2-(4--(methylamino)phenyl)-6-hydroxybenzothiazole and Cerebral-Hemorrhage

To describe the prevalence of cerebral microbleeds (CMBs) and determine the association between CMBs and β-amyloid burden on PET.. From the population-based Mayo Clinic Study of Aging, 1,215 participants (53% male) underwent 3-tesla MRI scans with T2* gradient recalled echo sequences from October 2011 to February 2017. A total of 1,123 participants (92%) underwent. Two hundred seventy-four participants (22.6%) had at least one CMB. CMB frequency increased with age by decade (11% aged 60-69 years, 22% 70-79 years, and 39% 80 years and older). After adjusting for age, sex, and hypertension, PiB standardized uptake value ratio (SUVR) was associated with increased odds of a CMB. The association between PiB SUVR and CMBs was location-specific; PiB SUVR was associated with lobar CMBs but not deep CMBs. Age, hypertension, and PiB SUVR were associated with increasing CMB count. CMB density was greatest in parietal and occipital regions; β-amyloid burden correlated with concentration of CMBs in all lobar regions. Among participants with multiple CMBs, greater PiB uptake occurred in the pre- and postcentral gyri superiorly, the superior parietal lobe and precuneus, the angular gyrus, inferior temporal gyrus, and temporal poles.. The prevalence of CMBs increases with age. In this population-based sample, β-amyloid load was associated with lobar but not with deep CMBs.

Topics: Aged; Aged, 80 and over; Amyloid; Aniline Compounds; Apolipoproteins E; Cerebral Amyloid Angiopathy; Cerebral Hemorrhage; Community Health Planning; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Prevalence; Thiazoles

To test the hypothesis that patients with concomitant lobar and deep intracerebral hemorrhages/microbleeds (mixed ICH) have predominantly hypertensive small vessel disease (HTN-SVD) rather than cerebral amyloid angiopathy (CAA), using in vivo amyloid imaging.. Eighty Asian patients with primary ICH without dementia were included in this cross-sectional study. All patients underwent brain MRI and. Patients with mixed ICH were younger (62.8 ± 11.7 vs 73.3 ± 11.9 years in CAA,. Patients with mixed ICH have much lower amyloid load than patients with CAA-ICH, while being similar to HTN-ICH. Overall, mixed ICH is probably caused by HTN-SVD, an important finding with clinical relevance.

Topics: Aged; Aged, 80 and over; Aniline Compounds; Brain; Cerebral Amyloid Angiopathy; Cerebral Hemorrhage; Cerebral Small Vessel Diseases; Cross-Sectional Studies; Female; Humans; Intracranial Hemorrhage, Hypertensive; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Taiwan; Thiazoles

The underlying pathology of cerebral microbleeds (CMBs) with mixed lobar and deep distribution remains contentious. The aim of this study was to correlate CMBs distribution to β-amyloid burden in patients with primary intracerebral hemorrhage (ICH). Fourty-seven ICH patients underwent magnetic resonance susceptibility-weighted imaging and

Topics: Aged; Aged, 80 and over; Amyloid; Aniline Compounds; Cerebral Hemorrhage; Demography; Female; Humans; Image Processing, Computer-Assisted; Male; Multivariate Analysis; Thiazoles

To determine whether amyloid and hypertensive cerebral small vessel disease (hCSVD) changes synergistically affect the progression of lobar microbleeds in patients with subcortical vascular mild cognitive impairment (svMCI).. Among 72 patients with svMCI who underwent brain MRI and [. Over 3 years, 31 of 52 patients (59.6%) had incident cerebral microbleeds (CMBs) in the lobar and deep regions. Both baseline and longitudinal changes in lacune numbers were associated with increased numbers of lobar and deep microbleeds, while baseline and longitudinal changes in PiB uptake ratio were associated only with the progression of lobar microbleeds, especially in the temporal, parietal, and occipital areas. Regional white matter hyperintensity severity was also associated with regional lobar CMBs in the parietal and occipital regions. There were interactive effects between baseline and longitudinal lacune number and PiB retention on lobar microbleed progression. Increased lobar, but not deep, CMBs were associated with decreased scores in the digit span backward task and Rey-Osterrieth Complex Figure Test.. Our findings suggest that amyloid-related pathology and hCSVD have synergistic effects on the progression of lobar microbleeds, providing new clinical insight into the interaction between amyloid burden and hCSVD on CMB progression and cognitive decline with implications for developing effective prevention strategies.

