The studies described in this Thesis were designed to investigate the patterns of cerebral blood flow (CBF) deficits that occur in Dementia of the Alzheimer Type (DAT) and relate them to performance on a variety of cognitive tasks. Previous work investigating the relationship between CBF and cognition in DAT (Bonte et al. 1986; Burns et al., 1989; Hunter et al., 1989) has produced large numbers of non-specific associations which are difficult to interpret. It was hypothesised that more meaningful associations might be produced if the assessment of cognition involved more specific neuropsychological tests. Therefore these studies aimed to investigate the CBF-cognition relationship using a general cognitive test as well as a number of specific neuropsychological tasks. In recent years the focus of research in this field has shifted from the later to the earlier stages of DAT. This shift is reflected here with the investigations of rCBF and cognition not only in a moderate to severe DAT group, but also in a mild and a minimal group. Using a dedicated neuroimager (SME 810) and the relatively recently developed radiopharmaceutical, 99m-Technetium labelled Hexamethyl-propylenamine oxime (HMPAO). Single Photon Emission Computerised Tomography (SPECT) was carried out to measure regional cerebral blood flow in DAT patients and controls. SPECT images were obtained for two slices; a 'standard' slice containing medial and lateral frontal, temporal, posterior temporal, occipital, calcarine, thalamic and basal ganglia regions; and a 'high' slice containing high frontal and parietal regions. Measures of blood flow were obtained and expressed as proportions of calcarine activity for normalisation purposes. The patient populations were recruited from a psychiatric hospital (moderate and severe cases), and from a memory clinic (minimal and mild cases.) All patients were diagnosed as suffering from DAT according to the CAMDEX diagnostic criteria (Roth, Tym, Mountjoy et al., 1986) and severity was classified according to cognitive performance on the CAMCOG (Roth et al., 1986) a general cognitive assessment procedure. Further cognitive assessment involved recall and recognition memory performance on a Delayed Recognition Span Task (DRST) (Moss et al.,1986), performance on four established 'Frontal' tasks (word fluency, Wisconsin card sorting task, delayed alternation task, subject ordered pointing task) and performance on a standardised confrontational naming task (Graded Naming Test, McKenna & Warrington 1983). Performance of the DAT patients compared to controls was examined for both the memory and frontal investigations, while performance on the naming task was examined for the presence of highly specific subgroups within the DAT population itself. SPECT scanning was carried out within four weeks of neuropsychological assessment. Correlational analyses were performed in order to investigate the relationship between cognition and rCBF. In particular, correlations were carried out between CBF and performance on the GAMGOG (and its subscores) , GBF and performance on the Recognition Span Task and GBF and performance on the frontal tasks. The relationship between performance on the naming task and GBF was investigated quite differently. Subgroups of patients were selected on the basis of the types of naming error they made and their GBF patterns were examined to see whether they reflected their particular cognitive impairment. These studies found that a memory clinic provides a suitable method of recruiting cases of early DAT for research purposes and that the analysis of presenting symptoms may contribute to the difficult task of identifying very early cases of dementia. The results of the CBF studies support the view that deficits develop very early on in the degenerative process since the minimal group display a clear left temporal deficit. The increased severity of the mild DAT group is reflected in their CBF picture; this group display deficits in much of the cortex as well as the thalamic region. The moderate to severe group also displayed extensive CBF deficits reflecting severe damage to all cortical regions. The cognitive assessment of the patients with the CAMCOG revealed ceiling and floor effects suggesting that this type of task is more suitable for general cognitive monitoring rather than for the investigation of specific cognitive functions. The Recognition Span task illustrated very early deficits in both recall and recognition and demonstrated that recall scores distinguished the minimal DAT group from the control group. While recall scores drop to floor level by the moderate stage of DAT, performance on the recognition tasks shows that some recognition memory ability remains beyond this point. Performance on the frontal tasks was also shown to be impaired by DAT and related to overall severity. No outliers were found on any of these tasks therefore making it unlikely that a disproportionate frontal deficit exists in these patients. (Abstract shortened by ProQuest.)
