Search PubMed⌕ Search

Biomedical subjects

E V Sullivan

Publications and source records attributed to E V Sullivan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Magnetic resonance relaxometry reveals central pontine abnormalities in clinically asymptomatic alcoholic men.

BACKGROUND: Central pontine myelinolysis (CPM) is a rare, debilitating, life-threatening condition, associated with chronic alcoholism, rapid correction of hyponatremia, and advanced age. It is unknown, however, whether older alcoholic patients who by age and diagnosis are at risk for CPM have objectively determined neuroimaging evidence of preclinical CPM that could be valuable in understanding its development and in initiating appropriate treatment. Accordingly, we examined central pontine magnetic resonance (MR) transverse relaxation time (T2), which reflects myelin and axonal integrity when measured in white matter and is prolonged with pathology that causes increased free water content in tissue. METHODS: The subjects were 46 alcoholic men who were abstinent from alcohol for about 1 month and were asymptomatic for CPM, 9 men and 1 woman with alcoholic Korsakoff's syndrome (KS), and 74 healthy control men. All subjects received coronally acquired dual-echo MR imaging (MRI), from which T2 times were calculated in central pons. MRI films were read clinically and independently of relaxometry results. Hematological and neuropsychological data were also available for many subjects. RESULTS: Only the KS group showed prolonged T2 times; however, pontine T2 prolongation increased significantly with older age in the asymptomatic alcoholics but not controls. Clinical radiological readings detected pontine signal hyperintensity in five KS subjects (two without dementia and three with dementia), one control, and no alcoholic patient. Hematologic indexes of macrocytic anemia and nutritional deficiency and neuropsychological measures of verbal and nonverbal fluency correlated with prolonged T2 times in alcoholic men. CONCLUSIONS: This CPM-like condition, manifest as prolonged T2, may occur with higher incidence than previously thought in clinically asymptomatic alcoholism and may contribute to neuropsychological compromise of initiation and production. Preclinical detection of abnormal pontine signal properties with MR relaxometry may identify patients at high risk for developing CPM.

Adult↗
PubMed2000

Alpha2 macroglobulin and the risk of Alzheimer's disease.

BACKGROUND: alpha2 Macroglobulin is a panproteinase inhibitor that is found immunohistochemically in neuritic plaques, a requisite neuropathologic feature of AD. Recently, a pentanucleotide deletion near the 5' end of the "bait region" of the alpha2 macroglobulin (A2M) gene was reported to be associated with AD in a large cohort of sibpairs, in which the mutation conferred a similar odds ratio with AD as the APOE-epsilon4 allele for carriers of at least one copy of the A2M gene (Mantel-Haenszel odds ratio, 3.56). METHODS: We studied three independent association samples of AD patients (n = 309) with an age range of 50 to 94 years and representative controls (n = 281) to characterize the allele frequency of the pentanucleotide deletion in this cohort. We detected the mutation near the 5' splice site of exon 18 using standard PCR and restriction fragment length polymorphism methods. The results were adjusted for age, gender, education, and APOE polymorphism. RESULTS: We found that the A2M gene polymorphism conferred an increased risk for AD, with an estimated Mantel-Haenszel ratio of 1.5 (95% CI 1.1 to 2.2; p = 0.025). There was no age- or gender-dependent increase in A2M gene allele frequencies in AD patients compared with controls. The combined sample showed the expected association between AD and APOE-epsilon 4. In one of our three samples there was an interaction between the A2M and APOE-epsilon4 genes, but the other two samples showed no interaction between the two risk factors. CONCLUSIONS: Our data support an association between the A2M gene and AD. This association is less pronounced, however, in our cohort than in the previously reported sample of sibpairs.

Aged↗
PubMed2000

Contribution of alcohol abuse to cerebellar volume deficits in men with schizophrenia.

