Rabinstein, Alejandro A.

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.

Background: Non-traumatic convexal subarachnoid hemorrhages (cSAH) in the elderly can be a manifestation of cerebral amyloid angiopathy (CAA) and predict future intracerebral hemorrhage risk. The frequency of cSAH in the elderly population is unknown. Our objective was to determine the frequency of convexal subarachnoid hemorrhage in a population-based study among individuals who underwent amyloid PET imaging. Methods: Between 11/29/2004 and 3/11/2017 there were 1,687 participants ages 50-years and older in the population-based Mayo Clinic Study of Aging (MCSA) with Pittsburgh compound B (PiB) PET imaging. All intracerebral hemorrhages among participants were identified utilizing the Rochester Epidemiology Project’s records linkage system, and records and images were reviewed to identify those with both symptomatic and asymptomatic convexal subarachnoid hemorrhage. Neuroimaging characteristics, demographics, medications, and ApoE genotype were recorded. Results: Four (0.23%) cSAHs were identified among the individuals who underwent PiB PET imaging. Three were women and median age was 73 (range: 67-84). cSAH occurred in the following locations: right frontal (3), and right parieto-occipital (1). Two went on to develop a lobar intracerebral hemorrhage at a median of 4.75 years after cSAH. Coexisting cerebral microbleeds were identified in one case. The APOE allele combinations of the four participants were: 3/3, 3/3, 2/2, and 2/3. On PiB PET imaging, the median SUVR was 1.81 (range: 1.38-2.34). Conclusion: cSAH is a relatively rare manifestation of CAA occurring in less than 1% of the general population, but may represent a subset with a high risk of future intracerebral hemorrhage. Half of the participants with cSAH had an APOE e2 allele.