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Biomedical subjects

Wei Wen

Publications and source records attributed to Wei Wen.

At least 19 recordsLinked to original sources
PubMed2007

Progression of white matter hyperintensities in elderly individuals over 3 years.

OBJECTIVE: The aims of this study were to examine white matter hyperintensities (WMHs) in the brains of elderly individuals, the rate of progression, the anatomic regions most vulnerable, and the predictors of change. METHODS: We examined 51 healthy volunteers (mean age 71 years) with T2-weighted brain MRI on the same scanner 3 years apart. WMH volumes were determined by an automated method, and the anatomic location of change was determined for both deep WMHs (DWMHs) and periventricular WMHs (PVWMHs). RESULTS: The total brain WMH volume increased by 39.6%, i.e., 13.2% per year, with the change in DWMH being 43.8% and 29.7% in PVWMH. The increase was significant in all regions except the occipital lobe and cerebellum. Age, sex, and cerebrovascular risk factors were not significant predictors of WMH progression. The main predictor of progression was baseline level of WMH. The number of WMH lesions increased by a mean of 1.78, and the progression was mainly accounted for by an increase in very large (>16 mm) lesions. Eight subjects showed a slight decrease in WMH. CONCLUSIONS: White matter hyperintensities are progressive in most elderly individuals with an increasing rate of progression as the burden of lesions increases. The rate of progression is greater in deep white matter and in the anterior brain regions. Risk factors for progression are not well understood, and genetic and other environmental factors must be examined. Quantitation of white matter hyperintensities may serve as a surrogate marker of the progression of small vessel disease.

Aged↗
PubMed2006

Prediction of cognitive decline after stroke using proton magnetic resonance spectroscopy.

Structural MRI measures have been used to predict cognitive decline in elderly subjects, but few studies have used proton magnetic resonance spectroscopy ((1)H-MRS) for this purpose, particularly after stroke. We studied the potential of (1)H-MRS to predict cognitive decline in patients with stroke or TIA and healthy ageing controls over 12 months and 3 years. Structural MRI and single-voxel (1)H-MRS in the frontal white matter and the occipito-parietal gray matter were performed at the index assessment (3-6 months post-stroke) in 49 stroke/TIA patients and 60 controls. Neuropsychological testing was performed at the index assessment and repeated at 12 months in 30 stroke/TIA patients and 49 controls, and at 3 years in 25 patients and 48 controls. In stroke/TIA patients, frontal NAA/Cr predicted cognitive decline over 12 months and 3 years, and in elderly control subjects frontal NAA predicted cognitive decline over 12 months only. In stroke/TIA patients, the (1)H-MRS measures were better predictors of cognitive decline than structural measures. (1)H-MRS may be useful in assessing early cognitive impairment after stroke/TIA and in normal ageing.

Aged↗
PubMed2006

Metastasis-suppressing potential of ribonucleotide reductase small subunit p53R2 in human cancer cells.

PURPOSE: Previous gene transfection studies have shown that the accumulation of human ribonucleotide reductase small subunit M2 (hRRM2) enhances cellular transformation, tumorigenesis, and malignancy potential. The latest identified small subunit p53R2 has 80% homology to hRRM2. Here, we investigate the role of p53R2 in cancer invasion and metastasis. EXPERIMENTAL DESIGN: The immunohistochemistry was conducted on a tissue array including 49 primary and 59 metastatic colon adenocarcinoma samples to determine the relationship between p53R2 expression and metastasis. A Matrigel invasive chamber was used to sort the highly invasive cells and to evaluate the invasion potential of p53R2. RESULTS: Univariate and multivariate analyses revealed that p53R2 is negatively related to the metastasis of colon adenocarcinoma samples (odds ratio, 0.23; P<0.05). The decrease of p53R2 is associated with cell invasion potential, which was observed in both p53 wild-type (KB) and mutant (PC-3 and Mia PaCa-2) cell lines. An increase in p53R2 expression by gene transfection significantly reduced the cellular invasion potential to 54% and 30% in KB and PC-3 cells, respectively, whereas inhibition of p53R2 by short interfering RNA resulted in a 3-fold increase in cell migration. CONCLUSIONS: Opposite regulation of hRRM2 and p53R2 in invasion potential might play a critical role in determining the invasion and metastasis phenotype in cancer cells. The expression level of ribonucleotide reductase small subunits may serve as a biomarker to predict the malignancy potential of human cancers in the future.

