Neuroimaging correlates of pathologically defined subtypes of Alzheimer's disease: a case-control study.

Background: Three subtypes of Alzheimer's disease (AD) have been pathologically defined on the basis of the distribution of neurofibrillary tangles: typical AD, hippocampal-sparing AD, and limbic-predominant AD. Compared with typical AD, hippocampal-sparing AD has more neurofibrillary tangles in the cortex and fewer in the hippocampus, whereas the opposite pattern is seen in limbic-predominant AD. We aimed to determine whether MRI patterns of atrophy differ between these subtypes and whether structural neuroimaging could be a useful predictor of pathological subtype at autopsy.

Genome-wide association identifies genetic variants associated with lentiform nucleus volume in N = 1345 young and elderly subjects.

Deficits in lentiform nucleus volume and morphometry are implicated in a number of genetically influenced disorders, including Parkinson's disease, schizophrenia, and ADHD. Here we performed genome-wide searches to discover common genetic variants associated with differences in lentiform nucleus volume in human populations. We assessed structural MRI scans of the brain in two large genotyped samples: the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 706) and the Queensland Twin Imaging Study (QTIM; N = 639).

SMALL WORLD NETWORK MEASURES PREDICT WHITE MATTER DEGENERATION IN PATIENTS WITH EARLY-STAGE MILD COGNITIVE IMPAIRMENT.

Alzheimer's Disease (AD) has long been considered a cortical degenerative disease, but impaired brain connectivity, due to white matter injury, may exacerbate cognitive problems. Predicting brain changes is critically important for early treatment. In a longitudinal diffusion tensor imaging study, we investigated white matter fiber integrity in 19 patients (mean age: 74.

PREDICTING TEMPORAL LOBE VOLUME ON MRI FROM GENOTYPES USING L(1)-L(2) REGULARIZED REGRESSION.

Penalized or sparse regression methods are gaining increasing attention in imaging genomics, as they can select optimal regressors from a large set of predictors whose individual effects are small or mostly zero. We applied a multivariate approach, based on L(1)-L(2)-regularized regression (elastic net) to predict a magnetic resonance imaging (MRI) tensor-based morphometry-derived measure of temporal lobe volume from a genome-wide scan in 740 Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. We tuned the elastic net model's parameters using internal crossvalidation and evaluated the model on independent test sets.

HOW DO SPATIAL AND ANGULAR RESOLUTION AFFECT BRAIN CONNECTIVITY MAPS FROM DIFFUSION MRI?

Diffusion tensor imaging (DTI) is sensitive to the directionally- constrained flow of water, which diffuses preferentially along axons. Tractography programs may be used to infer matrices of connectivity (anatomical networks) between pairs of brain regions. Little is known about how these computed connectivity measures depend on the scans' spatial and angular resolutions.

Altered functional MR imaging language activation in elderly individuals with cerebral leukoaraiosis.

Purpose: To test the hypothesis that leukoaraiosis alters functional activation during a semantic decision language task.

Materials And Methods: With institutional review board approval and written informed consent, 18 right-handed, cognitively healthy elderly participants with an aggregate leukoaraiosis lesion volume of more than 25 cm(3) and 18 age-matched control participants with less than 5 cm(3) of leukoaraiosis underwent functional MR imaging to allow comparison of activation during semantic decisions with that during visual perceptual decisions. Brain statistical maps were derived from the general linear model.

Discovery and Replication of Gene Influences on Brain Structure Using LASSO Regression.

We implemented least absolute shrinkage and selection operator (LASSO) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures.

Focal atrophy on MRI and neuropathologic classification of dementia with Lewy bodies.

Objective: To determine the association between the focal atrophy measures on antemortem MRI and postmortem neuropathologic classification of dementia with Lewy bodies (DLB) using the Third Report of the DLB Consortium criteria.

Methods: We retrospectively identified 56 subjects who underwent antemortem MRI and had Lewy body (LB) pathology at autopsy. Subjects were pathologically classified as high (n = 25), intermediate (n = 22), and low likelihood DLB (n = 9) according to the Third Report of the DLB Consortium criteria.

Imaging and acetylcholinesterase inhibitor response in dementia with Lewy bodies.

Acetylcholinesterase inhibitors are commonly used to treat patients with dementia with Lewy bodies. Hippocampal atrophy on magnetic resonance imaging and amyloid-β load on positron emission tomography are associated with the Alzheimer's disease-related pathology in patients with dementia with Lewy bodies. To date, few studies have investigated imaging markers that predict treatment response in patients with dementia with Lewy bodies.

Comparison of imaging biomarkers in the Alzheimer Disease Neuroimaging Initiative and the Mayo Clinic Study of Aging.

Objective: To determine whether magnetic resonance imaging measurements observed in the Alzheimer Disease Neuroimaging Initiative (ADNI) convenience sample differ from those observed in the Mayo Clinic Study of Aging (MCSA) population-based sample.

Design: Comparison of 2 samples.

Setting: Fifty-nine recruiting sites for the ADNI in the United States and Canada and the MCSA, a population-based cohort in Olmsted County, Minnesota.

Non-stationarity in the "resting brain's" modular architecture.

Task-free functional magnetic resonance imaging (TF-fMRI) has great potential for advancing the understanding and treatment of neurologic illness. However, as with all measures of neural activity, variability is a hallmark of intrinsic connectivity networks (ICNs) identified by TF-fMRI. This variability has hampered efforts to define a robust metric of connectivity suitable as a biomarker for neurologic illness.

Characterization of a family with c9FTD/ALS associated with the GGGGCC repeat expansion in C9ORF72.

