Graff‐Radford, Jonathan

Objective: To determine the frequency and characteristics of symptomatic intracerebral hemorrhage in a population-based study Patients and Methods: The population-based Mayo Clinic Study of Aging included 4,994 participants age ≥50 years entered from 11/29/2004 to 3/11/2017. Participants with intracranial hemorrhage were identified using the Rochester Epidemiology Project medical records linkage system. Medical records of these individuals were reviewed. Each hemorrhage was classified as deep, lobar, or cerebellar intracerebral hemorrhage (ICH) or convexity subarachnoid hemorrhage (cSAH). Traumatic, subdural, non-convexal SAH, and epidural hemorrhages were excluded. Patient demographics, presence of hypertension, antithrombotic regimen, APOE genotype, and amyloid PET scan results were collected when available. Individuals with hemorrhages were matched 3:1 on age and gender to controls without symptomatic hemorrhage. Analyses within the cases and between the groups were performed. Results: Symptomatic hemorrhages were identified in 57 individuals for a frequency of 1.14%. Twenty-one were classified as deep, 26 lobar, 5 cerebellar, and 5 cSAH. Mean age at the time of hemorrhage was 80.9 years (SD ±7.9). 54.4% of hemorrhages occurred in men. Hypertension was present in 45.6%. Of those with lobar ICH or cSAH, 87.1% were on an antithrombotic compared to 65.6% of controls (p=0.02) and 32.3% of these were on warfarin compared to 12.9% of controls (p=0.01). APOE genotype was available in 54 of the 57. APOE e2 and/or e4 was found in 46.7% of those with lobar ICH/cSAH compared to 39.1% of controls (p=0.47) and 35.0% of those with deep ICH versus 39.3% of controls (p=0.73). Of the 31 with either lobar ICH or cSAH, 7 underwent amyloid PET scans; of these, 71.4% were abnormal compared to 42.9% of controls with mean SUVR of 1.911 and 1.565, respectively (p=0.08). Conclusions: Symptomatic ICH occurred in approximately 1 in 100 individuals age 50-94 years in this population-based study. In a matched case-control study, antithrombotic use (particularly warfarin) was statistically associated with the development of an ICH. While only a subset underwent amyloid PET, there was a trend towards greater amyloid load in those who developed a lobar or cSAH compared to controls.

Background: Although white matter hyperintensities (WMH) have been viewed as a marker of vascular disease, pathology studies have found an association of WMH with Alzheimer’s disease (AD) pathologies. Our objective was to investigate the topographic patterns of WMH associated with AD biomarkers. Methods: From the population-based Mayo Clinic Study of aging, 434 non-demented participants with FLAIR-MRI, tau-PET and PiB-PET scans were identified. A subset had microbleeds on T2* GRE scans. We ran SPM12 based voxel-wise multiple regression analyses to detect WMH regions associated with AD biomarkers (global amyloid from PiB-PET and meta-ROI tau uptake from tau-PET) adjusting for age, sex, and hypertension. For amyloid associations, we additionally adjusted for tau and vice versa. Results: Topographic patterns of WMH associated with amyloid after both voxel and cluster level corrections primarily included periventricular WMH (frontal and parietal lobes). Masks with lenient threshold (greater detection sensitivity) and strict thresholds (greater detection specificity) are shown in the figure. (A) and (B) show the areas of positive associations between PIB ratio and WMHs adjusted by age, sex, education, hypertension and Tau meta ROI. The sensitive mask (A) was thresholded at FDR p<0.05 at voxel level and FWE p<0.05 at cluster level. The specific mask (B) was thresholded at FDR p<0.001 at voxel level and FDR p<0.05 at cluster level. (C) Shows the frequency of WMHs in the study sample, ranging from infrequent (dark blue) to frequent (green to red). Both the sensitive (p<0.001, Cohen’s D=0.615) and specific WMH maps (p<0.001, Cohen’s D = 0.705) were associated with microbleeds. No WMH regions were associated with tau. Conclusion: Amyloid but not tau load on PET was associated with WMH topographically. The WMH regions associated with amyloid were associated with CMBs suggesting that cerebral amyloid angiopathy may be contributing to the relationship between amyloid and WMH.

AbstractBackgroundPosterior cortical atrophy and dementia with Lewy bodies are 2 distinct clinical syndromes, yet they can overlap in symptoms and occipital hypometabolism. Patients with dementia with Lewy bodies often have overlapping Alzheimer's disease pathology. Similarly, Lewy bodies can be found in patients with posterior cortical atrophy. We investigated differences in the distribution and magnitude of F18‐AV‐1451 uptake in patients with these 2 syndromes.MethodsConsecutive patients with probable dementia with Lewy bodies (n = 33), posterior cortical atrophy (n = 18), and cognitively unimpaired controls (n = 100) underwent 18F‐AV‐1451 positron emission tomography. Regional differences in AV‐1451 uptake were assessed using voxel‐wise and an atlas‐based approach. The greatest differences in AV‐1451 uptake between patient groups were identified using area under receiver operating curve statistics, and a composite region was derived.ResultsAV‐1451 uptake in both patient groups was predominantly localized to the lateral occipital regions, but the magnitude of uptake was markedly greater in posterior cortical atrophy compared with dementia with Lewy bodies. The posterior cortical atrophy group showed the greatest AV‐1451 uptake throughout all the gray matter compared with that in other groups. The occipital composite region, consisting of superior, middle, and inferior occipital cortices, distinguished posterior cortical atrophy from dementia with Lewy bodies (area under the curve >0.97; P < 0.001, Bonferroni‐corrected) with excellent sensitivity (88%) and specificity (100%).ConclusionsPosterior cortical atrophy and dementia with Lewy bodies can share clinical features, and although the pattern of AV‐1451 uptake in occipital cortices overlaps between these 2 syndromes, its magnitude is significantly higher in posterior cortical atrophy. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

AbstractAlzheimer's disease (AD) can present with atypical clinical forms where the prominent domain of deficit is not memory, that is, atypical AD. Atypical AD patients show cortical atrophy on MRI, hypometabolism on [18F]fluorodeoxyglucose (FDG) PET, tau uptake on [18F]AV‐1451 PET, and white matter tract degeneration on diffusion tensor imaging (DTI). How these disease processes relate to each other locally and distantly remains unclear. We aimed to examine multimodal neuroimaging relationships in individuals with atypical AD, using univariate and multivariate techniques at region‐ and voxel‐level. Forty atypical AD patients underwent MRI, FDG‐PET, tau‐PET, beta‐amyloid PET, and DTI. Patients were all beta‐amyloid positive. Partial Pearson's correlations were performed between tau and FDG standardized uptake value ratios, gray matter MRI‐volumes and white matter tract fractional anisotropy. Sparse canonical correlation analysis was applied to identify multivariate relationships between the same quantities. Voxel‐level associations across modalities were also assessed. Tau showed strong local negative correlations with FDG metabolism in the occipital and frontal lobes. Tau in frontal and parietal regions was negatively associated with temporoparietal gray matter MRI‐volume. Fractional anisotropy in a set of posterior white matter tracts, including the splenium of the corpus callosum, cingulum, and posterior thalamic radiation, was negatively correlated with parietal and occipital tau, atrophy and, predominantly, with hypometabolism. These results support the view that tau is the driving force behind neurodegeneration in atypical AD, and that a breakdown in structural connectivity is related to cortical neurodegeneration, particularly hypometabolism.