The pathobiology of vascular dementia

Positron emission tomography (PET) of brain amyloid b is a technology that is becoming more available, but its clinical utility in medical practice requires careful definition. To provide guidance to dementia care practitioners, patients, and caregivers, the Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging convened the Amyloid Imaging Taskforce (AIT). The AIT considered a broad range of specific clinical scenarios in which amyloid PET could potentially be used appropriately. Peer-reviewed, published literature was searched to ascertain available evidence relevant to these scenarios, and the AIT developed a consensus of expert opinion. Although empirical evidence of impact on clinical outcomes is not yet available, a set of specific appropriate use criteria (AUC) were agreed on that define the types of patients and clinical circumstances in which amyloid PET could be used. Both appropriate and inappropriate uses were considered and formulated,and are reported and discussed here. Because both dementia care and amyloid PET technology are in active development, these AUC will require periodic reassessment. Future research directions are also outlined, including diagnostic utility and patient-centered outcomes.

/pdf/appropriate-use-criteria-for-amyloid-pet-a-report-of-the-blfrt8ffio.pdf

Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer's Association.

Cerebral amyloid angiopathy (CAA) is a disorder characterized by amyloid deposition in the walls of leptomeningeal and cortical arteries, arterioles, and less often capillaries and veins of the central nervous system. CAA occurs mostly as a sporadic condition in the elderly, its incidence associating with advancing age. All sporadic CAA cases are due to deposition of amyloid-β, originating from proteolytic cleavage of the Amyloid Precursor Protein. Hereditary forms of CAA are generally familial (and therefore rare in the general population), more severe and earlier in onset. CAA-related lobar intracerebral hemorrhage is the most well-studied clinical condition associated with brain amyloid deposition. Despite ever increasing understanding of CAA pathogenesis and availability of reliable clinical and diagnostic tools, preventive and therapeutic options remain very limited. Further research efforts are required in order to identify biological targets for novel CAA treatment strategies. We present a systematic review of existing evidence regarding the epidemiology, genetics, pathogenesis, diagnosis and clinical management of CAA.

/pdf/cerebral-amyloid-angiopathy-a-systematic-review-4r0dd3pdmo.pdf

Cerebral Amyloid Angiopathy: A Systematic Review

Positron emission tomography (PET) of brain amyloid b is a technology that is becoming more available, but its clinical utility in medical practice requires careful definition. To provide guidance to dementia care practitioners, patients, and caregivers, the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging convened the Amyloid Imaging Taskforce (AIT). The AIT considered a broad range of specific clinical scenarios in which amyloid PET could potentially be used appropriately. Peer-reviewed, published literature was searched to ascertain available evidence relevant to these scenarios, and the AIT developed a consensus of expert opinion. Although empirical evidence of impact on clinical outcomes is not yet available, a set of specific appropriate usecriteria(AUC)wereagreedonthatdefinethetypesofpatientsandclinicalcircumstancesinwhich amyloid PET could be used. Both appropriate and inappropriate uses were considered and formulated, and are reported and discussed here. Because both dementia care and amyloid PET technology are in active development, these AUC will require periodic reassessment. Future research directions are also outlined, including diagnostic utility and patient-centered outcomes. 2013 The Alzheimer’s Association. All rights reserved.

https://jnm.snmjournals.org/content/jnumed/54/3/476.full.pdf

Appropriate Use Criteria for Amyloid PET: A Report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association

Background and Purpose- We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome. Methods- We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2-4, ≥5, and >10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3- to 6-month functional outcome (modified Rankin score >2). Results- In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09-2.07; P=0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73-5.35; P 10 CMBs independently predicted poor 3- to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10-3.12; P=0.020; and odds ratio: 3.99; 95% confidence interval: 1.55-10.22; P=0.004, respectively). Conclusions- Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3- to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke.

Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Stroke Thrombolysis: Individual Patient Data Meta-Analysis.

Background and Purpose—Conflicting evidence exists as to whether focal cerebral ischemia contributes to cerebral amyloid deposition. We aimed to look at Aβ deposits, detected by N-methyl-2-(4′-methylaminophenyl)-6-hydroxybenzothiazole (PiB) positron emission tomography, in patients with recent ischemic stroke. Specifically, we hypothesized that patients with recent ischemic stroke have higher local and neocortical PiB positron emission tomography retention and that this may be associated with major vascular risk factors. Methods—Ischemic stroke patients were studied using PiB positron emission tomography within 30 days and compared to age-matched controls. Distribution volume ratio maps were created using Logan graphical analysis with the cerebellar cortex as a reference. Results—Among the 21 ischemic stroke patients (median age, 76 years; interquartile range, 68–77), the ipsilateral peri-infarct region PiB retention was higher compared to the contralateral mirror region, with a PiB distribution volume ra...

Subacute Ischemic Stroke Is Associated With Focal 11C PiB Positron Emission Tomography Retention But Not With Global Neocortical Aβ Deposition

Cerebral amyloid angiopathy (CAA) may be an important predisposing factor for the hemorrhagic complications of recombinant tissue-type plasminogen activator (rt-PA) therapy We studied patients treated within 3 hours of onset of ischemic stroke with rt-PA using positron emission tomography to compare Pittsburgh compound B (PiB) (a cerebral β-amyloid ligand) retention in those with and without parenchymal hemorrhage (PH) and normal controls Neocortical PiB retention was higher among patients with PH compared with patients without PH and normal controls, suggesting underlying CAA as a predisposing factor for rt-PA-related hemorrhage This finding may provide an impetus for the development of a more practical rapid pretreatment screening technique

Cerebral β-amyloid detected by Pittsburgh compound B positron emission topography predisposes to recombinant tissue plasminogen activator-related hemorrhage†‡

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Subacute Ischemic Stroke Is Associated With Focal 11C PiB Positron Emission Tomography Retention But Not With Global Neocortical Aβ Deposition

Cerebral β-amyloid detected by Pittsburgh compound B positron emission topography predisposes to recombinant tissue plasminogen activator-related hemorrhage†‡