Showing papers by "Charles DeCarli published in 2010"

Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions

Abstract: Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.

Association of MRI Markers of Vascular Brain Injury With Incident Stroke, Mild Cognitive Impairment, Dementia, and Mortality The Framingham Offspring Study

Abstract: 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 o...

Update on the Magnetic Resonance Imaging core of the Alzheimer's Disease Neuroimaging Initiative

Abstract: Functions of the Alzheimer's Disease Neuroimaging Initiative (ADNI) magnetic resonance imaging (MRI) core fall into three categories: (1) those of the central MRI core laboratory at Mayo Clinic, Rochester, Minnesota, needed to generate high quality MRI data in all subjects at each time point; (2) those of the funded ADNI MRI core imaging analysis groups responsible for analyzing the MRI data; and (3) the joint function of the entire MRI core in designing and problem solving MR image acquisition, pre-processing, and analyses methods. The primary objective of ADNI was and continues to be improving methods for clinical trials in Alzheimer's disease. Our approach to the present ("ADNI-GO") and future ("ADNI-2," if funded) MRI protocol will be to maintain MRI methodological consistency in the previously enrolled "ADNI-1" subjects who are followed up longitudinally in ADNI-GO and ADNI-2. We will modernize and expand the MRI protocol for all newly enrolled ADNI-GO and ADNI-2 subjects. All newly enrolled subjects will be scanned at 3T with a core set of three sequence types: 3D T1-weighted volume, FLAIR, and a long TE gradient echo volumetric acquisition for micro hemorrhage detection. In addition to this core ADNI-GO and ADNI-2 protocol, we will perform vendor-specific pilot sub-studies of arterial spin-labeling perfusion, resting state functional connectivity, and diffusion tensor imaging. One of these sequences will be added to the core protocol on systems from each MRI vendor. These experimental sub-studies are designed to demonstrate the feasibility of acquiring useful data in a multicenter (but single vendor) setting for these three emerging MRI applications.

A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly

Abstract: m Radiology, n Epidemiology, o Psychiatry, p Psychology, q understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scannedwithMRIandgenotypedaspartoftheAlzheimer'sDisease Neuroimaging Initiative. We found a pattern of systematic brain volumedeficitsincarriersoftheobesity-associatedriskalleleversus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain vol- ume difference of ∼8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attrib- utable to differences in cholesterol levels, hypertension, or the vol- ume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain mapsrevealthatacommonlycarriedsusceptibilityalleleforobesity isassociatedwithstructuralbrainatrophy,withimplicationsforthe health of the elderly.

Longitudinal Changes in White Matter Disease and Cognition in the First Year of the Alzheimer Disease Neuroimaging Initiative

Abstract: Objective To evaluate relationships between magnetic resonance imaging (MRI)–based measures of white matter hyperintensities (WMHs), measured at baseline and longitudinally, and 1-year cognitive decline using a large convenience sample in a clinical trial design with a relatively mild profile of cardiovascular risk factors Design Convenience sample in a clinical trial design Subjects A total of 804 participants in the Alzheimer Disease Neuroimaging Initiative who received MRI scans, cognitive testing, and clinical evaluations at baseline, 6-month follow-up, and 12-month follow-up visits For each scan, WMHs were detected automatically on coregistered sets of T1, proton density, and T2 MRI images using a validated method Mixed-effects regression models evaluated relationships between risk factors for WMHs, WMH volume, and change in outcome measures including Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale–Cognitive Subscale (ADAS-Cog), and Clinical Dementia Rating Scale sum of boxes scores Covariates in these models included race, sex, years of education, age, apolipoprotein E genotype, baseline clinical diagnosis (cognitively normal, mild cognitive impairment, or Alzheimer disease), cardiovascular risk score, and MRI-based hippocampal and brain volumes Results Higher baseline WMH volume was associated with greater subsequent 1-year increase in ADAS-Cog and decrease in MMSE scores Greater WMH volume at follow-up was associated with greater ADAS-Cog and lower MMSE scores at follow-up Higher baseline age and cardiovascular risk score and more impaired baseline clinical diagnosis were associated with higher baseline WMH volume Conclusions White matter hyperintensity volume predicts 1-year cognitive decline in a relatively healthy convenience sample that was similar to clinical trial samples, and therefore should be considered as a covariate of interest at baseline and longitudinally in future AD treatment trials

