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Biomedical subjects

C DeCarli

Publications and source records attributed to C DeCarli.

At least 55 records · Page 3Linked to original sources

Correlation between computed tomographic brain scan abnormalities and neuropsychological function in children with symptomatic human immunodeficiency virus disease.

OBJECTIVE: To evaluate the clinical significance of computed tomographic brain scan abnormalities observed in children with symptomatic human immunodeficiency virus disease. PATIENTS: Eighty-seven previously untreated children with symptomatic human immunodeficiency virus type 1 disease. METHODS: General levels of cognitive functioning, obtained from age-appropriate intelligence tests, and social-emotional behavior were correlated with computed tomographic brain scan abnormality ratings. RESULTS: A significant relation between computed tomographic brain scan abnormalities and cognitive dysfunction as well as aberrant behavior was found, which appeared stronger in (younger) vertically infected children compared with transfusion-infected patients. Calcifications, independent from the degree of brain atrophy, were associated with significantly greater delays in neurocognitive development. CONCLUSION: Computed tomographic brain scan abnormalities, even when mild, were of clinical significance, suggesting that human immunodeficiency virus-associated central nervous system compromise is a continuous process and that scans may be helpful at baseline in defining patients at risk and for monitoring them during therapy.

Brain↗

Relation between stage of disease and neurobehavioral measures in children with symptomatic HIV disease.

OBJECTIVE: To study the relationships between stage of HIV disease, reflected by CD4+ lymphocyte percentages and p24 antigen levels, and HIV-associated central nervous system (CNS) abnormalities, measured by computed tomography (CT) brain-scan ratings and neurobehavioral tests. DESIGN: Consecutive case series. SETTING: Government medical research center. PATIENTS: Eighty-six previously untreated children with symptomatic HIV-1 disease. RESULTS: CD4% measures correlated significantly with overall CT brain-scan severity ratings (r = -0.45; P < 0.001) as well as with its component parts (cortical atrophy, white matter abnormalities, and intracerebral calcifications); they were of comparable magnitude for vertically and transfusion-infected children. CD4% measures were also associated with the general level of cognitive function (r = 0.32; P < 0.005). Furthermore, patients with detectable serum p24 antigen levels (n = 39) had CT brain scans that were more abnormal than patients with undetectable p24 levels (n = 20; CT abnormality ratings of 21.3 versus 35.9; P < 0.02); similar differences were found for the cortical atrophy and calcification ratings. p24 levels also correlated with the overall CT brain-scan severity rating (r = 0.34; P < 0.01). CONCLUSIONS: Degree of CT brain-scan abnormality and level of cognitive dysfunction were significantly associated with the stage of HIV-1 disease, as reflected by either CD4 leukocyte measures or elevations of p24 antigen. The relation between the CT brain-scan lesions and markers of HIV disease (both CD4 and p24) suggest that these CNS abnormalities are most likely associated with HIV-1 infection, and further support the hypothesis that the interaction between systemic disease progression and CNS manifestations is continuous rather than discrete.

AIDS Dementia Complex↗

Changes in the amount of diseased white matter over time in patients with relapsing-remitting multiple sclerosis.

MRI is a sensitive technique for assessing disease activity in MS. Diseased white matter (WM) can be identified on T2-weighted images, and active disease is reflected by abnormalities in the blood-brain barrier (BBB) shown on T1-weighted images after administration of paramagnetic contrast agents. Active disease may be demonstrated by contrast-enhanced MRI in patients with early, mild relapsing-remitting (RR) MS even during periods of clinical stability, which indicates that MS is an active process even during the early phase of the illness. To examine the amount of abnormal WM at frequent intervals over time, we studied seven mildly affected RRMS patients, all of whom had frequent contrast-enhancing lesions. These RRMS patients were imaged monthly for 26 to 36 months at 1.5 tesla; the area of abnormal increased WM signal was calculated by image-processing software that utilizes both the T2- and T1-weighted images. All patients showed fluctuations over time in amount of abnormal WM signal, which reflected factors such as the amount of BBB breakdown (measured by number or area of enhancing lesions) and measurement error. All seven RRMS patients, however, showed an overall increase in abnormal WM. Because of the fluctuations between individual measurements, the increase was most accurately reflected when the mean of the first 6 months' measurements was compared with the mean of the final 6 months' measurements, or when a linear regression model was applied.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults.