Topics: Aged; Amyloidosis; Aniline Compounds; Apolipoproteins E; Brain; Cerebral Hemorrhage; Cerebral Small Vessel Diseases; Disease Progression; Female; Follow-Up Studies; Humans; Incidence; Longitudinal Studies; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Thiazoles; White Matter

Microbleeds in the brain have been shown to occur in Alzheimer's disease (AD), affecting approximately a third of subjects that present with typical dementia of the Alzheimer's type (DAT). However, little is known about the frequency or distribution of microbleeds in subjects with AD that present with atypical clinical presentations.. To determine whether the frequency and regional distribution of microbleeds in atypical AD differs from that observed in subjects with DAT, and to determine whether microbleeds in atypical AD are associated with age, demographics, or cognitive impairment.. Fifty-five subjects with amyloid-β deposition on Pittsburgh compound B (PiB) PET who presented with predominant language (n = 37) or visuospatial/perceptual (n = 18) deficits underwent T2*weighted MRI. These subjects were compared to 41 PiB-positive subjects with DAT. Microbleeds were identified and assigned a lobar location.. The proportion of subjects with microbleeds did not differ between atypical AD (42%) and DAT (32%). However, atypical AD had larger numbers of microbleeds than DAT. In addition, the topographic distribution of microbleeds differed between atypical AD and DAT, with atypical AD showing the highest density of microbleeds in the frontal lobes. Among atypical AD, number of microbleeds was associated with age, but not gender or cognition. Microbleeds were more common in subjects with language (51%) versus visuospatial/perceptual deficits (22%).. Microbleeds are relatively common in both DAT and atypical AD, although atypical AD subjects appear to be at particular risk for developing large numbers of microbleeds and for developing microbleeds in the frontal lobe.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Brain; Cerebral Hemorrhage; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Phenotype; Positron-Emission Tomography; Radiopharmaceuticals; Thiazoles

Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently high uptake in healthy aged subjects. By detecting perfusion-like abnormalities, early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1-6min) 11C-PiB-PET was obtained in 11 non-demented patients with probable CAA-related symptomatic lobar intracerebral haemorrhage (70±7yrs), 9 age-matched healthy controls (HCs) and 10 HCs <55yrs. There was a significant decrease in early-phase atrophy-corrected whole-cortex SUV relative to cerebellar vermis (SUVR) in the CAA vs age-matched HC group. None of the age-matched controls fell below the lower 95% confidence limit derived from the young HCs, while 6/11 CAA patients did (sensitivity = 55%, specificity = 100%). Combining both early- and late-phase 11C-PiB data did not change the sensitivity and specificity of late-phase PiB, but combined early- and late-phase positivity entails a very high suspicion of underlying Aβ-related clinical disorder, i.e., CAA or Alzheimer disease (AD). In order to clarify this ambiguity, we then show that the occipital/posterior cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with respect to the unclear situation of late-phase positivity, but also help differentiate CAA from AD.

Topics: Aged; Aniline Compounds; Brain; Cerebral Amyloid Angiopathy; Cerebral Hemorrhage; Female; Humans; Male; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Thiazoles

By detecting β-amyloid (Aβ) in the wall of cortical arterioles, amyloid positron emission tomography (PET) imaging might help diagnose cerebral amyloid angiopathy (CAA) in patients with lobar intracerebral hemorrhage (l-ICH). No previous study has directly assessed the diagnostic value of (11)C-Pittsburgh compound B (PiB) PET in probable CAA-related l-ICH against healthy controls (HCs). (11)C-PiB-PET and magnetic resonance imaging (MRI) including T2* were obtained in 11 nondemented patients fulfilling the Boston criteria for probable CAA-related symptomatic l-ICH (sl-ICH) and 20 HCs without cognitive complaints or impairment. After optimal spatial normalization, cerebral spinal fluid (CSF)-corrected PiB distribution volume ratios (DVRs) were obtained. There was no significant difference in whole cortex or regional DVRs between CAA patients and age-matched HCs. The whole cortex DVR was above the 95% confidence limit in 4/9 HCs and 10/11 CAA patients (sensitivity=91%, specificity=55%). Region/frontal or occipital ratios did not have better discriminative value. Similar but less accurate results were found using visual analysis. In patients with sl-ICH, (11)C-PiB-PET has low specificity for CAA due to the frequent occurrence of high (11)C-PiB uptake in the healthy elderly reflecting incipient Alzheimer's disease (AD), which might also be present in suspected CAA. However, a negative PiB scan rules out CAA with excellent sensitivity, which has clinical implications for prognostication and selection of candidates for drug trials.