Cardiac Index Is Associated With Brain Aging: The Framingham Heart Study

Abstract: Background— Cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults with prevalent cardiovascular disease, theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to subclinical brain injury. We hypothesized that cardiac function, as measured by cardiac index, would be associated with preclinical brain magnetic resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer disease in the community. Methods and Results— Brain MRI, cardiac MRI, neuropsychological, and laboratory data were collected on 1504 Framingham Offspring Cohort participants free of clinical stroke, transient ischemic attack, or dementia (age, 61±9 years; 54% women). Neuropsychological and brain MRI variables were related to cardiac MRI–assessed cardiac index (cardiac output/body surface area). In multivariable-adjusted models, cardiac index was positively related to total brain volume (P=0.03) and information processing speed (P=0.02) and inve...

Measuring cognitive reserve based on the decomposition of episodic memory variance

Abstract: In later adulthood brain pathology becomes common and trajectories of cognitive change are heterogeneous. Among the multiple determinants of late-life cognitive course, cognitive reserve has been proposed as an important factor that modifies or buffers the impact of brain pathology on cognitive function. This article presents and investigates a novel method for measuring and investigating such factors. The core concept is that in a population where pathology is common and variably present, ‘reserve’ may be defined as the difference between the cognitive performance predicted by an individual's level of pathology and that individual's actual performance. By this definition, people whose measured cognitive performance is better than predicted by pathology have high reserve, whereas those who perform worse than predicted have low reserve. To test this hypothesis, we applied a latent variable model to data from a diverse ageing cohort and decomposed the variance in a measure of episodic memory into three components, one predicted by demographics, one predicted by pathology as measured by structural MRI and a ‘residual’ or ‘reserve’ term that included all remaining variance. To investigate the plausibility of this approach, we then tested the residual component as an operational measure of reserve. Specific predictions about the effects of this putative reserve measure were generated from a general conceptual model of reserve. Each was borne from the results. The results show that the current level of reserve, as measured by this decomposition approach, modifies rates of conversion from mild cognitive impairment to dementia, modifies rates of longitudinal decline in executive function and, most importantly, attenuates the effect of brain atrophy on cognitive decline such that atrophy is more strongly associated with cognitive decline in subjects with low reserve than in those with high reserve. Decomposing the variance in cognitive function scores offers a promising new approach to the measure and study of cognitive reserve.

Visceral fat is associated with lower brain volume in healthy middle-aged adults.

Abstract: Objective Midlife obesity has been associated with an increased risk of dementia. The underlying mechanisms are poorly understood. Our aim was to examine the cross-sectional association of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and computed tomography (CT)-based measurements of subcutaneous (SAT) and visceral (VAT) adipose tissue with various magnetic resonance imaging (MRI) markers of brain aging in middle-aged community adults. Methods Participants from the Framingham Offspring cohort were eligible if in addition to having measurements of BMI, WC, WHR, SAT, and VAT, they had undergone a volumetric brain MRI scan with measurements of total brain volume (TCBV), temporal horn volume (THV), white matter hyperintensity volume (WMHV), and MRI-defined brain infarcts (BI). All analyses were adjusted for age, sex, and time interval between abdominal CT and brain MRI. Results In a sample of 733 community participants (mean age, 60 years; 53% women), we observed an inverse association of BMI (estimate by standard deviation unit ± standard error = −0.27 ± 0.12; p = 0.02), WC (−0.30 ± 0.12; p = 0.01), WHR (−0.37 ± 0.12; p = 0.02), SAT (−0.23 ± 0.11; p = 0.04), and VAT (−0.36 ± 0.12; p = 0.002) with TCBV, independent of vascular risk factors. The association between VAT and TCBV was the strongest and most robust, and was also independent of BMI (−0.35 ± 0.15; p = 0.02) and insulin resistance (−0.32 ± 0.13; p = 0.01). When adjusting for C-reactive protein levels, the associations were attenuated (−0.17 ± 0.13; p = 0.17 for VAT). No consistently significant association was observed between the anthropometric or CT-based abdominal fat measurements and THV, WMHV, or BI. Interpretation In middle-aged community participants, we observed a significant inverse association of anthropometric and CT-based measurements of abdominal, especially visceral, fat with total brain volume. ANN NEUROL 2010