BACKGROUND: It is controversial whether cerebellar tissue volume deficits occur in schizophrenia and, if so, what regions and tissue types are affected. Complicating such investigations is the high incidence of alcoholism comorbidity in patients with schizophrenia that itself can contribute to cerebellar abnormalities. METHOD: We studied 61 healthy men (control subjects), 25 men with alcoholism, 27 men with schizophrenia, and 19 men comorbid for schizophrenia and alcoholism with the use of magnetic resonance imaging. Cerebellar structures were outlined manually, tissue classification was determined statistically, and regional volumes were corrected for normal variation in head size and age. RESULTS: Patients with schizophrenia alone had enlarged fourth ventricles (1.5 SD relative to controls) but showed no cerebellar tissue volume deficits. The alcoholic group had gray and white matter vermian deficits (-0.5 SD), most prominent in anterior superior lobules, and gray matter hemisphere deficits (-0.8 SD), but not fourth ventricle enlargement. The comorbid group had cerebellar hemisphere (-1.3 SD) and vermian gray matter volume deficits (-0.7 SD) and fourth ventricular enlargement (1.6 SD); these abnormalities were greater than in either single-diagnosis group, despite significantly lower levels of alcohol consumption compared with the alcoholic group. Gray matter volume in the anterior superior vermis correlated with lifetime alcohol consumption in the schizophrenic and comorbid groups when combined. CONCLUSIONS: Cerebellar tissue volume deficits were detected in schizophrenia only when accompanied by alcoholism. By contrast, fourth ventricular enlargement occurred in schizophrenia even without alcoholism, although it was exacerbated by alcoholism. These findings support a model of cerebellar supersensitivity to alcohol-related tissue volume deficits in schizophrenia.

Adult↗
PubMed2000

Age-related decline in brain white matter anisotropy measured with spatially corrected echo-planar diffusion tensor imaging.

Echo planar (EP) diffusion tensor imaging (DTI) permits in vivo identification of the orientation and coherence of brain white matter tracts but suffers from field inhomogeneity-induced geometric distortion. To reduce spatial distortion, polynomial warping corrections were applied and the effects tested on measures of fractional anisotropy (FA) in the genu and splenium of corpus callosum. Implementation entailed spatially warping EP images obtained without diffusion weighting (b = 0) to long-echo T(2)-weighted fast spin echo images, collected for anatomical delineation, tissue segmentation, and coregistration with the diffusion images. Using the optimal warping procedure (third-order polynomial), the effects of age on FA and a quantitative measure of intervoxel coherence (C) in the genu, splenium, centrum semiovale, and frontal and parietal pericallosal white matter were examined in 31 healthy men (23-76 years). FA declined significantly with age in all regions except the splenium, whereas intervoxel coherence positively correlated with age in the genu. Magn Reson Med 44:259-268, 2000.

Adult↗
PubMed2000

Extent, pattern, and correlates of remote memory impairment in Alzheimer's disease and Parkinson's disease.

Content and contextual memory for remote public figures and events was assessed with a modified version of the Presidents Test in patients with Alzheimer's disease (AD) or Parkinson's disease (PD). Contributions of executive functioning, semantic memory, and explicit anterograde memory to remote memory abilities were also examined. The AD group had temporally extensive deficits in content and contextual remote memory not accountable for by dementia severity. The PD group did not differ from the control group in remote memory, despite anterograde memory impairment. These results support the position that different component processes characterize remote memory, various mnemonic and nonmnemonic cognitive processes contribute to remote memory performance, and anterograde and remote memory processes are dissociable and differentially disrupted by neurodegenerative disease.

Aged↗
PubMed2000

Cerebellar volume decline in normal aging, alcoholism, and Korsakoff's syndrome: relation to ataxia.

The authors used magnetic resonance imaging to measure gray and white matter volumes in cerebellar hemispheres and 4 vermian regions in 61 normal control (NC) men aged 23-72 years, 25 men with uncomplicated alcoholism (ALC), and 8 men and 1 woman with alcoholic Korsakoff s syndrome (KS). NC and ALC took quantitative gait and balance tests. Gray but not white matter volume declined with normal age in both hemispheres and anterior-superior vermis. ALC had gray but not white matter cerebellar hemisphere volume deficits, whereas KS had deficits in both tissue types. ALC and KS had gray and white matter volume deficits in anterior superior but not posterior inferior vermis. ALC had a 1 SD ataxia deficit, significantly and selectively correlated with white matter volume in anterior superior vermis. Regional distribution but not severity of cerebellar volume deficits is similar in alcoholic individuals whether or not complicated by KS and relates to ataxia.

Adult↗
PubMed2000

Sniffing longer rather than stronger to maintain olfactory detection threshold.

