Biomedical subjects

C L Grady

Publications and source records attributed to C L Grady.

At least 73 records · Page 4Linked to original sources

PubMed1991

Cerebral metabolic pattern in obsessive-compulsive disorder: altered intercorrelations between regional rates of glucose utilization.

Correlations between normalized regional cerebral metabolic rates for glucose, determined by positron emission tomography with 18F-2-fluoro-2-deoxy-D-glucose, were used to investigate functional associations between pairs of brain regions in 18 adult patients with primary obsessive-compulsive disorder (OCD) of childhood-onset, as compared with 18 age- and sex-matched control subjects. The number of correlations that differed significantly between the two groups exceeded chance, although as many of these correlations were larger in the OCD group relative to controls as were smaller. The two regions that had the largest number of correlations that differed significantly between groups were a left hemisphere superior parietal region and the left hemisphere anterior medial temporal area (which includes principally the amygdala). Correlations involving the caudate nuclei did not differ between the two groups for the most part. Anterior limbic/paralimbic regions had correlations in the OCD group that were significantly larger with frontal areas than in controls, and correlations that were significantly smaller with posterior brain regions. This pattern was especially pronounced for the left hemisphere anterior medial temporal region. These results suggest that the correlation pattern in OCD is not characterized by an overall loss of functional integration but, rather, by functional reorganization.

Adult↗

PubMed1991

Quantitative comparison of measurements of cerebral glucose metabolic rate made with two positron cameras.

The rapid progress in PET technology has created the dilemma of how to compare data from old and new tomographs. We examined cerebral metabolic data from two scanners, with different spatial resolutions and methods of attenuation correction, to see if metabolic values from the lower-resolution tomograph (ECAT II) could be adjusted to make them comparable to data from the higher-resolution scanner (Scanditronix PC1024-7B). Nine subjects were scanned on both tomographs after a single injection of [18F]2-fluoro-2-deoxy-D-glucose. Regional and lobar gray matter metabolic rates for glucose were obtained from comparable images from each scanner. Ratios of lobar to global gray matter metabolism also were calculated. Regression coefficients and percent differences were computed to compare ECAT II and PC1024 data. Two-thirds of the region pairs showed significant regressions, although percent differences were quite variable, with measures of glucose utilization ranging from 30 to 120% higher on the PC1024 compared to those from the ECAT II. Comparisons of lobar glucose rates between the two machines were less variable (50 to 80%), and ratios differed by only +/- 5% (except for the temporal ratios). Since there was no simple and consistent relationship between regional metabolic rates on the two tomographs, an overall adjustment of regional ECAT values for comparison to PC1024 values would be impossible. A region-by-region adjustment would be necessary. Lobar ratios are sufficiently similar that direct comparisons might be possible.

Aged↗

PubMed1990

Longitudinal study of cerebral metabolic asymmetries and associated neuropsychological patterns in early dementia of the Alzheimer type.

Regional cerebral metabolic rates for glucose (rCMRglc), as measured with positron emission tomography, and neuropsychological function were studied longitudinally (range, 15 to 48 months) in 11 mildly impaired patients with dementia of the Alzheimer type (DAT) and compared with results from patients with moderate and severe DAT and from controls. At initial evaluation, association cortex metabolic asymmetries were greater in patients with DAT than in controls for all dementia severities and correlated significantly with neuropsychological discrepancies between visuospatial and language abilities in patients with moderate dementia. In mildly impaired patients, right-left metabolic asymmetries in the association cortices were directionally stable and became more pronounced over time. At initial evaluation, these patients had significant impairment, relative to controls, on tests of memory and attention to complex tasks but not on tests of language and visuospatial function. Memory, attention, language, and visuospatial impairments, however, all worsened significantly over time. In mildly impaired patients, correlations between right-left metabolic asymmetries and neuropsychological discrepancies were insignificant initially but were significant at last evaluation. These results demonstrate that heterogeneous nonmemory language and visuospatial impairments in early DAT are related to and predicted by the earlier-appearing distribution of metabolic reductions in the association neocortex.

Aged↗

PubMed1990

Plasticity in the aging brain. Reversibility of anatomic, metabolic, and cognitive deficits in normal-pressure hydrocephalus following shunt surgery.