OBJECTIVE: To assess the association of MRI white matter hyperintensities (WMHI) with cognitive performance, cerebral structure, and cerebral metabolism in 51 healthy individuals aged 19 to 91 years without cerebrovascular risk factors. BACKGROUND: Abnormal white matter signals have been associated with brain atrophy, reduced cerebral blood flow, focal neurologic signs, gait disorder, and poorer neuropsychological test performance. Most studies of WMHI, however, include subjects with hypertension or other identifiable causes of cerebrovascular disease that may have an independent effect on brain structure and function. To assess brain changes associated with WMHI independent of cerebrovascular risk factors, we determined WMHI volume, brain volume, cerebral metabolism, and cognitive performance for a group of subjects free of medical illness. Regional cerebral metabolism and cognitive domains were also assessed to evaluate the possible role of frontal lobe dysfunction in subjects with WMHI. DESIGN: Cross-sectional study of 51 very healthy subjects aged 19 to 91 years. METHODS: WMHI, brain, and CSF volumes were determined by MRI segmentation. Neuropsychological tests were employed to assess multiple cognitive domains. Brain metabolism was determined from 18-fluoro-2-deoxy-D-glucose PET. Multivariate relations were tested with stepwise linear regression. Models included the potential confounders of age and education where appropriate. RESULTS: The distribution of WMHI volume was bimodal, with five subjects having WMHI volumes beyond three SDs from the normally distributed population. A WMHI volume of greater than 0.5% of intracranial volume was considered abnormal. Within the multivariate models, WMHI volumes were significantly predictive of increased ventricular volume, reduced brain volume, and reduced cognitive scores. Subjects with greater than 0.5% WMHI volume also had significantly lower frontal lobe metabolism, significantly higher systolic blood pressure, significantly larger ventricular volume, and significantly lower scores on frontal lobe-mediated neuropsychological tests than age-matched controls. CONCLUSION: WMHI volume is associated with structural and functional brain changes even within a group of very healthy individuals. WMHI is associated with poorer frontal lobe cognitive function and, when severe, is accompanied by significantly reduced frontal lobe metabolism. Subjects with large WMHI volumes have significantly higher systolic blood pressure, brain atrophy, reduced cerebral metabolism, and lower scores on tests of frontal lobe function than age-matched controls. Large amounts of WMHI are, therefore, pathologic and may be related to elevated systolic blood pressure even when it is within the normal age-related range.

Adult↗

Use of positron emission tomography for the evaluation of epilepsy.

After a brief introduction to the theoretic aspects of positron emission tomography, four areas of positron emission tomography research are discussed with an emphasis on current concepts and future directions. The use of positron emission tomography as a tool for the localization of the pathologic brain region and as a predictor of surgical outcome in focal epilepsy is reviewed and compared with the sensitivity, specificity, and outcome predicted by other neuroimaging techniques. Research on positron emission tomography measures of regional metabolism, bloodflow, and neuroreceptors is reviewed from the perspective of epileptic pathophysiology with a special emphasis on elucidative integrative neural circuits involved in epileptic spread and termination. A brief review and discussion of the use of positron emission tomography for the understanding of potential neural reorganization of cognitive processes in epilepsy follows. In the final section, an overview of recently developed methods of positron emission tomography data analysis with a focus on application to research questions in epilepsy is presented.