Topics: Aged; Aged, 80 and over; Aniline Compounds; Brain; Cerebral Amyloid Angiopathy; Cerebral Hemorrhage; Female; Humans; Male; Middle Aged; Positron-Emission Tomography; Thiazoles

The dynamics of β-amyloid deposition and related second-order physiological effects, such as regional cerebral blood flow (rCBF), are key factors for a deeper understanding of Alzheimer's disease (AD). We present longitudinal in vivo data on the dynamics of β-amyloid deposition and the decline of rCBF in two different amyloid precursor protein (APP) transgenic mouse models of AD. Using a multiparametric positron emission tomography and magnetic resonance imaging approach, we demonstrate that in the presence of cerebral β-amyloid angiopathy (CAA), β-amyloid deposition is accompanied by a decline of rCBF. Loss of perfusion correlates with the growth of β-amyloid plaque burden but is not related to the number of CAA-induced microhemorrhages. However, in a mouse model of parenchymal β-amyloidosis and negligible CAA, rCBF is unchanged. Because synaptically driven spontaneous network activity is similar in both transgenic mouse strains, we conclude that the disease-related decline of rCBF is caused by CAA.

Topics: Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Aniline Compounds; Animals; Benzothiazoles; Brain; Cerebral Amyloid Angiopathy; Cerebral Hemorrhage; Cerebrovascular Circulation; Disease Models, Animal; Female; Longitudinal Studies; Magnetic Resonance Imaging; Mice; Mice, Transgenic; Multimodal Imaging; Perfusion Imaging; Plaque, Amyloid; Positron-Emission Tomography; Radiopharmaceuticals; Thiazoles

Cerebral microbleeds (CMBs) are a neuroimaging marker of small vessel disease (SVD) with relevance for understanding disease mechanisms in cerebrovascular disease, cognitive impairment, and normal aging. It is hypothesized that lobar CMBs are due to cerebral amyloid angiopathy (CAA) and deep CMBs are due to subcortical ischemic SVD. We tested this hypothesis using structural magnetic resonance imaging (MRI) markers of subcortical SVD and in vivo imaging of amyloid in patients with cognitive impairment.. We included 226 patients: 89 with Alzheimer disease-related cognitive impairment (ADCI) and 137 with subcortical vascular cognitive impairment (SVCI). All subjects underwent amyloid imaging with [(11) C] Pittsburgh compound B (PiB) positron emission tomography, and MRI to detect CMBs and markers of subcortical SVD, including the volume of white matter hyperintensities (WMH) and the number of lacunes.. Parietal and occipital lobar CMBs counts were higher in PiB(+) ADCI with moderate WMH than PiB(+) ADCI with minimal WMH, whereas PiB(-) patients with SVCI (ie, "pure" SVCI) showed both lobar and deep CMBs. In multivariate analyses of the whole cohort, WMH volume and lacuna counts were positively associated with both lobar and deep CMBs, whereas amyloid burden (PiB) was only associated with lobar CMBs. There was an interaction between lacuna burden and PiB retention on lobar (but not deep) CMBs (p<0.001).. Our findings suggest that although deep CMBs are mainly linked to subcortical SVD, both subcortical SVD and amyloid-related pathologies (eg, CAA) contribute to the pathogenesis of lobar CMBs, at least in subjects with mixed lobar and deep CMBs. Furthermore, subcortical SVD and amyloid-related pathologies interact to increase the risk of lobar CMBs.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid; Aniline Compounds; Cerebral Amyloid Angiopathy; Cerebral Hemorrhage; Cognition Disorders; Female; Humans; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Stroke, Lacunar; Thiazoles