The course of idiopathic normal-pressure hydrocephalus was studied in a 78-year-old woman with a 4-year history of progressive dementia who underwent neuropsychologic testing, quantitative x-ray computed tomography, magnetic resonance imaging, and positron emission tomography with fludeoxyglucose F 18 to measure rates of regional cerebral glucose utilization. Preshunt cognitive testing demonstrated progressive deterioration during 2 years, and positron emission tomography showed significant reductions in regional cerebral glucose utilization of 34% to 49% as compared with age- and sex-matched control subjects in frontal, temporal, parietal, and whole brain regions. Periodic testing, carried out during a 2-year period after shunt surgery, showed steady improvement in clinical status. Parallel to the clinical changes, there was a significant reversal in neuropsychologic test scores with increased brain volume and increased regional cerebral glucose utilization in several brain regions. These results documented the considerable potential for recovery of compromised brain function in older subjects even after 4 years of progressive brain disease.

Aged↗

PubMed1990

Effect of gender on glucose utilization rates in healthy humans: a positron emission tomography study.

Positron emission tomography (PET) was used with 18fluorodeoxyglucose to see if gender differences in resting cerebral glucose utilization could be detected. Thirty-two healthy subjects (15 women and 17 men; age range: 21-38 yr) were examined using a high-resolution PET scanner to determine the regional cerebral metabolic rate for glucose (CMRglc) in 65 gray matter regions of interest. Whole brain CMRglc did not differ significantly between the two genders, nor did any of the regional CMRglc values. Only 1 of 65 ratios of regional-to-whole brain CMRglc differed significantly between men and women, which is consistent with chance. These results indicate that there are no differences in resting regional cerebral glucose utilization between young men and women.

Adult↗

PubMed1990

Cerebral metabolic and cognitive studies in dementia with frontal lobe behavioral features.

Three subjects with dementia of the Alzheimer type (DAT) with frontal lobe features of behavioral disinhibition were studied using positron emission tomography with [18F]2-fluoro-2-deoxy-D-glucose (18 FDG) and standardized neuropsychological tests. The three subjects showed significant decrements (p less than .05) in relative glucose metabolism (regional/mean gray metabolism) in the orbitofrontal, prefrontal and anterior cingulate regions when compared to healthy controls. Severity-matched subjects with DAT without the associated frontal lobe features did not show the relative reductions in glucose metabolism in these regions when compared to controls. However, on neuropsychological testing of frontal lobe cognitive functions the three subjects did not show decrements that were more severe than those shown by severity-matched DAT patients without the behavioral features. These data demonstrate physiologic dysfunction in specific cortical regions in subjects with behavioral aberrations attributed to these regions and an apparent dissociation between behavioral and cognitive functions of the frontal lobe.

Aged↗

PubMed1990

Regional cerebral glucose metabolism is normal in young adults with Down syndrome.

Regional CMRglc (rCMRglc) values were measured with [18F]2-fluoro-2-deoxy-D-glucose (18FDG) and positron emission tomography (PET), using a Scanditronix PC-1024-7B scanner, in 14 healthy, noninstitutionalized subjects with trisomy 21 (Down syndrome; DS) (mean age 30.0 years, range 25-38 years) and in 13 sex-matched, healthy volunteers (mean age 29.5 years, range 22-38 years). In the DS group, mean mental age on the Peabody Picture Vocabulary Test was 7.8 years and dementia was not present. Resting rCMRglc was determined with eyes covered and ears occluded in a quiet, darkened room. Global gray CMRglc equaled 8.76 +/- 0.76 mg/100 g/min (mean +/- SD) in the DS group as compared with 8.74 +/- 1.19 mg/100 g/min in the control group (p greater than 0.05). Gray matter regional measurements also did not differ between groups. The ratio of rCMRglc to global CMRglc, calculated to reduce the variance associated with absolute rCMRglc, and right/left ratios did not show any consistent differences. These results show that healthy young DS adults do not have alterations in regional or global brain glucose metabolism, as measured with 18FDG and PET, prior to an age at which the neuropathological changes in Alzheimer disease are reported to occur.