Brain↗

Interrelations among patterns of change in neurocognitive, CT brain imaging and CD4 measures associated with anti-retroviral therapy in children with symptomatic HIV infection.

The interrelationships of patterns of change and variability between baseline and after 6 months of anti-retroviral therapy in neurocognitive, brain imaging, and immune measures were studied in 77 children with symptomatic HIV disease. Overall improvement in CNS structure/function after 6 months of anti-retroviral therapy was limited; new intracerebral calcifications tended to occur and old ones tended to progress in young children with vertically acquired HIV infection, despite treatment. Substantial inter-individual differences in change were however observed. Factors which explained part of the variance in the magnitude and direction of change were baseline structural and functional abnormalities, rating of degree of CNS penetration of the drug protocol, and concurrent changes on other variables. These preliminary data suggest that CNS specific effects of therapies as well as pretreatment status of CNS function/structure need to be taken into consideration when evaluating future trials of anti-retroviral therapy for children with symptomatic HIV infection.

AIDS Dementia Complex↗

Three-dimensional echo-planar MR spectroscopic imaging at short echo times in the human brain.

PURPOSE: To demonstrate the feasibility of three-dimensional echo-planar spectroscopic imaging (EPSI) at short echo time (13 msec) with a conventional clinical imager in the human brain. MATERIALS AND METHODS: Periodic inversions of a readout gradient were used during data acquisition to simultaneously encode chemical shift and one spatial dimension in one excitation. Aliasing artifacts were avoided with a modified acquisition-and-processing method based on oversampling. A double outer-volume suppression technique that adapts to the ovoid brain shape was used to strongly reduce extracranial lipid resonances. RESULTS: Three-dimensional spatial encoding in vivo of eight sections with 32 x 32 voxels each (0.75 cm3) was performed in 34 minutes with four signal averages. The spectral resolution and signal-to-noise ratio (S/N) of resonances of inositol, choline, creatine, glutamate and glutamine, and N-acetyl aspartate were consistent with those previously recorded with conventional phase encoding. CONCLUSION: EPSI substantially reduces acquisition time for three-dimensional spatial encoding and yields a spectral quality similar to that obtained with conventional techniques without affecting the S/N per unit time and unit volume.

Aspartic Acid↗

Lack of age-related differences in temporal lobe volume of very healthy adults.

PURPOSE: To evaluate age-related differences in temporal and supratemporal brain regions in carefully selected, very healthy men 19 to 92 years of age. METHODS: MR quantification of brain regions used image segmentation into cerebrospinal fluid and brain matter based on nonlinear modeling of pixel intensity distributions. RESULTS: There was a significant age-related decrease (approximately 1% per decade) of posterior frontal lobe volume, but not of temporal lobe volume. The mean volume of the right temporal lobe was significantly greater than the left, and this relation did not change with age. CONCLUSION: In very healthy aging, the volume of the temporal lobes remains constant over the age range of human life.

Adult↗

X-chromosome effects on female brain: a magnetic resonance imaging study of Turner's syndrome.

Many neuropsychiatric disorders differ between the sexes in incidence, symptoms, and age at onset. To investigate the effects of X-chromosome aneuploidy and of sex steroid deficiency during childhood on brain structure and function, we used neuropsychological tests and quantitative magnetic resonance imaging (MRI) to study the brains of eighteen women with Turner's syndrome (TS) and nineteen healthy control women of similar age. Nine TS subjects had mosaic 45,X karyotypes, and 9 had non-mosaic 45,X. The TS group had significantly lower scores than the controls for all the Wechsler adult intelligence scale tests, except verbal comprehension and reading level. The greatest difference was in visuospatial construction (mean 90 [SD12] vs 118 [13], p < 0.0001). The TS subjects also had a greater discrepancy than controls between verbal and performance intelligence quotients (9 [8] vs -5 [9], p < 0.001). We found that TS subjects had significantly smaller values than controls in MRI-measured volumes of hippocampus, caudate, lenticular, and thalamic nuclei, and parieto-occipital brain matter, on both sides. Women with mosaic TS had values between the full TS and control groups for cerebral hemisphere and lenticular and thalamic nuclei volume and for verbal ability. Within the mosaic TS group, visuospatial ability was significantly correlated with the percentage of lymphocytes that had the 45,X karyotype. Hippocampal volume and memory test scores were significantly lower in mosaic and non-mosaic 45,X TS subjects than in controls. We postulate that in human beings the X chromosome plays an important part in the development and ageing of grey matter in striatum, diencephalon, and cerebral hemispheres.

