Showing papers by "Charles DeCarli published in 2008"

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

Abstract: Dementia, one of the most feared associates of increasing longevity, represents a pressing public health problem and major research priority. Alzheimer's disease (AD) is the most common form of dementia, affecting many millions around the world. There is currently no cure for AD, but large numbers of novel compounds are currently under development that have the potential to modify the course of the disease and slow its progression. There is a pressing need for imaging biomarkers to improve understanding of the disease and to assess the efficacy of these proposed treatments. Structural magnetic resonance imaging (MRI) has already been shown to be sensitive to presymptomatic disease (1-10) and has the potential to provide such a biomarker. For use in large-scale multicenter studies, however, standardized methods that produce stable results across scanners and over time are needed. The Alzheimer's Disease Neuroimaging Initiative (ADNI) study is a longitudinal multisite observational study of elderly individuals with normal cognition, mild cognitive impairment (MCI), or AD (11,12). It is jointly funded by the National Institutes of Health (NIH) and industry via the Foundation for the NIH. The study will assess how well information (alone or in combination) obtained from MRI, (18F)-fludeoyglucose positron emission tomography (FDG PET), urine, serum, and cerebrospinal fluid (CSF) biomarkers, as well as clinical and neuropsychometric assessments, can measure disease progression in the three groups of elderly subjects mentioned above. At the 55 participating sites in North America, imaging, clinical, and biologic samples will be collected at multiple time points in 200 elderly cognitively normal, 400 MCI, and 200 AD subjects. All subjects will be scanned with 1.5 T MRI at each time point, and half of these will also be scanned with FDG PET. Subjects not assigned to the PET arm of the study will be eligible for 3 T MRI scanning. The goal is to acquire both 1.5 T and 3 T MRI studies at multiple time points in 25% of the subjects who do not undergo PET scanning [R2C1]. CSF collection at both baseline and 12 months is targeted for 50% of the subjects. Sampling varies by clinical group. Healthy elderly controls will be sampled at 0, 6, 12, 24, and 36 months. Subjects with MCI will be sampled at 0, 6, 12, 18, 24, and 36 months. AD subjects will be sampled at 0, 6, 12, and 24 months. Major goals of the ADNI study are: to link all of these data at each time point and make this repository available to the general scientific community; to develop technical standards for imaging in longitudinal studies; to determine the optimum methods for acquiring and analyzing images; to validate imaging and biomarker data by correlating these with concurrent psychometric and clinical assessments; and to improve methods for clinical trials in MCI and AD. The ADNI study overall is divided into cores, with each core managing ADNI-related activities within its sphere of expertise: clinical, informatics, biostatistics, biomarkers, and imaging. The purpose of this report is to describe the MRI methods and decision-making process underlying the selection of the MRI protocol employed in the ADNI study.

The Measurement of Everyday Cognition (ECog): Scale Development and Psychometric Properties

Abstract: 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. Convergent validity was evaluated by comparing it to established measures of everyday function. External validity was evaluated by comparing ECog results across different clinical groups [cognitively normal, mild cognitive impairment (MCI), dementia]. CFA supported a seven-factor model including one global factor and six domain-specific factors (Everyday Memory, Language, Visuospatial Abilities, Planning, Organization, and Divided attention). The ECog correlated with established measures of functional status and global cognition, but only weakly with age and education. The clinical groups performed differently in each domain. In addition to the global factor, the Everyday Memory factor independently differentiated MCI from Normal, while the Everyday Language domain differentiated Dementia from MCI. Different subtypes of MCI also showed different patterns. Results suggest the ECog shows promise as a useful tool for the measurement of general and domain-specific everyday functions in the elderly.

Prevalence and Correlates of Silent Cerebral Infarcts in the Framingham Offspring Study

Abstract: 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, pr...

Neuropathological basis of magnetic resonance images in aging and dementia.