Adult↗

PubMed1990

Cerebral metabolic pattern in young adult Down's syndrome subjects: altered intercorrelations between regional rates of glucose utilization.

Correlations between regional cerebral metabolic rates for glucose, determined by positron emission tomography with [18F]-2-fluoro-2-deoxy-D-glucose, have been used to indicate functional associations between pairs of brain regions. This method was applied to data from 14 healthy adult subjects with trisomy 21 Down's syndrome (age less than 34 years) and from 24 age-matched healthy controls. Correlations were obtained between ratios of regional-to-global resting glucose utilization. In comparison to age-matched controls, the Down's syndrome group had many smaller correlations for region-pairs within and between the frontal and parietal lobes; some correlations were large and negative in the Down's syndrome group, but large and positive in the controls. One region so affected was the inferior frontal gyrus that includes Broca's area. This result is consistent with the relatively greater language impairment in Down's syndrome subjects. The thalamus also had smaller correlations with temporal and occipital regions in the Down's syndrome group compared to controls. These results suggest that Down's syndrome is accompanied by a functional disruption of neural circuits associated with directed attention.

Adult↗

PubMed1990

Subgroups in dementia of the Alzheimer type identified using positron emission tomography.

We examined patterns of cerebral glucose metabolism in 33 patients with dementia of the Alzheimer type by applying principal component analysis to identify subgroups. Four subgroups were identified: one with predominant parietotemporal hypometabolism (15 patients); one with paralimbic metabolic deficits (8 patients); one with left hemisphere neocortical abnormality (5 patients); and one with frontal and parietotemporal deficit (5 patients). Differences among the subgroups were found in neuropsychological impairments and prevalence of psychiatric symptoms. These metabolic subgroups could not be explained on the basis of dementia severity, illness duration, or age, but were most likely related to an underlying pathology with a variable regional distribution.

Aged↗

PubMed1989

Divided attention, as measured by dichotic speech performance, in dementia of the Alzheimer type.

To determine if impaired dichotic performance in patients with dementia of the Alzheimer type is due to the inability to divide attention or the inability to perceive degraded auditory stimuli, we measured performance on tasks of both dichotic and degraded monotic speech materials. We also examined whether perception of degraded speech stimuli presented monaurally is related to abnormalities of temporal lobe anatomy and physiology, as we have shown for dichotic performance. Although the patients were impaired on both dichotic and monotic tests, significantly greater impairment was seen on the dichotic test. Our earlier finding of a significant relation between dichotic performance and measures of anterior temporal lobe atrophy and reduced glucose metabolism was replicated, but no significant relation was found between monotic tests and measures to temporal lobe integrity. We conclude that the inability to divide attention, rather than abnormal processing of degraded stimuli per se, is reflected in poor dichotic performance in patients with dementia of the Alzheimer type, and that dichotic performance, unlike degraded monotic perception, depends directly on the integrity of temporal cortex in these patients.

Aged↗

PubMed1989

Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder.

The cerebral metabolic rate for glucose was studied in 18 adults with childhood-onset obsessive-compulsive disorder (OCD) and in age- and sex-matched controls using positron emission tomography and fludeoxyglucose F 18. Both groups were scanned during rest, with reduced auditory and visual stimulation. The group with OCD showed an increased glucose metabolism in the left orbital frontal, right sensorimotor, and bilateral prefrontal and anterior cingulate regions as compared with controls. Ratios of regional activity to mean cortical gray matter metabolism were increased for the right prefrontal and left anterior cingulate regions in the group with OCD as a whole. Correlations between glucose metabolism and clinical assessment measures showed a significant relationship between metabolic activity and both state and trait measurements of OCD and anxiety as well as the response to clomipramine hydrochloride therapy. These results are consistent with the suggestion that OCD may result from a functional disturbance in the frontal-limbic-basal ganglia system.

Adolescent↗

PubMed1989

Quantitative comparison of cerebral glucose metabolic rates from two positron emission tomographs.

