2-(4--(methylamino)phenyl)-6-hydroxybenzothiazole and Intracranial-Hemorrhages

We sought to determine the incidence and associations of lobar microbleeds (LMBs) in a longitudinal cohort with (11)C-Pittsburgh compound B (PiB) PET imaging.. One hundred seventy-four participants from the observational Australian Imaging, Biomarkers and Lifestyle Study of Ageing (97 with normal cognition [NC], 37 with mild cognitive impairment [MCI], and 40 with Alzheimer disease [AD] dementia) were assessed at 3 time points over 3 years with 3-tesla susceptibility-weighted MRI and (11)C-PiB PET. MRIs were inspected for microbleeds, siderosis, infarction, and white matter hyperintensity severity, blind to clinical and PiB findings. Neocortical PiB standardized uptake value ratio, normalized to cerebellar cortex, was dichotomized as positive or negative (PiB+/-, standardized uptake value ratio >1.5). Annualized LMB incidence was calculated, and logistic regression was used to determine the association of incident LMBs with PiB, APOE ε4+ status, and cerebrovascular disease.. LMBs were present in 18.6% of NC, 24.3% of MCI, and 40% of AD participants (p < 0.05 vs NC). LMB incidence was 0.2 ± 0.6 per year in NC participants, 0.2 ± 0.5 in MCI, and 0.7 ± 1.4 in AD (p < 0.03 vs NC) and was 6-fold higher in PiB+ than PiB-NC. Incident LMBs were associated with age, APOE ε4+, PiB+, and baseline LMBs. Incidence of multiple LMBs was also associated with lacunar infarction and white matter hyperintensity severity.. Older age, baseline LMBs, higher β-amyloid burden, and concomitant cerebrovascular disease may all confer higher risk of incident LMBs. This should be considered when designing protocols for amyloid-modifying clinical trials.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Amyloid; Aniline Compounds; Australia; Brain; Cerebral Small Vessel Diseases; Female; Humans; Incidence; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Thiazoles

Most subjects with logopenic variant of primary progressive aphasia (lvPPA) have β-amyloid (Aβ) deposition on Pittsburgh Compound B positron emission tomography (PiB-PET), usually affecting prefrontal and temporoparietal cortices, with less occipital involvement.. To assess clinical and imaging features in lvPPA subjects with unusual topographic patterns of Aβ deposition with highest uptake in occipital lobe.. Thirty-three lvPPA subjects with Aβ deposition on PiB-PET were included in this case-control study. Line plots of regional PiB uptake were created, including frontal, temporal, parietal and occipital regions, for each subject. Subjects in which the line sloped downwards in occipital lobe (lvPPA-low), representing low uptake, were separated from those where the line sloped upwards in occipital lobe (lvPPA-high), representing unusually high occipital uptake compared to other regions. Clinical variables, atrophy on MRI, hypometabolism on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and presence and distribution of microbleeds and white matter hyperintensities (WMHs) were assessed.. Seventeen subjects (52%) were classified as lvPPA-high. Mean occipital PiB uptake in lvPPA-high was higher than all other regions and higher than all regions in lvPPA-low. The lvPPA-high subjects performed more poorly on cognitive testing, including executive and visuospatial testing, but the two groups did not differ in aphasia severity. Proportion of microbleeds and WMH was higher in lvPPA-high than lvPPA-low. Parietal hypometabolism was greater in lvPPA-high than lvPPA-low.. Unusually high occipital Aβ deposition is associated with widespread cognitive impairment and different imaging findings in lvPPA. These findings help explain clinical heterogeneity in lvPPA and suggest that Aβ influences severity of overall cognitive impairment but not aphasia.

Topics: Aged; Amyloid beta-Peptides; Aniline Compounds; Aphasia, Primary Progressive; Atrophy; Case-Control Studies; Cognition Disorders; Female; Fluorodeoxyglucose F18; Humans; Intracranial Hemorrhages; Male; Middle Aged; Nerve Fibers, Myelinated; Neuroimaging; Neuropsychological Tests; Occipital Lobe; Radionuclide Imaging; Thiazoles

Advanced cerebrovascular β-amyloid deposition (cerebral amyloid angiopathy, CAA) is associated with cerebral microbleeds, but the precise relationship between CAA burden and microbleeds is undefined. We used T2*-weighted magnetic resonance imaging (MRI) and noninvasive amyloid imaging with Pittsburgh Compound B (PiB) to analyze the spatial relationship between CAA and microbleeds. On coregistered positron emission tomography (PET) and MRI images, PiB retention was increased at microbleed sites compared to simulated control lesions (p = 0.002) and declined with increasing distance from the microbleed (p < 0.0001). These findings indicate that microbleeds occur preferentially in local regions of concentrated amyloid and support therapeutic strategies aimed at reducing vascular amyloid deposition.

Topics: Aged; Amyloid; Aniline Compounds; Cerebral Amyloid Angiopathy; Female; Humans; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Thiazoles