Adenocarcinoma↗
PubMed2006

Effects of cerebrovascular risk factors on gray matter volume in adults aged 60-64 years: a voxel-based morphometric study.

The effect of putative cerebrovascular risk factors on gray matter volume in a community-dwelling, non-demented 60- to 64-year-old cohort was investigated. Cranial T1-weighted MRI scans were obtained in 337 adults and voxel-based morphometric analyses were applied to detect regional gray matter volume differences related to hypertension, diabetes, smoking, and hyperlipidemia in men and women, respectively. Hypertension-related gray matter volume reduction was found in right superior, bilateral medial frontal, left superior temporal and left precentral gyri in men. No regional differences in gray matter related to hypertension were seen in women. Conversely, female but not male smokers had more gray matter volume in right fusiform gyrus and right temporal subgyral gray matter. No differences were observed in gray matter volume in association with diabetes or hyperlipidemia for men or women. Our results suggest that there are different patterns of regional effects in gray matter volume in relation to different cerebrovascular risk factors, and sex differences for the same risk factors.

Brain↗
PubMed2006

PQN and DQN: algorithms for expression microarrays.

An ideal expression algorithm should be able to tell truly different expression levels with small false positive errors and be robust to assay changes. We propose two algorithms. PQN is the non-central trimmed mean of perfect match intensities with quantile normalization. DQN is the non-central trimmed mean of differences between perfect match and mismatch intensities with quantile normalization. The quantiles for normalization can be either empirical or theoretical. When array types and/or assay change in a study, the normalization to common quantiles at the probe set level is essential. We compared DQN, PQN, RMA, GCRMA, DCHIP, PLIER and MAS5 for the Affymetrix Latin square data and our data of two sets of experiments using the same bone marrow but different types of microarrays and different assay. We found the computation for AUC of ROC at affycomp.biostat.jhsph.edu can be improved.

Algorithms↗
PubMed2006

A high-resolution single photon emission computed tomography study of verbal recognition memory in Alzheimer's disease.

BACKGROUND: In view of the recent technological advances and its ease of availability, we used single photon emission computed tomography (SPECT) to examine the performance of early Alzheimer's disease (AD) subjects on a verbal recognition memory task. METHODS: Eighteen early AD and 10 matched healthy control subjects underwent split-dose (99m)Tc-HMPAO (Ceretec) SPECT using a verbal recognition memory and control task. SPECT images co-registered with MRI scans were used to determine relative regional cerebral blood flow (rCBF) changes in regions of interest. RESULTS: In healthy control subjects, verbal recognition increased rCBF in the right occipital region, thalamus, left prefrontal pole, posterior parietal region and cerebellum, and decreased rCBF in the right hippocampus. AD subjects showed bilateral prefrontal, posterior parietal and occipital increases, unilateral increase in the left posterior temporal region, and bilateral reductions in the hippocampus. Although activation was significantly different between the two groups in the right thalamus and left medial prefrontal region, the verbal recognition task did not enhance discrimination between groups. CONCLUSIONS: Compared with controls, AD subjects activate a similar but more extensive bilateral network during verbal recognition, possibly reflecting an attempt to compensate for impaired processing.

Aged↗
PubMed2006

Hormone replacement therapy, brain volumes and white matter in postmenopausal women aged 60-64 years.

Research on the structural and functional effects of hormone replacement therapy on the brain has produced inconsistent results. This paper reports on cross-sectional associations between hormone replacement therapy use and volumes of brain structures measured using magnetic resonance imaging in 213 postmenopausal women aged 60-64 years recruited from a large population study. Of these, 64 were current hormone replacement therapy users, 69 previous users and 80 had never used hormone replacement therapy. No differences were observed between groups in total grey matter, white matter, hippocampal or amygdalar volumes, severity or volume of white matter hyperintensities, or in different measures of brain atrophy. While acknowledging the limitations of a cross-sectional study, the results argue against hormone replacement therapy being protective against brain changes associated with ageing in women in their early 60s.

