Biomedical subjects

P K Shear

Publications and source records attributed to P K Shear.

33 records · Page 2Linked to original sources

PubMed1996

Mammillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia.

Mammillary body and cerebellar atrophy have been described as postmorten neuropathologic markers of Korsakoff's syndrome. This study examined whether shrinkage in the mammillary bodies and cerebellum is present consistently in amnesic chronic alcoholics during life and whether the degree of abnormality in these patients differs from that in nonamnesic alcoholic and healthy controls. The severity of shrinkage in the mammillary bodies, cerebellar hemispheres, and cerebellar vermis visualizable on MRI scans was rated on a three-point scale in 33 chronic nonamnesic alcoholics, 9 amnesic alcoholics, and 20 healthy controls. Although both alcoholic groups showed significant mammillary body and cerebellar shrinkage relative to controls, the two patient groups did not differ from each other. Furthermore, four of eight amnesic patients in our sample did not demonstrate clinically significant mammillary body atrophy. These results suggest that alcoholism is associated with mammillary body and cerebellar tissue volume loss but do not provide evidence that these markers distinguish accurately between amnesic and nonamnesic patients. In addition, they suggest that visualizable mammillary body atrophy is not necessary for the development of amnesia in alcoholic patients.

Adult↗

PubMed1995

Longitudinal volumetric computed tomographic analysis of regional brain changes in normal aging and Alzheimer's disease.

OBJECTIVE: This study used a semiautomated image analysis technique to quantify the rate and regional pattern of cerebrospinal fluid (CSF) volume changes in the computed tomographic brain examinations of healthy adults and patients with Alzheimer's disease (AD). DESIGN: Longitudinal, within-subject design, with statistical correction for longitudinal method error (eg, head repositioning effects). SETTING: Palo Alto (Calif) Department of Veterans Affairs Medical Center. PATIENTS AND OTHER PARTICIPANTS: The 41 patients with AD were recruited from the Geriatric Psychiatry Research Unit and the National Institute of Mental Health Clinical Research Center of the Palo Alto Department of Veterans Affairs Medical Center. The 35 healthy control subjects were recruited from the local community. MAIN OUTCOME MEASURES: Cerebrospinal fluid volumes estimated from computed tomographic scans. RESULTS: Even after accounting for an estimate of method error (eg, head positioning effects) across computed tomographic examinations, the patients with AD showed greater annual CSF volume increases than did the control group. This CSF volume enlargement was not uniform across brain regions of interest; rather, the patients with AD showed disproportionate volume increases in the ventricular system and the sylvian fissures. Greater CSF volume changes in the patients with AD were significantly associated with greater cognitive decline on the Mini-Mental State Examination. Furthermore, younger patients with AD showed more rapid progression on computed tomographic scans than did older patients. CONCLUSIONS: The rate of CSF volume enlargement is region specific, with the most marked annual rate of change occurring in the ventricular system and the sylvian fissures. In addition, younger patients show more rapid progression in the ventricular and frontal sulcal brain regions of interest than do older patients.

Aged↗

PubMed1995

Functional MRI measurement of language lateralization in Wada-tested patients.

In this study the use of functional MRI (fMRI) for measuring language lateralization non-invasively was examined. The subjects were seven patients with histories of temporal lobe epilepsy who had undergone Wada testing for pre-surgical evaluation. Four patients were left-hemisphere-dominant and three were right-hemisphere-dominant for language. They received fMRI scans while they made semantic or perceptual judgments about visually presented words. Regions of the inferior frontal gyrus (pars triangularis and pars orbitalis) and neighbouring orbital cortex, corresponding to portions of Brodmann areas 45, 46 and 47, exhibited significant increases in activation during semantic relative to perceptual judgments. Lateralization of the increases in activation were consistent with the Wada test assessments of hemispheric language dominance in each of the seven patients. These results suggest that, in addition to providing a tool for investigating human cognitive processes, fMRI has significant clinical potential as a non-invasive measure of language lateralization.

Adult↗

PubMed1995

Longitudinal changes in magnetic resonance imaging brain volumes in abstinent and relapsed alcoholics.