Air flow-rate is usually higher in one nostril in comparison to the other. Also, within bounds, higher nasal flow-rate improves odorant detection. It follows from the above that odorant detection should be better in the nostril with higher flow-rate in comparison to the nostril with lower flow-rate. Paradoxically, previous research has shown that odorant detection thresholds are equal for the high and low flow-rate nostrils. Here we resolve this apparent paradox by showing that when detecting through the nostril with lower air flow-rate, humans sniffed longer than when detecting through the nostril with higher air flow-rate, thus equalizing performance between the nostrils. When this compensatory mechanism was blocked, a pronounced advantage in odorant detection was seen for the nostril with higher air flow-rate over the nostril with lower air flow-rate. Finally, we show that normal birhinal sniff duration may enable only one nostril to reach optimal threshold. This finding implies that during each sniff, each nostril conveys to the brain a slightly different image of the olfactory world. It remains to be shown how the brain combines these images into a single olfactory percept.

Adult↗
PubMed2000

Time course of odorant-induced activation in the human primary olfactory cortex.

Paradoxically, attempts to visualize odorant-induced functional magnetic resonance imaging (fMRI) activation in the human have yielded activations in secondary olfactory regions but not in the primary olfactory cortex-piriform cortex. We show that odorant-induced activation in primary olfactory cortex was not previously made evident with fMRI because of the unique time course of activity in this region: in primary olfactory cortex, odorants induced a strong early transient increase in signal amplitude that then habituated within 30-40 s of odorant presence. This time course of activation seen here in the primary olfactory cortex of the human is almost identical to that recorded electrophysiologically in the piriform cortex of the rat. Mapping activation with analyses that are sensitive to both this transient increase in signal amplitude, and temporal-variance, enabled us to use fMRI to consistently visualize odorant-induced activation in the human primary olfactory cortex. The combination of continued accurate odorant detection at the behavioral level despite primary olfactory cortex habituation at the physiological level suggests that the functional neuroanatomy of the olfactory response may change throughout prolonged olfactory stimulation.

Adult↗
PubMed2000

Structural brain correlates of verbal and nonverbal fluency measures in Alzheimer's disease.

This study examined the relationships between regional brain volumes and semantic, phonological, and nonverbal fluency in 32 participants with Alzheimer's disease (AD). Object but not animal semantic fluency correlated with frontal and temporal gray matter volumes. Phonological fluency was not significantly associated with any brain volume examined. Nonverbal fluency was selectively associated with bilateral frontal gray matter volumes. Hippocampal volumes, although markedly reduced in these patients, were not related to any of the fluency measures. Results lend evidence to the importance of the frontal lobes in the directed generation of nonverbal and verbal exemplars by AD patients. Furthermore, both left- and right-hemisphere regions contribute to the generation of verbal and nonverbal exemplars.

Adult↗
PubMed2000

Longitudinal changes in cognition, gait, and balance in abstinent and relapsed alcoholic men: relationships to changes in brain structure.

Chronic alcoholism is associated with cognitive and motor deficits, and there is evidence for reversibility with sobriety. Alcoholic men were examined after 1 month of sobriety and 2 to 12 months later with cognitive and motor tests and magnetic resonance imaging. In this naturalistic study, 20 alcoholic participants had abstained and 22 had resumed drinking at retesting. Abstainers sustained greater improvement than relapsers on tests of delayed recall of drawings, visuospatial function, attention, gait, and balance. Shrinkage in 3rd ventricle volume across all participants significantly correlated with improvement in nonverbal short-term memory. Additional brain structure-function relationships, most involving short-term memory, were observed when analyses were restricted to alcoholic men who had maintained complete abstinence, were light relapsers for at least 3 months, or had consumed no more than 10 drinks prior to follow-up testing. Thus, alcoholic men who maintain abstinence can show substantial functional improvement that is related to improvement in brain structure condition.

Adult↗
PubMed2000

Pattern of motor and cognitive deficits in detoxified alcoholic men.

