PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-13 (13)
 

Clipboard (0)
None
Journals
Year of Publication
Document Types
1.  A Mediterranean-Style Diet and White Matter Hyperintensity Volume: the Northern Manhattan Study 
Archives of Neurology  2012;69(2):251-256.
Objective
To examine the association between a Mediterranean-style diet (MeDi) and brain MRI white matter hyperintensities (WMH). The MeDi has previously been associated with a reduced risk of cardiovascular morbidity, possibly including stroke. A greater understanding of modifiable risk factors for small vessel damage may facilitate the prevention of stroke and cognitive decline.
Design
A cross-sectional analysis within a longitudinal population-based cohort study. A semi-quantitative food frequency questionnaire was administered and a score (range 0-9) was calculated to reflect increasing similarity to the MeDi pattern.
Setting
The Northern Manhattan Study.
Participants
1,091 participants, of which 966 had dietary information (mean age 72, 59% women, 65% Hispanic, 16% White, 17% Black).
Main outcome measures
WMH volume was measured by quantitative brain MRI. Linear regression models were constructed to examine the relation between the MeDi score and the log-transformed WMH volume as a proportion of total cranial volume, controlling for sociodemographic and vascular risk factors.
Results
On the MeDi scale, 12% scored 0-2, 16 scored 3, 23% scored 4, 23% scored 5, 26% scored 6-9. Each 1-point increase in MeDi score was associated with a lower log WMH volume (β=-0.04, p=0.02). The only MeDi score component that was an independent predictor of WMH volume was the ratio of monounsaturated to saturated fat (β=-0.20, p=0.001).
Conclusions
A Mediterranean-style diet was associated with a lower WMH burden, a marker of small vessel damage in the brain. However, white matter hyperintensities are etiologically heterogenous and can include neurodegeneration. Replication by other population-based studies is needed.
doi:10.1001/archneurol.2011.548
PMCID: PMC3281550  PMID: 22332193
2.  Brain Morphology and Cerebrovascular Risk in Mild Cognitive Impairment and Dementia: SCOBHI-P study 
Archives of neurology  2010;67(10):1231-1237.
Objective
To investigate associations between MRI brain morphology, cerebrovascular risk (VR), clinical diagnosis and cognition among elders living in urban Shanghai.
Design
Cross-sectional study.
Setting
Memory Disorders Clinic and community normal control (NC) subject recruitment.
Participants
Ninety-six older subjects, 32 with normal cognition, 30 with amnestic MCI (aMCI) and 34 with dementia.
Main outcome measures
Each subject received medical history, neurological/physical exams, neuropsychological evaluations, brain MRI and apolipoprotein E-ε4 (APOE -ε4) genotype test. MRI volumes were assessed using a semi-automatic method.
Results
Brain volume (BV) was significantly smaller in the demented compared with NC (p < 0.001) or aMCI (p = 0.043). Hippocampal volume (HV) was lower, and white matter hyperintensity volume (WMH) was higher, in aMCI (HV: p = 0.028; WMH: p = 0.041) and dementia (HV: p < 0.001; WMH: p = 0.002) compared with NC. APOE -ε4 presence was significantly associated with reduced HV (p = 0.02). Systolic blood pressure was positively associated with VR score (p = 0.037); diastolic blood pressure (p = 0.021) and VR score (p = 0.036) were both positively associated with WMH. WMH (p = 0.029) and VR (p = 0.031) were both higher among the demented than NC.
Conclusion
MRI brain morphology changes were significantly associated clinical diagnosis, in addition, blood pressure was highly associated with VR score and WMH. These results suggest that MRI is a valuable measure of brain injury in a Chinese cohort and can serve to assess the effects of various degenerative and cerebrovascular pathologies.
doi:10.1001/archneurol.2010.230
PMCID: PMC3051396  PMID: 20937951
Dementia; Mild Cognitive Impairment; Magnetic Resonance Imaging; white matter hyperintensities; hippocampal volume; cerebrovascular risk; apolipoprotein E genotype; cognition
3.  Longterm blood pressure fluctuation and cerebrovascular disease in an elderly cohort 
Archives of neurology  2010;67(5):564-569.
Objective
To determine the association of blood pressure (BP) level and longterm fluctuation in BP with cerebrovascular disease.
