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.

Genomewide association studies of stroke.

Background: The genes underlying the risk of stroke in the general population remain undetermined.

Methods: We carried out an analysis of genomewide association data generated from four large cohorts composing the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, including 19,602 white persons (mean [+/-SD] age, 63+/-8 years) in whom 1544 incident strokes (1164 ischemic strokes) developed over an average follow-up of 11 years. We tested the markers most strongly associated with stroke in a replication cohort of 2430 black persons with 215 incident strokes (191 ischemic strokes), another cohort of 574 black persons with 85 incident strokes (68 ischemic strokes), and 652 Dutch persons with ischemic stroke and 3613 unaffected persons.

Association of TTR polymorphisms with hippocampal atrophy in Alzheimer disease families.

In vitro and animal model studies suggest that transthyretin (TTR) inhibits the production of the amyloid β protein, a major contributor to Alzheimer disease (AD) pathogenesis. We evaluated the association of 16 TTR single nucleotide polymorphisms (SNPs) with AD risk in 158 African American and 469 Caucasian discordant sibships from the MIRAGE Study. There was no evidence for association of TTR with AD in either population sample.

Age and education effects on relationships of cognitive test scores with brain structure in demographically diverse older persons.

This study examined how age and education influence the relationship between neuropsychological test scores and brain structure in demographically diverse older adults spanning the range from normal cognition to dementia. A sample of 351 African Americans, 410 Hispanics, and 458 Whites underwent neuropsychological testing. Volumetric magnetic resonance imaging (MRI) measures of total brain, white matter hyperintensity, and hippocampus were available for 79 African Americans, 102 Hispanics, and 134 Whites.

Carotid artery atherosclerosis, MRI indices of brain ischemia, aging, and cognitive impairment: the Framingham study.

Background And Purpose: Carotid atherosclerosis has been associated with increased risk of stroke and poorer cognitive performance in older adults. The relation of carotid atherosclerosis to cognitive impairment and MRI indices of ischemia and aging in midlife is less clear.

Methods: We studied 1975 Framingham Offspring Study participants free of stroke and dementia with available carotid ultrasound, brain MRI, and neuropsychological testing.

Alzheimer abnormalities of the amygdala with Klüver-Bucy syndrome symptoms: an amygdaloid variant of Alzheimer disease.

Background: Neurofibrillary tangles and beta-amyloid plaques have been observed in the amygdala in Alzheimer disease. A disproportionate abundance of this abnormality in the amygdala may cause behavioral symptoms similar to Klüver-Bucy syndrome.

Objectives: To describe an atypical behavioral presentation of Alzheimer disease and to review the literature on the subject.

Association of matrix metalloproteinases with MRI indices of brain ischemia and aging.

Magnetic resonance imaging (MRI) findings of large white matter hyperintensities (LWMH), decreased brain volume and silent cerebral infarcts (SCI) are subclinical indices of brain ischemia and aging. Although the pathophysiology of these findings remains uncertain, extracellular matrix (ECM) remodeling, a process regulated by matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), may be implicated. We evaluated the cross-sectional relations of circulating MMP-9 and TIMP-1 to these MRI indices in 583 stroke and dementia-free, Framingham Offspring participants (mean age 57 years, 58% women).

The brain in the age of old: the hippocampal formation is targeted differentially by diseases of late life.

Objective: To rely on the anatomical organization of the hippocampal formation in understanding whether and how late-life diseases such as diabetes and stroke contribute to age-related cognitive decline.

Methods: Magnetic resonance imaging (MRI) was used to document brain infarcts and to generate high-resolution functional maps of the hippocampal formation in 240 community-based nondemented elders (mean age, 79.7 years) who received a comprehensive medical evaluation.

Brain behavior relationships among African Americans, whites, and Hispanics.

