial dysfunction and low antioxidantcapacity of the cell. Thus, insulin/IGF-1 signaling is important for increased neural processing andsystemic metabolism, and could be a specific target for therapeutic strategies to decreasealterations associated with age-related cognitive decline.
基金National Natural Science Foundation of China(Nos.61633018,82020108013,and 82001773)
文摘Alzheimer's disease(AD)is a neurodegenerative disease that gradually impairs cognitive functions.Recently,there has been a conceptual shift toward AD to view the disease as a continuum.Since AD is currently incurable,effective intervention to delay or prevent pathological cognitive decline may best target the early stages of symptomatic disease,such as subjective cognitive decline(SCD),in which cognitive function remains relatively intact.Diagnostic methods for identifying AD,such as cerebrospinal fluid biomarkers and positron emission tomography,are invasive and expensive.Therefore,it is imperative to develop blood biomarkers that are sensitive,less invasive,easier to access,and more cost effective for AD diagnosis.This review aimed to summarize the current data on whether individuals with SCD differ reliably and effectively in subjective and objective performances compared to cognitively normal elderly individuals,and to find one or more convenient and accessible blood biomarkers so that researchers can identify SCD patients with preclinical AD in the population as soon as possible.Owing to the heterogeneity and complicated pathogenesis of AD,it is difficult to make reliable diagnoses using only a single blood marker.This review provides an overview of the progress achieved to date with the use of SCD blood biomarkers in patients with preclinical AD,highlighting the key areas of application and current challenges.
文摘Epidemiological and biological evidences support a link between type 2 diabetes mellitus(DM2) and Alzheimer's disease(AD). Persons with diabetes have a higher incidence of cognitive decline and an increased risk of developing all types of dementia. Cognitive deficits in persons with diabetes mainly affect the areas of psychomotor efficiency, attention, learning and memory, mental flexibility and speed, and executive function. The strong epidemiological association has suggested the existence of a physiopathological link. The determinants of the accelerated cognitive decline in DM2, however, are less clear. Increased cortical and subcortical atrophy have been evidenced after controlling for diabetic vascular disease and inadequate cerebral circulation. Most recent studies have focused on the role of insulin and insulin resistance as possible links between diabetes and AD. Disturbances in brain insulin signaling mechanisms may contribute to the molecular, biochemical, and histopathological lesions in AD. Hyperglycemia itself is a risk factor for cognitive dysfunction and dementia. Hypoglycemia may also have deleterious effects on cognitive function. Recurrent symptomatic and asymptomatic hypoglycemic episodes have been suggested to cause sub-clinical brain damage, and permanent cognitive impairment. Futuretrials are required to clarify the mechanistic link, to address the question whether cognitive decline may be prevented by an adequate metabolic control, and to elucidate the role of drugs that may cause hypoglycemic episodes.
文摘Study Objectives: Growing evidence suggests that sleep disturbances is common in vascular dementia (VaD). The goal of the current study is to assess the disturbance in sleep pattern in patients with VaD, and compare it to healthy normally cognitive elderly individuals. We next studied whether there are meaningful differences in the Subjective sleep assessment: Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and sleep measurements by polysomnography (PSG) in VaD patients. Study design: Case control study. Subject and methods: Overnight PSG recordings and self-reported sleep measures were obtained from 20 healthy elderly subjects and 20 VaD patients at the sleep laboratory. Results: This study showed abnormal subjective sleep quality in all patients and revealed that the most common sleep complaints among VaD patients were: excessive daytime sleepiness (EDS), sleep disordered breathing (SDB), insomnia, restless leg syndrome (RLS), periodic limb movements (PLMS) and REM behavioral disordered (RBD) respectively. Moreover, patients spent more time in stage I sleep, but less time in slow wave sleep (SWS) and REM sleep compared to control populations, with delayed REML and less 1st REML. Also, increased sleep fragmentation;wakefulness after sleep onset (WASO) & sleep fragmentation index (SFI), increased arousal index (AI) & PLMS index were detected in VaD patients. Finally, VaD patients had significant high Apnea, Hypopnea and Respiratory Distress Index (RDI) score with high average SpO2 Desaturation. Conclusions: Sleep is significantly impaired in patients with VaD at both the objective and subjective level, which may be used as a diagnostic marker of VaD. SDB is a common feature of VaD and leads to fragmented sleep, increased nocturnal confusion, and excessive daytime sleepiness. Subjective sleep assessment questionnaire (ESS and PSQI) can be used in VaD patients when objective sleep assessment by PSG recordings is difficult to be done. The PSG study of sleep continuity, sleep architecture, and REM sleep may help in the prevention of progression of VaD.
文摘Alzheimer’s disease affects millions of persons every year. Negative emotions such as stress and frustration have a negative impact on memory function and Alzheimer's patients experience more negative emotions than healthy adults. Non-pharmacological treatment such as immersion in virtual environments could help Alzheimer patients by reducing their negative emotions, but it has restrictions and requirements. In this work, we present three virtual reality relaxing systems in which the patients are immersed in relaxing environments. We propose to use intelligent agents in order to adapt the relaxing environment to each participant and optimize its relaxation effect. The intelligent agents track the emotions of patients using electroencephalography as input in order to adapt</span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the environments. We designed each system with different levels of intelligence in order to analyze the impact of the adaptation on the patients. Experiments were performed for each system on participants with subjective cognitive decline. Results show that these relaxing systems can reduce negative emotions and improve participants’ memory performance. The positive effects on affective state and memory persisted for a longer period of time and were generally more effective for the systems with more intelligence. We believe that the combination of </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">a </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">relaxing environment, virtual reality, intelligent agents for adapting</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the environment, and brain assessment is a promising method for helping Alzheimer’s patients.
