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Different patterns of white matter degeneration using multiple diffusion indices and volumetric data in mild cognitive impairment and Alzheimer patients
Alzheimeŕs disease (AD) represents the most prevalent neurodegenerative disorder that causes cognitive decline in old age. In its early stages, AD is associated with microstructural abnormalities in white matter (WM). In the current study, multiple indices of diffusion tensor imaging (DTI) and brain volumetric measurements were employed to comprehensively investigate the landscape of AD pathology. The sample comprised 58 individuals including cognitively normal subjects (controls), amnestic mild cognitive impairment (MCI) and AD patients. Relative to controls, both MCI and AD subjects showed widespread changes of anisotropic fraction (FA) in the corpus callosum, cingulate and uncinate fasciculus. Mean diffusivity and radial changes were also observed in AD patients in comparison with controls. After controlling for the gray matter atrophy the number of regions of significantly lower FA in AD patients relative to controls was decreased; nonetheless, unique areas of microstructural damage remained, e.g., the corpus callosum and uncinate fasciculus. Despite sample size limitations, the current results suggest that a combination of secondary and primary degeneration occurrs in MCI and AD, although the secondary degeneration appears to have a more critical role during the stages of disease involving dementia
Rotationally-invariant mapping of scalar and orientational metrics of neuronal microstructure with diffusion MRI
We develop a general analytical and numerical framework for estimating intra-
and extra-neurite water fractions and diffusion coefficients, as well as
neurite orientational dispersion, in each imaging voxel. By employing a set of
rotational invariants and their expansion in the powers of diffusion weighting,
we analytically uncover the nontrivial topology of the parameter estimation
landscape, showing that multiple branches of parameters describe the
measurement almost equally well, with only one of them corresponding to the
biophysical reality. A comprehensive acquisition shows that the branch choice
varies across the brain. Our framework reveals hidden degeneracies in MRI
parameter estimation for neuronal tissue, provides microstructural and
orientational maps in the whole brain without constraints or priors, and
connects modern biophysical modeling with clinical MRI.Comment: 25 pages, 12 figures, elsarticle two-colum
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Rates of lobar atrophy in asymptomatic MAPT mutation carriers.
IntroductionThe aim of this study was to investigate the rates of lobar atrophy in the asymptomatic microtubule-associated protein tau (MAPT) mutation carriers.MethodsMAPT mutation carriers (n = 14; 10 asymptomatic, 4 converters from asymptomatic to symptomatic) and noncarriers (n = 13) underwent structural magnetic resonance imaging and were followed annually with a median of 9.2 years. Longitudinal changes in lobar atrophy were analyzed using the tensor-based morphometry with symmetric normalization algorithm.ResultsThe rate of temporal lobe atrophy in asymptomatic MAPT mutation carriers was faster than that in noncarriers. Although the greatest rate of atrophy was observed in the temporal lobe in converters, they also had increased atrophy rates in the frontal and parietal lobes compared to noncarriers.DiscussionAccelerated decline in temporal lobe volume occurs in asymptomatic MAPT mutation carriers followed by the frontal and parietal lobe in those who have become symptomatic. The findings have implications for monitoring the progression of neurodegeneration during clinical trials in asymptomatic MAPT mutation carriers
On the primacy and irreducible nature of first-person versus third-person information
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An MRI-Derived Definition of MCI-to-AD Conversion for Long-Term, Automati c Prognosis of MCI Patients
Alzheimer's disease (AD) and mild cognitive impairment (MCI), continue to be
widely studied. While there is no consensus on whether MCIs actually "convert"
to AD, the more important question is not whether MCIs convert, but what is the
best such definition. We focus on automatic prognostication, nominally using
only a baseline image brain scan, of whether an MCI individual will convert to
AD within a multi-year period following the initial clinical visit. This is in
fact not a traditional supervised learning problem since, in ADNI, there are no
definitive labeled examples of MCI conversion. Prior works have defined MCI
subclasses based on whether or not clinical/cognitive scores such as CDR
significantly change from baseline. There are concerns with these definitions,
however, since e.g. most MCIs (and ADs) do not change from a baseline CDR=0.5,
even while physiological changes may be occurring. These works ignore rich
phenotypical information in an MCI patient's brain scan and labeled AD and
Control examples, in defining conversion. We propose an innovative conversion
definition, wherein an MCI patient is declared to be a converter if any of the
patient's brain scans (at follow-up visits) are classified "AD" by an
(accurately-designed) Control-AD classifier. This novel definition bootstraps
the design of a second classifier, specifically trained to predict whether or
not MCIs will convert. This second classifier thus predicts whether an
AD-Control classifier will predict that a patient has AD. Our results
demonstrate this new definition leads not only to much higher prognostic
accuracy than by-CDR conversion, but also to subpopulations much more
consistent with known AD brain region biomarkers. We also identify key
prognostic region biomarkers, essential for accurately discriminating the
converter and nonconverter groups
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