Long-term blood pressure fluctuation and cerebrovascular disease in an elderly cohort

Abstract: Background The importance of subclinical cerebrovascular disease in the elderly is increasingly recognized, but its determinants have not been fully explicated. Elevated blood pressure (BP) and fluctuation in BP may lead to cerebrovascular disease through ischemic changes and compromised cerebral autoregulation. Objective To determine the association of BP and long-term fluctuation in BP with cerebrovascular disease. Design A community-based epidemiological study of older adults from northern Manhattan. Setting The Washington Heights–Inwood Columbia Aging Project. Participants A total of 686 nondemented older adults who had BP measurements during 3 study visits at 24-month intervals and underwent structural magnetic resonance imaging (corresponding temporally with the third assessment). We derived the mean (SD) of the mean BP for each participant during the 3 intervals and divided the participants into 4 groups defined as below or above the group median (≤96.48 or >96.48 mm Hg) and further subdivided them as below or above the median SD (≤7.21 or >7.21 mm Hg). This scheme yielded 4 groups representing the full range of BPs and fluctuations in BP. Main Outcome Measures Differences in white matter hyperintensity (WMH) volume and presence of brain infarctions across groups. Results White matter hyperintensity volume increased across the 4 groups in a linear manner, with the lowest WMH volume in the lowest mean/lowest SD group and the highest WMH volume in the highest mean/highest SD group ( F 3,610 = 3.52, P = .02). Frequency of infarction also increased monotonically across groups (from 22% to 41%, P for trend = .004). Conclusions Compared with individuals with low BP and low fluctuations in BP, the risk of cerebrovascular disease increased with higher BP and BP fluctuations. Given that cerebrovascular disease is associated with disability, these findings suggest that interventions should focus on long-term fluctuating BP and elevated BP.

Heterogeneity of cognitive trajectories in diverse older persons.

Abstract: This study examined trajectories of cognitive change in psychometrically matched measures of episodic memory, semantic memory, and executive function in an ethnically, demographically, and cognitively diverse sample of older persons. Individual rates of change showed considerable heterogeneity in each domain. Baseline clinical diagnosis predicted differential change in semantic memory and executive function, dementia > mild cognitive impairment (MCI) > normal, but average decline in verbal episodic memory was similar across all 3 diagnostic groups. There was substantial overlap of distributions of cognitive change across baseline diagnostic groups for all 3 measures. Cognitive change was strongly related to change in clinical diagnosis. Rapid and similar change was present for all 3 cognitive measures in patients with dementia and in those with normal cognition and those with MCI who progressed clinically. In cognitively normal patients, verbal episodic memory change was greater than change in the other two domains. Global status, measured by the Clinical Dementia Rating scale (Morris, 1993), predicted change in semantic memory and executive function, whereas APOE genotype predicted change in verbal episodic memory, and age had no effect on rates of change in any domain independent of global status and APOE. Results show important limitations in using cross-sectional diagnosis to predict prognosis and suggest that research to identify robust predictors of cognitive change across the full spectrum from normal to dementia is needed for better early identification of diseases that cause progressive decline.

Randomized, Placebo-Controlled, Clinical Trial of Donepezil in Vascular Dementia Differential Effects by Hippocampal Size

Abstract: Background and Purpose— We sought to assess the efficacy and safety of donepezil in patients with vascular dementia (VaD) fulfilling National Institute of Neurological Disorders and Stroke–Association Internationale pour la Recherche et l’Enseignement en Neurosciences criteria. Methods— This international, multicenter, 24-week trial was conducted from March 2003 to August 2005. Patients (N=974; mean age, 73.0 years) with probable or possible VaD were randomized 2:1 to receive donepezil 5 mg/d or placebo. Coprimary outcome measures were scores on the Vascular-Alzheimer Disease Assessment Scale–Cognitive Subscale and Clinician’s Interview–Based Impression of Change, plus carer interview. Analyses were performed for the intent-to-treat population with the last-observation-carried-forward method. Results— Compared with placebo, donepezil-treated patients showed significant improvement from baseline to end point on the Vascular-Alzheimer Disease Assessment Scale–Cognitive Subscale (least-squares mean differenc...

