Association of MRI markers of vascular brain injury with incident stroke, mild cognitive impairment, dementia, and mortality: the Framingham Offspring Study.

Background And Purpose: White matter hyperintensities and MRI-defined brain infarcts (BIs) have individually been related to stroke, dementia, and mortality in population-based studies, mainly in older people. Their significance in middle-aged community-dwelling persons and the relative importance of these associations remain unclear. We simultaneously assessed the relation of white matter hyperintensities and BI with incident stroke, mild cognitive impairment, dementia, and mortality in a middle-aged community-based cohort.

3D comparison of low, intermediate, and advanced hippocampal atrophy in MCI.

We applied the hippocampal radial atrophy mapping technique to the baseline and follow-up magnetic resonance image data of 169 amnestic mild cognitive impairment (MCI) participants in the imaging arm of the Alzheimer's Disease Cooperative Study MCI Donepezil/Vitamin E trial. Sixty percent of the subjects with none to mild hippocampal atrophy rated with the visual medial temporal atrophy rating scale (MTA score < 2) and 33.8% of the subjects with moderate to severe (MTA > or = 2) hippocampal atrophy converted to Alzheimer's disease (AD) during 3-year follow-up.

Effects of apolipoprotein E-epsilon4 and -epsilon2 in amnestic mild cognitive impairment and dementia in Shanghai: SCOBHI-P.

Objective: To determine apolipoprotein E (APOE)-epsilon4 and -epsilon2 frequencies and risk of mild cognitive impairment (MCI) and dementia in Shanghai, China.

Methods: A total of 34 MCI and 34 dementia cases were recruited from an urban Memory Disorders Clinic and 32 controls were recruited from a residential community served by the clinic. Apolipoprotein E was genotyped using standard methods.

Genome-wide association studies of MRI-defined brain infarcts: meta-analysis from the CHARGE Consortium.

Background And Purpose: Previous studies examining genetic associations with MRI-defined brain infarct have yielded inconsistent findings. We investigated genetic variation underlying covert MRI infarct in persons without histories of transient ischemic attack or stroke. We performed meta-analysis of genome-wide association studies of white participants in 6 studies comprising the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.

Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging.

Context: The adipokine leptin facilitates long-term potentiation and synaptic plasticity in the hippocampus, promotes beta-amyloid clearance, and improves memory function in animal models of aging and Alzheimer disease (AD).

Objective: To relate baseline circulating leptin concentrations in a community-based sample of individuals without dementia to incident dementia and AD during follow-up and magnetic resonance imaging (MRI) measures of brain aging in survivors.

Design, Setting, And Participants: Prospective study of plasma leptin concentrations measured in 785 persons without dementia (mean [SD] age, 79 [5] years; 62% female), who were in the Framingham original cohort at the 22nd examination cycle (1990-1994).

Association of parental dementia with cognitive and brain MRI measures in middle-aged adults.

Objectives: Studies of autosomal dominant Alzheimer disease (AD) have shown structural and cognitive changes in mutation carriers decades prior to clinical disease. Whether such changes are detectable in offspring of persons with sporadic dementia remains unknown. We related prospectively verified parental dementia to brain MRI and cognitive testing in the offspring, within a 2-generational community-based cohort.

White matter hyperintensities and cognition: testing the reserve hypothesis.

Objective: White matter hyperintensities (WMH), visualized on T2-weighted MRI, are thought to reflect small-vessel vascular disease. Much like other markers of brain disease, the association between WMH and cognition is imperfect. The concept of reserve may account for this imperfect relationship.

Psychological symptoms correlate with reduced hippocampal volume in fragile X premutation carriers.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder occurring in male and occasional female carriers of a premutation expansion (55-200 CGG repeats) of the fragile X mental retardation 1 gene (FMR1). This study assessed the relationship between hippocampal volume and psychological symptoms in carriers, both with and without FXTAS, and controls. Volumetric MRI measures, clinical staging, cognitive testing, molecular analysis, and measures of psychological symptoms were performed for female premutation carriers both with FXTAS (n = 16, age: 57.

