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Biomedical subjects

H Creasey

Publications and source records attributed to H Creasey.

At least 19 recordsLinked to original sources

Brain stem serotonin-synthesizing neurons in Alzheimer's disease: a clinicopathological correlation.

The location and number of brain stem serotonin-synthesizing neurons were analyzed in 11 patients with Alzheimer's disease (AD) and 5 age-matched controls using immunohistochemical techniques. In addition, the number of neuritic plaques and neurofibrillary tangles in the cortex and brain stem raphe was evaluated, as was the number of Nissl-stained raphe neurons. AD patients could be classified into two groups based on their raphe pathology; patients with such pathology (AD+) and those without (AD-). The number of large raphe neurons correlated significantly with the number of serotonin-synthesizing neurons in control material, indicating that all large neurons were serotonergic. This relationship was not apparent in AD+ patients, in whom the number of serotonin-synthesizing neurons correlated with the number of neurofibrillary tangles in the raphe of these patients. This indicates that in AD+ patients the serotonin-synthesizing neurons were selectively affected. There was no correlation between raphe and cortical pathology or raphe pathology and patient sex, age, mini-mental score or depression score, even when such scores were weighted for the interval between testing and death. There was a trend for the raphe pathology to correlate with the age of onset and duration of dementia and the Blessed dementia score in AD+ patients. Most AD+ patients with severe raphe lesions had clinical dementia only, while AD- patients had additional clinical features. The raphe lesions were more dramatic in AD+ patients with a rapid progression of symptoms.

Aged

Environmental risk factors for Alzheimer's disease: their relationship to age of onset and to familial or sporadic types.

Data from a case-control study of Alzheimer's disease (AD) were analysed in relation to age of onset and familial/sporadic status. The analyses were restricted to environmental exposures which might injure the brain. Later-onset AD was found to be positively associated with starvation/malnutrition and with nose-picking and negatively with analgesics, while earlier-onset was associated with physical underactivity and nervous breakdown more than 10 years before. Sporadic AD was associated with starvation/malnutrition and with head injury. These analyses merit replication in other large case-control studies of AD.

Age Factors

Cholinergic 'blockade' as a model of the cognitive deficits in Alzheimer's disease.

The performance of 44 Alzheimer patients and 33 controls was examined on tests previously found to be differentially affected by scopolamine administration. Tests of secondary memory, performance intelligence, primary memory, semantic retrieval, procedural memory and verbal intelligence were included. It was found that Alzheimer patients performed more poorly than controls on tests of secondary memory, as measured by selective reminding, recall and recognition. Procedural memory, as measured by stem completion, homophone spelling and transformed text reading, did not differ between Alzheimer patients and controls. Semantic memory, verbal intelligence and primary memory were impaired in moderate and severe cases. However, patients with 'mild' dementia, as measured by the Mini-Mental State Examination, did not differ from controls on tests of semantic memory, verbal intelligence and primary memory. It was concluded that the pattern of anterograde memory deficits and preserved abilities in mild dementia mimicked that previously observed in scopolamine administration in young subjects.

Aged

Control-informant agreement on exposure history in case-control studies of Alzheimer's disease.

Data on control-informant agreement from four published case-control studies of Alzheimer's disease are compared, using both the kappa statistic and proportion of agreement for the presence and absence of exposures. Agreement was best for exposures involving lifestyle, medical interventions or disorders of more recent origin, and worst for exposures which involved judgements by the respondent. Agreement levels are similar across studies, and are commensurate with levels of specificity and sensitivity to be expected in this type of enquiry. We discuss the problems and implications associated with the interpretation of data from such studies of the elderly.

Aged

Season of birth for Alzheimer's disease in the Southern Hemisphere.

Season of birth was compared in 170 clinically diagnosed cases of Alzheimer's disease (AD) in Australia and 170 matched controls. A further comparison was made with a large population sample of the elderly. No evidence for seasonality of birth was found. This finding held not only for the total series of 170 cases, but also for the 143 born in the Southern Hemisphere, for sporadic cases, and for those with earlier onset. These negative findings in Australia contrast with the positive finding in London by Philpot et al. (1989).

Aged

A case-control study of Alzheimer's disease in Australia.

We conducted a case-control study of clinically diagnosed Alzheimer's disease (AD) on 170 cases aged 52 to 96 years, and 170 controls matched for age, sex and, where possible, the general practice of origin. Trained lay interviewers naive to the hypotheses and to the clinical status of the elderly person carried out risk-factor interviews with informants. Significant odds ratios were found for 4 variables: a history of either dementia, probable AD, or Down's syndrome in a 1st-degree relative, and underactivity as a behavioral trait in both the recent and more distant past. Previously reported or suggested associations not confirmed by this study include head injury, starvation, thyroid disease, analgesic abuse, antacid use (aluminum exposure), alcohol abuse, smoking, and being left-handed.