Abstract: Alterations in brain structure are a profound concomitant of aging and dementia. From a clinical perspective, structural magnetic resonance imaging (MRI) has become a standard component of the dementia evaluation,1 helping to rule out infarcts and other nonneurodegenerative causes of dementia. Research studies have linked brain atrophy, especially in the hippocampus and medial temporal lobe structures, to clinically diagnosed Alzheimer’s disease (AD),2–4 and prediction of AD in patients with mild cognitive impairment,5,6 whereas epidemiological studies show convincing associations between white matter hyperintensities (WMH) and a host of vascular factors.7,8 There are, however, few studies that examine relations between MRI and neuropathology, which is a serious limitation because the extent of AD pathology cannot be ascertained without neuropathological examination. Knowing the pathological phenomena that underlie changes in MR measures of brain structure may help to clarify the significance of neuroimaging in complex clinical situations and elucidate underlying mechanisms of disease. Because of the early and severe involvement of the hippocampus by neurofibrillary pathological change in AD,9 it is not surprising that hippocampal atrophy seen on MRI is frequently associated with the accumulation of neurofibrillary tangles at postmortem examination.10 However, hippocampal atrophy may be associated with other pathological processes, including hippocampal sclerosis (HS) and frontotemporal dementia.10 Although WMH are associated with vascular risk factors, they may also be associated with AD-associated amyloid angiopathy.11,12 Conversely, evidence linking cerebrovascular risk factors with cerebral atrophy13,14 suggests that brain atrophy may reflect the effects of vascular pathology as well as AD. Thus, although some data support relatively specific relations between postmortem findings and MRI, the reality of these associations is complex. This is a particularly important issue when multiple pathological processes occur simultaneously, as is frequently the case in older individuals who often have coexistent pathologically confirmed AD and cerebrovascular disease (CVD).15 We have enrolled and followed a cohort of subjects with a wide range of cognitive ability and a high prevalence of both CVD and AD in a longitudinal study. Previous reports from this project have shown that measures of cerebral cortical and hippocampal atrophy are major determinants of cognition16 and cognitive decline,17 with relatively small contributions from WMH and lacunes. We now report the associations between neuropathology and MR findings among cohort cases who have been autopsied. The goal of this report is to define how AD and CVD together produce changes in brain structure that are related to cognitive decline and dementia. Our approach involved the prospective evaluation of antemortem quantitative MR followed up with neuropathological evaluation, relating imaging and pathological variables to one another together with continuous dimensions of severity because that is how these processes occur in the “real world.” The analysis of this cohort is useful both for defining the pathological basis of MR findings observed during life and for understanding how different pathological processes might lead to cognitive decline through specific and overlapping pathways.

Brain Morphology in Older African Americans, Caribbean Hispanics, and Whites From Northern Manhattan

Abstract: 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 Sex × race/ethnicity interactions were also considered Setting The Washington Heights–Inwood Columbia Aging Project, a community-based epidemiological study of older adults from 3 racial/ethnic groups (white, Hispanic, and African American) from northern Manhattan Participants Beginning in 2003, high-resolution quantitative magnetic resonance (MR) images were acquired in 769 participants without dementia Main Outcome Measures Relative brain volume (total brain volume/intracranial volume), ventricular volume, and hippocampus and entorhinal cortex volumes were derived manually on high-resolution MR images White matter hyperintensities were quantified semiautomatically on fluid-attenuated inversion recovery–T2-weighted MR images Results Older age was associated with decreased relative brain volume and with increased ventricular and WMH volumes Hispanic and African American participants had larger relative brain volumes and more severe WMH burden than white participants, but the associations of these variables with age were similar across racial/ethnic groups Compared with men, women had larger relative brain volumes Vascular disease was associated with smaller relative brain volume and with higher WMH burden, particularly among African Americans Conclusions Older age and vascular disease, particularly among African Americans, are associated with increased brain atrophy and WMH burden African American and Hispanic subjects have larger relative brain volumes and more WMH than white subjects Racial/ethnic group differences in WMH severity seem to be partially attributable to differences in vascular disease Future work will focus on the determinants and cognitive correlates of these differences

