Neuroimaging of Function in Alzheimer's Disease and Other Dementias

Hunter, Robert (1992) Neuroimaging of Function in Alzheimer's Disease and Other Dementias. MD thesis, University of Glasgow.

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Abstract

Interest in Alzheimer's disease (AD) has increased considerably in the last decade. As a result of demographic changes the number of AD sufferers is steadily increasing and AD is recognised as a major public health challenge. This has been paralleled by recent advances in understanding the biology of AD, particularly using neuroimaging and molecular biological methods. This thesis describes an investigation using functional brain imaging techniques of presenile AD patients, and two control groups, Korsakoff's psychosis (KOR) and healthy subjects. Current understanding of the concept of AD is reviewed, together with the contribution of clinical and neuropathological findings to the establishment of diagnostic criteria. The experimental chapters describe investigations carried out on presenile AD patients, therefore the relationship of early onset AD to that presenting at an older age is also discussed. The rationale of using cerebral blood flow (CBF) as an index of brain metabolism rests on evidence that supports the hypothesis that there is close coupling of CBF and brain metabolism during 'resting' conditions, and possibly also under at least some conditions of brain activation. The development of methods for measuring CBF, from the early estimates of global CBF provided by the Kety-Schmidt technique to the introduction of functional tomographic imaging, such as single photon emission computed tomography (SPECT) and positron emission tomography (PET), in the last decade is described. The contribution of these techniques to understanding the brain dysfunction of AD is critically reviewed. A method for measuring the cerebral vascular transit time of pertechnetate (99mTc), after intravenous bolus injection using a gamma camera is described. Estimates of net mean transit time (net MTT) in a planar non-tomographic vertex projection of brain were determined in 17 patients with presenile AD, 9 abstinent patients with Korsakoff's psychosis (KOR), and 10 healthy matched controls. The CAMDEX was used to assess patients and the CAMCOG to describe cognitive function. In both AD and KOR groups net MTTs were significantly lengthened compared with controls, although without information on volume of distribution it is not possible to relate net MTT results to CBF. There was no significant difference between net MTT results of AD and KOR groups. More importantly, examination of individual net MTT scores in the three groups showed some degree of overlap. Using net MTT data from healthy control subjects, 'normal' cut-off values of net MTT for all regions were established, and positive predictive values calculated. For posterior cortical regions in AD patients, positive predictive values were greater than 70% suggesting that for this region the method may have some degree of clinical utility. The pattern of cognitive function was differentially impaired in AD and KOR groups and there was a tendency for estimates of net MTT to be inversely associated with CAMCOG measures. The prolongation of transit times in cortex of KOR patients suggests cortical involvement in a disorder usually considered primarily subcortical. Positive predictive value of net MTT in posterior regions of interest in AD patients support the case for further investigation of the clinical utility of the method. The radiotracer 99mTc-HMPAO was used with SPECT to determine patterns of regional uptake of radiolabel into brain regions of patients with presenile Alzheimer's disease and Korsakoff's psychosis, and age-matched controls. Using occipital cortical uptake as a reference area, the pattern of relative regional cerebral blood flow (rCBF) was determined in other cortical areas and basal ganglia. In Alzheimer's disease reduction in rCBF occurred in posterior temporal and parietal areas. By contrast, in Korsakoff's psychosis posterior temporal rCBF was maintained, although there was a trend to reduced tracer uptake in other cortical areas. There was considerable overlap of individual relative rCBF values in both patient groups and controls. As a result positive predictive values are low and only greater than 50% in posterior temporal regions of AD patients. The degree of overlap of individual test results of different diagnositc groups casts doubt on the diagnostic utility of SPECT imaging using HMPAO. These impairments of flow were correlated with impairments of neuropsychological function. (Abstract shortened by ProQuest.).

Item Type: Thesis (MD)
Qualification Level: Doctoral
Additional Information: Adviser: G Fink
Keywords: Medicine, Medical imaging, Neurosciences
Date of Award: 1992
Depositing User: Enlighten Team
Unique ID: glathesis:1992-75193
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 21:49
Last Modified: 19 Nov 2019 21:49
URI: http://theses.gla.ac.uk/id/eprint/75193

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