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Compound B (compound + b)
Kinds of Compound B Selected AbstractsCognition, reserve, and amyloid deposition in normal agingANNALS OF NEUROLOGY, Issue 3 2010Dorene M. Rentz PsyD Objective To determine whether amyloid deposition is associated with impaired neuropsychological (NP) performance and whether cognitive reserve (CR) modifies this association. Methods In 66 normal elderly controls and 17 patients with Alzheimer disease (AD), we related brain retention of Pittsburgh Compound B (PiB) to NP performance and evaluated the impact of CR using education and American National Adult Reading Test intelligence quotient as proposed proxies. Results We found in the combined sample of subjects that PiB retention in the precuneus was inversely related to NP performance, especially in tests of memory function, but also in tests of working memory, semantic processing, language, and visuospatial perception. CR significantly modified the relationship, such that at progressively higher levels of CR, increased amyloid deposition was less or not at all associated with poorer neuropsychological performance. In a subsample of normal controls, both the main effect of amyloid deposition of worse memory performance and the interaction with CR were replicated using a particularly challenging memory test. Interpretation Amyloid deposition is associated with lower cognitive performance both in AD patients and in the normal elderly, but the association is modified by CR, suggesting that CR may be protective against amyloid-related cognitive impairment. ANN NEUROL 2010;67:353,364 [source] Amyloid imaging in mild cognitive impairment subtypes,ANNALS OF NEUROLOGY, Issue 5 2009David A. Wolk MD Objective We utilized the amyloid imaging ligand Pittsburgh Compound B (PiB) to determine the presence of Alzheimer's disease (AD) pathology in different mild cognitive impairment (MCI) subtypes and to relate increased PiB binding to other markers of early AD and longitudinal outcome. Methods Twenty-six patients with MCI (13 single-domain amnestic-MCI [a-MCI], 6 multidomain a-MCI, and 7 nonamnestic MCI) underwent PiB imaging. Twenty-three had clinical follow-up (21.2 ± 16.0 [standard deviation] months) subsequent to their PiB scan. Results Using cutoffs established from a control cohort, we found that 14 (54%) patients had increased levels of PiB retention and were considered "amyloid-positive." All subtypes were associated with a significant proportion of amyloid-positive patients (6/13 single-domain a-MCI, 5/6 multidomain a-MCI, 3/7 nonamnestic MCI). There were no obvious differences in the distribution of PiB retention in the nonamnestic MCI group. Predictors of conversion to clinical AD in a-MCI, including poorer episodic memory, and medial temporal atrophy, were found in the amyloid-positive relative to amyloid-negative a-MCI patients. Longitudinal follow-up demonstrated 5 of 13 amyloid-positive patients, but 0 of 10 amyloid-negative patients, converted to clinical AD. Further, 3 of 10 amyloid-negative patients "reverted to normal." Interpretation These data support the notion that amyloid-positive patients are likely to have early AD, and that the use of amyloid imaging may have an important role in determining which patients are likely to benefit from disease-specific therapies. In addition, our data are consistent with longitudinal studies that suggest a significant percentage of all MCI subtypes will develop AD. Ann Neurol 2009;65:557,568 [source] Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer's diseaseANNALS OF NEUROLOGY, Issue 1 2008Nina M. Kemppainen MD Objective The reduced risk for Alzheimer's disease (AD) in high-educated individuals has been proposed to reflect brain cognitive reserve, which would provide more efficient compensatory mechanisms against the underlying pathology, and thus delayed clinical expression. Our aim was to find possible differences in brain amyloid ligand 11C-labeled Pittsburgh Compound B ([11C]PIB) uptake and glucose metabolism in high- and low-educated patients with mild AD. Methods Twelve high-educated and 13 low-educated patients with the same degree of cognitive deterioration were studied with PET using [11C]PIB and 18F-fluorodeoxyglucose as ligands. The between-group differences were analyzed with voxel-based statistical method, and quantitative data were obtained with automated region-of-interest analysis. Results High-educated patients showed increased [11C]PIB uptake in the lateral frontal cortex compared with low-educated patients. Moreover, high-educated patients had significantly lower glucose metabolic rate in the temporoparietal cortical regions compared with low-educated patients. Interpretation Our results suggesting more advanced pathological and functional brain changes in high-educated patients with mild AD are in accordance with the brain cognitive reserve hypothesis and point out the importance of development of reliable markers of underlying AD pathology for early AD diagnostics. Ann Neurol 2007 [source] Imaging of amyloid burden and distribution in cerebral amyloid angiopathyANNALS OF NEUROLOGY, Issue 3 2007Keith A. Johnson MD Objective Cerebrovascular deposition of ,-amyloid (cerebral amyloid angiopathy [CAA]) is a major cause of hemorrhagic stroke and a likely contributor to vascular cognitive impairment. We evaluated positron emission tomographic imaging with the ,-amyloid,binding compound Pittsburgh Compound B (PiB) as a potential