This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral ang...This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral angiography-MRI revealed features indicative of CAA. Symptomatic treatment resulted in improvement, but the patient later developed a fatal hematoma. The discussion navigates the intricate therapeutic landscape of repetitive TIAs in the elderly with cardiovascular risk factors, emphasizing the pivotal role of cerebral MRI and meticulous bleeding risk management. The conclusion stresses the importance of incorporating SWI sequences, specifically when suspecting a cardioembolic TIA, as a diagnostic measure to explore and exclude CAA in the differential diagnosis. This case report provides valuable insights into these challenges, highlighting the need to consider CAA in relevant cases.展开更多
BACKGROUND Diagnosis of a dementia subtype can be complex and often requires comprehensive cognitive assessment and dedicated neuroimaging.Clinicians are prone to cognitive biases when reviewing such images.We present...BACKGROUND Diagnosis of a dementia subtype can be complex and often requires comprehensive cognitive assessment and dedicated neuroimaging.Clinicians are prone to cognitive biases when reviewing such images.We present a case of cognitive impairment and demonstrate that initial imaging may have resulted in misleading the diagnosis due to such cognitive biases.CASE SUMMARY A 76-year-old man with no cognitive impairment presented with acute onset word finding difficulty with unremarkable blood tests and neurological examination.Magnetic resonance imaging(MRI)demonstrated multiple foci of periventricular and subcortical microhaemorrhage,consistent with cerebral amyloid angiopathy(CAA).Cognitive assessment of this patient demonstrated marked impairment mainly in verbal fluency and memory.However,processing speed and executive function are most affected in CAA,whereas episodic memory is relatively preserved,unlike in other causes of cognitive impairment,such as Alzheimer’s dementia(AD).This raised the question of an underlying diagnosis of dementia.Repeat MRI with dedicated coronal views demonstrated mesial temporal lobe atrophy which is consistent with AD.CONCLUSION MRI brain can occasionally result in diagnostic overshadowing,and the application of artificial intelligence to medical imaging may overcome such cognitive biases.展开更多
Background Cerebral amyloid angiopathy is a common cause of subcortical hemorrhage in older adults.Although open hematoma removal may be performed for severe subcortical hemorrhage,its safety in patients with cerebral...Background Cerebral amyloid angiopathy is a common cause of subcortical hemorrhage in older adults.Although open hematoma removal may be performed for severe subcortical hemorrhage,its safety in patients with cerebral amyloid angiopathy has not been established,and postoperative rebleeding may occur.Therefore,this study aimed to investigate factors associated with postoperative rebleeding.Methods Out of 145 consecutive patients who had undergone craniotomy for surgical removal of subcortical intracerebral hemorrhage between April 2010 and August 2019 at a single institution in Japan,we examined 109 patients with subcortical hemorrhage who met the inclusion criteria.After excluding 30 patients whose tissue samples were unsuitable for the study,the final study cohort comprised 79 patients.Results Of the 79 patients,50(63%)were diagnosed with cerebral amyloid angiopathy(cerebral amyloid angiopathy group)and 29(37%)were not diagnosed with noncerebral amyloid angiopathy(noncerebral amyloid angiopathy group).Postoperative rebleeding occurred in 12 patients(24%)in the cerebral amyloid angiopathy group and in 2 patients(7%)in the noncerebral amyloid angiopathy group.Preoperative prothrombin time-international normalized ratio and intraoperative bleeding volume were significantly associated with postoperative rebleeding in the cerebral amyloid angiopathy group(odds ratio=42.4,95%confidence interval=1.14-1578;p=0.042 and odds ratio=1.005,95%confidence interval=1.001-1.008;p=0.007,respectively).Conclusions Patients with cerebral amyloid angiopathy-related cerebral hemorrhage who are receiving antithrombotic therapy,particularly warfarin therapy,are at a high risk of postoperative rebleeding.Trial registration Registry and Registration Number of the study:19-220,2019/12/23,retrospectively registered.展开更多
Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related an...Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related angiitis. Acute or subacute onset of cognitive decline or behavioral changes is the most common symptom of CAA-RI. Rapid progressive dementia, headache, seizures, or focal neurological deficits, with patchy or confluent hyperintensity on T2 or fluid-attenuated inversion recovery sequences and evidence of strictly lobar microbleeds or cortical superficial siderosis on susceptibility-weighted imaging imply CAA-RI. The gold standard for diagnosis is autopsy or brain biopsy. However, biopsy is invasive;consequently, most clinically diagnosed cases have been based on clinical and radiological data. Other diagnostic indexes include the apolipoprotein E ε4 allele, Aβ and anti-Aβ antibodies in cerebral spinal fluid and amyloid positron emission tomography. Many diseases with similar clinical manifestations should be carefully ruled out. Immunosuppressive therapy is effective both during initial presentation and in relapses. The use of glucocorticoids and immunosuppressants improves prognosis. This article reviews the pathology and pathogenesis, clinical and imaging manifestations, diagnostic criteria, treatment, and prognosis of CAA-RI, and highlights unsolved problems in the existing research.展开更多
Cerebral amyloid angiopathy(CAA)is characterized by the deposition of amyloid β-protein(Aβ)in the leptomeningeal and cortical blood vessels,which is an age-dependent risk factor for intracerebral hemorrhage(ICH),isc...Cerebral amyloid angiopathy(CAA)is characterized by the deposition of amyloid β-protein(Aβ)in the leptomeningeal and cortical blood vessels,which is an age-dependent risk factor for intracerebral hemorrhage(ICH),ischemic stroke and contributes to cerebrovascular dysfunction leading to cognitive impairment.However clinical prevention and treatment of the disease is very difficult because of its occult onset and severity of the symptoms.In recent years,many anti-amyloid β immunotherapies have not demonstrated clinical efficacy in subjects with Alzheimer’s disease(AD),and the failure may be due to the deposition of Aβ in the cerebrovascular export pathway resulting in further damage to blood vessels and aggravating CAA.So decreased clearance of Aβ in blood vessels plays a crucial role in the development of CAA and AD,and identification of the molecular pathways involved will provide new targets for treatment.In this review,we mainly describe the mechanisms of Aβ clearance through vessels,especially in terms of some proteins and receptors involved in this process.展开更多
Background:Vascular impairment is one of the major contributors to dementia.We aimed to identify blood biomarkers suggestive of potential impairment of the blood-brain barrier(BBB)in subjects with Alzheimer’s disease...Background:Vascular impairment is one of the major contributors to dementia.We aimed to identify blood biomarkers suggestive of potential impairment of the blood-brain barrier(BBB)in subjects with Alzheimer’s disease(AD).Methods:We used administrative data from the VA Informatics and Computing Infrastructure Resource Center to study both inpatients and outpatients with AD.Plasma samples from healthy control and AD individuals were analyzed using enzyme-linked immunosorbent assay and proteomics approaches to identify differentially expressed proteins.Bioinformatic analysis was applied to explore significantly enriched pathways.Results:In the same cohort of patients with AD,we found twice number of subjects with cerebral amyloid angiopathy in the two-year period after the onset of AD,compared to the number of subjects with cerebral amyloid angiopathy in the two-year period prior to AD onset.Different pathways related to BBB,like cell adhesion,extracellular matrix organization and Wnt signaling,were activated and differentially expressed proteins such as ADAM22,PDGFR-α,DKK-4,Neucrin and RSOP-1 were identified.Moreover,matrix metalloproteinase-9,which is implicated in causing degradation of basal lamina and BBB disruption,was significantly increased in the plasma of AD patients.Conclusions:Alteration of proteins found in AD subjects could provide new insights into biomarkers regulating permeability and BBB integrity.展开更多