There is an increasing racial and ethnic diversity within the elderly population of the United States. Although increased diversity offers unique opportunities to study novel influences on aging and dementia, some aspects of racial and ethnic research have been hampered by the lack of culturally and linguistically consistent testing protocols. Structural brain imaging is commonly used to study the biology of normal aging and cognitive impairment and may therefore serve to explore potential biologic differences of cognitive impairment among racially and ethnically diverse individuals.

Quantitative brain measurements in community-dwelling elderly persons with mild parkinsonian signs.

Background: Mild parkinsonian signs (MPS) are a marker of incident dementia. They have been linked with cerebrovascular disease, which can be evaluated using magnetic resonance imaging (MRI). Also, if MPS are a marker for developing Alzheimer-type changes, hippocampal volume on MRI might be diminished in individuals with MPS.

Association of distinct variants in SORL1 with cerebrovascular and neurodegenerative changes related to Alzheimer disease.

Background: Single-nucleotide polymorphisms (SNPs) in 2 distinct regions of the gene for the sortilin-related receptor (SORL1) (bounded by consecutively numbered SNPs 8-10 and 22-25) were shown to be associated with Alzheimer disease (AD) in multiple ethnically diverse samples.

Objective: To test the hypothesis that SORL1 is associated with brain magnetic resonance imaging (MRI) measurements of atrophy and/or vascular disease.

Design, Setting, And Patients: We evaluated the association of 30 SNPs spanning SORL1 with MRI measures of general cerebral atrophy, hippocampal atrophy, white matter hyperintensities, and overall cerebrovascular disease in 44 African American and 182 white sibships from the MIRAGE Study.

Olfactory identification deficits and MCI in a multi-ethnic elderly community sample.

Odor identification deficits occur in Alzheimer's disease (AD) and mild cognitive impairment (MCI), and predict clinical conversion from MCI to AD. In an epidemiologic study conducted in a multi-ethnic community elderly sample (average 80 years old), the University of Pennsylvania Smell Identification Test (UPSIT, range 0-40) was administered to 1092 non-demented subjects. Women (mean 26.

Association of alcohol consumption with brain volume in the Framingham study.

Background: While adults who drink low to moderate amounts of alcohol have lower rates of cardiovascular disease than other adults, the effect of alcohol on the brain is less clear. There is evidence that drinking large amounts of alcohol is related to brain atrophy. It is uncertain what the effects of low to moderate consumption might be.

Periventricular white matter hyperintensities increase the likelihood of progression from amnestic mild cognitive impairment to dementia.

Background: White matter hyperintensities (WMH) have an effect on cognition and are increased in severity among individuals with amnestic mild cognitive impairment (aMCI). The influence of WMH on progression of aMCI to Alzheimer's disease (AD) is less clear.

Methods: Data were drawn from a three-year prospective, double blind, placebo controlled clinical trial that examined the effect of donepezil or vitamin E on progression from aMCI to AD.

Magnetic resonance imaging traits in siblings discordant for Alzheimer disease.

Background: Magnetic resonance imaging (MRI) can aid clinical assessment of brain changes potentially correlated with Alzheimer disease (AD). MRI traits may improve our ability to identify genes associated with AD-outcomes. We evaluated semi-quantitative MRI measures as endophenotypes for genetic studies by assessing their association with AD in families from the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) Study.

Brain morphology in older African Americans, Caribbean Hispanics, and whites from northern Manhattan.

Background: Aging is accompanied by a decrease in brain volume and by an increase in cerebrovascular disease.

Objective: To examine the effects of age, sex, race/ethnicity, and vascular disease history on measures of brain morphology, including relative brain volume, ventricular volume, hippocampus and entorhinal cortex volumes, and white matter hyperintensity (WMH) burden, in a large community-based cohort of racially/ethnically diverse older adults without dementia.

Design: The associations of age, sex, race/ethnicity, and self-reported vascular disease history with brain morphology were examined in a cross-sectional study using multiple linear regression analyses.

The measurement of everyday cognition (ECog): scale development and psychometric properties.