Brain↗
PubMed2006

Longitudinal changes during aging using proton magnetic resonance spectroscopy.

OBJECTIVE: We aimed to examine the longitudinal change in proton magnetic resonance spectroscopy ((1)H-MRS) visible metabolites (N-acetyl aspartate [NAA], creatine [Cr], choline [Cho], and myo-Inositol [mI]) in brains of elderly individuals over 3 years and relate them to cognitive function. METHODS: Neurologically and psychiatrically normal volunteers (n = 40) were examined at baseline and 3 years later with (1)H-MRS in two voxels (frontal white matter n = 29, and occipitoparietal gray matter n = 36) and with detailed neuropsychological assessments. Longitudinal analyses were performed with age, educational level, sex, and white matter hyperintensities (WMH) in voxels as covariates. RESULTS: Frontal mI was significantly increased over time in male participants, but all other metabolites were stable over time. Neuropsychological performance was not significantly changed over 3 years, and there was no relationship between change in metabolite levels and change in neuropsychological function. CONCLUSIONS: MRS-visible metabolites are stable in elderly persons over 3 years, with the exception of mI which shows an increase. Increasing mI may be a marker of aging or a preclinical neurodegenerative process. MRS changes do not correlate with change in neurocognitive function during aging.

Aged↗
PubMed2006

Combined cerebral blood flow effects of a cholinergic agonist (milameline) and a verbal recognition task in early Alzheimer's disease.

RU 35926/CI-979 (milameline) is a partial muscarinic agonist with promnestic effects in animal models. Preliminary animal studies suggest that this agent has the capacity to reverse cholinergic dysfunction and that it may impact on regional cerebral blood flow (rCBF). A total of 10 subjects with Alzheimer's disease (AD) of mild severity underwent high resolution split-dose single photon emission computed tomography (SPECT) during performance of a verbal recognition and control task, both before and after 18 weeks treatment with melameline or placebo. SPECT images were coregistered with individual's magnetic resonance imaging scans allowing extraction of rCBF values from multiple anatomical regions of interest (ROI). The effect of milameline was examined in eight individuals who were found after unblinding to be taking active drug. Effects of milameline were most apparent in the frontal regions, basal ganglia and thalamus. In the group as a whole, the greatest increase in rCBF due to milameline treatment was observed in the left globus pallidus. Response to milameline treatment was associated with increases in rCBF in the cingulate gyrus bilaterally, and less so for the left thalamus. Milameline-related increases in rCBF values were exaggerated by the verbal recognition task. Milameline has a demonstrable effect on cerebral blood flow in mild AD. Consistent with emerging animal data, the effects on rCBF appear most prominent in frontal and subcortical regions in AD subjects. The effects on rCBF appear to be augmented by the performance of a cognitively demanding task, raising the possibility that such tasks could assist in building an awareness of the functional neuropsychopharmacology of drugs designed for cognitive enhancement.

Alzheimer Disease↗
PubMed2005

Gray matter reduction is correlated with white matter hyperintensity volume: a voxel-based morphometric study in a large epidemiological sample.

Both brain atrophy and T2-weighted white matter hyperintensities (WMH) are common findings in the brains of asymptomatic elderly individuals as well as in disease-specific brains. The study of the relationship between these two salient features is therefore important. To investigate such a relationship, we performed a brain magnetic resonance imaging (MRI) study on 397 asymptomatic individuals aged between 60 and 64 years, who were recruited randomly from a large community sample. WMH were delineated on T2-weighted fluid attenuation inversion recovery (FLAIR) whole brain scans using an automated procedure. The results showed that gray matter reduction, subarachnoid CSF (SA-CSF) increase and lateral ventricular dilation were significantly correlated with WMH load. Deep white matter hyperintensity (DWMH) had significant correlation with all three global atrophy indices, but periventricular white matter hyperintensity (PVWMH) was correlated only with gray matter volume. Voxel-based morphometric (VBM) analysis showed that regional gray matter reduction correlated more closely with WMH load of the proximate region than with WMH elsewhere. The results suggest that WMH have a relationship with brain atrophy in middle age, although the study cannot determine which process, i.e. the development of WMH or atrophy, is primary. The study also demonstrates that DWMH has a more significant relationship with structural brain changes, and may therefore be more functionally relevant than PVWMH. Further delineation of this relationship needs a longitudinal study of the changes in both WMH and indices of brain atrophy.