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

Abstract: 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 or = 2) hippocampal atrophy converted to Alzheimer's disease (AD) during 3-year follow-up. MTA > or = 2 showed a trend for greater left sided hippocampal atrophy versus MTA < 2 groups at baseline (P(corrected) = 0.08). Higher MTA scores were associated with progressive atrophy of the subiculum and the CA1-3 subregions. The MTA < 2 group demonstrated significant bilateral atrophy progression at follow-up (left P(corrected) = 0.008; right P(corrected) = 0.05). Relative to MTA < 2 nonconverters, MTA < 2 converters showed further involvement of the subiculum and CA1 and additional involvement of CA2-3 at follow-up. Right CA1 atrophy was significantly associated with conversion to dementia (for 1 mm greater right CA1 radial distance subjects had 50% reduced hazard for conversion). Greater CA1 and subicular atrophy can be demonstrated early and is predictive of future conversion to AD, whereas CA2-3 involvement becomes more evident as the disease progresses.

Genome-Wide Association Studies of MRI-Defined Brain Infarcts. Meta-Analysis From the CHARGE Consortium

Abstract: 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. Methods-Using 2.2 million genotyped and imputed single nucleotide polymorphisms, each study performed crosssectional genome-wide association analysis of MRI infarct using age- and sex-adjusted logistic regression models. Study-specific findings were combined in an inverse-variance-weighted meta-analysis, including 9401 participants with mean age 69.7 (19.4% of whom had 1 MRI infarct). Results-The most significant association was found with rs2208454 (minor allele frequency, 20%), located in intron 3 of MACRO domain containing 2 gene and in the downstream region of fibronectin leucine-rich transmembrane protein 3 gene. Each copy of the minor allele was associated with lower risk of MRI infarcts (odds ratio, 0.76; 95% confidence interval, 0.68-0.84; P4.64107). Highly suggestive associations (P1.0105) were also found for 22 other single nucleotide polymorphisms in linkage disequilibrium (r20.64) with rs2208454. The association with rs2208454 did not replicate in independent samples of 1822 white and 644 black participants, although 4 single nucleotide polymorphisms within 200 kb from rs2208454 were associated with MRI infarcts in the black population sample. Conclusions-This first community-based, genome-wide association study on covert MRI infarcts uncovered novel associations. Although replication of the association with top single nucleotide polymorphisms failed, possibly because of insufficient power, results in the black population sample are encouraging, and further efforts at replication are needed.

Recruitment of a community-based cohort for research on diversity and risk of dementia

Abstract: We describe the history, development, and success of the recruitment and screening procedures used by researchers at the University of California, Davis Alzheimer's Disease Center (UCD ADC) to facilitate minority enrollment in research. After an initial, unsuccessful approach with satellite clinics in minority neighborhoods, the ADC shifted to an active community outreach approach. Multiple strategies were implemented to remove barriers to research participation such as providing transportation to clinical appointments and offering in-home cognitive screening. Considerable resources were directed toward hiring and training bicultural and bilingual individuals with knowledge of the target populations, both as recruiters and staff involved in clinical assessment. Implementation of these methods resulted in a dramatic increase in the number of ethnic minorities enrolled (and retained) in research protocols, including protocols that are complex and longitudinal. Diversity was achieved on other variables as well; years of education in the cohort range from 0 to 21, with 26% having 8 years or less. The community screen identified candidates for an in depth clinical evaluation and enrollment in longitudinal research, and we examined factors that predicted a positive response to invitation for the clinical evaluation. Individuals with a broader fund of knowledge were more likely to participate independent of other variables including ethnicity and education. When diversity is an important goal active outreach is far more efficacious than clinic-based and advertising-based approaches to recruitment.

