Citations

Bilateral oophorectomy in premenopausal women is a unique condition causing the abrupt and premature loss of ovarian hormones, primarily estrogen. Bilateral oophorectomy causes an alteration of several fundamental aging processes at the cellular, tissue, organ, and system levels, leading to multimorbidity, frailty, and reduced survival. However, many questions remain unanswered.

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.

ObjectiveRecent availability of amyloid and tau positron emission tomography (PET) has provided us with a unique opportunity to measure the association of systemic vascular health with brain health after accounting for the impact of Alzheimer disease (AD) pathologies. We wanted to quantify early cerebrovascular health–related magnetic resonance imaging brain measures (structure, perfusion, microstructural integrity) and evaluate their utility as a biomarker for cerebrovascular health.MethodsWe used 2 independent samples (discovery, n = 390; validation, n = 1,035) of individuals, aged ≥ 60 years, along the cognitive continuum with imaging from the population‐based sample of Mayo Clinic Study of Aging. We ascertained vascular health by summing up recently existing cardiovascular and metabolic conditions (CMC) from health care records (hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke). Using multiple regression models, we quantified associations between CMC and brain health after accounting for age, sex, education/occupation, and AD burden (from amyloid and tau PET).ResultsSystemic vascular health was associated with medial temporal lobe thinning, widespread cerebral hypoperfusion, and loss of microstructural integrity in several white matter tracts including the corpus callosum and fornix. Further investigations suggested that microstructural integrity of the genu of the corpus callosum was suitable for assessing prodromal cerebrovascular health, had similar distributions in the discovery and independent validation datasets, and predicted cognitive performance above and beyond amyloid deposition.InterpretationSystemic vascular health has significant impact on brain structure and function. Quantifying prodromal cerebrovascular health–related brain measures that are independent of AD pathology–related changes has great utility for cognitive aging. Ann Neurol 2018;84:713–724

Abstract Introduction Precision medicine methodologies and approaches have advanced our understanding of the clinical presentation, development, progression, and management of Alzheimer's disease (AD) dementia. However, sex and gender have not yet been adequately integrated into many of these approaches. Methods The Society for Women's Health Research Interdisciplinary Network on AD, comprised of an expert panel of scientists and clinicians, reviewed ongoing and published research related to sex and gender differences in AD. Results The current review is a result of this Network's efforts and aims to: (1) highlight the current state‐of‐the‐science in the AD field on sex and gender differences; (2) address knowledge gaps in assessing sex and gender differences; and (3) discuss 12 priority areas that merit further research. Discussion The exclusion of sex and gender has impeded faster advancement in the detection, treatment, and care of AD across the clinical spectrum. Greater attention to these differences will improve outcomes for both sexes.

Background: 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. Objective: 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. Methods: 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. Results: 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%). Conclusions: 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.

PurposeTo develop a fast and automated volume‐of‐interest (VOI) prescription pipeline (AutoVOI) for single‐voxel MRS that removes the need for manual VOI placement, allows flexible VOI planning in any brain region, and enables high inter‐ and intra‐subject consistency of VOI prescription.MethodsAutoVOI was designed to transfer pre‐defined VOIs from an atlas to the 3D anatomical data of the subject during the scan. The AutoVOI pipeline was optimized for consistency in VOI placement (precision), enhanced coverage of the targeted tissue (accuracy), and fast computation speed. The tool was evaluated against manual VOI placement using existing T1‐weighted data sets and corresponding VOI prescriptions. Finally, it was implemented on 2 scanner platforms to acquire MRS data from clinically relevant VOIs that span the cerebrum, cerebellum, and the brainstem.ResultsThe AutoVOI pipeline includes skull stripping, non‐linear registration of the atlas to the subject's brain, and computation of the VOI coordinates and angulations using a minimum oriented bounding box algorithm. When compared against manual prescription, AutoVOI showed higher intra‐ and inter‐subject spatial consistency, as quantified by generalized Dice coefficients (GDC), lower intra‐ and inter‐subject variability in tissue composition (gray matter, white matter, and cerebrospinal fluid) and higher or equal accuracy, as quantified by GDC of prescribed VOI with targeted tissues. High quality spectra were obtained on Siemens and Philips 3T systems from 6 automatically prescribed VOIs by the tool.ConclusionRobust automatic VOI prescription is feasible and can help facilitate clinical adoption of MRS by avoiding operator dependence of manual selection.

AbstractIntroductionMedial temporal lobe (MTL) uptake on tau–positron emission tomography (PET) is seen not only in Alzheimer's disease (AD) dementia but also in the aging population. The relationship of these findings to the development of AD dementia needs to be better understood.MethodsTau‐PET with AV‐1451 was performed on 576 cognitively unimpaired (CU) participants aged 50–94 years. The number of CUs with and without abnormal MTL regions and those with or without extra‐MTL abnormalities was determined. Left and right regions were compared within each subject.ResultsOf CUs, 58% (334/576) had abnormal tau‐PET findings. MTL abnormalities were present in 41% (238/576) of subjects.DiscussionMTL tau‐PET signal is often associated with abnormal extra‐MTL tau‐PET signal in CU participants and may represent neurofibrillary tangle development that could identify participants most likely to develop AD dementia. Tau‐PET signal exclusively outside of the MTL is seen in 17% of CU participants and could be the initial findings in participants in different AD dementia pathways. Significant (P < .001) differences in tau–standardized uptake value ratio between sides were noted in 26 of 41 examined brain regions implicating further study of side‐specific deficits.