BACKGROUND: Chronic excessive consumption of alcohol produces marked deficits in cognitive and motor abilities, although not all functions are affected to the same extent. Furthermore, although the occurrence of neuropsychological deficits in recently detoxified alcoholics is firmly established, the relative severity of these deficits, the specific neural systems that underlie the deficits, and their relationship to age and alcohol consumption variables either are less established or have proven elusive altogether. METHODS: We administered an extensive battery of neuropsychological tests, chosen for their known sensitivity to brain lesions in specific locations, to 71 recently (1 month) detoxified alcoholic men and 74 healthy controls who spanned the adult age range. Test scores were standardized to the controls for age and grouped a priori into composites that reflected performance in six functional domains: executive functions, short-term memory, upper limb motor ability, declarative memory, visuospatial abilities, and gait and balance. Analogous verbal and nonverbal materials and left- and right-hand upper limb motor tasks were used to test whether alcohol-related deficits were greater for left or right hemisphere. RESULTS: Compared with controls, the alcoholics were impaired on executive functions, visuospatial abilities, and gait and balance even after we accounted for group differences in estimated premorbid IQ and education. Within the alcoholic group, the most salient deficits were in gait and balance and visuospatial abilities. No consistent lateralized deficit was observed across the four domains tested. Unlike the cognitive composites, the upper limb motor ability and gait and balance composites both showed increasing vulnerability to age, with an independent contribution to the gait and balance dysfunction from the amount of alcohol consumed over a lifetime. CONCLUSIONS: The pattern of functional deficits implicates at least two principal neural systems: the cerebellar-frontal system and the corticocortical system between the prefrontal and parietal cortices. In addition, age and amount of alcohol consumption were better predictors of motor than cognitive impairments.

Adult↗
PubMed2000

In vivo detection and functional correlates of white matter microstructural disruption in chronic alcoholism.

BACKGROUND: Postmortem studies report degradation of brain white matter microstructure in chronic alcoholism, but until recently, in vivo neuroimaging could provide measurement only at a macrostructural level. The development of magnetic resonance diffusion tensor imaging (DTI) for clinical use offers a method for depicting and quantifying the diffusion properties of white matter expressed as intravoxel and intervoxel coherence of tracts and fibers. METHODS: This study used DTI to examine the intravoxel coherence measured as fractional anisotropy (FA) and intervoxel coherence (C) of white matter tracts of the genu and splenium of the corpus callosum and of the centrum semiovale in 15 detoxified alcoholic men and 31 nonalcoholic control subjects. Exploratory correlational analyses examined the relationships between regional DTI measures and tests of attention and working memory in the alcoholic patients. RESULTS: The alcoholic group had lower regional FA than the control group. C was lower in the alcoholics than controls in the splenium only. Working memory correlated positively with splenium FA, whereas attention correlated positively with genu C. CONCLUSIONS: These results provide in vivo evidence for disruption of white matter microstructure in alcoholism and suggest that interruption of white matter fiber coherence contributes to disturbance in attention and working memory in chronic alcoholism.

Adult↗
PubMed1999

Cortical gray matter deficit in patients with bipolar disorder.

BACKGROUND: cortical gray matter volume deficit and ventricular enlargement are well documented in schizophrenia, but their presence in bipolar disorder is less well established. METHODS: global cortical gray matter, white matter and sulcal CSF, as well as lateral and third ventricular volume measures, were derived from axial MRI brain images obtained on age-matched bipolar (n=9), schizophrenic (n=9), and control (n=16) subjects. All subjects were free of history of alcohol or other substance dependence. RESULTS: relative to controls, bipolar patients had widespread volume deficits of cortical gray matter but not of cortical white matter. Schizophrenic patients had an even more severe cortical gray matter deficit and greater sulcal and lateral ventricular enlargement than the bipolar patients. CONCLUSIONS: this group of patients with bipolar disorder had a widespread deficit of cortical gray matter similar to, but less pronounced than, that observed in patients with schizophrenia.

Adult↗
PubMed1999

Brain gray and white matter transverse relaxation time in schizophrenia.