Neurovascular dysfunction,as an integral part of Alzheimer's disease,may have an important influence on the onset and progression of chronic neurodegenerative processes.The bloodbrain barrier(BBB)pathway is one of...Neurovascular dysfunction,as an integral part of Alzheimer's disease,may have an important influence on the onset and progression of chronic neurodegenerative processes.The bloodbrain barrier(BBB)pathway is one of the main pathways that mediates the clearance of amyloidbeta(Aβ)in the brain parenchyma.A large number of studies have shown that receptors and ATPbinding cassette transporte rs expressed on endothelial cells play an important role in Aβtransport across the BBB,but the specific mechanism is not clear.In this review,we summarize the possible mechanisms of Aβproduction and clearance,and in particular the relationship between Aβand brain capillary endothelial cells.Aβis produced by abnormal cleavage of the amyloid precursor protein via amyloidogenic processing under pathological conditions.Dys regulation of Aβclearance is considered to be the main reason for the massive accumulation of Aβin the brain parenchyma.Several pathways mediating Aβclearance from the brain into the periphery have been identified,including the BBB pathway,the blood-cerebros pinal fluid barrier and arachnoid granule pathway,and the lymphoidrelated pathway.Brain ca pilla ry endothelial cells are the key components of Aβclearance mediated by BBB.Receptors(such as LRP1,RAGE,and FcRn)and ATP-binding cassette transporters(such as P-gp,ABCA1,and ABCC1)expressed on endothelial cells play a critical role in Aβtranscytosis across the BBB.The toxic effects of Aβcan induce dysregulation of receptor and transpo rter expression on endothelial cells.Excessive Aβexerts potent detrimental cerebrovascular effects by promoting oxidative stress,inducing chronic inflammation,and impairing endothelial structure and functions.All of these are main causes for the reduction in Aβclearance across the BBB and the accumulation of Aβin the brain parenchyma.Therefo re,studies on the intera ctions between Aβand brain capillary endothelial cells,including their receptors and transporters,studies on inhibition of the toxic effects of Aβon endothelial cells,and studies on promoting the ability of endothelial cells to mediate Aβclearance may provide new therapeutic strategies for Aβclearance in Alzheimer's disease.展开更多
文摘This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral angiography-MRI revealed features indicative of CAA. Symptomatic treatment resulted in improvement, but the patient later developed a fatal hematoma. The discussion navigates the intricate therapeutic landscape of repetitive TIAs in the elderly with cardiovascular risk factors, emphasizing the pivotal role of cerebral MRI and meticulous bleeding risk management. The conclusion stresses the importance of incorporating SWI sequences, specifically when suspecting a cardioembolic TIA, as a diagnostic measure to explore and exclude CAA in the differential diagnosis. This case report provides valuable insights into these challenges, highlighting the need to consider CAA in relevant cases.
文摘BACKGROUND Diagnosis of a dementia subtype can be complex and often requires comprehensive cognitive assessment and dedicated neuroimaging.Clinicians are prone to cognitive biases when reviewing such images.We present a case of cognitive impairment and demonstrate that initial imaging may have resulted in misleading the diagnosis due to such cognitive biases.CASE SUMMARY A 76-year-old man with no cognitive impairment presented with acute onset word finding difficulty with unremarkable blood tests and neurological examination.Magnetic resonance imaging(MRI)demonstrated multiple foci of periventricular and subcortical microhaemorrhage,consistent with cerebral amyloid angiopathy(CAA).Cognitive assessment of this patient demonstrated marked impairment mainly in verbal fluency and memory.However,processing speed and executive function are most affected in CAA,whereas episodic memory is relatively preserved,unlike in other causes of cognitive impairment,such as Alzheimer’s dementia(AD).This raised the question of an underlying diagnosis of dementia.Repeat MRI with dedicated coronal views demonstrated mesial temporal lobe atrophy which is consistent with AD.CONCLUSION MRI brain can occasionally result in diagnostic overshadowing,and the application of artificial intelligence to medical imaging may overcome such cognitive biases.
