Kantarci, Kejal

PurposeRelaxation time constants are useful as markers of tissue properties. Imaging ex vivo tissue is done for research purposes; however, T1 relaxation time constants are altered by tissue fixation in a time‐dependent manner. This study investigates regional changes in T1 relaxation time constants in ex vivo brain tissue over 6 months of fixation.MethodsFive ex vivo human brain hemispheres in 10% formalin were scanned over 6 months. Mean T1 relaxation time constants were measured in regions of interest (ROIs) representing gray matter (GM) and white matter (WM) regions and analyzed as a function of fixation time.ResultsCortical GM ROIs had longer T1 relaxation time constants than WM ROIs; the thalamus had T1 relaxation time constants similar to those of WM ROIs. T1 relaxation time constants showed rapid shortening within the first 6 weeks after fixation followed by a slower rate of decline.ConclusionBoth GM and WM T1 relaxation time constants of fixed brain tissue show rapid decline within the first 6 weeks after autopsy and slow by 6 months. This information is useful for optimizing MR imaging acquisition parameters according to fixation time for ex vivo brain imaging studies. Magn Reson Med 77:774–778, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

Background: Different clinical syndromes can arise from Alzheimer’s disease (AD) neuropathology, including dementia of the Alzheimer’s type (DAT), logopenic primary progressive aphasia (lvPPA), and posterior cortical atrophy (PCA). Objective: To assess similarities and differences in patterns of white matter tract degeneration across these syndromic variants of AD. Methods: Sixty-four subjects (22 DAT, 24 lvPPA, and 18 PCA) that had diffusion tensor imaging and showed amyloid-β deposition on PET were assessed in this case-control study. A whole-brain voxel-based analysis was performed to assess differences in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity across groups. Results: All three groups showed overlapping diffusion abnormalities in a network of tracts, including fornix, corpus callosum, posterior thalamic radiations, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and uncinate fasciculus. Subtle regional differences were also observed across groups, with DAT particularly associated with degeneration of fornix and cingulum, lvPPA with left inferior fronto-occipital fasciculus and uncinate fasciculus, and PCA with posterior thalamic radiations, superior longitudinal fasciculus, posterior cingulate, and splenium of the corpus callosum. Conclusion: These findings show that while each AD phenotype is associated with degeneration of a specific structural network of white matter tracts, striking spatial overlap exists among the three network patterns that may be related to AD pathology.

AbstractIntroductionThe objective of our study was to investigate cross‐sectional associations of atrial fibrillation with neuroimaging measures of cerebrovascular disease and Alzheimer's disease and their interactions with mild cognitive impairment (MCI).MethodsMagnetic resonance imaging scans of individuals from a population‐based study were analyzed for infarctions, total gray matter, and hippocampal and white matter hyperintensity volumes. A subsample underwent positron emission tomography imaging.ResultsAtrial fibrillation was associated with infarctions and lower total gray matter volume. Compared with subjects with no atrial fibrillation and no infarction, the odds ratio (95% confidence intervals) for MCI was 2.99 (1.57–5.70; P = .001) among participants with atrial fibrillation and infarction, 0.90 (0.45–1.80; P = .77) for atrial fibrillation and no infarction, and 1.50 (0.96–2.34; P = .08) for no atrial fibrillation and any infarction.DiscussionParticipants with both atrial fibrillation and infarction are more likely to have MCI than participants with either infarction or atrial fibrillation alone.

Background and objectives: We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology. Methods and results: Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex. Conclusions: Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry.

AbstractIntroductionAlzheimer's Disease Neuroimaging Initiative (ADNI) is now in its 10th year. The primary objective of the magnetic resonance imaging (MRI) core of ADNI has been to improve methods for clinical trials in Alzheimer's disease (AD) and related disorders.MethodsWe review the contributions of the MRI core from present and past cycles of ADNI (ADNI‐1, ‐Grand Opportunity and ‐2). We also review plans for the future‐ADNI‐3.ResultsContributions of the MRI core include creating standardized acquisition protocols and quality control methods; examining the effect of technical features of image acquisition and analysis on outcome metrics; deriving sample size estimates for future trials based on those outcomes; and piloting the potential utility of MR perfusion, diffusion, and functional connectivity measures in multicenter clinical trials.DiscussionOver the past decade the MRI core of ADNI has fulfilled its mandate of improving methods for clinical trials in AD and will continue to do so in the future.

Background and Purpose— The relationships between cerebrovascular lesions visible on imaging and cognition are complex. We explored the possibility that the cerebral cortical volume mediated these relationships. Methods— Total of 1906 nondemented participants (59% women; 25% African–American; mean age, 76.6 years) in the Atherosclerosis Risk in Communities (ARIC) study underwent cognitive assessments, risk factor assessments, and quantitative MRI for white matter hyperintensities (WMH) and infarcts. The Freesurfer imaging analysis pipeline was used to determine regional cerebral volumes. We examined the associations of cognitive domain outcomes with cerebral volumes (hippocampus and separate groups of posterior and frontal cortical regions of interest) and cerebrovascular imaging features (presence of large or small cortical/subcortical infarcts and WMH volume). We performed mediation pathway analyses to assess the hypothesis that hippocampal and cortical volumes mediated the associations between cerebrovascular imaging features and cognition. Results— In unmediated analyses, WMH and infarcts were both associated with worse psychomotor speed/executive function. In mediation analyses, WMH and infarct associations on psychomotor speed/executive function were significantly attenuated, but not abolished, by the inclusion of the posterior cortical regions of interest volume in the models, and the infarcts on psychomotor speed/executive function association were attenuated, but not abolished, by inclusion of the frontal cortical regions of interest volume. Conclusions— Both WMH and infarcts were associated with cortical volume, and both lesions were also associated with cognitive performance, implying shared pathophysiological mechanisms. Although cross-sectional, our findings suggest that WMH and infarcts could be proxies for clinically covert processes that directly damage cortical regions. Microinfarcts are 1 candidate for such a clinically covert process.

AbstractBackgroundInexpensive, non‐invasive tools for assessing Alzheimer‐type pathophysiologies are needed. Computerized cognitive assessments are prime candidates.MethodsCognitively normal participants, aged 51–71, with magnetic resonance imaging, fluorodeoxyglucose‐positron emission tomography (FDG‐PET), amyloid PET, CogState computerized cognitive assessment, and standard neuropsychological tests were included. We first examined the association between the CogState battery and neuroimaging measures. We then compared that association to the one between standard neuropsychological z‐scores and neuroimaging.ResultsSlower reaction times for CogState Identification and One Back, and lower memory and attention z‐scores, were associated (P < .05) with FDG‐PET hypometabolism. Slower time on the Groton Maze Learning Task and worse One Card Learning accuracy were associated (P < .05) with smaller hippocampal volumes. There were no associations with amyloid PET. Associations of CogState and neuropsychological Z‐scores with neuroimaging were small and of a similar magnitude.ConclusionsCogState subtests were cross‐sectionally comparable to standard neuropsychological tests in their relatively weak associations with neurodegeneration imaging markers.