Adult↗

An in vivo study of phosphorus and glucose metabolism in Alzheimer's disease using magnetic resonance spectroscopy and PET.

OBJECTIVES: To study phosphorus and glucose metabolism in whole-brain slices of otherwise healthy patients with dementia of the Alzheimer type (DAT) and healthy controls. DESIGN: We used proton nuclear magnetic resonance imaging phosphorus spectroscopy and positron emission tomography to study in vivo brain phosphorus and glucose metabolism. PATIENTS: Whole-brain slice phosphorus metabolism was studied in nine drug free patients with mild to moderately severe dementia of the Alzheimer type (DAT) and in eight age- and sex-matched healthy controls. Mean ages (+/- SD) of the patients and controls were 60 +/- 10 years and 64 +/- 16 years, respectively. Positron emission tomography was used to study cerebral glucose metabolism in seven of the patients with DAT and seven of the healthy controls. RESULTS: Patients with DAT had significant brain glucose hypometabolism compared with controls, but there was no significant group difference in any phosphorus metabolite concentration or ratio in the same volume of brain tissue. Also, within patients with DAT there was no correlation between any phosphorus metabolite concentration or ratio and either severity of dementia or glucose metabolism. CONCLUSIONS: We suggest glucose metabolism is reduced early in DAT (reflecting decreased basal synaptic functioning) and is unrelated to a rate limitation in glucose delivery, abnormal glucose metabolism, or abnormal coupling between oxidation and phosphorylation. Normal or near-normal levels of phosphorus metabolites are maintained in mild, moderate, and severe DAT. Therefore, altered high-energy phosphate levels are not a consequence of reduced glucose metabolism in DAT, and do not play a major role in the pathophysiology of the disorder, at least in whole-brain sections.

Aged↗

The prevalence of computed tomographic abnormalities of the cerebrum in 100 consecutive children symptomatic with the human immune deficiency virus.

Qualitative analysis of 100 consecutive computed tomographic (CT) studies of the brain in children with symptomatic but untreated acquired immunodeficiency syndrome was performed. After excluding children with associated medical illnesses that might confound the diagnosis of encephalopathy or alter brain structure, an abnormality of at least one of the measures of ventricular size, cortical atrophy, white matter attenuation (leukoaraiosis), or cerebral calcification was found in 86% of the patients studied. Ventricular enlargement was the most common abnormality, followed by cortical atrophy, leukoaraiosis, and cerebral calcification. Cerebellar atrophy was an unexpected but relatively common finding in 12% of the children. Sixty-five percent of the children were encephalopathic at the time of evaluation. All 16 children with cerebral calcification were encephalopathic and had acquired human immunodeficiency virus (HIV) through vertical transmission. Encephalopathic children were significantly younger and had significantly greater abnormality ratings on each CT measure when compared with the nonencephalopathic children. Discriminant analysis using age and the qualitative CT measures was applied as a method to identify the presence of encephalopathy. CT measures proved to have a specificity and a sensitivity of only 76%. We conclude that abnormalities of cerebral structure are seen in a high percentage of children symptomatic with HIV. Although most of the children are encephalopathic, CT abnormalities are seen in children without encephalopathy, suggesting presymptomatic brain disease. The presence of cerebral calcification on CT suggests in utero infection with HIV and the presence of encephalopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex↗

Reductions in parietal and temporal cerebral metabolic rates for glucose are not specific for Alzheimer's disease.

