Abstract:We hypothesize that cerebral microbleeds (CMB) in patients with different neuropsychological profiles (amnestic or non-amnestic) and MRI features of vascular damage could provide important information on the underlying pathological process in early Alzheimer's disease. The study was performed at two trial sites. We studied 136 outpatients with cognitive decline. MRI was performed using a magnetic field of 1.5 and 3 T. Neuropsychological assessment included Mini-Mental State Examination (MMSE), Montreal Cogniti… Show more
“…AD patients without CMBs ( n = 99) ( 48 ). The eighth study showed increased BBB dysfunction in the form of an increased CSF/serum albumin ratio in patients with cognitive decline with CMBs ( n = 15) compared with patients with cognitive decline but no CMBs ( n = 13) ( 50 ). In contrast, the last study could not identify any difference in BBB dysfunction measured as CSF/serum albumin ratios between AD patients with CMBs ( n = 26) and AD patients without CMBs ( n = 26) ( 52 ).…”
Background and Purpose: Hypertensive vasculopathy and cerebral amyloid angiopathy are the two most common forms of cerebral small vessel disease. Both forms are associated with the development of primary intracerebral hemorrhage, but the pathophysiological mechanisms underlying spontaneous vessel rupture remain unknown. This work constitutes a systematic review on blood-brain barrier dysfunction in the etiology of spontaneous intracerebral hemorrhage due to cerebral small vessel disease.Methods: We searched Medline (1946–2018) and Embase (1974–2018) for animal and human studies reporting on blood-brain barrier dysfunction associated with intracerebral hemorrhage or cerebral microbleeds.Results: Of 26 eligible studies, 10 were animal studies and 16 were in humans. The authors found indications for blood-brain barrier dysfunction in all four animal studies addressing hypertensive vasculopathy-related intracerebral hemorrhage (n = 32 hypertensive animals included in all four studies combined), and in four of six studies on cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 47). Of the studies in humans, five of six studies in patients with cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 117) and seven out of nine studies examining intracerebral hemorrhage with mixed or unspecified underlying etiology (n = 489) found indications for blood-brain barrier dysfunction. One post-mortem study in hypertensive vasculopathy-related intracerebral hemorrhage (n = 82) found no evidence for blood-brain barrier abnormalities.Conclusions: Signs of blood-brain barrier dysfunction were found in 20 out of 26 studies. Blood-brain barrier integrity deserves further investigation with a view to identification of potential treatment targets for spontaneous intracerebral hemorrhage.
“…AD patients without CMBs ( n = 99) ( 48 ). The eighth study showed increased BBB dysfunction in the form of an increased CSF/serum albumin ratio in patients with cognitive decline with CMBs ( n = 15) compared with patients with cognitive decline but no CMBs ( n = 13) ( 50 ). In contrast, the last study could not identify any difference in BBB dysfunction measured as CSF/serum albumin ratios between AD patients with CMBs ( n = 26) and AD patients without CMBs ( n = 26) ( 52 ).…”
Background and Purpose: Hypertensive vasculopathy and cerebral amyloid angiopathy are the two most common forms of cerebral small vessel disease. Both forms are associated with the development of primary intracerebral hemorrhage, but the pathophysiological mechanisms underlying spontaneous vessel rupture remain unknown. This work constitutes a systematic review on blood-brain barrier dysfunction in the etiology of spontaneous intracerebral hemorrhage due to cerebral small vessel disease.Methods: We searched Medline (1946–2018) and Embase (1974–2018) for animal and human studies reporting on blood-brain barrier dysfunction associated with intracerebral hemorrhage or cerebral microbleeds.Results: Of 26 eligible studies, 10 were animal studies and 16 were in humans. The authors found indications for blood-brain barrier dysfunction in all four animal studies addressing hypertensive vasculopathy-related intracerebral hemorrhage (n = 32 hypertensive animals included in all four studies combined), and in four of six studies on cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 47). Of the studies in humans, five of six studies in patients with cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 117) and seven out of nine studies examining intracerebral hemorrhage with mixed or unspecified underlying etiology (n = 489) found indications for blood-brain barrier dysfunction. One post-mortem study in hypertensive vasculopathy-related intracerebral hemorrhage (n = 82) found no evidence for blood-brain barrier abnormalities.Conclusions: Signs of blood-brain barrier dysfunction were found in 20 out of 26 studies. Blood-brain barrier integrity deserves further investigation with a view to identification of potential treatment targets for spontaneous intracerebral hemorrhage.