Head circumference, atrophy, and cognition Implications for brain reserve in Alzheimer disease

Abstract: Background: Clinical and epidemiologic studies suggest that patients with Alzheimer disease (AD) with larger head circumference have better cognitive performance at the same level of brain pathology than subjects with smaller head circumference. Methods: A total of 270 patients with AD participating in the Multi-Institutional Research in Alzheimer9s Genetic Epidemiology (MIRAGE) study underwent cognitive testing, APOE genotyping, and MRI of the brain in a cross-sectional study. Linear regression analysis was used to examine the association between cerebral atrophy, as a proxy for AD pathology, and level of cognitive function, adjusting for age, duration of AD symptoms, gender, head circumference, APOE genotype, diabetes mellitus, hypertension, major depression, and ethnicity. An interaction term between atrophy and head circumference was introduced to explore if head circumference modified the association between cerebral atrophy and cognition. Results: There was a significant inverse association between atrophy and cognitive function, and a significant interaction between atrophy and head circumference. With greater levels of atrophy, cognition was higher for individuals with greater head circumference. Conclusion: This study suggests that larger head circumference is associated with less cognitive impairment in the face of cerebral atrophy. This finding supports the notion that head circumference (and presumably brain size) offers protection against AD symptoms through enhanced brain reserve.

Vascular and degenerative processes differentially affect regional interhemispheric connections in normal aging, mild cognitive impairment, and Alzheimer disease

Abstract: Background and Purpose— Despite the critical importance of the corpus callosum (CC) to the connection between brain hemispheres, little is known about the independent contribution of degenerative and vascular processes to regional changes in the microstructural integrity of the CC. Here, we examine these changes in subjects with mild cognitive impairment, with Alzheimer disease, and in cognitively normal elderly adults. Methods— We used 3-dimensional brain MRI with diffusion tensor imaging in 47 Alzheimer disease, 77 mild cognitive impairment, and 107 cognitively normal subjects, and we calculated mean fractional anisotropy (FA) values for 4 CC regions corresponding to 4 homologous regions of cortical gray matter (GM). To assess vascular and degenerative processes, we also measured cortical GM and white matter hyperintensity (WMH) volume in corresponding regions and evaluated their vascular risk. Results— We found that GM volumes in anterior and posterior regions were significantly related to FA values in...

Distinctive RNA Expression Profiles in Blood Associated With White Matter Hyperintensities in Brain

Abstract: Background and Purpose—White matter hyperintensities (WMH) are areas of high signal detected by T2 and fluid-attenuated inversion recovery sequences on brain MRI. Although associated with aging, cerebrovascular risk factors, and cognitive impairment, the pathogenesis of WMH remains unclear. Thus, RNA expression was assessed in the blood of individuals with and without extensive WMH to search for evidence of oxidative stress, inflammation, and other abnormalities described in WMH lesions in brain. Methods—Subjects included 20 with extensive WMH (WMH+), 45% of whom had Alzheimer disease, and 18 with minimal WMH (WMH−), 44% of whom had Alzheimer disease. All subjects were clinically evaluated and underwent quantitative MRI. Total RNA from whole blood was processed on human whole genome Affymetrix HU133 Plus 2.0 microarrays. RNA expression was analyzed using an analysis of covariance. Results—Two hundred forty-one genes were differentially regulated at ±1.2-fold difference (P<0.005) in subjects with WMH+ as c...

The association of magnetic resonance imaging measures with cognitive function in a biracial population sample.

Abstract: Background White matter hyperintensity volume (WMHV), cerebral infarcts, and total brain volume (TBV) are associated with cognitive function, but few studies have examined these associations in the general population or whether they differ by race.

Interactive Effects of Apolipoprotein E Type 4 Genotype and Cerebrovascular Risk on Neuropsychological Performance and Structural Brain Changes