Chronic alcoholism is associated with smaller volumes of cortical gray matter and white matter and a complementary increase in brain cerebrospinal fluid (CSF) volumes, relative to age norms. This longitudinal study quantified the extent of brain volume changes associated with abstinence and drinking at three time points in chronic alcoholics. We obtained magnetic resonance imaging (MRI) on 58 alcoholic men after an average of 12 days (MRI-1) and 32 days (MRI-2) of sobriety. In addition, 58 healthy control subjects were scanned at a comparable interval. At MRI-3, 11 controls and 39 alcoholics were rescanned, 2-12 months after MRI-2; 19 alcoholics had abstained, and 20 had resumed drinking. Axial MRI slices were segmented into cortical gray matter, white matter, and CSF and summed over seven slices; lateral and third ventricular volumes were also estimated. MRI volume changes were corrected using an estimate of interscan measurement error caused by head positioning differences, and then divided by the interval to yield rates of change (slopes). From MRI-1 to MRI-2, the alcoholic group showed declines in CSF volumes of the lateral ventricles and posterior cortical sulci, and a trend toward an increase in anterior cortical gray matter volume relative to the control group. From MRI-2 to MRI-3, third ventricular volumes decreased in the abstainers relative to the relapsers and controls; cortical white matter volume decreased in the relapsers. In the relapsers, lifetime consumption of alcohol (as of MRI-1) predicted later vulnerability to white matter volume decline and third ventricular enlargement with resumption of drinking. These data suggest that improvement in cortical gray matter, sulcal, and lateral ventricular volumes occur early in the course of abstinence, and that improvement in third ventricular volume appears later with continued abstinence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Cognitive recovery with abstinence and its relationship to family history for alcoholism.

OBJECTIVE: The relationship between drinking relapse and family history for alcoholism to cognitive functioning was investigated in alcoholics who completed a 28-day inpatient treatment program. METHOD: The current study examined 144 primary alcoholics who completed a battery of cognitive tests on admission to treatment and at a 3-4 month follow-up visit. Participants were classified as either family history positive (FH+) (n = 86) or family history negative (FH-) (n = 58) based on information on alcohol dependence in first degree relatives. The subjects were further classified as drinkers (n = 56) or abstainers (n = 88) at follow-up, based upon information gathered about their drinking practices during the interval. RESULTS: There were no differences between the groups based on family history status at admission to treatment. Comparisons made at follow-up revealed that the abstainers' (both FH+ and FH-) performance improved. The FH+ drinkers' performance was worse than that of both the FH- drinkers and the FH+ abstainers at follow-up. The poor performance of the FH+ drinkers relative to the FH- drinkers was not attributable to differences in drinking consumption during the test-retest interval. CONCLUSIONS: These results suggest that alcoholics who maintain abstinence following treatment show improvement on cognitive testing at follow-up; both FH+ and FH- abstainers showed improvement, indicating that a positive family history of alcoholism does not impede recovery that occurs with abstinence. The most important finding, however, is that the FH+ drinkers show greater deterioration at follow-up compared to the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

A deficit profile of executive, memory, and motor functions in schizophrenia.

This study examined the neuropsychological deficits associated with schizophrenia and the interrelationships among multiple dissociable cognitive and motor functions. The tests were selected for their previously demonstrated sensitivity to circumscribed brain pathology and included four functional domains: executive functions, short-term memory and production, motor ability, and declarative memory. Each test composite was divided according to verbal versus nonverbal material or left- versus right-hand performance; this distinction permitted functions principally subserved by the left or right cerebral hemispheres to be tested separately. Data reduction was theoretically driven by the test selection and was achieved first by standardizing the scores of each test for age-related differences observed in the normal control group, and then by calculating test composite scores as an average of the age-corrected Z-scores of the tests comprising a functional composite. The schizophrenic group was impaired equivalently on all composites for both cerebral hemispheres; on average, the Z-scores of the patients were 1 standard deviation below those of the control group. The cognitive test composite scores were highly intercorrelated but showed only weak associations with motor ability. Multiple regression analyses suggested that symptom severity was a significant predictor of the Declarative Memory and Short-Term Memory/Production composite scores after accounting for disease duration, whereas disease duration uniquely contributed to the Executive Functions composite scores after controlling for symptom severity. Even though the schizophrenics as a group showed an equivalent level of deficit across all test composites, 1) the deficits were associated with different aspects of psychiatric symptomatology, 2) the motor deficit was independent of the cognitive deficits, and 3) each neuropsychological domain contributed independently to the deficit pattern. Thus, what appears to be a generalized functional deficit in schizophrenia may actually be, at least in part, combinations of multiple specific deficits.

Adult↗

PubMed1994

Volumetric MRI assessment of temporal lobe structures in schizophrenia.

This magnetic resonance imaging (MRI) study was designed to investigate whether patients with schizophrenia have focal or lateralized deficits in the volumes of temporal lobe structures. Estimated volumes of the temporal lobes, hippocampi, superior temporal gyri, lateral ventricles, third ventricle, temporal horns of the lateral ventricles, and a frontal-parietal reference area (FPRA) were quantified for each hemisphere. The schizophrenic group had less gray matter (GM) in the temporal lobes and the FPRA relative to controls. Ventricular volumes were significantly larger in the schizophrenic group, as was cerebrospinal fluid (CSF) volume for temporal lobe sulci. No significant differences in hippocampal volumes emerged between groups. The magnitude of GM deficit was not greater in the temporal lobes relative to the FPRA. These results confirm the presence of bilateral GM volume deficits of the temporal lobes in schizophrenia but do not support the hypothesis that structural changes preferentially affect the temporal lobes or the left cerebral hemisphere.