“…Damage to blood vessels can lead to pronounced BBB breakdown manifested as cerebral microbleeds (microhaemorrhages), which is frequently seen in AD 86–93 , MCI 94 , and in APOE*ε4 individuals who have increased genetic risk of AD 94 . CAA is one of the main causes of vascular degeneration and lobar microbleeds in AD, and contributes to BBB breakdown, infarcts, white matter changes and cognitive impairment 26 .…”
Section: Neuroimaging Evidence Of Bbb Disruptionmentioning
confidence: 99%
“…Amyloid deposition in the brain, as detected by 18 F-florbetapir PET, is positively associated with the number of microbleeds in individuals with MCI and AD 99 . Several studies that reported a high prevalence of microbleeds in patients with AD 86–93 or MCI 94 did not perform amyloid-PET imaging 86–93 , however, precluding a direct comparison of microbleeds and CAA severity.…”
Section: Neuroimaging Evidence Of Bbb Disruptionmentioning
The blood–brain barrier (BBB) is a continuous endothelial membrane within brain microvessels that has sealed cell-to-cell contacts, and is sheathed by mural vascular cells and perivascular astrocyte end-feet. The BBB protects neurons from factors present in the systemic circulation, and maintains the highly regulated CNS internal milieu, which is required for proper synaptic and neuronal functioning. BBB disruption allows influx into the brain of neurotoxic blood-derived debris, cells, and microbial pathogens, and is associated with inflammatory and immune responses, which can initiate multiple pathways of neurodegeneration. This Review discusses neuroimaging studies in the living human brain, post-mortem tissue and biomarker studies demonstrating BBB breakdown in Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, multiple sclerosis, HIV-1-associated dementia and chronic traumatic encephalopathy. The pathogenic mechanisms by which BBB breakdown leads to neuronal injury, synaptic dysfunction, loss of neuronal connectivity and neurodegeneration are described. The importance of a healthy BBB for therapeutic drug delivery, and the adverse effects of disease-initiated, pathological BBB breakdown in relation to brain delivery of neuropharmaceuticals are briefly discussed. Finally, future directions, gaps in the field and opportunities to control the course of neurological diseases by targeting BBB are presented.
“…The gradual spreading of the intracellular aggregation of hyperphosphorylated tau (P-tau) in the brain is associated with AD progression [ 1 ]. Studies also reveal the association between cerebral microbleeds and P-tau [ 33 , 34 ]. Interestingly, our data did not reveal increased hemorrhagic stroke in both AD and DLB patients when compared to NC individuals.…”
Background Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) share many risk factors. Evidence suggests that metabolic risk factors are important to AD; however, their association with DLB is unclear. The risk of cardiovascular diseases (CVD) associated with AD and DLB is also uncertain. Thus, this nationwide, population-based study was designed to evaluate the metabolic and CVD risks in AD and DLB. Materials and Methods Data were obtained from the Taiwan National Health Insurance Research Database. AD patients, DLB patients, and normal control (NC) individuals from 1996 to 2013 were enrolled for risk assessment. Results In total, 7544 NC individuals, 1324 AD patients, and 562 DLB patients were enrolled. Participants with one or more metabolic risk factors had significantly higher odds of AD or DLB. No significant differences in metabolic risk factors were observed between DLB and AD patients. AD patients had a lower risk of CVD (aHR = 0.67, 95% CI = 0.59–0.76, p value < 0.001) and coronary artery disease (CAD) (aHR = 0.59, 95% CI = 0.51–0.69, p value < 0.001) than NC. DLB patients had a higher risk of ischemic stroke (aHR = 2.27, 95% CI = 1.68–3.06, p value < 0.001) than NC. Conclusion Metabolic risk factors are important in AD and DLB. Patients with AD might have a lower risk of CAD and ischemic strokes. Patients with DLB might have a higher risk of ischemic stroke.
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