Focal hemosiderin deposits and β-amyloid load in the ADNI cohort.

Background: Prevalence and risk factors for focal hemosiderin deposits are important considerations when planning amyloid-modifying trials for treatment and prevention of Alzheimer's disease (AD).

Methods: Subjects were cognitively normal (n = 171), early-mild cognitive impairment (MCI) (n = 240), late-MCI (n = 111), and AD (n = 40) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Microhemorrhages and superficial siderosis were assessed at baseline and on all available MRIs at 3, 6, and 12 months.

Corticospinal tract degeneration associated with TDP-43 type C pathology and semantic dementia.

Four subtypes of frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions have been described (types A-D). Of these four subtypes, motor neuron disease is more commonly associated with type B pathology, but has also been reported with type A pathology. We have noted, however, the unusual occurrence of cases of type C pathology having corticospinal tract degeneration.

Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers.

In 2010, we put forward a hypothetical model of the major biomarkers of Alzheimer's disease (AD). The model was received with interest because we described the temporal evolution of AD biomarkers in relation to each other and to the onset and progression of clinical symptoms. Since then, evidence has accumulated that supports the major assumptions of this model.

Patterns of brain atrophy in clinical variants of frontotemporal lobar degeneration.

Background/aims: The clinical syndromes of frontotemporal lobar degeneration include behavioral variant frontotemporal dementia (bvFTD) and semantic (SV-PPA) and nonfluent variants (NF-PPA) of primary progressive aphasia. Using magnetic resonance imaging (MRI), tensor-based morphometry (TBM) was used to determine distinct patterns of atrophy between these three clinical groups.

Methods: Twenty-seven participants diagnosed with bvFTD, 16 with SV-PPA, and 19 with NF-PPA received baseline and follow-up MRI scans approximately 1 year apart.

Maximizing power to track Alzheimer's disease and MCI progression by LDA-based weighting of longitudinal ventricular surface features.

We propose a new method to maximize biomarker efficiency for detecting anatomical change over time in serial MRI. Drug trials using neuroimaging become prohibitively costly if vast numbers of subjects must be assessed, so it is vital to develop efficient measures of brain change. A popular measure of efficiency is the minimal sample size (n80) needed to detect 25% change in a biomarker, with 95% confidence and 80% power.

Effect of lifestyle activities on Alzheimer disease biomarkers and cognition.

Objective: A study was undertaken to investigate the association of intellectual and physical activity with biomarkers of Alzheimer disease (AD) pathophysiology and cognition in a nondemented elderly population. The biomarkers evaluated were brain Aβ load via Pittsburgh compound B (PiB)-positron emission tomography (PET), neuronal dysfunction via (18) F-fluorodeoxyglucose (FDG)-PET, and neurodegeneration via structural magnetic resonance imaging (MRI).

Methods: We studied 515 nondemented (428 cognitively normal and 87 mild cognitive impairment) participants in the population-based Mayo Clinic Study of Aging who completed a 3T MRI, PET scans, and APOE genotype, and had lifestyle activity measures and cognition data available.

Mapping Dynamic Changes in Ventricular Volume onto Baseline Cortical Surfaces in Normal Aging, MCI, and Alzheimer's Disease.

Ventricular volume (VV) is a powerful global indicator of brain tissue loss on MRI in normal aging and dementia. VV is used by radiologists in clinical practice and has one of the highest obtainable effect sizes for tracking brain change in clinical trials, but it is crucial to relate VV to structural alterations underlying clinical symptoms. Here we identify patterns of thinner cortical gray matter (GM) associated with dynamic changes in lateral VV at 1-year (N=677) and 2-year (N=536) intervals, in the ADNI cohort.

Alzheimer's Disease Disrupts Rich Club Organization in Brain Connectivity Networks.

Diffusion imaging and brain connectivity analyses can monitor white matter deterioration, revealing how neural pathways break down in aging and Alzheimer's disease (AD). Here we tested how AD disrupts the 'rich club' effect - a network property found in the normal brain - where high-degree nodes in the connectivity network are more heavily interconnected with each other than expected by chance. We analyzed 3-Tesla whole-brain diffusionweighted images (DWI) from 66 subjects (22 AD/44 normal elderly).

Fat-mass-related hormone, plasma leptin, predicts brain volumes in the elderly.