Age Factors↗
PubMed2005

Cognitive correlates of 1H MRS measures in the healthy elderly brain.

Ageing is associated with cognitive decline, with some studies indicating that this decline can be mostly accounted for by slowing of information processing speed. Whilst it is likely that this is associated with age-related changes in fronto-subcortical neuronal circuits, such changes are not visible on routine neuroimaging. We examined the integrity of this brain region using proton magnetic resonance spectroscopy (1H MRS) and hypothesised that functional changes measured by 1H MRS would be associated with cognitive performance. Fifty-nine healthy elderly subjects (age 58-85 years) underwent single-voxel 1H MRS in frontal white matter and occipito-parietal gray matter, and a comprehensive neuropsychological battery. The results showed a significant correlation between frontal white matter NAA/H2O and a composite measure of neuropsychological performance representing speed of information processing, attentional function and visual memory, controlling for age and sex. This research highlights the importance of the relationship between regional brain changes and cognitive function in the ageing brain, and suggests that MRS may be a sensitive marker of subclinical change in cognition.

Aged↗
PubMed2005

Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample.

BACKGROUND: Case control studies have supported a relationship between low folic acid and vitamin B112 and high homocysteine levels as possible predictors of depression. The results from epidemiological studies are mixed and largely from elderly populations. METHOD: A random subsample of 412 persons aged 60-64 years from a larger community sample underwent psychiatric and physical assessments, and brain MRI scans. Subjects were assessed using the PRIME-MD Patient Health Questionnaire for syndromal depression and severity of depressive symptoms. Blood measures included serum folic acid, vitamin B12, homocysteine and creatinine levels, and total antioxidant capacity. MRI scans were quantified for brain atrophy, subcortical atrophy, and periventricular and deep white-matter hyperintensity on T2-weighted imaging. RESULTS: Being in the lowest quartile of homocysteine was associated with fewer depressive symptoms, after adjusting for sex, physical health, smoking, creatinine, folic acid and B12 levels. Being in the lowest quartile of folic acid was associated with increased depressive symptoms, after adjusting for confounding factors, but adjustment for homocysteine reduced the incidence rate ratio for folic acid to a marginal level. Vitamin B12 levels did not have a significant association with depressive symptoms. While white-matter hyperintensities had significant correlations with both homocysteine and depressive symptoms, the brain measures and total antioxidant capacity did not emerge as significant mediating variables. CONCLUSIONS: Low folic acid and high homocysteine, but not low vitamin B12 levels, are correlates of depressive symptoms in community-dwelling middle-aged individuals. The effects of folic acid and homocysteine are overlapping but distinct.

Aged↗
PubMed2005

Regional cerebral blood flow deficits in mild Alzheimer's disease using high resolution single photon emission computerized tomography.

In spite of its wide availability, single photon emission computerized tomography (SPECT) scanning is uncommonly used in the assessment of Alzheimer's disease (AD) and related dementias. In light of recent advances in scanning protocols and image analysis, SPECT needs to be re-examined as a tool in the diagnosis of dementia. A total of 18 subjects with early AD and 10 healthy elderly control subjects were examined with high resolution SPECT during the performance of a simple word discrimination task. SPECT images were coregistered with individual magnetic resonance imaging scans, allowing delineation of predetermined neuroanatomical Regions of Interest (ROI). There was a gradation of regional cerebral blood flow (rCBF) values in both groups, with the lowest values being in the hippocampus and the highest in the striatum, thalamus and cerebellum. Compared to healthy controls, AD subjects demonstrated lower relative rCBF in parietal and prefrontal cortices. Analysis of individual ROI demonstrated bilateral reduction of rCBF in prefrontal poles, posterior temporal and anterior parietal cortex, and unilateral reduction of rCBF in left dorsolateral prefrontal cortex, right posterior parietal cortex and the left cingulate body. There were no significant differences for hippocampal, occipital or basal ganglia rCBF. Discriminant function analysis indicated that rCBF in the prefrontal polar regions achieved the best classification of cases. SPECT has utility in the diagnostic assessment of AD if standardized and semiquantitative techniques are used.