The clinical role of amyloid brain positron emission tomographic imaging in the diagnosis of Alzheimer disease is currently being formulated. The specificity of a positive amyloid scan is a matter of contention.. An 83-year-old Canadian man presented with a 5-year history of predominantly short-term memory loss and functional impairment. Clinical evaluation revealed significant, gradually progressive short-term memory loss in the absence of any history of strokes or other neuropsychiatric symptoms. The patient met clinical criteria for probable Alzheimer disease but had a higher than expected burden of white matter disease on magnetic resonance imaging. A positron emission tomographic Pittsburgh Compound B scan was highly positive in typical Alzheimer disease distribution. The patient died of an intracerebral hemorrhage 6 months after the assessment. Autopsy revealed cerebral amyloid angiopathy in the complete absence of amyloid plaques or neurofibrillary tangles.. This patient demonstrates that a positive Pittsburgh Compound B scan in a patient with clinical dementia meeting criteria for probable Alzheimer disease is not proof of an Alzheimer disease pathophysiological process. A positive Pittsburgh Compound B scan in typical Alzheimer disease distribution in a patient with dementia can be secondary to cerebral amyloid angiopathy alone.

Topics: Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Cerebral Hemorrhage; Diagnosis, Differential; Fatal Outcome; Humans; Magnetic Resonance Imaging; Male; Memory Disorders; Neuropsychological Tests; Positron-Emission Tomography; Sensitivity and Specificity; Thiazoles

Incidental cerebral microhemorrhage (MH) is frequently found in older individuals scanned with susceptibility-weighted MRI (SWI) or gradient-recalled echo MRI. MH have been linked with β-amyloid (Aβ) deposition using (11)C-Pittsburgh compound B (PiB) PET in Alzheimer disease (AD) and cerebral amyloid angiopathy (CAA). We hypothesized that Aβ deposition in asymptomatic elderly individuals is associated with lobar MH (LMH).. This was a cross-sectional study of 84 elderly healthy controls (HC), 28 subjects with mild cognitive impairment (MCI), and 26 subjects with probable AD who underwent 3-T SWI and (11)C-PiB PET. (11)C-PiB cortical binding was quantified normalized to cerebellar cortex (standardized uptake value ratio [SUVR]) and scans classified as positive (PiB+) or negative (PiB-) by visual inspection. MH were manually counted and categorized by region and as lobar or nonlobar.. LMH were present in 30.8% of AD, 35.7% of MCI, and 19.1% of HC. The prevalence of LMH among PiB+ subjects was similar, regardless of clinical classification (AD 30.8%, MCI 38.9%, HC 41.4%, p > 0.7). HC with LMH had significantly higher mean neocortical SUVR (1.7 ± 0.5) than HC without LMH (1.3 ± 0.3, p ± 0.01). In HC, there was a positive correlation between number of LMH and SUVR, and between LMH and age. In HC, PiB+ (odds ratio [OR] 7.3, 95% confidence interval [CI] 1.6-33.7, p = 0.01) and age (OR 1.2, 95% CI 1.03-1.3, p = 0.02) both independently predicted the occurrence of LMH using logistic regression.. Asymptomatic Aβ deposition in older adults is strongly associated with LMH.

Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Apolipoprotein E4; Benzothiazoles; Brain; Brain Mapping; Carbon Radioisotopes; Cerebral Hemorrhage; Cognition Disorders; Female; Humans; Logistic Models; Magnetic Resonance Imaging; Male; Nerve Fibers, Myelinated; Positron-Emission Tomography; Psychiatric Status Rating Scales; Thiazoles

Topics: Aniline Compounds; Carbon Radioisotopes; Cerebral Arteries; Cerebral Cortex; Cerebral Hemorrhage; Cerebrovascular Disorders; Echocardiography, Three-Dimensional; Female; Fibrinolytic Agents; Heart Atria; Heart Neoplasms; Humans; Intracranial Embolism; Magnetic Resonance Imaging; Middle Aged; Myxoma; Peripheral Vascular Diseases; Positron-Emission Tomography; Predictive Value of Tests; Thiazoles; Tissue Plasminogen Activator; Treatment Outcome

Cerebrovascular deposition of beta-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 beta-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.. 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).. 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).. We conclude that PiB-positron emission tomography can detect cerebrovascular beta-amyloid and may serve as a method for identifying the extent of CAA in living subjects.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Biopsy; Cerebral Amyloid Angiopathy; Cerebral Hemorrhage; Cohort Studies; Education; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Occipital Lobe; Positron-Emission Tomography; Radiopharmaceuticals; Thiazoles