The rapid progress in positron emission tomography technology has created the dilemma of how to compare data from old and new tomographs. We examined cerebral metabolic data from two scanners, with different spatial resolutions and methods of attenuation correction, to see if data from the lower resolution tomograph (ECAT II) could be "corrected" and then compared to data from the higher resolution scanner (Scanditronix PC1024-7B). Nine subjects were scanned on both tomographs after a single injection of [18F]2-fluoro-2-deoxy-D-glucose. Regional and lobar gray matter metabolic rates for glucose were obtained from comparable images from each scanner. Ratios of lobar to global gray matter metabolism also were calculated. Regression coefficients and percent differences were computed to compare ECAT II and PC1024 data. Twenty-four of the 36 regions showed significant regression slopes, and PC1024 measures of glucose utilization ranged from 30% to 120% higher than those from the ECAT II. Lobar differences between the two machines were less variable (50% to 80%), and ratios generally differed by only +/- 5%. Since there was no simple and consistent relation between regional metabolic rates on the two tomographs, an overall adjustment of regional ECAT values for comparison to PC1024 values would be impossible. A region-by-region adjustment would be necessary. On the other hand, ratios are sufficiently similar that direct comparisons could be made.

Aged↗

PubMed1988

NIH conference. Alzheimer disease: clinical and biological heterogeneity.

The clinical and biological features of Alzheimer disease are not uniform in their expression; heterogeneity is evident in the disease's clinical, anatomic, and physiologic characteristics. The presence of considerable intersubject and intrasubject heterogeneity suggests that subtypes of the disease exist. We define subtypes of Alzheimer disease in regard to the behavioral features (for example, predominant right or left hemisphere, or symmetrical impairment), inheritance (familial or sporadic), dosage of chromosome 21 (presence of the Down syndrome), time course of progression, age of onset (presenile or senile), and presence or absence of motor deficit (myoclonus or signs of an extrapyramidal syndrome). Studies of regional cerebral glucose metabolism with positron emission tomography and [18-fluorine] fluorodeoxyglucose show focal alterations in glucose use, with cerebral metabolic asymmetries in patients with Alzheimer disease that are related to the nature of the cognitive deficit. Serial roentgenographic computed tomographic studies show heterogeneous rates of lateral ventricle enlargement in the disease that are related to rates of cognitive decline. Similar anatomic and physiologic abnormalities are also found in persons 45 years of age or older who have the Down syndrome. Furthermore, patients with Alzheimer disease who have extrapyramidal dysfunction or myoclonus are a distinct subgroup, with specific abnormalities of central monoamine markers of dopamine metabolism, serotonin metabolism, and the hydroxylation cofactor, biopterin. The concept of subtypes in Alzheimer disease serves as a model with which the interactions of genetic influences with environmental factors can be examined.

Alzheimer Disease↗

PubMed1988

The cerebral metabolic landscape in autism. Intercorrelations of regional glucose utilization.

Correlations between regional cerebral metabolic rates for glucose (rCMRglc), determined by positron emission tomography using 18F-2-deoxy-2-fluoro-D-glucose, provide a measure of the functional associations between brain regions. We compared correlations between ratios of resting rCMRglc to global brain metabolism from 14 healthy autistic men (ages, 18 to 39 years) with those from 14 matched control subjects. The autistic group showed significantly fewer large positive correlations between frontal and parietal regions, particularly those with the left inferior frontal region and its right hemispheric homologue, and significantly lower correlations of the thalamus, caudate nucleus, lenticular nucleus, and insula with frontal and parietal regions, with many correlations negative in the autistic group that were positive in the control group. These results are compatible with functionally impaired interactions between frontal/parietal regions and the neostriatum and thalamus, regions that subserve directed attention.

Adolescent↗

PubMed1988

Longitudinal study of the early neuropsychological and cerebral metabolic changes in dementia of the Alzheimer type.