Adult↗

PubMed1994

Volumetric magnetic resonance imaging quantification of longitudinal brain changes in abstinent alcoholics.

Magnetic resonance imaging (MRI) of the brain was performed on a group of 24 recently detoxified, male alcoholics approximately 1 month after their date of last drink. The imaging was repeated 3 months later, at which point 9 subjects had resumed drinking and 15 had maintained abstinence. Contrasts between these two drinking groups revealed that, despite comparable baseline values, the Abstainers exhibited volumetric white matter increases and cerebrospinal fluid reductions over the follow-up interval, whereas the Drinkers did not show significant change on either of these MRI indices. These results provide the first evidence suggestive of significant volumetric white matter increase with abstinence.

Adult↗

PubMed1993

Greater abnormalities of brain cerebrospinal fluid volumes in younger than in older patients with Alzheimer's disease.

OBJECTIVE: This study used a semiautomated analysis technique to quantify differences in regional brain cerebrospinal fluid volumes observed with computed tomography between healthy adults and patients with Alzheimer's disease (AD). DESIGN: Cross-sectional, between-subject design, using an age-regression model. SETTING: Palo Alto (Calif) Department of Veterans Affairs Medical Center. PATIENTS AND OTHER PARTICIPANTS: The 117 patients with probable or definite AD were recruited from the Geriatric Psychiatry Research Unit and National Institute of Mental Health Clinical Research Center of the Palo Alto Department of Veterans Affairs Medical Center. The 114 healthy volunteers were recruited from the local community. MAIN OUTCOME MEASURES: Cerebrospinal fluid volumes estimated from computed tomographic scans and neuropsychological test scores. RESULTS: The computed tomographic estimates of ventricular and sulcal cerebrospinal fluid volumes increased significantly in all sampled brain regions in normal aging and were vastly larger in AD than in normal aging. Furthermore, younger patients with AD had significantly greater cerebrospinal fluid volume enlargement than did older patients with AD compared with healthy controls of their age. When the AD group was divided on the basis of reported age at symptom onset, patients in the early-onset group (onset before age 65 years) were quantitatively more abnormal than and showed a different pattern of abnormality from the patients in the late-onset group. This onset difference was also evident in neuropsychological test performance. CONCLUSIONS: This cross-sectional study revealed a number of converging findings that suggested greater abnormality in the early-onset than in the late-onset group of patients with AD. The possibility remains, however, that the two onset groups represent different stages along a continuum of pathologic changes.

Adult↗

PubMed1993

Increase in brain cerebrospinal fluid volume is greater in older than in younger alcoholic patients: a replication study and CT/MRI comparison.

This cross-sectional study used a semi-automated analysis technique to quantify regional brain cerebrospinal fluid (CSF) volumes derived from computed tomography (CT) in 84 healthy men ranging from 21 to 82 years of age and 28 patients meeting Research Diagnostic Criteria for alcohol dependence. The goals were to replicate an earlier CT study of an independent sample of alcoholic and control subjects (Pfefferbaum et al., 1988a; Zipursky et al., 1988) and to compare CT assessments of brain changes with magnetic resonance imaging (MRI) assessments made in the same alcoholic patients (Pfefferbaum et al., 1992). Regional brain changes associated with normal aging were derived by regression analysis, using CT data collected from the healthy control subjects. As in the earlier CT study and in the concurrent MRI study, ventricular and sulcal CSF volumes in alcoholic patients were greater than would be expected for their age. Furthermore, the present CT study replicated the previous CT and MRI findings of a positive relationship between age and CSF volume enlargement in alcoholic patients over and above the normal age-related increase in CSF volume, suggesting greater vulnerability of the aging brain to alcohol. Comparison of CT- and MRI-derived estimates of ventricular and cortical sulcal volume revealed high correlations (> 0.80). MRI and CT produced similar absolute ventricular volumes, while MRI produced larger sulcal volume estimates than did CT. The difference in sulcal volume estimate may be due to differences between CT and MRI in slice thickness and sensitivity to partial volume effects.

Adult↗

PubMed1992

Verbal learning and memory in language impaired children.

The present study investigated patterns of verbal learning and memory in Language Impaired (LI) and normal children, using the California Verbal Learning Test--Children's Version. The LI children showed a normal immediate memory span; however, they were impaired in the total number of correct responses that they generated across repeated trials. They reported significantly more perseverations, but not intrusions, relative to the controls. The LI children were not impaired on a delayed free recall task, but they were significantly impaired relative to the controls on semantically cued recall. The implications of these findings for future research and for remediation are discussed.