Reduction in the regional cerebral metabolic rate for glucose (rCMRglc) in the parietal and temporal regions has been shown in Alzheimer's disease (AD). The specificity of these findings for this disease state is uncertain. We repeatedly measured rCMRglc with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose in the resting state in a 68 year old man with slowly progressive dementia who, during life, was initially diagnosed as having dementia of the Alzheimer type, then Parkinson disease with dementia, but was found to have only Parkinson's disease at necropsy. Metabolic ratios (rCMRglc/mean grey CMRglc) were significantly (p < 0.05) reduced in parietal and temporal regions, as well as in the prefrontal and premotor areas. This pattern was similar in regional distribution and magnitude of the defect to that seen in patients with probable AD. These results suggest that reductions of glucose metabolism in association neocortex in AD are not specific to the disease process, but may be related to the dementia state.

Aged↗

Gender differences in correlations of cerebral glucose metabolic rates in young normal adults.

Correlational analysis of normalized regional cerebral metabolic data obtained by positron emission tomography, in healthy subjects in the 'resting' state (eyes covered, ears plugged) using [18F]2-fluoro-2-deoxy-D-glucose, demonstrated gender differences in patterns of functional associations. Fifteen women and 18 men (less than 40 yr) were scanned with a Scanditronix PC1024-7B tomograph. The brain was divided into 65 regions of interest (ROIs). There were no differences between men and women in global or regional metabolic rates, or in metabolic right-left asymmetries. Although the total number of significant correlations did not differ between men and women, patterns differed: female correlations rF were most positive than male correlations rM more often than rM greater than rF; and most rF greater than rM cases involved left frontal and sensorimotor ROIs, whereas most rM greater than rF cases involved right sensorimotor and occipital ROIs. The findings demonstrate gender differences in the pattern of functional neocortical interactions at the 'resting' state.

Adult↗

Age-related differences in volumes of subcortical nuclei, brain matter, and cerebrospinal fluid in healthy men as measured with magnetic resonance imaging.

Magnetic resonance imaging was used to determine the volumes of brain, subcortical gray matter nuclei, and the ventricular and sulcal cerebrospinal fluid in 27 healthy men. Subjects were divided into young (less than 35 years, n = 10) and old (greater than 60 years, n = 17) groups. Volumes were normalized as percent intracranial volume. Older subjects had significantly less brain mass and significantly larger ventricular and peripheral cerebrospinal fluid volumes than the younger men. The caudate and lenticular nuclei were significantly smaller in older than younger men. This significant difference remained when their volumes were expressed as a ratio of cerebral brain matter volume. This cross-sectional study demonstrates age-related atrophy and concurrent dilation of cerebrospinal fluid spaces in healthy subjects. Of brain regions affected, the caudate and lenticular nuclei are significantly more affected by healthy aging than is cerebral brain matter; this may account for some of the motor abnormalities in aging.

Adult↗

The significance of age-related enlargement of the cerebral ventricles in healthy men and women measured by quantitative computed X-ray tomography.