Differences in brain volume, hippocampal volume, cerebrovascular risk factors, and apolipoprotein E4 among mild cognitive impairment subtypes.

Objectives: To evaluate demographics, magnetic resonance imaging (MRI) measures, and vascular risk among mild cognitive impairment (MCI) subtypes.

Design: Cross-sectional study.

Setting: Both clinics and the community.

Linking hippocampal structure and function to memory performance in an aging population.

Background: Hippocampal atrophy and reductions in basal cerebral blood volume (CBV), a hemodynamic correlate of brain function, occur with cognitive impairment in Alzheimer disease, but whether these are early or late changes remains unclear. Magnetic resonance imaging is used to assess structure and function in the hippocampal formation.

Objective: To estimate differences in the associations of hippocampal and entorhinal cortex volumes and CBV with memory function in the early and late stages of cognitive impairment by relating these measures to memory function in persons with and without dementia who underwent detailed brain imaging and neuropsychological assessment.

Regional pattern of white matter microstructural changes in normal aging, MCI, and AD.

Objective: To cross-sectionally compare the regional white matter fractional anisotropy (FA) of cognitively normal (CN) older individuals and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD), separately focusing on the normal-appearing white matter (NAWM) and white matter hyperintensities (WMH), and to test the independent effects of presumed degenerative and vascular process on FA differences.

Methods: Forty-seven patients with AD, 73 patients with MCI, and 95 CN subjects received diffusion tensor imaging and vascular risk evaluation. To properly control normal regional variability of FA, we divided cerebral white matter into 4 strata as measured from a series of young healthy individuals (H1 = highest; H2 = intermediate high; H3 = intermediate low; H4 = lowest anisotropy stratum).

Bivariate heritability of total and regional brain volumes: the Framingham Study.

Heritability and genetic and environmental correlations of total and regional brain volumes were estimated from a large, generally healthy, community-based sample, to determine if there are common elements to the genetic influence of brain volumes and white matter hyperintensity (WMH) volume. There were 1538 Framingham Heart Study participants with brain volume measures from quantitative magnetic resonance imaging who were free of stroke and other neurologic disorders that might influence brain volumes and who were members of families with at least 2 Framingham Heart Study participants. Heritability was estimated using variance component methodology and adjusting for the components of the Framingham stroke risk profile.

Computer-based cognitive training for mild cognitive impairment: results from a pilot randomized, controlled trial.

We performed a pilot randomized, controlled trial of intensive, computer-based cognitive training in 47 subjects with mild cognitive impairment. The intervention group performed exercises specifically designed to improve auditory processing speed and accuracy for 100 min/d, 5 d/wk for 6 weeks; the control group performed more passive computer activities (reading, listening, visuospatial game) for similar amounts of time. Subjects had a mean age of 74 years and 60% were men; 77% successfully completed training.

Progression of mild cognitive impairment to dementia in clinic- vs community-based cohorts.

Background: Mild cognitive impairment is increasingly recognized as an important public health problem associated with increased risk of developing dementia. Annual conversion rates, however, vary across different studies with clinic samples showing higher rates of conversion than community-based samples.

Objectives: To establish whether the rates of conversion from mild cognitive impairment to dementia differed according to recruitment source and, if so, to investigate factors that might explain this discrepancy.

Inflammatory biomarkers of vascular risk as correlates of leukoariosis.

Background And Purpose: Inflammatory biomarkers, including lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO), and high-sensitivity C-reactive protein (hsCRP) are associated with ischemic stroke risk. White matter hyperintensities (WMH) seen on brain MRI scans are associated with vascular risk factors and an increased risk of incident stroke, but their relation to inflammatory biomarkers is unclear.

Methods: The Northern Manhattan Study includes a stroke-free community-based sample of Hispanic, black, and white participants with quantitative measurement of WMH volume (WMHV) and inflammatory biomarkers.