基金The Hidaka Research Projects(grant number:01-D-1-07)
文摘Background Cerebral amyloid angiopathy is a common cause of subcortical hemorrhage in older adults.Although open hematoma removal may be performed for severe subcortical hemorrhage,its safety in patients with cerebral amyloid angiopathy has not been established,and postoperative rebleeding may occur.Therefore,this study aimed to investigate factors associated with postoperative rebleeding.Methods Out of 145 consecutive patients who had undergone craniotomy for surgical removal of subcortical intracerebral hemorrhage between April 2010 and August 2019 at a single institution in Japan,we examined 109 patients with subcortical hemorrhage who met the inclusion criteria.After excluding 30 patients whose tissue samples were unsuitable for the study,the final study cohort comprised 79 patients.Results Of the 79 patients,50(63%)were diagnosed with cerebral amyloid angiopathy(cerebral amyloid angiopathy group)and 29(37%)were not diagnosed with noncerebral amyloid angiopathy(noncerebral amyloid angiopathy group).Postoperative rebleeding occurred in 12 patients(24%)in the cerebral amyloid angiopathy group and in 2 patients(7%)in the noncerebral amyloid angiopathy group.Preoperative prothrombin time-international normalized ratio and intraoperative bleeding volume were significantly associated with postoperative rebleeding in the cerebral amyloid angiopathy group(odds ratio=42.4,95%confidence interval=1.14-1578;p=0.042 and odds ratio=1.005,95%confidence interval=1.001-1.008;p=0.007,respectively).Conclusions Patients with cerebral amyloid angiopathy-related cerebral hemorrhage who are receiving antithrombotic therapy,particularly warfarin therapy,are at a high risk of postoperative rebleeding.Trial registration Registry and Registration Number of the study:19-220,2019/12/23,retrospectively registered.
基金National Key Research and Development Program of China(No.2016YFC1300500-505)。
文摘Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related angiitis. Acute or subacute onset of cognitive decline or behavioral changes is the most common symptom of CAA-RI. Rapid progressive dementia, headache, seizures, or focal neurological deficits, with patchy or confluent hyperintensity on T2 or fluid-attenuated inversion recovery sequences and evidence of strictly lobar microbleeds or cortical superficial siderosis on susceptibility-weighted imaging imply CAA-RI. The gold standard for diagnosis is autopsy or brain biopsy. However, biopsy is invasive;consequently, most clinically diagnosed cases have been based on clinical and radiological data. Other diagnostic indexes include the apolipoprotein E ε4 allele, Aβ and anti-Aβ antibodies in cerebral spinal fluid and amyloid positron emission tomography. Many diseases with similar clinical manifestations should be carefully ruled out. Immunosuppressive therapy is effective both during initial presentation and in relapses. The use of glucocorticoids and immunosuppressants improves prognosis. This article reviews the pathology and pathogenesis, clinical and imaging manifestations, diagnostic criteria, treatment, and prognosis of CAA-RI, and highlights unsolved problems in the existing research.
基金This work was supported by national natural science grant(81570035).
文摘Cerebral amyloid angiopathy(CAA)is characterized by the deposition of amyloid β-protein(Aβ)in the leptomeningeal and cortical blood vessels,which is an age-dependent risk factor for intracerebral hemorrhage(ICH),ischemic stroke and contributes to cerebrovascular dysfunction leading to cognitive impairment.However clinical prevention and treatment of the disease is very difficult because of its occult onset and severity of the symptoms.In recent years,many anti-amyloid β immunotherapies have not demonstrated clinical efficacy in subjects with Alzheimer’s disease(AD),and the failure may be due to the deposition of Aβ in the cerebrovascular export pathway resulting in further damage to blood vessels and aggravating CAA.So decreased clearance of Aβ in blood vessels plays a crucial role in the development of CAA and AD,and identification of the molecular pathways involved will provide new targets for treatment.In this review,we mainly describe the mechanisms of Aβ clearance through vessels,especially in terms of some proteins and receptors involved in this process.