OBJECTIVE: (1) To establish the range of cerebral atrophy across the adult age spectrum in optimally healthy, rigorously evaluated individuals. (2) To determine, across the age spectrum, the relation of gender and cerebral atrophy (as measured by ventricular enlargement) to cognitive function. DESIGN: Cross-sectional comparison by age and gender. SETTING: Ambulatory research unit. PARTICIPANTS: Sixty-four healthy men (mean age +/- SD = 49 +/- 18 yr) and 43 healthy women (51 +/- 18 yr) volunteers enrolled in a longitudinal study of healthy aging. The population was selected for optimal health; all were rigorously screened to exclude medical and psychiatric illness. MAIN OUTCOME MEASURES: Brain atrophy by CT scan and cognitive function by standardized neuropsychological testing. RESULTS: After correction for inter-subject variability in cranial volume, women had smaller lateral, but not third, ventricles. For both genders, there were significant differences with age in ventricular volume. After an approximately constant 20% increase in ventricular volume per decade in both genders, a precipitous increase in volume was found beginning in the fifth decade in men and in the sixth decade in women. In men and women, there was a significant negative correlation between ventricular volume and the sum of performance scale scores on the Wechsler Adult Intelligence Scale (WPSS) but not in the sum of the verbal scale scores (WVSS). However, after controlling for age, ventricular volume no longer significantly contributed to the relation between age and WPSS. CONCLUSIONS: In unequivocally healthy individuals, gender plays an important role in age-associated central cerebral atrophy as measured by progressive ventricular enlargement. Increase in ventricle volume independent of age, does not explain normal age-related declines seen in WPSS scores.

Adult↗

Brain atrophy in hypertension. A volumetric magnetic resonance imaging study.

To determine whether hypertension, the predominant risk factor for stroke and vascular dementia, is associated with brain atrophy, magnetic resonance imaging (MRI) scans were performed to quantify brain volumes and cerebrospinal fluid spaces. Eighteen otherwise healthy, cognitively normal older hypertensive men (mean +/- SD age, 69 +/- 8 years, duration of hypertension 10-35 years) and 17 age-matched healthy, normotensive male control subjects were studied in a cross-sectional design. Axial proton-density image slices were analyzed using region-of-interest and segmentation analyses. The hypertensive subjects had significantly larger mean volumes of the right and left lateral ventricles (p less than 0.05, both absolute volume and volume normalized to intracranial volume) and a significantly smaller normalized mean left hemisphere brain volume (p less than 0.05) with a trend toward significance for a smaller normalized mean right hemisphere volume (p less than 0.09). Four hypertensive subjects and one healthy control subject were found to have severe periventricular hyperintensities on T2-weighted MRI images. When data for these subjects were removed from the analyses, the normalized lateral ventricle volumes remained significantly larger in the hypertensive group. Lateral ventricle enlargement was not related to age or use of diuretics in the hypertensive group nor to duration of hypertension between 10 and 24 years. Our findings suggest that long-standing hypertension results in structural changes in the brain. Longitudinal studies will determine whether MRI-associated changes are progressive and if such changes identify hypertensive subjects at increased risk for clinically apparent brain dysfunction.

Adult↗

Longitudinal changes in lateral ventricular volume in patients with dementia of the Alzheimer type.

We determined the rates of lateral ventricular enlargement and decline in cognitive performance for 11 men and nine women with dementia of the Alzheimer type (DAT), and compared these rates with the same measures obtained for age-matched healthy controls (nine men and eight women). DAT patients, as a group, had only mild cognitive impairment at initial evaluation, and each patient was followed from 9 months to over 7 years with yearly evaluations. Six DAT patients had isolated memory impairment as their only cognitive deficit early in the course of the disease. The rate of total lateral ventricle enlargement (cm3/yr) was significantly different between DAT and healthy controls, and was more specific and sensitive to the diagnosis of DAT than comparison of cross-sectional volumes at final evaluation. The rate of total lateral ventricular enlargement did not differ significantly by patient sex, ventricular size at initial evaluation, age, or degree of cognitive impairment as measured by Mini Mental State Examination scores. However, in the six DAT patients initially found to have isolated memory impairment, the rate of ventricular enlargement during the period of isolated memory impairment was significantly less than the rate of ventricular enlargement after the onset of nonmemory cognitive impairment. The diagnostic power of total lateral ventricular measures made from two CTs separated by 1 year and obtained early in the course of the illness, however, was only 0.33. We conclude that the total lateral ventricular enlargement accompanying DAT is due to continuous, pathologic cell loss, significantly greater than cell loss due to the healthy aging process.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