noninvasive method for detection of CAA. We hypothesized that amyloid deposition would be observed with PiB in CAA, and based on the occipital predilection of CAA pathology and associated hemorrhages, that specific PiB retention would be disproportionately greater in occipital lobes. Methods We compared specific cortical PiB retention in 6 nondemented subjects diagnosed with probable CAA with 15 healthy control subjects and 9 patients with probable Alzheimer's disease (AD). Results All CAA and AD subjects were PiB-positive, both by distribution volume ratio measurements and by visual inspection of positron emission tomographic images. Global cortical PiB retention was significantly increased in CAA (distribution volume ratio 1.18 ± 0.06) relative to healthy control subjects (1.04 ± 0.10; p = 0.0009), but was lower in CAA than in AD subjects (1.41 ± 0.17; p = 0.002). The occipital-to-global PiB ratio, however, was significantly greater in CAA than in AD subjects (0.99 ± 0.07 vs 0.86 ± 0.05; p = 0.003). Interpretation We conclude that PiB-positron emission tomography can detect cerebrovascular ,-amyloid and may serve as a method for identifying the extent of CAA in living subjects. Ann Neurol 2007 [source] Neuroimaging and Cognition in Parkinson's Disease DementiaBRAIN PATHOLOGY, Issue 3 2010Lisa C. Silbert MD Abstract The prevalence of cognitive impairment and dementia in Parkinson's disease (PD) is high and can potentially occur as the result of multiple differing pathologies. Neuroimaging has provided evidence of decreased cortical volume, increased white matter diffusion changes, and decreased resting metabolic activity that appears to begin prior to the onset of dementia in PD patients. Cognitive impairment has been found to be associated with multiple neurotransmitter transmission deficiencies, including dopamine and acetylcholine, indicating a widespread neurotransmitter dysfunction in PD-related dementia. Findings of increased Pittsburgh Compound B (PiB) binding in subjects with Lewy Body Disease (LBD) compared with Parkinson's disease and dementia (PDD) may explain phenotype differences in the spectrum of Dementia with Lewy Bodies (DLB), and show promise in guiding future therapeutic trials aimed at this disease. Advances in neuroimaging now allow for the detection of volumetric, pharmacologic, and pathological changes that may assist in the diagnosis and prediction of cognitive impairment in Parkinson's patients so that better evaluation of disease progression and treatment can be obtained. [source] 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: A phase 2 trialANNALS OF NEUROLOGY, Issue 3 2010Rik Vandenberghe MD Objective The most widely studied positron emission tomography ligand for in vivo ,-amyloid imaging is 11C-Pittsburgh compound B (11C-PIB). Its availability, however, is limited by the need for an on-site cyclotron. Validation of the 18F-labeled PIB derivative 18F-flutemetamol could significantly enhance access to this novel technology. Methods Twenty-seven patients with early-stage clinically probable Alzheimer disease (AD), 20 with amnestic mild cognitive impairment (MCI), and 15 cognitively intact healthy volunteers (HVs) above and 10 HVs below 55 years of age participated. The primary endpoint was the efficacy of blinded visual assessments of 18F-flutemetamol scans in assigning subjects to a raised versus normal uptake category, with clinical diagnosis as the standard of truth (SOT). As secondary objectives, we determined the correlation between the regional standardized uptake value ratios (SUVRs) for 18F-flutemetamol and its parent molecule 11C-PIB in 20 of the AD subjects and 20 of the MCI patients. We also determined test-retest variability of 18F-flutemetamol SUVRs in 5 of the AD subjects. Results Blinded visual assessments of 18F-flutemetamol scans assigned 25 of 27 scans from AD subjects and 1 of 15 scans from the elderly HVs to the raised category, corresponding to a sensitivity of 93.1% and a specificity of 93.3% against the SOT. Correlation coefficients between cortical 18F-flutemetamol SUVRs and 11C-PIB SUVRs ranged from 0.89 to 0.92. Test-retest variabilities of regional SUVRs were 1 to 4%. Interpretation 18F-Flutemetamol performs similarly to the 11C-PIB parent molecule within the same subjects and provides high test-retest replicability and potentially much wider accessibility for clinical and research use. ANN NEUROL 2010 [source] Relationship between atrophy and ,-amyloid deposition in Alzheimer diseaseANNALS OF NEUROLOGY, Issue 3 2010Gaël Chételat PhD Objective Elucidating the role of aggregated ,-amyloid in relation to gray matter atrophy is crucial to the understanding of the pathological mechanisms of Alzheimer disease and for the development of therapeutic trials. The present study aims to assess this relationship. Methods Brain magnetic resonance imaging and [11C]Pittsburgh compound B (PiB)-positron emission tomography scans were obtained from 94 healthy elderly subjects (49 with subjective cognitive impairment), 34 patients with mild cognitive impairment, and 35 patients with Alzheimer disease. The correlations between global and regional neocortical PiB retention and atrophy were analyzed in each clinical group. Results Global and regional atrophy were strongly related to ,-amyloid load in participants with subjective cognitive impairment but not in patients with mild cognitive impairment or Alzheimer disease. Global neocortical ,-amyloid deposition correlated to atrophy