Abstract: Objective We sought to determine whether the presence of the apolipoprotein E type 4 (apoE4) allele, a known risk factor for Alzheimer disease, interacts with cerebrovascular risk factors to produce a disproportionate impairment in neuropsychological (NP) performance and alterations in structural morphometry as measured by magnetic resonance imaging (MRI). Methods In all, 1995 participants from the community-based Framingham Offspring Cohort participants (mean age 61 years; 1063 women) underwent NP testing and structural MRI in 1999 to 2002. Multivariate linear regression was used to estimate the relationships among Framingham Stroke Risk Profile scores, NP variables, and MRI measures; interaction terms were included to examine modification of these relationships by the presence of the apoE4 allele. All analyses were cross sectional. Results We found significant interactions between the presence of the apoE4 allele and the top sex-specific quartile of the stroke risk profile and their effects on verbal memory ( P ≤ .001), verbal organization ( P ≤ .001), nonverbal memory ( P =.015), as well as set shifting and complex attention ( P =.005). Systolic blood pressure (SBP) was the only individual risk factor significantly linked to these cognitive measures. With the exception of lateral ventricular volume, there were no significant interactions among presence of apoE4, the top sex-specific quartile of the stroke risk profile, and any of the MRI variables. Conclusion The apoE4 allele exacerbates the effects of cerebrovascular risk factors on NP function. This relationship appears to be driven by SBP, suggesting that treatment of high SBP could potentially reduce risk of cognitive impairment among those already at increased risk for Alzheimer disease.

White Matter Hyperintensity and Cognitive Functioning in the Racial and Ethnic Minority Cohort of the Framingham Heart Study

Abstract: Background: Previous studies have demonstrated an association between white matter hyperintensities (WMH) and cognitive performance primarily in Caucasian samples, limiting generalizability to other ethnic and racial groups. This study investigated the association of WMH and cognition in an ethnic and racial minority cohort (Omni) of the Framingham Heart Study and compared these results to the Caucasian (Offspring) cohort. Methods: Quantitative brain MRI and neuropsychological evaluations were performed on stroke- and dementia-free participants. Cognitive assessment included verbal memory, visuospatial memory and organization, language, and executive functioning. Linear regression models were conducted to assess the association between WMH and cognitive function. Results: The Omni group presented with demographic factors that significantly differed from those of the Offspring group: they were younger, but had more stroke risk factors such as hypertension. In the Offspring group, WMH volume was significantly associated with poorer performance on tests of executive function and visual organization. No significant associations between WMH and cognitive measures were found in the Omni group, but no differences (significant interaction terms) were seen between the regression coefficients. Conclusions: The Omni cohort had greater variability in factors that may mediate the association of WMH and cognition. More research is needed to investigate how stroke risk factors impact on the occurrence of WMH and its association with cognition in more diverse cohorts.

High normal fasting blood glucose is associated with dementia in Chinese elderly.

Abstract: Background Diabetes is a risk factor for mild cognitive impairment (MCI) and dementia. However, the association between high normal fasting blood glucose (FBG) and dementia has not been studied. Methods Polytomous logistic regression was used to assess the association of dementia and MCI with FBG in an age- and sex-matched sample of 32 dementia patients, 27 amnestic MCI (aMCI) patients, and 31 normal controls (NC). Analyses were repeated for those with normal FBG. Correlations between FBG and cognitive test scores were obtained. Results Controlling for age, gender, education, body mass index, Hachinski Ischemic Score, magnetic resonance imaging (MRI) stroke, and normalized brain, hippocampal, and white matter hyperintensity MRI volumes; higher FBG was associated with dementia versus aMCI status (OR = 3.13; 95% CI, 1.28–7.69). This association remained (OR = 7.75; 95% CI, 1.10–55.56) when analyses were restricted to subjects with normal FBG. When dementia patients were compared with NC adjusting for age, gender, and education, a significant association with FBG also was seen (OR = 1.83; 95% CI, 1.09–3.08), but it was lost when vascular covariates were added to the model. FBG was not associated with aMCI status versus NC. Higher FBG was correlated with poorer performance on the Trailmaking Test Part B ( P = .003). The percentage of dementia patients with high normal FBG (90%) was significantly higher than that of aMCI patients with high normal FBG (32.9%) (χ 2 = 13.9, P Conclusions Higher FBG was associated with dementia (vs. aMCI) independent of vascular risk factors and MRI indicators of vascular disease, and remained a significant risk factor when analyses were restricted to subjects with normal FBG. The results of this cross-sectional study suggest that a high normal level of FBG may be a risk factor for dementia.

Effects of Apolipoprotein E-ε4 and -ε2 in Amnestic Mild Cognitive Impairment and Dementia in Shanghai: SCOBHI-P

Abstract: Objective To determine apolipoprotein E (APOE)-e4 and -e2 frequencies and risk of mild cognitive impairment (MCI) and dementia in Shanghai, China.