Aged

Monozygotic twins discordant for Alzheimer's disease.

We identified 3 pairs of monozygotic twins discordant for probable Alzheimer's disease from a twin register and found no systematic differences in potential risk factor exposures between affected and unaffected twins. Such cases predict a role for environmental factors in the etiology or clinical onset of Alzheimer's disease.

Aged

Hemispheric asymmetries, fourth ventricular size, and cerebellar morphology in autism.

Hemispheric asymmetries, fourth ventricular size, and cerebellar morphology were examined in 15 healthy men, aged 18 to 39 years, with documented childhood diagnoses of infantile autism, and in 20 healthy age- and sex-matched controls using computerized transverse axial tomography (CT). Nine patients were of approximately average intelligence, 3 showed specific language impairments, and 3 were mentally retarded. No significant group differences were seen in the distributions of frontal or posterior asymmetries of width or petalia. No subject showed evidence of cerebellar atrophy or an enlarged fourth ventricle. These results fail to support a hypothesis of unusual hemispheric asymmetry or macroscopic abnormalities of the posterior fossa in autism.

Adolescent

Relation of measured brain glucose utilisation and cerebral atrophy in man.

The effect of cerebral atrophy on measured cerebral metabolic rates for glucose (CMRglc), as determined with positron emission tomography (PET), was examined in 49 healthy males aged 21-83 years. Global CMRglc and regional CMRglc for 34 grey matter regions parallel to and from 30 to 80 mm above the inferior orbital meatal (IOM) line were measured under resting conditions, using [18F]-fluorodeoxyglucose and an ECAT II positron emission tomograph. Using a GE 8800 CT/T scanner, slices parallel to and from 30 to 80 mm above the IOM line were analysed for CSF volume. Cerebral atrophy, indicated by increased CSF volume, was correlated significantly with global CMRglc, but accounted for no more than 13% of the variance in the CMRglc measurements. Methods for correcting for inter-subject variation in CSF volume were proposed. Global values for CMRglc, uncorrected or corrected for CSF volume, were found to be age invariant. These findings indicate that (a) cerebral atrophy has a small, but statistically significant effect on CMRglc as measured with PET; (b) CMRglc is age invariant in healthy males.

Adult

Rate of ventricular enlargement in dementia of the Alzheimer type correlates with rate of neuropsychological deterioration.

We studied twelve men and six women with dementia of the Alzheimer type (DAT) and twelve healthy men at intervals of 6 months to 5 years. In the male DAT patients, mean CT rates of enlargement of third ventricle and of total lateral ventricular volumes differed significantly from zero and exceeded respective control values (p less than 0.05). The rate of neuropsychological decline correlated with rates of enlargement of the third ventricle or right lateral ventricle. Women with DAT also had significant rates of enlargement of the third and total lateral ventricles. The rate of lateral ventricular dilatation discriminated DAT patients from controls.

Aged

Quantitative CT analysis of brain morphometry in adult Down's syndrome at different ages.

Quantitative CT demonstrated that healthy adults with Down's syndrome (DS) have smaller brains and smaller intracranial volumes than controls. Normalized volumes of CSF, ventricles, and brain parenchyma did not differ in patients and controls. Both DS subjects and controls showed similar significant age-related increments in volumes of CSF and ventricles. Of seven older DS subjects, one was demented, whereas the group as a whole showed reductions in cognitive test scores as compared with younger DS subjects. The results demonstrate cognitive decline in older DS subjects, but no brain atrophy other than that expected with aging.

Adult

Brain morphometry in autistic men as measured by volumetric computed tomography.

Brains of 12 physically healthy men, aged 18 to 39 years, with clear childhood diagnoses of infantile autism, and those of 16 healthy age- and sex-matched normal controls, were examined with computed transverse axial tomography. No significant group differences were seen in volumes of cerebrospinal fluid, white matter, gray matter, the third ventricle, the lateral ventricles, the caudate nuclei, lenticular nuclei, or the thalami, or in the relative symmetry of these structures. These results suggest that the cerebral defect in autism is functional or microscopic, without major gross anatomic correlate.

Adolescent

Cerebrospinal fluid biopterin is decreased in Alzheimer's disease.