Design
Participants received structural MRI and BP measurements in 3, 24 month intervals prior to scanning. We derived the mean and standard deviation (SD) of the mean BP for each participant over the 3 intervals and divided them into four groups defined as above and below the group median (≤ 96.48 mmHg or >96.48mmHg) and further subdivided by the median standard deviation (below SD ≤ 7.21 mmHg or above SD > 7.21 mmHg). This scheme yielded four groups representing the full range of BP and fluctuations in BP. We examined differences in white matter hyperintensity (WMH) volume and brain infarctions across these groups.
Setting
The Washington Heights-Inwood Columbia Aging Project, a community-based epidemiological study of older adults from northern Manhattan.
Participants
686 non-demented older adults who received structural MRI and had BP measurements over three study visits.
Results
WMH volume increased across the four groups in a linear fashion with the lowest WMH volume in the lowest mean/lowest SD group and the highest in the highest mean/highest SD group (F(3,610)=27.43, p=0.0017). Frequency of infarction also increased monotonically across groups (from 22% to 41%; p-for-trend=0.004).
Conclusions
Compared to individuals with low BP with low fluctuations in BP, the risk of cerebrovascular disease increases with increasing BP and BP fluctuation. Given that cerebrovascular disease is associated with disability, findings suggest that interventions should focus on longterm fluctuating BP as well as elevated BP.
doi:10.1001/archneurol.2010.70
PMCID: PMC2917204  PMID: 20457955
blood pressure; cerebrovascular disease; white matter hyperintensities
4.  Longitudinal Changes in White Matter Disease and Cognition in the First Year of the Alzheimer Disease Neuroimaging Initiative 
Archives of neurology  2010;67(11):1370-1378.
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.
doi:10.1001/archneurol.2010.284
PMCID: PMC3082636  PMID: 21060014
5.  The Association of Magnetic Resonance Imaging Measures With Cognitive Function in a Biracial Population Sample 
Archives of neurology  2010;67(4):475-482.
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.
Objective
To examine the association of WMHV, cerebral infarcts, and TBV with global cognition and cognition in 5 separate domains in a biracial population sample.
Setting
A biracial community population of Chicago, Illinois.
Design
Cross-sectional population study.
Participants
The study population comprised 575 participants from the Chicago Health and Aging Project (CHAP).
Main Outcome Measures
Volumetric magnetic resonance imaging (MRI) measures of WMHV, TBV, and cerebral infarcts and detailed neuropsychological testing assessments of global cognition and 5 cognitive domains.
Results
Overall and among those without dementia, cognition was inversely associated with WMHV and number of infarcts but was positively associated with TBV. When all 3 measures were simultaneously added to the model, the association of global cognition with WMHV and TBV remained significant and unchanged but was no longer significant with infarcts. Among subjects without dementia, all 3 MRI measures were associated with performance in multiple cognitive domains, specifically perceptual speed. However, among subjects with dementia, only TBV was associated with cognition and performance in multiple cognitive systems. Race did not significantly modify any of these associations.
Conclusions
In this biracial general population sample, the associations of MRI measures with cognition differed according to clinical status of subjects (stronger among subjects without dementia) and were not modified by race. These associations did not affect all cognitive domains equally but were more consistent with impairments in perceptual speed.
doi:10.1001/archneurol.2010.42
PMCID: PMC2947487  PMID: 20385915
6.  Differences of Brain volume, Hippocampal volume, Cerebrovascular risk factors and APOE4 among MCI subtypes 
Archives of neurology  2009;66(11):1393-1399.
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.
Participants
A total of 153 subjects with MCI, 218 cognitively normal older individuals (controls), and 68 patients with Alzheimer disease.
Main Outcome Measures
Classification of subjects with MCI according to current subtype diagnostic convention based on neuropsychological performance, estimates of vascular risk based on medical history, research MRI unless there was a specific contraindication, and apolipoprotein E genotype.
Results
Of the 153 subjects with MCI, 65 were diagnosed with amnestic single-domain, 46 with amnestic multiple-domain, 27 with nonamnestic single-domain, and 15 with nonamnestic multiple-domain MCI. Analyses of control, MCI, and Alzheimer disease cases revealed significant differences in brain and hippocampal volumes between each group. Post hoc analyses of MRI measures among the MCI subtypes found that patients with amnestic single-domain MCI had significantly less brain atrophy and that hippocampal volume differed significantly from controls for the 2 amnestic forms of MCI. Apolipoprotein E genotype prevalence was significantly greater in the amnestic and nonamnestic subtypes of MCI. Conversely, the nonamnestic subtypes were more likely to have increased vascular risk and to be African American.