Brain Structure and Cerebrovascular Risk in Cognitively Impaired Patients: Shanghai Community Brain Health Initiative–Pilot Phase

Abstract: Objective To investigate associations between MRI brain morphology, cerebrovascular risk (VR), clinical diagnosis and cognition among elders living in urban Shanghai.

Profiles by sex of brain MRI and cognitive function in the framingham offspring study.

Abstract: Objective: To examine whether there are sex-specific associations between brain magnetic resonance imaging (MRI) measures and neuropsychologic (NP) test performance Background: Differences in cardiovascular risk factors have been linked to decreased total cerebral brain volume and white matter hyperintensities (WMHs) Although brain morphology has been related to cognitive performance, few studies have addressed sex-specific effects in this relationship Methods: Framingham Offspring who were stroke and dementia-free underwent a brain MRI scan and NP testing (n = 2085; 978 men) Factor analysis identified 4 domain-specific NP factors MRI participants were divided into 4 MRI subgroups based on measures of total cerebral brain volume and combinations of the presence of WMH and silent cerebral infarcts (≥ 3 mm) Results: Overall, the relationship between MRI and NP measures was similar between the sexes The exception was that only men showed a positive relationship between executive function and cerebrovascular disease defined as large WMH volume plus silent cerebral infarct This finding was attributed only among men with Framingham Stroke Risk Profile scores > 90th percentile range (P = 00019) Conclusions: Measures of brain atrophy and subclinical markers of vascular disease showed that sex does not significantly alter the relationship between MRI and NP, except among men and women who are at high risk for stroke; these men show poorer performance on executive function, whereas the women do not

Aging Effects on Recollection and Familiarity: The Role of White Matter Hyperintensities

Abstract: Previous studies have indicated that aging is associated with declines in recollection whereas familiarity-based recognition is left largely unaffected. The brain changes underlying these recollection declines are yet not well understood. In the current study we examined the role of white matter integrity as measured by white matter hyperintensities (WMH) on age-related changes in recollection and familiarity. Recognition was measured using a remember/know procedure (Experiment 1) and a source-memory process-dissociation procedure (Experiment 2). Robust age related declines in recollection were observed, but there was no evidence that white matter damage was related to the observed memory declines. Although future studies with larger samples will be necessary to fully characterize the role of WMH in normal age-related declines in different types of memory, the results suggest that declines in recollection are not strongly related to the brain changes indexed by WMHs.

Update on the Magnetic Resonance Imaging core of the Alzheimer's Disease Neuroimaging Initiative

Abstract: Functions of the Alzheimer's Disease Neuroimaging Initiative (ADNI) magnetic resonance imaging (MRI) core fall into three categories: (1) those of the central MRI core laboratory at Mayo Clinic, Rochester, Minnesota, needed to generate high quality MRI data in all subjects at each time point; (2) those of the funded ADNI MRI core imaging analysis groups responsible for analyzing the MRI data; and (3) the joint function of the entire MRI core in designing and problem solving MR image acquisition, pre-processing, and analyses methods. The primary objective of ADNI was and continues to be improving methods for clinical trials in Alzheimer's disease. Our approach to the present ("ADNI-GO") and future ("ADNI-2," if funded) MRI protocol will be to maintain MRI methodological consistency in the previously enrolled "ADNI-1" subjects who are followed up longitudinally in ADNI-GO and ADNI-2. We will modernize and expand the MRI protocol for all newly enrolled ADNI-GO and ADNI-2 subjects. All newly enrolled subjects will be scanned at 3T with a core set of three sequence types: 3D T1-weighted volume, FLAIR, and a long TE gradient echo volumetric acquisition for micro hemorrhage detection. In addition to this core ADNI-GO and ADNI-2 protocol, we will perform vendor-specific pilot sub-studies of arterial spin-labeling perfusion, resting state functional connectivity, and diffusion tensor imaging. One of these sequences will be added to the core protocol on systems from each MRI vendor. These experimental sub-studies are designed to demonstrate the feasibility of acquiring useful data in a multicenter (but single vendor) setting for these three emerging MRI applications.