Recent in vivo diffusion brain imaging studies of schizophrenic patients have revealed microstructural abnormalities, with low diffusion anisotropy present throughout much of cortical white matter. Brain anisotropy is produced when proton movement reflects physically restricted water movement, for example, by myelin sheaths. Conditions that increase self-diffusion, such as edema, may also alter the longitudinal and transverse relaxation time of protons, and it is possible that such changes could explain the observed anisotropy diminution seen in schizophrenia. To test this possibility, we calculated pixel-by-pixel transverse relaxation time (T2) and proton density (PD) maps for gray matter and white matter across eight 5-mm-thick axial slices of fast spin echo MRI in 10 control men (age 30-57 years) and 10 men with schizophrenia (age 32-64 years). Schizophrenics had significantly longer mean white matter T2 (84.0 vs. 81.9 ms, P<0.03) and gray matter T2 (95.1 vs. 92.2, P = 0.003); their mean white and gray matter PD values were not significantly different from those of controls. Correlations were not significant between anisotropy and T2 in either grey or white matter but were significant between anisotropy and PD in white matter. T2 relaxation times are longer in schizophrenics than in controls in both gray and white matter whereas anisotropy reduction is restricted to white matter. Taken together, these results suggest that the process producing prolonged T2 does not fully account for the abnormally low anisotropy observed selectively in white matter in this group of schizophrenic patients.

Adult↗
PubMed1999

Severity of schizophrenia and magnetic resonance imaging abnormalities: a comparison of state and veterans hospital patients.

BACKGROUND: The relationship between illness severity and neuroanatomical abnormalities in schizophrenia remains unclear. The purpose of this study was to test whether the pattern and extent of brain volume abnormalities differed between two patient groups, distinguished by their overall severity and clinical course of schizophrenia. METHODS: Subjects were 56 severely ill, chronically hospitalized schizophrenic men from Napa State Hospital (SH-SZ), 44 moderately ill, acutely hospitalized schizophrenic men from the Palo Alto Veterans Administration Health Care System (VA-SZ), and 52 healthy male control subjects. Temporolimbic, ventricular, and frontoparietal volumes, quantified from 3-mm coronal spin-echo magnetic resonance images and adjusted for cerebral volume and age, were compared using analysis of variance. RESULTS: Compared to control subjects, both SZ groups had smaller (p < .05) temporal lobe and frontoparietal gray matter volumes and larger ventricles and temporal sulci. Whereas SH-SZ had more pronounced cerebrospinal fluid and frontoparietal abnormalities relative to VA-SZ; VA-SZ had greater temporal lobe gray matter deficits. Neither patients group had hippocampal or cerebral volume deficits relative to control subjects. There were no differences between diagnostic subtypes. CONCLUSIONS: The magnitude of volume abnormalities in schizophrenia varies with respect to disease severity and to brain region, but disease severity is not associated with anatomically distinct subgroups.

Adult↗
PubMed1999

In vivo brain concentrations of N-acetyl compounds, creatine, and choline in Alzheimer disease.

BACKGROUND: Alzheimer disease (AD) and normal aging result in cortical gray matter volume deficits. The extent to which the remaining cortex is functionally compromised can be estimated in vivo with magnetic resonance spectroscopic imaging. OBJECTIVE: To assess the effects of age and dementia on gray matter and white matter concentrations of 3 metabolites visible in the proton spectrum: N-acetyl compounds, present only in living neurons; creatine plus phosphocreatine, reflecting high-energy phosphate metabolism; and choline, increasing with membrane synthesis and degradation. METHOD: Fifteen healthy young individuals, 19 healthy elderly individuals, and 16 patients with AD underwent 3-dimensional magnetic resonance spectroscopic imaging and memory and language testing. RESULTS: Gray matter N-acetyl compound concentrations (signal intensity corrected for the amount of brain tissue contributing to the magnetic resonance spectroscopic imaging signal) was significantly reduced only in patients with AD, even though both the AD and elderly control groups had substantial gray matter volume deficits relative to the young control group. Both the healthy elderly and AD groups had abnormally high gray matter creatine plus phosphocreatine concentrations. Gray matter choline concentrations were higher in the elderly than the younger controls, and even higher in the AD group than in the elderly control group. Functional significance of these findings was supported by correlations between poorer performance on recognition memory tests and lower gray matter N-acetyl compounds in elderly controls and higher gray matter creatine plus phosphocreatine and choline concentrations in patients with AD. CONCLUSION: Cortical gray matter volume deficits in patients with AD are accompanied by disease-related increases in gray matter choline concentrations suggestive of cellular degeneration and reduced N-acetyl compound concentrations, with possible effects on behavioral function.

Adult↗