基金University of Massachusetts Lowell-Bedford VA Healthcare System Pilot Award(NM,WX,EG),I01 BX004730 and I01 BX003527 Merit Awards from the Biomedical Laboratory Research and Development of the Veterans Affairs Office of Research and Development(WX)RF1AG063913 from the NIH(WX).
文摘Background:Vascular impairment is one of the major contributors to dementia.We aimed to identify blood biomarkers suggestive of potential impairment of the blood-brain barrier(BBB)in subjects with Alzheimer’s disease(AD).Methods:We used administrative data from the VA Informatics and Computing Infrastructure Resource Center to study both inpatients and outpatients with AD.Plasma samples from healthy control and AD individuals were analyzed using enzyme-linked immunosorbent assay and proteomics approaches to identify differentially expressed proteins.Bioinformatic analysis was applied to explore significantly enriched pathways.Results:In the same cohort of patients with AD,we found twice number of subjects with cerebral amyloid angiopathy in the two-year period after the onset of AD,compared to the number of subjects with cerebral amyloid angiopathy in the two-year period prior to AD onset.Different pathways related to BBB,like cell adhesion,extracellular matrix organization and Wnt signaling,were activated and differentially expressed proteins such as ADAM22,PDGFR-α,DKK-4,Neucrin and RSOP-1 were identified.Moreover,matrix metalloproteinase-9,which is implicated in causing degradation of basal lamina and BBB disruption,was significantly increased in the plasma of AD patients.Conclusions:Alteration of proteins found in AD subjects could provide new insights into biomarkers regulating permeability and BBB integrity.
基金Shanxi Provincial Special Fund for the Transformation of Scientific and Technological Achievements,No.201704D13111584(to JHG)。
文摘Neurovascular dysfunction,as an integral part of Alzheimer's disease,may have an important influence on the onset and progression of chronic neurodegenerative processes.The bloodbrain barrier(BBB)pathway is one of the main pathways that mediates the clearance of amyloidbeta(Aβ)in the brain parenchyma.A large number of studies have shown that receptors and ATPbinding cassette transporte rs expressed on endothelial cells play an important role in Aβtransport across the BBB,but the specific mechanism is not clear.In this review,we summarize the possible mechanisms of Aβproduction and clearance,and in particular the relationship between Aβand brain capillary endothelial cells.Aβis produced by abnormal cleavage of the amyloid precursor protein via amyloidogenic processing under pathological conditions.Dys regulation of Aβclearance is considered to be the main reason for the massive accumulation of Aβin the brain parenchyma.Several pathways mediating Aβclearance from the brain into the periphery have been identified,including the BBB pathway,the blood-cerebros pinal fluid barrier and arachnoid granule pathway,and the lymphoidrelated pathway.Brain ca pilla ry endothelial cells are the key components of Aβclearance mediated by BBB.Receptors(such as LRP1,RAGE,and FcRn)and ATP-binding cassette transporters(such as P-gp,ABCA1,and ABCC1)expressed on endothelial cells play a critical role in Aβtranscytosis across the BBB.The toxic effects of Aβcan induce dysregulation of receptor and transpo rter expression on endothelial cells.Excessive Aβexerts potent detrimental cerebrovascular effects by promoting oxidative stress,inducing chronic inflammation,and impairing endothelial structure and functions.All of these are main causes for the reduction in Aβclearance across the BBB and the accumulation of Aβin the brain parenchyma.Therefo re,studies on the intera ctions between Aβand brain capillary endothelial cells,including their receptors and transporters,studies on inhibition of the toxic effects of Aβon endothelial cells,and studies on promoting the ability of endothelial cells to mediate Aβclearance may provide new therapeutic strategies for Aβclearance in Alzheimer's disease.