Tetrahydrobiopterin is the cofactor in the hydroxylation of phenylalanine, tyrosine, and tryptophan leading to the eventual synthesis of the monoaminergic neurotransmitters, dopamine, norepinephrine, and serotonin, respectively. Total biopterin (90% of which is in the tetrahydro form) was measured in cerebrospinal fluid (CSF) and plasma of 30 patients with Alzheimer's disease and of 19 healthy controls. Plasma and CSF biopterin concentrations were not significantly correlated, but the mean CSF biopterin concentration in patients with Alzheimer's disease was significantly less than in age-matched controls, 13.5 pmol/mL as compared with 18.9 pmol/mL. The CSF biopterin concentration was not correlated with ventricular volume, as estimated by quantitative computed tomography, nor with the severity of dementia, as measured by various cognitive tests. The results suggest that a central biopterin deficiency exists in Alzheimer's disease.

Adult

Quantitative computed tomography in dementia of the Alzheimer type.

Men and women with dementia of the Alzheimer type (DAT) had more brain atrophy and ventricular dilatation, measured by quantitative CT, than did respective age- and sex-matched healthy controls (p less than 0.05). The male DAT patients with mild dementia had a larger mean third ventricle volume, whereas male patients with severe dementia had larger lateral and third ventricle volumes, more CSF, and less gray matter than did controls. Statistically significant and appropriate correlations between several dementia scales and CT measures in the DAT patients indicated that brain atrophy and ventricular dilatation were related to the severity of dementia.

Age Factors

The aging human brain.

Postmortem and computed tomographic studies demonstrate many anatomical, morphological, and neurochemical differences between brains of old and young human beings. The variability of the results is great, however, and brains of some old subjects have characteristics of brains of younger controls. Furthermore, important aspects of brain functional activity are not reduced in the elderly. These include resting cerebral oxidative metabolism and "crystallized" intelligence as represented by verbal subtests on the Wechsler Adult Intelligence Scale. In the absence of superimposed disease (which frequently limits aging studies), overall function can be maintained at high and effective levels because of the plasticity and redundancy capabilities of the human brain.

Aging

Computed tomographic analysis of brain morphometrics in 30 healthy men, aged 21 to 81 years.

Computed transverse axial tomography (CT) was employed to examine brain morphometrics in 30 healthy men, aged 21 to 81 years. Seven consecutive CT slices 30 to 80 mm above the inferior orbitomeatal line were analyzed. CT numbers in gray and white matter regions were not correlated significantly with age (p greater than 0.05), nor were right/left ratios for derived parameters. The volume of gray matter was correlated negatively with age (p less than 0.05), and the volume of cerebrospinal fluid correlated positively with age, in the seven slices. The volumes of the lateral and third ventricles were elevated in the elderly, and volumes of the thalamus and lenticular nucleus were reduced. The results demonstrate that brain atrophy, evidenced by a loss of gray matter and by dilatation of cerebrospinal fluid spaces, occurs in the healthy elderly, and provide baseline CT-derived brain morphometric data for healthy men in relation to age.

Adult

Computer-assisted categorization of brain computerized tomography pixels into cerebrospinal fluid, white matter, and gray matter.

A computer-assisted method was employed to estimate the amounts of cerebrospinal fluid (CSF), white matter, and gray matter in individual computerized tomography (CT) scans of brains. By means of an image processing procedure (DMORPH), the means +/- SD CT numbers of "pure" CSF, white matter, and gray matter were determined in each scan and stored. A CATSEG program used these means to define ranges for CT numbers for each of the three tissues on each scan, and to assign each pixel in a scan to one of the three categories. Summing over seven serial scans provided volumetric estimates of CSF, white matter, and gray matter in a brain segment. For 10 subjects aged 21 to 43 years, CSF volume equaled 1.4 to 4.7% of the total segment volume, white matter equaled 37.5 to 48.2%, and gray matter equaled 50.2 to 58.9%. Image processing hardware and software which allow standardized sampling from CT images for the evaluation of surface areas and CT numbers are described. These procedures, as applied to CT scans of the human brain, can be used to estimate the volumes of CSF, white matter, and gray matter in a selected intracranial segment.

Brain

NIH Conference. Brain imaging: aging and dementia.

The brain imaging techniques of positron emission tomography using [18F]-fluoro-2-deoxy-D-glucose, and computed tomography, together with neuropsychological tests, were used to examine overall brain function and anatomy in three study populations: healthy men at different ages, patients with presumptive Alzheimer's disease, and adults with Down's syndrome. Brain glucose use did not differ with age, whereas an age-related decrement in gray matter volume was found on computed tomographic assessment in healthy subjects. Memory deficits were found to precede significant reductions in brain glucose utilization in mild to moderate Alzheimer's dementia. Furthermore, differences between language and visuoconstructive impairments in patients with mild to moderate Alzheimer's disease were related to hemispheric asymmetry of brain metabolism. Brain glucose utilization was found to be significantly elevated in young adults with Down's syndrome, compared with controls. The importance of establishing strict criteria for selecting control subjects and patients is explained in relation to the findings.

Adult