Aged↗
PubMed2005

MRI hyperintensities and depressive symptoms in a community sample of individuals 60-64 years old.

OBJECTIVE: Previous studies have found associations of magnetic resonance imaging (MRI) signal hyperintensities with depression in the elderly. The present study investigates the association in a younger community sample (age 60-64 years) of depressed subjects and comparison groups for potential mediating and confounding variables. METHOD: A subsample of 475 persons 60-64 years of age from a larger community survey underwent brain MRI scans. White matter hyperintensities were quantified by using an automated procedure, and basal ganglia hyperintensities were quantified by using semiquantitative visual ratings. The study also assessed depressive symptoms and use of antidepressant medication. Potential mediating or confounding variables assessed included physical disability, hypertension, stroke, diabetes, head injury, cortisol, thyroid-stimulating hormone, cognitive functioning, smoking, and alcohol use. RESULTS: Depressive symptoms were found to be related to total brain white matter hyperintensities but not to basal ganglia hyperintensities. However, associations disappeared when statistical adjustment was made for physical disability and smoking. CONCLUSIONS: Depressive symptoms are related to white matter hyperintensities in mid-adult life in a community sample. Physical disability appears to play an important role in this association.

Age Factors↗
PubMed2004

Hippocampal and amygdalar volumes in relation to handedness in adults aged 60-64.

We evaluated the association between handedness and manual tracings of hippocampal and amygdalar volumes. Brain MRI and handedness data were obtained for 441 community dwelling participants aged 60-64 years of whom 31 were left-handed. Both absolute and normalized hippocampal volumes were larger in left-handed women than right-handed women. Hippocampal volume was not associated with handedness in men, and amygdalar volume was not associated with handedness in men or women. There was no right-left asymmetry in hippocampal or amygdalar volumes in either gender. We conclude that volumetric differences by handedness must be taken into account where hippocampal volumes are of clinical importance. Our results may also explain reports of lower rates of dementia in left-handed individuals.

Adult↗
PubMed2004

Extent and distribution of white matter hyperintensities in stroke patients: the Sydney Stroke Study.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) on T2-weighted MRI are common in stroke patients and healthy elderly individuals. The detailed anatomical distribution of these lesions in stroke patients has not been examined. METHODS: A total of 112 stroke or transient ischemic attack patients and 87 matched control subjects from the Sydney Stroke Study underwent MRI scans that included a T2-weighted fluid-attenuated inversion recovery (FLAIR) sequence. WMHs were delineated from each FLAIR MRI by an automated method. Region of interest and voxel-wise statistical parametric mapping approaches were applied to examine the volume, distribution, and severity of WMHs of the patient and control groups, and subgroups with large or lacunar infarcts. RESULTS: Stroke subjects had significantly more WMHs than controls in all brain regions except the occipital lobe and in all arterial territories except the anterior callosal and anterior medial lenticulostriate. In the frontotemporal regions, average WMH volumes in patients were >3.5x those in controls. The total number of discrete WMHs was not different in the 2 groups, but stroke patients had more large (>20 mm) and high-intensity lesions. Subjects with lacunar infarcts had more WMHs than those with large infarcts, who, in turn, had more WMHs than control subjects. Lacunar infarction subjects had more WMHs than subjects with large thromboembolic or cardioembolic strokes. Those with anterior arterial territory infarction had more WMHs in the frontal regions. Subjects with single or multiple lacunes did not differ in volumes of WMHs. CONCLUSIONS: Stroke patients have significantly more WMHs in nearly every brain region than healthy controls. Those with lacunar infarcts are particularly affected. WMHs represent a significant proportion of the ischemic lesion burden in stroke and transient ischemic attack patients.

Aged↗