Background: The hexanucleotide repeat in the chromosome 9 open reading frame 72 (C9ORF72) gene was recently discovered as the underlying genetic cause of many families with frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS) linked to chromosome 9 (c9FTD/ALS). We report the clinical, neuropsychologic, and neuroimaging findings of a family with the C9ORF72 mutation and clinical diagnoses bridging the FTD, parkinsonism, and ALS spectrum.

Objective: To characterize the antemortem characteristics of a family with c9FTD/ALS associated with the GGGGCC repeat expansion in C9ORF72.

MRS in early and presymptomatic carriers of a novel octapeptide repeat insertion in the prion protein gene.

To evaluate the proton magnetic resonance (MR) spectroscopy ((1) H MRS) changes in carriers of a novel octapeptide repeat insertion in the prion protein gene (PRNP) and family history of frontotemporal dementia with ataxia. Four at-risk mutation carriers and 13 controls were compared using single voxel, short TE, (1) H MRS from the posterior cingulate gyrus. The mutation carriers had an increased choline/creatine, P = .

Effects of MRI scan acceleration on brain volume measurement consistency.

Purpose: To evaluate the effects of recent advances in magnetic resonance imaging (MRI) radiofrequency (RF) coil and parallel imaging technology on brain volume measurement consistency.

Materials And Methods: In all, 103 whole-brain MRI volumes were acquired at a clinical 3T MRI, equipped with a 12- and 32-channel head coil, using the T1-weighted protocol as employed in the Alzheimer's Disease Neuroimaging Initiative study with parallel imaging accelerations ranging from 1 to 5. An experienced reader performed qualitative ratings of the images.

Angular versus spatial resolution trade-offs for diffusion imaging under time constraints.

Diffusion weighted magnetic resonance imaging (DW-MRI) are now widely used to assess brain integrity in clinical populations. The growing interest in mapping brain connectivity has made it vital to consider what scanning parameters affect the accuracy, stability, and signal-to-noise of diffusion measures. Trade-offs between scan parameters can only be optimized if their effects on various commonly-derived measures are better understood.

Alzheimer disease: new concepts on its neurobiology and the clinical role imaging will play.

Alzheimer disease (AD) is one of, if not the most, feared diseases associated with aging. The prevalence of AD increases exponentially with age after 60 years. Increasing life expectancy coupled with the absence of any approved disease-modifying therapies at present position AD as a dominant public health problem.

Primary lateral sclerosis as progressive supranuclear palsy: diagnosis by diffusion tensor imaging.

Background: Evaluating the integrity of white matter tracts with diffusion tensor imaging may differentiate primary lateral sclerosis from progressive supranuclear palsy.

Methods: Thirty-three prospectively recruited subjects had standardized evaluations and diffusion tensor imaging: 3 with primary lateral sclerosis who presented with features suggestive of progressive supranuclear palsy, 10 with probable or definite progressive supranuclear palsy, and 20 matched controls. We compared fractional anisotropy of the corticospinal tract, superior cerebellar peduncles, and body of the corpus callosum between groups.

Common variants at 6q22 and 17q21 are associated with intracranial volume.

During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 × 10(-8)) for brain volume.

Identification of common variants associated with human hippocampal and intracranial volumes.

Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies.

Frontal asymmetry in behavioral variant frontotemporal dementia: clinicoimaging and pathogenetic correlates.

We aimed to assess associations between clinical, imaging, pathologic, and genetic features and frontal lobe asymmetry in behavioral variant frontotemporal dementia (bvFTD). Volumes of the left and right dorsolateral, medial, and orbital frontal lobes were measured in 80 bvFTD subjects and subjects were classified into 3 groups according to the degree of asymmetry (asymmetric left, asymmetric right, symmetric) using cluster analysis. The majority of subjects were symmetric (65%), with 20% asymmetric left and 15% asymmetric right.

An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease.

Objective: A workgroup commissioned by the Alzheimer's Association (AA) and the National Institute on Aging (NIA) recently published research criteria for preclinical Alzheimer disease (AD). We performed a preliminary assessment of these guidelines.

Methods: We employed Pittsburgh compound B positron emission tomography (PET) imaging as our biomarker of cerebral amyloidosis, and (18) fluorodeoxyglucose PET imaging and hippocampal volume as biomarkers of neurodegeneration.

Imaging measures predict progression in progressive supranuclear palsy.

Objective: The aim of this work was to determine whether the progressive supranuclear palsy rating scale, a measure of disease severity, is associated with neuroanatomical changes in progressive supranuclear palsy.

Methods: We recruited 22 subjects with probable progressive supranuclear palsy who completed the progressive supranuclear palsy rating scale at 2 time points. All subjects had magnetic resonance imaging and diffusion tensor imaging.

Modifiable factors that alter the size of the hippocampus with ageing.

The hippocampus is particularly vulnerable to the neurotoxic effects of obesity, diabetes mellitus, hypertension, hypoxic brain injury, obstructive sleep apnoea, bipolar disorder, clinical depression and head trauma. Patients with these conditions often have smaller hippocampi and experience a greater degree of cognitive decline than individuals without these comorbidities. Moreover, hippocampal atrophy is an established indicator for conversion from the normal ageing process to developing mild cognitive impairment and dementia.

Shapes of the trajectories of 5 major biomarkers of Alzheimer disease.

Objective: To characterize the shape of the trajectories of Alzheimer disease biomarkers as a function of Mini-Mental State Examination (MMSE) score.

Design And Setting: Longitudinal registries from the Mayo Clinic and the Alzheimer's Disease Neuroimaging Initiative.

Patients: Two different samples (n = 343 and n = 598) were created that spanned the cognitive spectrum from normal to Alzheimer disease dementia.