Leptin, a hormone produced by body fat tissue, acts on hypothalamic receptors in the brain to regulate appetite and energy expenditure, and on neurons in the arcuate nucleus to signal that an individual has had enough to eat. Leptin enters the central nervous system at levels that depend on an individual's body fat. Obese people, on average, show greater brain atrophy in old age, so it is valuable to know whether brain atrophy relates to leptin levels, which can be targeted by interventions.

The GGGGCC repeat expansion in C9ORF72 in a case with discordant clinical and FDG-PET findings: PET trumps syndrome.

A hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 (C9ORF72) gene was recently discovered as the cause underlying frontotemporal degeneration (FTD) and/or amyotrophic lateral sclerosis (ALS) linked to chromosome 9 (c9FTD/ALS). In this atypical case of c9FTD/ALS, the proband presented with amnestic mild cognitive impairment which evolved into Alzheimer's disease (AD)-type dementia and later developed ALS. Fluorodeoxyglucose-positron emission tomography of the brain demonstrated mild hypometabolism involving the medial frontal and lateral temporal lobes, left more so than right, which progressed over time.

Mapping creatinine- and cystatin C-related white matter brain deficits in the elderly.

Poor kidney function is associated with increased risk of cognitive decline and generalized brain atrophy. Chronic kidney disease impairs glomerular filtration rate, and this deterioration is indicated by elevated blood levels of kidney biomarkers such as creatinine and cystatin C. Here we hypothesized that impaired renal function would be associated with brain deficits in regions vulnerable to neurodegeneration.

Unbiased tensor-based morphometry: improved robustness and sample size estimates for Alzheimer's disease clinical trials.

Various neuroimaging measures are being evaluated for tracking Alzheimer's disease (AD) progression in therapeutic trials, including measures of structural brain change based on repeated scanning of patients with magnetic resonance imaging (MRI). Methods to compute brain change must be robust to scan quality. Biases may arise if any scans are thrown out, as this can lead to the true changes being overestimated or underestimated.

A quantitative postmortem MRI design sensitive to white matter hyperintensity differences and their relationship with underlying pathology.

White matter hyperintensities (WMHs) associate with both cognitive slowing and motor dysfunction in the neurologically normal elderly. A full understanding of the pathology underlying this clinicoradiologic finding is currently lacking in autopsy-confirmed normal brains. To determine the histopathologic basis of WMH seen on magnetic resonance imaging, we studied the relationship between postmortem fluid-attenuated inversion recovery (FLAIR) intensity and neuropathologic markers of WM lesions (WMLs) that correspond to WMH in cognitively normal aging brains.

Standardization of analysis sets for reporting results from ADNI MRI data.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) three-dimensional T1-weighted magnetic resonance imaging (MRI) acquisitions provide a rich data set for developing and testing analysis techniques for extracting structural endpoints. To promote greater rigor in analysis and meaningful comparison of different algorithms, the ADNI MRI Core has created standardized analysis sets of data comprising scans that met minimum quality control requirements. We encourage researchers to test and report their techniques against these data.

Cardiovascular risk factors, cortisol, and amyloid-β deposition in Alzheimer's Disease Neuroimaging Initiative.

Background: There is epidemiological evidence that cardiovascular risk factors (CVRF) also are risk factors for Alzheimer's disease, but there is limited information on this from neuropathological studies, and even less from in vivo studies. Therefore, we examined the relationship between CVRF and amyloid-β (Aβ) brain burden measured by Pittsburgh Compound B-positron emission tomography (PiB-PET) studies in the Alzheimer's Disease Neuroimaging Initiative.

Methods: Ninety-nine subjects from the Alzheimer's Disease Neuroimaging Initiative cohort who had a PiB-PET study measure, apolipoprotein E genotyping data, and information available on CVRF (body mass index [BMI], systolic blood pressure, diastolic blood pressure [DBP], and cholesterol and fasting glucose test results) were included.

Indicators of amyloid burden in a population-based study of cognitively normal elderly.

Objectives: Secondary prevention trials in subjects with preclinical Alzheimer disease may require documentation of brain amyloidosis. The identification of inexpensive and noninvasive screening variables that can identify individuals who have significant amyloid accumulation would reduce screening costs.

Methods: A total of 483 cognitively normal (CN) individuals, aged 70-92 years, from the population-based Mayo Clinic Study of Aging, underwent Pittsburgh compound B (PiB)-PET imaging.

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.