Ajax E. George

Computed Tomography and Positron Emission Transaxial Tomography Evaluations of Normal Aging and Alzheimer's Disease

Young normal subjects, old normal subjects, and patients with senile dementia of the Alzheimers type (SDAT) were studied with both computed tomography (CT) and positron emission transaxial tomography (PETT). Increases in ventricular size with both aging and disease were measured. Regional glucose metabolic rate was not affected by age, but was markedly reduced in SDAT patients. These data indicate that in normal aging, structural brain changes may be more salient than biochemical changes. Although both structural and biochemical changes occur in SDAT, the biochemical changes are more marked. The results suggest that PETT is potentially more useful than CT in the in vivo diagnosis of SDAT.

Positron emission tomography in the study of aging and senile dementia.

(18)F-2-deoxy-2-fluoro-D-glucose ((18)FDG) is a positron emitting tracer for rate of glucose utilization in brain. When used in conjunction with positron emission tomography (PET), the PET-FDG technique permits in vivo quantitation of regional brain metabolism in man. We have applied this technique to the study of regional brain function in normal aging and senile dementia. Preliminary results for 7 patients with senile dementia of the Alzheimers type (SDAT) and 3 elderly normal subjects indicated a large, statistically significant (p < 0.01) diminution in rate of glucose utilization in SDAT. Furthermore, the degree of diminution in metabolic activity in SDAT was highly correlated with objective measures of degree of cognitive impairment. These results demonstrate the feasibility and potential utility of the PET-FDG technique for studying regional brain function in normal aging and dementia.

Computed tomography evaluations of brain-behavior relationships in senile d dementia of the Alzheimer's type☆

Neuropathological investigations have demonstrated brain-behavior relationships in senile dementia of the Alzheimers type (SDAT), but CT studies have not produced consistent findings. We hypothesized that these discouraging results were in part due to limitations in the methods of CT scan evaluations, and to non-homogeneity of patient populations. The present study examined 43 out-patients with the presumptive diagnosis of SDAT using 37 cognitive test measures and 3 independent CT evaluation strategies. The CT methods included a new rank ordering procedure and two previously used techniques, physical measurement and 4-point rating. Highly significant (p less than or equal to 0.01) brain-behavior correlations were attained using the ranking and rating procedures for evaluation of ventricular and cortical pathology. It was found that rank ordering has high interrater reliability and is superior to the other methods for the evaluation of the ventricular system. The physical measurement of the third ventricle is the single most powerful linear correlate of cognitive impairment. Measurement of cortical sulci are of no correlational significance. Multiple regression analyses indicated that global assessments are the best cognitive predictors of both ventricular and cortical pathology. Thus the present study has demonstrated brain-behavior relationships in vivo in SDAT.

Computed tomography in the diagnosis of extra-axial posterior fossa masses

Extra-axial posterior fossa masses can be diagnosed reliably by computed tomography (CT) in most cases. Acoustic and trigeminal neurinomas, meningiomas, cholesteatomas, and other extra-axial masses can usually be distinguished from intra-axial masses by asymmetric widening of the basal subarachnoid spaces, bone destruction, continuity of the tumor mass with the tentorium or bone, and more sharply defined margins. Multiple-cut study of the posterior fossa improved visualization of the fourth ventricle and basal cisterns. Interpretation of cisternal changes in association with changes in the fourth ventricle and abnormal attenuation coefficients permits accurate diagnosis of posterior fossa masses.

Positron Emission Tomography and Computed Tomography Assessments of the Aging Human Brain

The relationship between alterations in brain structure and brain function was studied in vivo in both young and elderly human subjects. Computed tomography revealed significant age-related ventricular and cortical sulcal dilatation. The cortical changes were most closely related to age. Positron emission tomography failed to show regional changes in brain glucose metabolic rate. The results suggest that the normal aging brain undergoes structural atrophic changes without incurring regional metabolic changes. Examination of the correlations between the structural and the metabolic measures revealed no significant relationships. These data are discussed with respect to the significant structure-function relationships that have been reported in Alzheimer disease.

Pergolide for the Treatment of Pituitary Tumors Secreting Prolactin or Growth Hormone

We gave pergolide mesylate, a new long-acting ergot derivative with dopaminergic properties, to 47 patients with hypersecretion of prolactin or growth hormone. Single doses produced long-lasting reductions of serum prolactin levels; after 24 hours, the values remained depressed at a mean of 28.8 per cent of the base-line value. Among 41 patients (22 women and 19 men) with hyperprolactinemia who took pergolide for three months or more, prolactin levels fell to normal in 37 and remained slightly elevated in 2. In the two patients in whom the levels fell to only 38 to 52 per cent of base line, treatment was regarded as a failure. The level of growth hormone fell to a mean of 52.8 per cent of base line in patients with acromegaly who were taking 100 micrograms of pergolide per day. Among patients for whom adequate CT scans were available, definite tumor shrinkage occurred in 10 of 13 with macroadenomas and definite or probable shrinkage in 5 of 9 with microadenomas. Menses returned in 76 per cent of treated women and testosterone levels rose in 10 of 14 men. We conclude that pergolide reduces hypersecretion and shrinks most prolactin-secreting macroadenomas. In some patients long-term pergolide therapy may be superior to surgery and x-ray treatment.