in a large brain network including the hippocampus, medial frontal and parietal areas, and lateral temporoparietal cortex, whereas regional ,-amyloid load was related to local atrophy in the areas of highest ,-amyloid load only, that is, medial orbitofrontal and anterior and posterior cingulate/precuneus areas. Interpretation There is a strong relationship between ,-amyloid deposition and atrophy very early in the disease process. As the disease progresses to mild cognitive impairment and Alzheimer disease clinical stages, pathological events other than, and probably downstream from, aggregated ,-amyloid deposition might be responsible for the ongoing atrophic process. These findings suggest that antiamyloid therapy should be administered very early in the disease evolution to minimize synaptic and neuronal loss. ANN NEUROL 2010;67:317,324 [source] A, amyloid and glucose metabolism in three variants of primary progressive aphasiaANNALS OF NEUROLOGY, Issue 4 2008Gil D. Rabinovici MD Objective Alzheimer's disease (AD) is found at autopsy in up to one third of patients with primary progressive aphasia (PPA), but clinical features that predict AD pathology in PPA are not well defined. We studied the relationships between language presentation, A, amyloidosis, and glucose metabolism in three PPA variants using [11C]-Pittsburgh compound B ([11C]PIB) and [18F]-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG-PET). Methods Patients meeting PPA criteria (N = 15) were classified as logopenic aphasia (LPA), progressive nonfluent aphasia (PNFA), or semantic dementia (SD) based on language testing. [11C]PIB distribution volume ratios were calculated using Logan graphical analysis (cerebellar reference). [18F]FDG images were normalized to pons. Partial volume correction was applied. Results Elevated cortical PIB (by visual inspection) was more common in LPA (4/4 patients) than in PNFA (1/6) and SD (1/5) (p < 0.02). In PIB-positive PPA, PIB uptake was diffuse and indistinguishable from the pattern in matched AD patients (n = 10). FDG patterns were focal and varied by PPA subtype, with left temporoparietal hypometabolism in LPA, left frontal hypometabolism in PNFA, and left anterior temporal hypometabolism in SD. FDG uptake was significant asymmetric (favoring left hypometabolism) in PPA (p < 0.005) but not in AD. Interpretation LPA is associated with A, amyloidosis, suggesting that subclassification of PPA based on language features can help predict the likelihood of AD pathology. Language phenotype in PPA is closely related to metabolic changes that are focal and anatomically distinct between subtypes, but not to amyloid deposition patterns that are diffuse and similar to AD. Ann Neurol 2008 [source] Contribution of specific binding to the central benzodiazepine site to the brain concentrations of two novel benzodiazepine site ligandsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 6 2007Andrew Pike Abstract The in vivo occupancy of brain benzodiazepine binding sites by compounds A and B was measured using a [3H]Ro 15-1788 binding assay and related to plasma and brain drug concentrations. The plasma concentration associated with 50% occupancy was higher for compound A than compound B (73 and 3.7 nM, respectively), however, there was little difference in the brain concentrations required (73 and 63 nM). Both compounds showed a non-linear relationship between plasma and brain concentrations such that above brain concentrations of ,100 nM increasing plasma concentrations did not result in a concomitant increase in brain concentrations. This is consistent with brain concentrations being dependent on a saturable compartment which was postulated to be the benzodiazepine binding site-containing GABAA receptors. This hypothesis was tested in ,1H101R mice, in which the ,1 subunit of the GABAA receptor is rendered insensitive to benzodiazepine binding resulting in an approximate 50% reduction in the total benzodiazepine-containing GABAA receptor population. It was shown that the Occ50 brain concentrations in the ,1H101R animals was lower (17 nM) than in wild type mice (63 nM), as was the plateau concentration in the brain (105 and 195 nM, respectively). These data suggest measured concentrations of compounds A and B in brain tissue are dependent on receptor expression with a minimal contribution from unbound and non-specifically bound compound. Copyright © 2007 John Wiley & Sons, Ltd. [source] Absolute configuration and conformational analysis of a degradation product of inhalation anesthetic Sevoflurane: A vibrational circular dichroism studyCHIRALITY, Issue 8 2002Feng Wang Abstract 1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane, compound B, is a product obtained in the degradation of the anesthetic Sevoflurane. Enantiopure (+)- B was investigated using vibrational circular dichroism (VCD). Experimental absorption and VCD spectra of (+)- B in CDCl3 solution in the 2,000,900 cm,1 region are compared with the ab initio predictions of absorption and VCD spectra obtained from density functional theory using B3LYP/6-31G* basis set for different conformers of (S)-1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane. This comparison indicates that (+)- B is of the (S)-configuration in CDCl3 solution, in agreement with previous literature results. Our results also indicate that this compound adopts six predominant conformations in CDCl3 solution. Chirality 14:618,624, 2002. © 2002 Wiley-Liss, Inc. [source] | ||||||||||