Mohammed T. Abou-Saleh

360 PRINCIPLES AND PRACTICE OF GERIATRIC PSYCHIATRYdemonstrated that buspirone (a partial agonist at serotonergic 5-variation arising from other factors. The difficulties in dealingdemonstrated in normal subjects. For example, Friston et al. 18 that activity in parietal cortex in one study 34 was increased relativewith the multiple sources of confounding variation in PET imageshas hitherto limited the contribution of PET to the delineation ofpsychiatric disorders. From the clinician’s viewpoint, the biologicalHT 1A receptors) caused an attenuation of the normal increase inrCBF in the parahippocampal gyrus produced by a verbalmemory task, as well as a transient impairment of memory testsources of variation are the most relevant, some of which are performance. Conversely, Furey et al. 19 have shown improvedconsidered below.performance and reduced activity in the frontal lobe during aIn the study of elderly patients, one of the potentially working memory task after administration of physostigmine, aconfounding differences between subjects is brain atrophy, cholinesterase antagonist. These studies suggest that modulationwhich is liable to produce variation in partial volume effects.Partial volume effects are due to the limited spatial resolvingpower of PET cameras, resulting in the contamination of thesignal from high-intensity regions by adjacent tissue with lowof neurotransmitter systems has specific effects on brain functionduring cognitive activity, and have interesting implications for theuse of pharmacologic modulation in understanding psychiatricdisorders.intensity. For example, if grey matter volume is reduced, themeasured functional activity of the grey matter will be lowered byan increased contribution from adjacent white matter or CSF. Anumber of studies have examined the effect of cerebral atrophy onBLOOD FLOW AND METABOLISM IN ADmetabolic measures obtained with PET in both healthy olderadults and patients with Alzheimer’s disease 6,7 PET studies have produced a moderately consistent picture of the. A recent study byIbanez et al. 8 abnormalities of blood flow and metabolism in AD. The mostused measures of grey matter volume obtained fromcommon pattern is bilateral reduction in parietal and temporoparietalflow and metabolism, especially in early casesMRI scans to correct PET FDG images in a group of mildly tomoderately demented AD patients. They found that metabolic, butthe patterns of flow and metabolism show considerable variationvalues in parietotemporal and frontal cortex were reducedbetween patientscompared to a control group, even after correction for atrophy.. These variations correlate with variation inbehavioural and neuropsychological impairmentsThese data suggest that, despite the undoubted contribution of. Longitudinalstudies have demonstrated that focal metabolic abnormalities arepartial volume effects, the metabolic deficits seen in these patientsdetectable before the corresponding neuropsychological impairmentbecomes apparent, and that the metabolic abnormalitiesare not due simply to atrophy, but reflect true decreases inmetabolic activity.progress as the disease progressesWhen evaluating images of brain function, it is necessary not. Recent studies have shownthat metabolic abnormalities similar to those seen in the cortex ofonly to be aware of confounding variance introduced byAD patients can be found in asymptomatic persons at risk forextraneous factors, but also to know that the functionalfamilial ADimpairments in a single disease are quite heterogeneous. Forand that these deficits are associated with thepresence of the APOE-4 alleleexample, the clinical manifestations of AD are diverse, including.A few activation experiments with AD patients also have beennot only impairments of memory but also many different aspectsconducted. Mildly demented AD patients have shown greaterof cognitive function and behaviour. In accord with thisfrontal activations, compared to healthy elderly, during memorybehavioural heterogeneity, PET studies reveal that cases differtasksin the degree of laterality of the abnormalities, and also in theand during perceptual tasks 28 . This is similar to thedegree of frontal involvement 9 increased frontal activity seen in the healthy elderly, compared to. On the other hand, differentyoung adults, and indicates that recruitment of cognitivediseases can produce phenomenologically similar mental states,resources mediated by frontal regions may be a common responseraising the possibility that different diseases might produce similarto a decline in brain function, whether caused by normal ageing orpatterns of perturbation of regional blood flow and metabolism.by disease.This possibility is illustrated by the fact that hypometabolism offrontal cortex has been reported in AD 9 , depression 10 , Parkinson’sdisease 11 and in the psychomotor poverty syndrome in schizophrenia12 . The greatest value of PET thus may lie in the sensitivemeasurement of particular patterns of brain malfunction, ratherBASAL GANGLION FUNCTION IN HUNTINGTON’SDISEASEthan the distinction between diseases differing in aetiology.The major neuropathological process in Huntington’s disease(HD) is degeneration of the basal ganglia, especially the corpusACTIVATION STUDIESstriatum. Hence, it would be expected that there would be a loss ofpostsynaptic D1 and D2 dopamine receptors in the striatum,A potentially useful approach to the measurement of brainfunction is within-subject comparison of brain activity duringwhich has been amply demonstrated with imaging of thesereceptors using [ 11 C]SCH 23390 and [ 11 C]raclopride, respectivelybehavioural or pharmacological activation with that in an29 . It has been shown that a striatal decrease in dopamineappropriate reference state. Behavioural activation has beenused to identify the brain areas involved in specific mentalactivities in healthy young adults 13,14 and in older individuals 15 .Interestingly, older adults have been found to have greateractivation in frontal areas during some types of cognitive activity,compared to younger adults 16,17 . These results have led to thesuggestion that frontal cortex may play a compensatory role in theface of reduced function in other task-relevant brain areas, an ideathat also is relevant to diseases of ageing.is detectable even in asymptomatic persons who carry the HDgene mutation 30 , and further that the degree of reduction iscorrelated with reduced performance on cognitive tests of frontallobe function 31 . Glucose metabolism is also reduced in thestriatum of HD patients and patients at risk for HD 32 . Longitudinalstudies of disease progression in HD have shown declinesin both striatum and frontal lobe metabolism 33 , indicating thatPET could be useful in following the effects of treatment overtime.Measurement of rCBF during pharmacological activation Only a few activation studies have been carried out with HDallows measurement of the response of the brain to drugs thatalter neurotransmission. Although not yet used in psychiatricpopulations, the feasibility of this type of strategy has beenpatients. Patients have been studied with [ 15 O]water during handor finger movements and show reduced flow in the striatum,motor areas and prefrontal cortex 34,35 . Of particular interest is