To examine the progression of neuropsychologic and metabolic changes in the early stages of dementia of the Alzheimer type (DAT), we studied 11 midly demented patients longitudinally. Three aspects of neuropsychological function were measured: memory, attention to complex sets and abstract reasoning, and lateralized functions, i.e., language and visuoconstruction. Regional cerebral metabolic rates for glucose were measured in frontal, parietal, and temporal association cortices. Our results show that, in general, memory deficits are the first neuropsychological impairments to occur in DAT, followed by problems with attention to complex cognitive sets and abstract reasoning, which are followed in turn by deficits in language and visuospatial abilities. In addition, neocortical metabolic abnormalities usually precede impairment of neocortically mediated attention and abstract reasoning by 8 to 16 months, and precede impairment of neocortically mediated language and visuospatial function by 12 to 37 months. These findings suggest that the first nonmnestic neuropsychological consequence of neocortical physiological dysfunction in DAT is a loss of attentional capacity. Since neocortical metabolic changes generally precede the appearance of neocortically mediated neuropsychological dysfunction, physiologic dysfunction may exist for some time before cognition is affected.

Aged↗

PubMed1988

Heterogeneous anterior-posterior metabolic patterns in dementia of the Alzheimer type.

The parietal-frontal distribution of reductions of regional cerebral metabolic rates for glucose (rCMRglc) was studied in 32 patients with mild to severe dementia of the Alzheimer type (DAT), using positron emission tomography and fluorodeoxyglucose, and was related to patterns of neuropsychological impairment. In moderate and severe DAT patients, one frontal association region, the premotor cortex, demonstrated significant metabolic reductions equivalent to reductions in the parietal association cortex, and the ratio of parietal to premotor rCMRglc had significantly greater variance than in controls. In moderately demented patients, parietal-premotor and parietal-prefrontal metabolic ratios correlated significantly with neuropsychological impairments. Disproportionate parietal hypometabolism was associated with more impairment of verbal comprehension, calculations, visuospatial construction, and immediate visuospatial memory span. Disproportionate frontal hypometabolism was associated with more impaired verbal fluency and attention. Longitudinal follow-up of 20 of the patients showed that parietal/frontal metabolic ratios and their correlated neuropsychological patterns were stable over time, as dementia severity worsened. These results indicate that in moderate to severe DAT patients, metabolic reductions in the premotor cortex are as severe as the reductions in the parietal association cortex. Moreover, the parietal-premotor distribution of metabolic reductions is variable and related to variable patterns of cognitive impairment.

Alzheimer Disease↗

PubMed1988

Dementia in Down's syndrome: cerebral glucose utilization, neuropsychological assessment, and neuropathology.

We measured the cerebral metabolic rate for glucose (CMRglc) with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose in a 47-year-old man with trisomy 21 Down's syndrome (DS) and autopsy-confirmed Alzheimer's disease. Dementia was evident from a confirmed history of cognitive decline, memory loss, and personality change. CMRglc in the subject was compared with the mean obtained in 13 healthy younger DS subjects, aged 19 to 33 years. Test scores of general intelligence, visuospatial ability, language, and memory function showed poorer performance in the older subject compared with the younger group. Mean hemispheric CMRglc in the older DS subject was 28% less than in the young DS group, and marked hypometabolism was evident in parietal and temporal lobe association cortices. At autopsy, extensive neuropathology was noted, especially in the parietal and temporal cortical regions, more so than reported in DS subjects without documented dementia. This study is the first complete assessment of cerebral metabolism, neuropsychological competence, and neuropathology in a DS subject with a documented course of dementia, and demonstrates the superimposition of Alzheimer type dementia on previous mental retardation.

Brain↗

PubMed1987

Intercorrelations of regional cerebral glucose metabolic rates in Alzheimer's disease.

Patterns of cerebral metabolic correlations were compared between 21 Alzheimer's disease patients and 21 healthy age-matched controls in the resting state. Cerebral metabolic rates for glucose were determined by positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose. Partial correlation coefficients, controlling for whole brain glucose metabolism, were evaluated between pairs of regional glucose metabolic rates in 59 brain regions. Reliable correlation coefficients were obtained with the 'jackknife' and 'bootstrap' statistical procedures. Compared with healthy controls, the Alzheimer patients had significantly fewer reliable partial correlation coefficients between frontal and parietal lobe regions, and more reliable correlations between the cerebellum and temporal lobe. The number of reliable correlations between many bilaterally symmetric brain regions was reduced in the Alzheimer patients, as compared with controls. These results suggest that in the early stages of Alzheimer's disease there is a breakdown of the organized functional activity between the two cerebral hemispheres, and between parietal and frontal lobe structures.

Aged↗