Estimating uncertainty in brain region delineations.

This paper presents a method for estimating uncertainty in MRI-based brain region delineations provided by fully-automated segmentation methods. In large data sets, the uncertainty estimates could be used to detect fully-automated method failures, identify low-quality imaging data, or endow downstream statistical analyses with per-subject uncertainty in derived morphometric measures. Region segmentation is formulated in a statistical inference framework; the probability that a given region-delineating surface accounts for observed image data is quantified by a distribution that takes into account a prior model of plausible region shape and a model of how the region appears in images.

Fully-automated white matter hyperintensity detection with anatomical prior knowledge and without FLAIR.

This paper presents a method for detection of cerebral white matter hyperintensities (WMH) based on run-time PD-, T1-, and T2-weighted structural magnetic resonance (MR) images of the brain along with labeled training examples. Unlike most prior approaches, the method is able to reliably detect WMHs in elderly brains in the absence of fluid-attenuated (FLAIR) images. Its success is due to the learning of probabilistic models of WMH spatial distribution and neighborhood dependencies from ground-truth examples of FLAIR-based WMH detections.

Subclinical cerebrovascular disease in mild cognitive impairment.

Background: Cerebrovascular disease (CVD) may contribute to mild cognitive impairment (MCI). We sought to determine the relation of white matter hyperintensity (WMH) volume and infarcts in brain MRI to MCI in a community-based sample.

Methods: A total of 679 elderly persons without dementia underwent brain MRI.

Association of plasma ADMA levels with MRI markers of vascular brain injury: Framingham offspring study.

Background And Purpose: Asymmetrical dimethylarginine (ADMA), an inhibitor of endothelial nitric oxide synthase, is a marker of endothelial dysfunction. Elevated circulating ADMA concentrations have been associated with systemic and carotid atherosclerosis, an elevated risk of developing stroke, and magnetic resonance imaging white-matter hyperintensities (WMHs). The relation of plasma ADMA to subclinical vascular brain injury has not been previously studied in a middle-aged, community-based sample.

Education attenuates the effect of medial temporal lobe atrophy on cognitive function in Alzheimer's disease: the MIRAGE study.

Functional imaging and neuropathological studies suggest that individuals with higher education have better cognitive performance at the same level of brain pathology than less educated subjects. No in vivo studies are available that directly test how education modifies the effect of structural pathology on cognition in Alzheimer's disease (AD). The present study therefore aimed to measure this effect using data from a large multi-center study.

The Alzheimer's Disease Centers' Uniform Data Set (UDS): the neuropsychologic test battery.

The neuropsychologic test battery from the Uniform Data Set (UDS) of the Alzheimer's Disease Centers (ADC) program of the National Institute on Aging consists of brief measures of attention, processing speed, executive function, episodic memory, and language. This paper describes development of the battery and preliminary data from the initial UDS evaluation of 3268 clinically cognitively normal men and women collected over the first 24 months of utilization. The subjects represent a sample of community-dwelling, individuals who volunteer for studies of cognitive aging.

Spatially localized hippocampal shape analysis in late-life cognitive decline.

We present a method for generating data-driven, concise, and spatially localized parameterizations of hippocampal (HP) shape, and use the method to analyze HP atrophy in late-life cognitive decline. The method optimizes a set of shape basis vectors (shape components) that strike a balance between spatial locality and compact representation of population shape characteristics. The method can be used for exploratory analysis of localized shape deformations in any population of HP on which point-to-point correspondence mappings have been established via anatomical landmarking or high-dimensional warping.

Validity of self-reported stroke in elderly African Americans, Caribbean Hispanics, and Whites.

Background: The validity of a self-reported stroke remains inconclusive.

Objective: To validate the diagnosis of self-reported stroke using stroke identified by magnetic resonance imaging (MRI) as the standard.

Design, Setting, And Participants: Community-based cohort study of nondemented, ethnically diverse elderly persons in northern Manhattan.