Contribution of Structural Neuroimaging to the Early Diagnosis of Alzheimer's Disease

There is compelling evidence for the early involvement of the hippocampal formation in the natural history of Alzheimers disease (AD). The evidence comes from recent neuropathology, neuropsychology, and neuroimaging studies. AD-type histopathologic changes limited to the hippocampus have been described and may be seen in normal aging subjects. The sites of maximal neuronal loss in the hippocampal formation are in the CA1, subiculum, and entorhinal cortex. Minimally cognitively impaired (MCI) individuals (defined by ratings of functional capacity and psychiatric symptomatology) exhibit a neuropsychological profile that is distinct from that of the unimpaired elderly. Pathologic evidence suggests that most of these cases already have AD brain changes accentuated in the hippocampal region, and our own longitudinal studies reveal that 70% of this group develop dementia within a 4-year period. We have developed a negative-angle axial view designed to cut parallel to the anterior-posterior plane of the hippocampus. Using this modified axial plane of section in conjunction with computed tomography (CT) and magnetic resonance imaging (MRI), we estimated the prevalence of hippocampal atrophy in normal aging and across severity levels of cognitively impaired elderly patients. Longitudinal study shows that hippocampal atrophy is a sensitive and specific predictor of future AD for patients with MCI. MRI volume study of AD patients, controls, and MCI patients shows specific hippocampal volume loss in MCI. We conclude that the atrophic changes associated with early AD can be visualized using qualitative techniques and are readily quantifiable with volumetry. This article is not intended to be comprehensive, but to provide an overview of some of the structural neuroimaging data from our laboratory.

Positron emission tomography studies of normal aging: a replication of PET III and 18-FDG using PET VI and 11-CDG

Using PET VI and 11-CDG we replicated our earlier PET III and 18-FDG normal aging findings. Examination of young and old normal volunteers revealed the absence of any absolute regional age-related changes in glucose utilization. For the combined sample (N = 81) we did find evidence to suggest a relative hypofrontal change with increasing age. A strong relationship between age and ventricular size (CT) was also found. These findings suggest the preserved glucose metabolism of the resting aging brain in the presence of structural atrophic changes.

Brain death: II. Neuropathological correlation with the radioisotopic bolus technique for evaluation of critical deficit of cerebral blood flow

An innocuous intravenous portable radioisotopic test using technetium 99m pertechnetate was employed to demonstrate the deficit of cerebral blood flow associated with brain death. The results are compared to those of bilateral carotid and vertebral angiography in 20 patients. Absence of a bolus tracing from the head in the presence of a control tracing of a bolus from the femoral artery in two successive studies one hour apart reliably correlated with the clinical and electroencephalographic findings signifying cerebal death in comatose, apneic patients. Angiography indicated absence of intracranial circulation in 10 patients. Stasis filling or retrograde emptying of arterial vessels (or both) occurred in 7 patients. There was no evidence of venous filling in any of these 17 patients; all of them had either an absent head bolus or an “intermediate tracing.” Results indicate that either form of tracing represents a critical decrease of cerebral blood flow. Two other patients had evidence of severely impaired abnormal posterior fossa circulation without angiographic evidence of cerebral circulation; both of these patients had an absent head bolus. An additional patient had an unusually small head bolus, and angiography revealed extravasation of radiopaque material but no evidence of intracranial circulation. We conclude that the bolus technique is a helpful adjunct in diagnosing brain death.

Long term survival among patients with malignant brain tumors

Eight of 57 patients (14%) with malignant astrocytomas lived at least 2 years. The mean survival time was 143 weeks (range, 104 to 250 weeks). All of the patients were treated with operation, radiation, and chemotherapy. Four of the 8 patients died because of tumor recurrence, 1 died from a second primary tumor, 2 died of cases unrelated to the tumor, and 1 is still alive. Diffuse cortical dysfunction associated with cortical atrophy that could not be related to tumor regrowth and was not explained by focal deficits, psychotic of depressive thought disorders, metabolic or endocrine abnormalities, or hydrocephalus developed in the 3 longest-surviving patients. The diffuse dysfunction was initially apparent only through psychometric testing, but eventually became so disabling as to result in 2 of the 3 patients retiring from work. Although small, but gratifying, gains have been made in the treatment of patients with malignant brain tumors, accompanying these gains have been problems of a magnitude that is only now beginning to be appreciated.