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

Abstract: 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. We used multivariate regression analysis to relate initial (1991-1995) and concurrent (1998-2001) plasma tHcy levels to total cerebral brain volume and lobar volumes as measures of neuronal loss and atrophy and to the presence or absence of silent brain infarcts and extensive white matter hyperintensity (log–white matter intensity ≥1 SD above the age-adjusted mean) as separate measures of vascular injury. Results Mean total cerebral brain volume was 78%. At MRI, 218 participants had silent brain infarcts and 250 demonstrated extensive white matter hyperintensity. Participants with a plasma tHcy level in the highest age- (−0.37%, P = .01) or sex-specific (−0.48%, P P = .02) and concurrent tHcy levels, with smaller frontal (−0.14%, P = .001) and temporal lobar (−0.10%, P = .04) volumes. Prevalence of extensive white matter hyperintensity did not differ according to initial or concurrent plasma tHcy levels (relative risk, both 1.0; 95% confidence interval, 0.7-1.4 and 0.8-1.4, respectively). Conclusions Higher plasma tHcy levels are associated with smaller brain volume and the presence of silent brain infarcts at MRI, even in healthy, middle-aged adults. Thus, both cellular and vascular mechanisms may underlie the association of plasma tHcy level with brain aging, as reflected by the effects on both subclinical and overt disease.

White Matter Hyperintensities and Subclinical Infarction: Associations With Psychomotor Speed and Cognitive Flexibility

Abstract: 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. Linear regression was used to examine WMHV and SI in relation to performance on tests of sequencing as measured by Color Trails 1, cognitive flexibility as measured by Color Trails 2, and sensorimotor ability as measured by Grooved Pegboard, using generalized estimating equations (GEE) to account for the correlation among the cognitive tests and other covariates. Results— Considering performance on the tests of sequencing, cognitive flexibility, and sensorimotor ability simultaneously using GEE, WMHV and subclinical infarction were each associated with w...

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

Abstract: 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. Objective To determine whether consumption of smaller amounts of alcohol negatively affects brain volume or is protective in reducing the well-documented age-related decline in brain volume. Design Total cerebral brain volume (TCBV) was computed, correcting for head size. Multivariate linear regression models were used to evaluate the association between 5 categories of alcohol consumption (abstainers, former drinkers, low, moderate, high) and TCBV, adjusting for age, sex, education, height, body mass index (calculated as weight in kilograms divided by height in meters squared), and the Framingham Stroke Risk Profile. Pairwise comparisons were also conducted between the alcohol consumption groups. Participants A total of 1839 subjects from the Framingham Offspring Study who had magnetic resonance imaging of the brain between 1999 and 2001. Results Most participants reported low alcohol consumption, and men were more likely than women to be moderate or heavy drinkers. There was a significant negative linear relationship between alcohol consumption and TCBV ( r = −0.25; P r = −0.29 vs −0.20). Conclusions In contrast to studies on cardiovascular disease, this study found that moderate alcohol consumption was not protective against normal age-related differences in total brain volume. Rather, the more alcohol consumed, the smaller the total brain volume.

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

Abstract: Objective—To rely on the anatomical organization of the hippocampal formation to understand 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) who received a comprehensive medical evaluation. Sixty participants had type 2 diabetes mellitus while 74 had MRI-documented brain infarcts, and the first analysis was designed to pinpoint hippocampal subregions differentially linked to each disorder. Then, guided by the results, additional fMRI studies in aging rhesus monkeys and mice were used to test proposed mechanisms of dysfunction. Results—Although both diabetes and brain infarcts were associated with hippocampal dysfunction, each was linked to separate hippocampal subregions, suggesting distinct underlying mechanisms. The hippocampal subregion linked to diabetes implicated blood glucose as a pathogenic mechanism, a hypothesis confirmed by imaging aging rhesus monkeys and a mouse model of diabetes. The hippocampal subregion linked to infarcts suggested transient hypoperfusion as a pathogenic mechanism, a hypothesis provisionally confirmed by comparing anatomical patterns across subjects with infarcts in different vascular territories. Interpretation—Taken together with previous findings, these results clarify how diseases of latelife differentially target the hippocampal formation, identify causes that contribute to age-related cognitive decline, and suggest specific interventions that can preserve cognitive health.