Conclusions
Amnestic forms of MCI appear to have demographic, genetic, and MRI findings suggestive of Alzheimer disease pathology, whereas the nonamnestic forms of MCI have findings suggestive of vascular disease. Importantly, however, all subjects with MCI showed evidence of brain injury, and the biological differences among subtypes are relatively subtle beyond the memory vs nonmemory groupings.
doi:10.1001/archneurol.2009.252
PMCID: PMC2909769  PMID: 19901172
Mild Cognitive Impairment; Subtypes; Magnetic Resonanace Imaging; white matter hyperintensities; cerebrovascular disease; Apolipoprotein E genotype; pathophysiology
7.  Progression of Mild Cognitive Impairment to Dementia in Clinic- vs Community-Based Cohorts 
Archives of neurology  2009;66(9):1151-1157.
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.
Design
Rates and predictors of conversion were examined in a prospective longitudinal study at a single center.
Setting
Among the participants, 46% were recruited from a clinical setting and 54% were recruited directly through community outreach.
Participants
One hundred eleven individuals with mild cognitive impairment were followed up longitudinally for an average of 2.4 years (range, 0.5–4.0 years).
Main Outcome Measures
Conversion from mild cognitive impairment to dementia.
Results
During the follow-up period, 28 individuals progressed to dementia with a mean (SD) time to conversion of 2.19 (0.72) years. The clinic sample had an annual conversion rate of 13%, whereas the community sample had an annual conversion rate of 3%. In a Cox proportional hazards model, clinic recruitment source alone was associated with an increased hazard of incident dementia (hazard ratio=3.50; 95% confidence interval, 1.31–9.18; P=.01). When other variables were added to the model, only baseline functional impairment as measured by the Clinical Dementia Rating Scale (and no demographic, cognitive, or neuroimaging variables or mild cognitive impairment subtype) accounted for the differences in conversion rates across the 2 cohorts.
Conclusions
These findings add to the growing literature to suggest that the degree of functional impairment at baseline is an important predictor of conversion to dementia and may help explain differences in findings between epidemiological and clinic-based studies.
doi:10.1001/archneurol.2009.106
PMCID: PMC2863139  PMID: 19752306
8.  Validity of self-reported Stroke in elderly African Americans, Caribbean Hispanics and Caucasians 
Archives of neurology  2009;66(7):834-840.
Background and Objective
The validity of a self-reported stroke remains inconclusive. The objective of the present study was to validate the diagnosis of self-reported stroke using stroke identified by magnetic resonance imaging (MRI) as the standard.
Design and Setting
Community-based cohort study of non-demented, ethnically diverse elderly in northern Manhattan.
Methods
High-resolution quantitative MRI was acquired on 717 participants without dementia. Sensitivity and specificity of stroke by self-report were examined using cross-sectional analyses and the χ2-test. Putative relations between factors potentially influencing the reporting of stroke, including memory performance, cognitive function and vascular risk factors were assessed using logistic regression models. Subsequently all analyses were repeated stratified by age, sex, ethnic group and level of education.
Results
In analyses for the whole sample, sensitivity of stroke self-report for a diagnosis of stroke on MRI was 32.4% and specificity was 78.9%. In analyses stratified by median of age (80.1 years), the validity between reported stroke and detection of stroke on MRI was significantly better in the younger than the older age group (for all vascular territories: sensitivity: 36.7% (specificity 81.3%) vs. sensitivity 27.6% (specificity: 26.2%), p=0.02). Impaired memory, cognitive or language ability, and the presence of hypertension or myocardial infarction were associated with higher false-negatives.
Conclusions
Using brain MRI as the standard, specificity and sensitivity of stroke self-report are low. Accuracy of self-report is influenced by age, presence of vascular disease and cognitive function. In stroke research, sensitive neuroimaging techniques rather than stroke self-report should be used to determine stroke history.
doi:10.1001/archneurol.2009.83
PMCID: PMC2881576  PMID: 19433651
9.  Alzheimer Abnormalities of the Amygdala With Klüver-Bucy Syndrome Symptoms 
Archives of neurology  2009;66(1):125-129.
Background
Neurofibrillary tangles and β-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.
