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1.  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.
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.
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.
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.
PMCID: PMC2881576  PMID: 19433651
2.  Risk of Parkinson's Disease in Carriers of Parkin mutations: Estimation Using the Kin-Cohort Method 
Archives of neurology  2008;65(4):467-474.
To estimate the risk of Parkinson's disease in individuals with mutations in the Parkin gene.
We assessed point mutations and exon deletions and duplications in the Parkin gene in 247 PD probands with age at onset ≤50 and 104 control probands enrolled in the Genetic Epidemiology of PD study. For each first-degree relative, a consensus diagnosis of PD was established. The probability that each relative carried a mutation was estimated from the proband's Parkin carrier status using Mendelian principles and the relationship of the relative to the proband .
Parkin mutations were identified in 25 PD probands (10.1%), 72% of whom were heterozygotes. One Parkin homozygote reported 2 siblings with PD. The cumulative incidence of PD to age 65 in carrier relatives (age-specific penetrance) was estimated to be 7.0% (95% CI: 0.4-71.9%) compared to 1.7% (95% CI: 0.8-3.4%) in non-carrier relatives of cases (p=0.59) and 1.1% (95% CI: 0.3-3.4%), in relatives of controls ( compared to non-carriers p=0.52).
The cumulative risk of PD to age 65 in a non-carrier relative of a case with AAO ≤50 is not significantly greater than the general population risk among controls. Age specific penetrance among Parkin carriers, in particular heterozygotes, deserves further study.
PMCID: PMC2836931  PMID: 18413468
Parkin; Mutations; Parkinson's disease; Kin-cohort study; Early onset
3.  Association of Glucocerebrosidase Mutations With Dementia With Lewy Bodies 
Archives of neurology  2009;66(5):578-583.
Mutations in the glucocerebrosidase (GBA) gene are associated with Lewy body (LB) disorders.
To determine the relationship of GBA mutations and APOE4 genotype to LB and Alzheimer disease (AD) pathological findings.
Case-control study.
Academic research.
The 187 subjects included patients with primary neuropathological diagnoses of LB disorders with or without AD changes (95 cases), randomly selected patients with AD (without significant LB pathological findings; 60 cases), and controls with neither LB nor AD pathological findings (32 cases).
Main Outcome Measures
GBA mutation status, APOE4 genotype, LB pathological findings (assessed according to the third report of the Dementia With Lewy Body Consortium), and Alzheimer plaque and tangle pathological findings (rated by criteria of Braak and Braak, the Consortium to Establish a Registry for Alzheimer Disease, and the National Institute on Aging–Reagan Institute).
GBA mutations were found in 18% (34 of 187) of all subjects, including 28% (27 of 95) of those with primary LB pathological findings compared with 10% (6 of 60) of those with AD pathological findings and 3% (1 of 32) of those without AD or LB pathological findings (P=.001). GBA mutation status was significantly associated with the presence of cortical LBs (odds ratio, 6.48; 95% confidence interval, 2.45–17.16; P<.001), after adjusting for sex, age at death, and presence of APOE4. GBA mutation carriers were significantly less likely to meet AD pathological diagnostic (National Institute on Aging–Reagan Institute intermediate or high likelihood) criteria (odds ratio, 0.35; 95% confidence interval, 0.15–0.79; P=.01) after adjustment for sex, age at death, and APOE4.
GBA mutations may be associated with pathologically “purer” LB disorders, characterized by more extensive (cortical) LB, and less severe AD pathological findings and may be a useful marker for LB disorders.
PMCID: PMC2758782  PMID: 19433657
4.  Brain morphology in elderly African Americans, Caribbean Hispanics, and Caucasians from Northern Manhattan 
Archives of neurology  2008;65(8):1053-1061.
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.
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.
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.
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.
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.
PMCID: PMC2692286  PMID: 18695055

Results 1-4 (4)