Prevalence and determinants of subclinical brain infarction: The Northern Manhattan Study

Abstract: Objective: Risk factors for subclinical brain infarcts (SBI) have not been well studied, especially in Hispanic and black populations who may be at higher risk for vascular disease. We examined the prevalence and determinants of SBI in a multiethnic community cohort. Methods: The Northern Manhattan Study (NOMAS) includes 892 stroke-free participants who underwent brain MRI. Baseline demographic and vascular risk factor data were collected. The presence of SBI was determined from the size, location, and imaging characteristics of the lesion based on fluid attenuated inversion recovery (FLAIR) T1 and T2, and proton density MRI sequences. We calculated the prevalence of SBI and cross-sectional associations with sociodemographic and vascular risk factors, using logistic regression to adjust for relevant covariates. Results: Among 892 subjects (mean age 71.3 years), 158 (17.7%) had SBI (13.5% had 1 lesion, 4.3% had >1 lesion). Of the total 216 infarcts, most were small ( 75: 26.1%), was increased among men (21.3% vs 15.2% in women), and was increased among blacks (24.0% vs 18.1% in whites and 15.8% in Hispanics). The presence of SBI was independently associated with older age (per year: OR 1.06, 95% CI 1.04 to 1.09), male sex (OR 1.79, 95% CI 1.22 to 2.61), and hypertension (OR 2.08, 95% CI 1.35 to 3.22) adjusting for age, sex, race-ethnicity, and vascular risk factors. A significant interaction (p = 0.002) between race and age was observed such that younger black subjects had greater odds of having SBI. Conclusions: SBI were detected in nearly 18% of subjects in a multiethnic community-based cohort. Age, male sex, and hypertension were independently associated with SBI. Subclinical cerebral infarcts are more prevalent than symptomatic infarcts and may increase the true public health burden of stroke.

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

Abstract: 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.

Multiple SNPs Within and Surrounding the Apolipoprotein E Gene Influence Cerebrospinal Fluid Apolipoprotein E Protein Levels

Abstract: 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 aim of this exploratory hypothesis generating investigation was to determine if some of these loci predict cerebrospinal fluid (CSF) apoE levels in healthy non-demented subjects CSF apoE levels were measured from healthy non-demented subjects 21-87 years of age (n=134) Backward regression models were used to evaluate the influence of 21 SNPs, within and surrounding APOE, on CSF apoE levels while taking into account age, gender, APOE epsilon4 and correlation between SNPs (linkage disequilibrium) APOE epsilon4 genotype does not predict CSF apoE levels Three SNPs within the TOMM40 gene, one APOE promoter SNP and two SNPs within distal APOE enhancer elements (ME1 and BCR) predict CSF apoE levels Further investigation of the genetic influence of these loci on apoE expression levels in the central nervous system is likely to provide new insight into apoE regulation as well as AD pathogenesis

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

Abstract: 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. To test this hypothesis, we recruited a cohort of approximately 400 African American, white, and Hispanic subjects with various degrees of cognitive ability. Each subject was carefully evaluated using standardized diagnostic protocols that included clinical review of brain magnetic resonance image (MRI) to arrive at a clinical diagnosis of normal cognition, mild cognitive impairment or dementia. Each MRI was then independently quantified for measures of brain, white matter hyperintensities, and hippocampal volumes by a technician blind to subject age, sex, ethnicity, race, and diagnostic category. The appearance of infarction on MRI was also rated by examining neurologists. Regression analyses were used to assess associations with various MRI measures across clinical diagnostic categories in relation to racial and ethnic differences. Hispanic subjects were, on average, significantly younger and had less years of education than African Americans or whites. Whites with dementia were significantly older than both African American and Hispanic dementia patients. Highly significant differences in MRI measures were associated with clinical diagnoses for the group as a whole after adjusting for the effects of age, sex, education, race, and ethnicity. Subsequent independent analyses by racial and ethnic status revealed consistent relationships between diagnostic category and MRI measures. Clinical diagnoses were associated with consistent differences in brain structure among a group of racially and ethnically diverse individuals. We believe these results help to validate current diagnostic assessment of individuals across a broad range of racial, ethnic, linguistic, and educational backgrounds. Moreover, interesting and potentially biologically relevant differences were found that might stimulate further research related to the understanding of dementia etiology within an increasingly racially and ethnically diverse population.