Design
Case study.
Setting
Outpatient specialty clinic.
Patient
A 70-year-old man with progressive behavioral symptoms of hyperorality, hypersexuality, hypermetamorphosis, visual agnosia, hyperphagia, and apathy who died at age 77 of asphyxiation on a foreign object.
Main Outcome Measures
Clinical symptomatology, brain imaging, and neuropathology.
Results
The pathologic diagnosis was Alzheimer disease with abundant tangles and plaques in the lateral amygdala.
Conclusions
This case represents a variant of Alzheimer disease with prominent amygdala abnormalities and a Klüver-Bucy phenotype that was misdiagnosed as frontotemporal dementia. Clinical and imaging findings that may aid in accurate diagnosis are reviewed.
doi:10.1001/archneurol.2008.517
PMCID: PMC2868923  PMID: 19139311
10.  Association of Distinct Variants in SORL1 With Cerebrovascular and Neurodegenerative Changes Related to Alzheimer Disease 
Archives of neurology  2008;65(12):1640-1648.
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. We performed single-and 3-SNP haplotype association analyses using family-based tests. Haplotypes found to be significantly associated with at least 1 MRI trait were tested for association with 6 pathological traits in a separate sample of 69 white patients with autopsy-confirmed AD.
Results
In white patients, white matter hyperintensities were associated with multiple markers in the region encompassing SNPs 6 to 10, whereas cerebral and hippocampal atrophy were associated with markers from the region including SNPs 21 to 26. Examination of specific 3-SNP haplotypes from these 2 regions in the autopsy-confirmed cases of AD revealed association of white matter disease with SNPs 8 to 10 and association of hippocampal atrophy with SNPs 22 to 26. The haplotype CGC at SNPs 8 to 10 was associated with fewer white matter changes in the clinical (P<.001) and autopsy (P=.02) samples.
Conclusions
Variants of SORL1 previously associated with AD are also associated with MRI and neuropathological measures of neurodegenerative and cerebrovascular disease. These findings not only support the hypothesis that multiple areas in SORL1 are of functional importance but also raise the possibility that multiple SORL1 variants influence amyloid precursor protein or endothelial lipoprotein processing or both in different regions of the brain.
doi:10.1001/archneur.65.12.1640
PMCID: PMC2719762  PMID: 19064752
11.  Brain morphology in elderly African Americans, Caribbean Hispanics, and Caucasians from Northern Manhattan 
Archives of neurology  2008;65(8):1053-1061.
Objective
To examine the impact of age, sex, ethnicity, and vascular disease on measures of brain morphology, including relative brain volume, ventricle volume, hippocampus and entorhinal cortex volume, and white matter hyperintensity (WMH) burden in a large community-based cohort of non-demented, ethnically diverse older adults.
Design
Beginning in 2003, high-resolution quantitative magnetic resonance imaging (MRI) was acquired on 769 participants without dementia. The relations of age, sex, self reported vascular disease history, and ethnicity, with brain morphology was examined in a cross-sectional study using multiple linear regression analyses. Sex and ethnicity interactions were also considered.
Setting
The Washington Heights/Hamilton Heights Aging Project (WHICAP), a community-based epidemiological study of older adults from three ethnic groups (i.e., Caucasian, Hispanic, African American) from northern Manhattan.
Main outcome measures
Relative brain volume (absolute brain volume/cranial volume), ventricular volume, hippocampus and entorhinal cortex volumes were derived manually on high-resolution MRI scans. White matter hyperintensities were quantified semi-automatically on FLAIR-weighted MRI.
Results
Increased age was associated with decreased relative brain volume and increased ventricular and WMH volume. Hispanic and African American participants had larger relative brain volumes and more severe WMH burden than Caucasians, but their associations with age were similar across ethnic groups. Compared with men, women had larger relative brain volumes. Vascular disease was associated with smaller relative brain volume and higher WMH burden, particularly among African Americans.
Conclusions
Increased age and vascular disease particularly among African Americans are associated with increased brain atrophy and WMH burden. African American and Hispanic participants have larger relative brain volumes and more WMH than Caucasians. Ethnic group differences in WMH severity appear to be partially attributable to differences in vascular disease. Future work will focus on the determinants and cognitive correlates of these differences.
doi:10.1001/archneur.65.8.1053
PMCID: PMC2692286  PMID: 18695055
12.  Association of Plasma Homocysteine Levels with Subclinical Brain Injury: Cerebral Volumes, White Matter Hyperintensity and Silent Brain Infarcts on Volumetric MRI in the Framingham Offspring Study 
Archives of neurology  2008;65(5):642-649.