Child↗

PubMed1992

Spatial cognition in Alzheimer's disease: subtypes of global-local impairment.

This study investigated whether subgroups of AD patients exhibit different patterns of impairment in analyzing global (configural) and local (detail) features of complex visual stimuli. A High Spatial AD subgroup (i.e., patients with better block constructions than naming) and a High Verbal AD subgroup (i.e., patients with better naming than block constructions) were impaired in analyzing both global and local forms. As predicted, however, the High Spatial AD patients exhibited greater impairment in analyzing the local forms than the High Verbal AD patients and normal controls. In contrast, the High Verbal AD patients exhibited greater impairment in analyzing the global forms than the High Spatial AD patients and normal controls. There was a striking separation of the subgroups: Using the local-global difference score, the hit rate for classifying these patients into the two subgroups was 91%. Robust correlations were found between the AD patients' ability to construct global and local forms and their scores on traditional visuospatial and verbal tests, respectively. The findings suggest that it may be misleading to subdivide AD patients using a verbal/spatial dichotomy, because even those AD patients who appear to have relative strengths on traditional visuospatial tests are likely to exhibit a primary impairment in analyzing local features of complex visual stimuli. The results underscore the importance of a process (qualitative) approach to neuropsychological assessment for a more valid understanding of the behavioral subtypes of Alzheimer's disease.

Aged↗

PubMedDate not supplied

Assessment of olfactory deficits in detoxified alcoholics.

Olfactory functioning was evaluated in 37 male detoxified alcoholics and in 21 age-matched nonalcoholic controls using the University of Pennsylvania Smell Identification Test (UPSIT). Of the original subjects, 23 alcoholics and 14 controls returned for reevaluation 3-4 months following initial testing. The results showed that alcoholics had significantly lower UPSIT scores than did the controls, both at baseline and follow-up testing. Thirty-two percent of the alcoholics' UPSIT scores, in comparison to five percent of the controls' scores, fell into the clinically impaired range. Although current smoking patterns correlated significantly with UPSIT indices, comparisons limited to nonsmokers still indicated that the alcoholics were significantly impaired on this olfactory task. Correlational analyses indicated that olfactory performance was unrelated to alcoholics' scores on visuoconceptual and language tasks. Correlations with MR-derived indices of CSF volume showed a highly significant relationship between UPSIT scores and cortical sulcal volumes. Additionally, alcoholics (N = 15) who remained abstinent had significantly higher scores at follow-up than those who were not abstinent (N = 8). These findings demonstrate that alcoholism is associated with basic olfactory impairments which are only partially reversible with abstinence and that cortical structures play an important role in this sensory loss.

Adult↗

PubMedDate not supplied

Olfactory loss in alcoholics: correlations with cortical and subcortical MRI indices.

The relationship between olfactory identification ability and MRI volumetric indices of specific cortical and subcortical brain regions was investigated in 36 recently detoxified male alcoholics. The results of correlational analyses between MRI indices and score on the University of Pennsylvania Smell Identification Test (UPSIT) revealed that impairment in olfactory identification was associated with elevated cortical and ventricular CSF volumes as well as with reduced tissue volumes in the cortical and subcortical grey matter. The volume of the thalamus was found to be a significant unique predictor of UPSIT score, even after accounting for variance shared with other MRI indices. These findings provide the first empirical support for existing hypotheses that olfactory loss in alcoholic subjects may be mediated by both cortical and subcortical structures.

Alcoholism↗

PubMedDate not supplied

Verbal fluency in mania: relationship to number of manic episodes.

OBJECTIVE: The objective of this study was to examine verbal fluency in a group of patients with bipolar disorder (BPD) during an acute episode of mania, and to determine whether performance was related to disease chronicity. We hypothesized that manic patients with BPD would be impaired on verbal fluency, and that this impairment would be greatest in those individuals who had experienced a greater number of manic episodes. METHOD: Forty-five manic inpatients with bipolar disorder, and 30 healthy volunteers completed tests of phonemic and semantic verbal fluency. The patients were dichotomized into those experiencing their first episode of mania (FE) and those who had experienced multiple episodes (ME). RESULTS: On the phonemic fluency task, ME patients produced significantly fewer words than both healthy volunteers and FE patients, and they made a greater number of errors. No significant group differences in overall output were found on the semantic fluency task, although the ME group was more error-prone than were the other groups. CONCLUSIONS: These findings suggest that verbal fluency is more impaired in ME patients than in patients who have experienced only a single manic episode.

Adult↗