Association of Distinct Variants in SORL1 With Cerebrovascular and Neurodegenerative Changes Related to Alzheimer Disease

Abstract: CONVERGING LINES OF EVIdence have implicated 1 member of the vacuolar proteinsorting 10 family—the sortilin-related receptor, low-density lipoprotein receptor class A repeat-containing protein (SORL1) (GenBank 6653)—in the pathogenesis of Alzheimerdisease (AD).1-3 Pathological studies4,5 have documented reduced SORL1 expression in the brains of some patients with AD. Association between the risk of AD and multiple SORL1 single-nucleotide polymorphisms (SNPs) has been demonstrated in several studies3,6-10 that included populations of diverse ethnic background, used various study designs(ie, clinic case-control, family-based, or population-based), and relied on clinical or pathological criteria for AD, whereas the evidence of the association was equivocal in another study.11 One hypothesis for the role of SORL1 in the pathogenesis of AD is that SORL1 modulates subcellular trafficking of the amyloid precursor protein (APP). Reduced expression of SORL1 may lead to routing of APP into compartments where it is cleaved by the presenilin 1 complex to generate the amyloid β peptide.3 The role of SORL1 in APP processing is strongly supported by the fact that SORL1 interacts with endogenous APP holoproteins3,12 but does not bind to APP C-terminal fragments or to other type I membrane proteins.3 The SORL1 protein also belongs to a superfamily of low-density lipoprotein receptors (SorLA/LR11) that bind apolipoprotein E (APOE) and are implicated in cholesterol metabolism13 and atherogenesis.14 Human macrophages exposed to SORL1 have elevated lipid levels, and mice genetically deficient for SORL1 show signs of thickening arteries and macrophage infiltration relative to SORL1 knockout controls. These observations suggest a role for SORL1 in the development of atherosclerosis14 and raise the intriguing possibility that, like APOE and other cholesterol metabolism genes (eg, paraoxonase15), SORL1 may also increase dementia risk through effects on cerebrovascular abnormalities. Indeed, cerebrovascular disease increases the odds of dementia16 and potentially interacts with AD pathologic mechanisms to alter memory.17 Neurodegenerative and cerebrovascular processes can be linked to the known protein structure of SORL1 (Figure). Figure Inferred biochemical basis for the role of the sortilin-related receptor SORL1 in Alzheimer disease and cerebrovascular disease. The SORL1 protein contains several functional domains. The N-terminus region of the protein contains the vacuolar protein ... The possibility of multiple mechanisms of action associated with distinct SORL1 polymorphisms is supported by previous association studies. The SNPs associated with AD are located in 2 regions in SORL1 separated by a mean (SD) of 100 (15) kilobases that contain areas of tight linkage disequilibrium in white and African American subjects.3,18 Associations with SNPs in the region near the 5′ end have been reported in white European subjects, Hispanic subjects from the Dominican Republic, and Israeli-Arab subjects,3,6 whereas SNPs in the region closer to the 3′ end show association in African American, Han Chinese, and some white European and Hispanic subjects.3,6,8,10 Furthermore, associations with a specific 3-SNP haplotype in each of these locations have been replicated in multiple data sets representing several ethnic groups.3,6 These results suggest the existence of AD predisposing variants in different functional domains of SORL1 and thus raise the possibility for variable effects of intragenic polymorphisms on the biochemical properties of SORL1, on its cell-type–specific patterns of expression, or on both. To further elucidate how SORL1 gene variants influence processes leading to AD, we evaluated the association of SORL1 SNPs with brain magnetic resonance imaging (MRI) findings in a multiethnic group of families containing at least 1 sibpair discordant for AD. In addition, we compared SORL1 haplotypes with analogous measures of severity of AD and vascular abnormalities in a separate group of deceased individuals with pathologically confirmed AD.