Objective
To evaluate the relation between plasma homocysteine (tHcy) and brain MRI in a community-based sample.
Background
Elevated tHcy levels have been associated with an increased risk of dementia and stroke, but it is uncertain if the mediating mechanisms are predominantly cellular, vascular or both.
Design
Our sample comprised 1965 Framingham Offspring participants (1050 women; age 62±9 yrs) who were free of clinical stroke, dementia, or other neurological disease affecting brain MRI and who had at least one measurement of plasma tHcy (1991-2001) and a brain MRI (1999-2002). We used multivariable regressions to relate initial (1991-95) and concurrent (1998-2001) plasma tHcy concentrations to total cerebral brain volume (TCBV) and lobar volumes as measures of neuronal loss and atrophy; and to the presence or absence of silent brain infarcts (SBI) and extensive white matter hyperintensity (log-WMH ≥1 SD above the age-adjusted mean) as separate measures of vascular injury.
Results
Mean TCBV was 78%. 218 participants had SBI; 250 had extensive WMH. Participants with a plasma tHcy level in the highest age-, sex-specific quartile had a smaller TCBV (-0.37% and -0.48%; p=0.01 and <0.001 respectively), compared to participants with lower levels. Initial tHcy levels were associated with an increased prevalence of SBI (RR: 1.5; 95% CI: 1.1-2.1; p=0.02) and concurrent tHcy levels with smaller frontal and temporal lobar volumes (-0.14% and -0.10%; p=0.001 and 0.04 respectively). Prevalence of extensive WMH did not differ according to initial or concurrent plasma tHcy levels (RR: both 1.0, 95% CIs: 0.7-1.4 and 0.8-1.4, respectively).
Conclusion
Higher plasma tHcy levels are associated with smaller brain volumes and presence of silent infarcts on MRI, even in healthy, middle-aged adults. Thus, both cellular and vascular mechanisms may underlie the association of plasma tHcy with brain aging, as reflected by the effects on subclinical as well as overt disease.
doi:10.1001/archneur.65.5.642
PMCID: PMC2700952  PMID: 18474741
magnetic resonance imaging; homocysteine; brain volume; silent brain infarcts; white matter hyperintensity; epidemiology
13.  Quantitative Brain Measures in the Community-Dwelling Elderly with Mild Parkinsonian Signs 
Archives of neurology  2008;65(12):1649-1654.
Background
Mild Parkinsonian signs (MPS) are a marker for incident dementia. MPS have been linked with cerebrovascular disease, which can be evaluated using magnetic resonance imaging (MRI). Also, if MPS are a marker for developing Alzheimer's type changes, hippocampal volume on MRI might be diminished among individuals with MPS.
Objective
To examine white matter hyperintensity (WMH) volume and total hippocampal volume in elderly with vs. without MPS.
Methods
Community-dwelling elderly in northern Manhattan had a neurological examination and brain MRI. WMH volume (derived on FLAIR-weighted MRI scans using a semi-automated thresholding approach) and total hippocampal volume (manually-derived) were expressed relative to total cranial volume.
Results
MPS were present in 111/666 (16.7%) participants. Relative WMH volume was larger in participants with vs. without MPS (1.70 ± 1.28 vs. 1.17 ± 1.18, p < 0.001) and, in a multivariate logistic regression analysis adjusting for age, gender, years of education, ethnicity, and depression, relative WMH volume was associated with MPS (OR = 1.26, 95% CI = 1.08 − 1.47, p = 0.004). In both unadjusted and adjusted analyses, total relative hippocampal volume was similar in participants with vs. without MPS, regardless of cognitive status.
Conclusions
In this MRI study of the community-dwelling elderly, WMH volume was associated with MPS and total relative hippocampal volume was not. These data raise the possibility that vascular disease could play a role in the development of MPS.
doi:10.1001/archneurol.2008.504
PMCID: PMC2676900  PMID: 19064753
elderly; mild parkinsonian signs; magnetic resonance imaging; hippocampus; Alzheimer's disease; population; epidemiology; white matter hyperintensities

Results 1-13 (13)