This article describes the development and validation of an instrument to assess cognitively mediated functional abilities in older adults, Everyday Cognition (ECog). The ECog is an informant-rated questionnaire comprised of multiple subscales. Confirmatory factor analysis (CFA) was used to examine its factor structure.

Prevalence and correlates of silent cerebral infarcts in the Framingham offspring study.

Background And Purpose: Previous estimates of the prevalence of silent cerebral infarction (SCI) on MRI in community-based samples have varied between 5.8% and 17.7% depending on age, ethnicity, presence of comorbidities, and imaging techniques.

Association of plasma total homocysteine levels with subclinical brain injury: cerebral volumes, white matter hyperintensity, and silent brain infarcts at volumetric magnetic resonance imaging in the Framingham Offspring Study.

Background: Elevated plasma total homocysteine (tHcy) levels have been associated with increased risk of dementia and stroke, but it is uncertain whether the mediating mechanisms are predominantly cellular, vascular, or both.

Objective: To evaluate the relationship between tHcy levels and findings at brain magnetic resonance imaging (MRI) in a community-based sample.

Design: Our sample comprised 1965 participants in the Framingham Offspring Study (1050 women; mean [SD] age, 62 [9] years) who were free of clinical stroke, dementia, or other neurologic disease affecting brain MRI and for whom at least 1 measurement of plasma tHcy level (1991-2001) and a brain MRI (1999-2002) were available.

Multiple SNPs within and surrounding the apolipoprotein E gene influence cerebrospinal fluid apolipoprotein E protein levels.

The epsilon4 allele of the apolipoprotein E gene (APOE) is associated with increased risk and earlier age at onset in late onset Alzheimer's disease (AD). Other factors, such as expression level of apolipoprotein E protein (apoE), have been postulated to modify the APOE related risk of developing AD. Multiple loci in and outside of APOE are associated with a high risk of AD.

The Alzheimer's Disease Neuroimaging Initiative (ADNI): MRI methods.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a longitudinal multisite observational study of healthy elders, mild cognitive impairment (MCI), and Alzheimer's disease. Magnetic resonance imaging (MRI), (18F)-fluorodeoxyglucose positron emission tomography (FDG PET), urine serum, and cerebrospinal fluid (CSF) biomarkers, as well as clinical/psychometric assessments are acquired at multiple time points. All data will be cross-linked and made available to the general scientific community.

White matter hyperintensities and subclinical infarction: associations with psychomotor speed and cognitive flexibility.

Background And Purpose: We examined white matter hyperintensity volume (WMHV) and subclinical infarction (no history of clinical stroke; SI) in relation to performance on tests of sequencing, cognitive flexibility, and sensorimotor ability.

Methods: The Northern Manhattan Study includes a stroke-free community-based sample of Hispanic, Black, and White participants. A subsample (n=656) has undergone measurement of WMHV, SI, and neuropsychological testing.

Neuropathological basis of magnetic resonance images in aging and dementia.

Objective: Magnetic resonance (MR) imaging is used widely for assessment of patients with cognitive impairment, but the pathological correlates are unclear, especially when multiple pathologies are present.

Methods: This report includes 93 subjects from a longitudinally followed cohort recruited for the study of Alzheimer's disease (AD) and subcortical cerebrovascular disease (CVD). MR images were analyzed to quantify cortical gray matter volume, hippocampal volume, white matter hyperintensities, and lacunes.

Diagnostic criteria for the behavioral variant of frontotemporal dementia (bvFTD): current limitations and future directions.

The most widely established diagnostic criteria for the behavioral variant of frontotemporal dementia have now been in use for almost a decade. Although consensus criteria have provided a much needed standard for frontotemporal dementia research, a growing body of evidence suggests that revisions are needed to improve their applicability. In this article, we discuss the limitations of current diagnostic criteria and propose the establishment of an international consortium to revise diagnostic and research criteria for the behavioral variant of frontotemporal dementia.