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

Abstract: 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. Objective To examine white matter hyperintensity (WMH) volume and total hippocampal volume in elderly individuals with and without MPS. Methods Community-dwelling elderly persons in northern Manhattan (New York), New York, underwent neurologic examination and brain MRI. The WMH volume (derived from fluid-attenuated inversion recovery–weighted MRIs using a semiautomated thresholding approach) and total hippocampal volume (derived manually) were expressed relative to total cranial volume. Results Mild parkinsonian signs were present in 111 of 666 participants (16.7%). Mean (SD) relative WMH volume was larger in participants with MPS vs those without MPS (1.70 [1.28] vs 1.17 [1.18]; P P = .004). In both unadjusted and adjusted analyses, total relative hippocampal volume was similar in participants with MPS vs those without MPS regardless of cognitive status. Conclusions In this MRI study of community-dwelling elderly persons, WMH volume was associated with MPS and total relative hippocampal volume was not. These data raise the possibility that vascular disease could have a role in the development of MPS.

Magnetic resonance imaging traits in siblings discordant for Alzheimer disease.

Abstract: 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

IC-P3-172: Brain morphology in elderly African-Americans, Caribbean Hispanics, and Caucasians from northern Manhattan

Abstract: taking into account the design effect, non-response on the community phase, and the positive and negative predictive values was 12.9%. Higher dementia rates were associated with older age, low schooling, stroke, head trauma and diabetes. Lower dementia rates were associated with present work activity, tumor (cancer), and reading books. Conclusions: Prevalence estimate of dementia was higher than previously reported in Brazil and association with factors that can be modified, stress the importance of preventive measures. The potential protective role of tumor (cancer) should be addressed in longitudinal studies.

AbstractPoster presentation: Wednesday posterP4-011: Brain morphology in elderly African-Americans, Caribbean Hispanics, and Caucasians from Northern Manhattan

Abstract: taking into account the design effect, non-response on the community phase, and the positive and negative predictive values was 12.9%. Higher dementia rates were associated with older age, low schooling, stroke, head trauma and diabetes. Lower dementia rates were associated with present work activity, tumor (cancer), and reading books. Conclusions: Prevalence estimate of dementia was higher than previously reported in Brazil and association with factors that can be modified, stress the importance of preventive measures. The potential protective role of tumor (cancer) should be addressed in longitudinal studies.

P3-089: Cerebrospinal fluid biomarkers distinguish mild Alzheimer's disease and mild cognitive impairment from cognitively healthy aging

Abstract: Elaine R. Peskind, Ge Li, Joseph F. Quinn , Jeffery A. Kaye , Christopher M. Clark , Martin R. Farlow , Charles DeCarli , Murray A. Raskind , Eric C. Petrie , James Leverenz , Gerard D. Schellenberg , Barbara Cottrell , Douglas R. Galasko , University of Washington and VA Puget Sound Health Care System, Seattle, WA, USA; University of Washington, Seattle, WA, USA; Oregon Health and Science University and Veterans Affairs Medical Center, Portland, OR, USA; Oregon Health and Science University, Portland, OR, USA; University of Pennsylvania, Philadelphia, PA, USA; Indiana University School of Medicine, Indianapoli, IN, USA; University of California Davis, Davis, CA, USA; University of California San Diego, San Diego, CA, USA; University of California San Diego and Veterans Affairs Medical Center San Diego, San Diego, CA, USA. Contact e-mail: peskind@u.washington.edu