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Title: Investigation and diagnosis of primary cerebral atrophy using single photon emission tomography and qualitative psychological assessment
Author: Goulding, Peter Jonathan
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1990
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Recent biopsy and necropsy studies have demonstrated that a significant proportion of patients with dementia due to primary cerebral atrophy do not have Alzheimer's disease. However, these patients are rarely identified during life despite the fact that different forms of primary cerebral atrophy may be characterised by specific patterns of impairment on neuropsychological assessment. This is because independent assessments of cerebral function have not been available. Single photon emission tomography, using brain seeking radiopharmaceuticals, such as 99mTc-HMPAO, has recently provided such a tool. An earlier preliminary study has shown single photon emission tomography to be successful in helping to distinguish between Alzheimer's disease and Dementia of Frontal Lobe Type. A close relationship was demonstrated between visually reported areas of reduced tracer uptake and the profile of neuropsychological breakdown determined clinically. Uptake was reduced in the posterior hemispheres of Alzheimer patients, whilst patients with Dementia of Frontal Lobe Type showed a selective anterior hemisphere abnormality. The appearances on single photon emission tomography allowed further patients with Dementia of Frontal Lobe Type to be identified with greater precision. In this study 23 patients, showing selective anterior hemisphere abnormalities, are compared with a group of 48 patients with biopsy-proven, subsequently autopsy proven and clinically suspected Alzheimer's disease, in whom scans demonstrated either posterior hemisphere defects or a normal distribution of tracer. Differences were demonstrated at the level of historical presentation, the findings on physical examination, the profile of neuropsychological breakdown, the results of electroencephalography and demographic data. Necropsy examination of the brains of similar patients to those studied has excluded Alzheimer's disease and revealed neuronal loss, spongiform change and gliosis, predominantly affecting the frontotemporal lobes of the brain. In a further study, four patients with the clinical manifestations of Dementia of Frontal Lobe Type who later developed features of motor neurone disease are described. Single photon emission tomography revealed prominent anterior hemisphere abnormalities. Three of the patients subsequently died and at autopsy the histological characteristics of both Dementia of Frontal Lobe Type and the amyotrophic form of motor neurone disease were detected, in all three brains and spinal cords, indicating an association between the two disorders. A further patient with presumed non-Alzheimer cerebral atrophy is described, who developed over five years, a progressive aphasic syndrome without other features of intellectual impairment. However, right sided pyramidal and extrapyramidal signs also emerged. Single photon emission tomography showed selective reduced tracer uptake in the left hemisphere and left subcortical grey matter, indicative of lobar atrophy. Since the histological changes of other documented cases of progressive aphasia are similar to those of Dementia of Frontal Lobe Type then both disorders may represent different lobar forms of a common and perhaps related pathological change. Visual assessment of single photon emission tomograms has been shown to be a useful qualitative tool in determining the anatomical distribution of pathology in primary cerebral atrophy. However the technique suffers the relative disadvantage of being non-quantitative. Accordingly, a new semi-automatic method of quantifying uptake of 99mTc-AMPAO has been developed. The technique has shown promise as an aid to qualitative reporting of images. It is simple and rapidly performed and is capable of distinguishing patients with Alzheimer's disease and those with Dementia of Frontal Lobe Type from normal controls. Moreover, assessment of two year follow-up images in both diseases showed significant measureable decreases in tracer uptake over time. The studies presented in this thesis indicate that single photon emission tomography is a valuable imaging technique in the investigation and diagnosis of dementia due to primary cerebral atrophy. The areas of reduced tracer uptake indicate the regions of impaired cerebral function that underlie the distinct clinical neuropsychological syndromes which characterise different forms of cerebral atrophy.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available