Mohammed T. Abou-Saleh

366 PRINCIPLES AND PRACTICE OF GERIATRIC PSYCHIATRYrCBF throughout the cortex on HMPAO SPECT study, but anormal CT scan 40 . Patients with the AIDS dementia complex havebeen found, using SPECT, to have multiple or focal rCBF deficits,correlating with focal signs or symptoms, while CT scans showeddiffuse cerebral atrophy 41 .DISCUSSIONStudies employing SPECT and PET can reveal cerebral abnormalitieswhen CT and MRI do not, because the latter are measuresof cerebral structure, while the former are measures of cerebralfunction. SPECT is, and is likely to remain, much more generallyavailable than PET, but it is not currently capable of absolutequantification.The characteristic SPECT findings in AD are bilaterallydecreased rCBF in the parietal and temporal lobes adjacent tothe occipital lobes, sometimes involving the frontal lobes,particularly in later cases. The primary motor, sensory and visualcortices and basal ganglia are relatively unaffected. This contrastswith typical CT findings of diffuse cerebral atrophy, although theCT scans have not generally been orientated along an axis thatobtains optimum views of any focal atrophy in the hippocampusand temporal lobe 42 . However the Oxford Project to InvestigateMemory and Aging (OPTIMA), which involved 200 patients withdementia and 119 normal controls evaluated annually tillnecropsy showed that medial temporal lobe atrophy (CT Scan),(80% diagnostic accuracy) and parietotemporal hypoperfusion bySPECT (83%) predicted the pathology of AD better than theestablished clinical criteria of NINCDS-ADRDA (66%) andDSM-IIIR (66%) 35 . On careful assessment, focal features can beseen on CT scans which correlate with individual symptoms, suchas aggression or wandering 43 , but the extent of the focal CTabnormalities is less than that seen on SPECT, and it appears thatstructural atrophy lags behind clinical deficit.The diagnosis of dementia and its differentiation from otherclinical syndromes, such as depression, is still primarily a clinicalmatter. If a structural lesion, such as a cerebral tumour, is suspected,then a structural scan, such as CT, is likely to be the best test for this.What, then, is the appropriate role of SPECT in current clinicalpractice in the assessment of dementia? The study by Upadhyaya etal. 34 suggests that it would be unwise to expect SPECT to assist inthe differentiation of dementia from depression in the elderlybecause similar, albeit less marked, changes are seen in depression,as in AD. It would be interesting to know if those elderly individualswho present with the clinical syndrome of depression, and who havethe characteristic AD abnormalities on SPECT, have a worseprognosis than those with normal SPECT scans. They might beindividuals at risk of developing AD where depression has been oneof the early clinical features, but much more information, includingfollow-up studies, is needed on this patient group to evaluate theutility of SPECT. More information is also needed on the frequencywith which perfusion deficits (particularly those with a patternsimilar to that in AD) are seen on visual inspection of SPECTstudies in healthy, elderly controls. Patients with PD, particularlythose who are cognitively impaired or receiving chronic anticholinergictreatment, also have similar SPECT abnormalities topatients with AD. Perhaps it is not surprising that there may besimilarities on this measure of brain function, as there can be adegree of overlap of the clinical syndromes.If the clinical diagnosis of dementia is made in an individualpatient and it appears to be a primary degenerative dementia, theSPECT study can add weight to the clinical impression that theunderlying diagnosis is that of AD, frontal lobe dementia (FLD)or progressive supranuclear palsy (PSP). AD is most characteristicallyassociated with posterior rCBF deficits, while FLD andPSP are strongly associated with anterior rCBF deficits andthemselves have distinctive patterns when CT scans are notparticularly helpful in this situation. Similarly, Korsakoff’spsychosis appears to be more characteristically associated withfrontal rCBF deficits than posterior temporal deficits 17 . SPECTcan also assist the clinical assessment in the differentiation of ADfrom MID: bilateral parietotemporal deficits are stronglysuggestive (but not diagnostic) of AD, although it must beremembered that AD and MID coexist in a substantial minorityof cases. There is no particular single pattern of rCBF deficits seenin MID. SPECT findings vary from normal to asymmetricaldeficits and theoretically MID could mimic any other pattern.However, if an asymmetrical pattern is found affecting areas otherthan the parietotemporal region, it is suggestive of MID. Thisimpression is strengthened if the rCBF deficits coincide withcerebral infarcts seen on structural imaging with CT or MRI. If apatient with relatively advanced dementia has a normal SPECT, itis unlikely to be AD and may be consistent with MID.All these conclusions, however, must be tempered by theknowledge that our present association of SPECT and PETpatterns with specific conditions is based on studies where clinicaldiagnoses of patients are made initially and are then correlatedwith the SPECT findings. We need follow-up studies andpathological findings at post mortem to make more definitiveassessments of the significance of specific SPECT patterns. Indeeda recent study evaluated early AD (mild cognitive impairment)using brain perfusion SPECT who were diagnosed to have AD 2years later with a follow-up SPECT 44 . Selective reduction in CBFwas observed in the left hippocampus and parahippocampal gyrusin the follow-up SPECT. We could also learn whether SPECTstudies can help predict clinical outcome in individual cases. Thereis evidence from PET studies of patients with early AD that focalcortical reductions in glucose metabolism precede the appearanceof focal neuropsychological deficits.However, if the early whole-brain studies are correct and themetabolic rate of glucose is uncoupled from CBF in early AD,such that it is decreased relative to CBF and the rCBF is reducedlater in the course of the disease, SPECT might have differentpredictive power in comparison with PET in early AD. It ispossible that patients at risk for HD may be diagnosed in thepresymptomatic phase by the SPECT finding of reduced rCBF inthe caudate nucleus.It is clear that SPECT will be used substantially in furtherresearch in AD. More significant advances in our knowledge ofAD are likely to come from follow-up and activation studies.The latter would involve paired SPECT studies, basal andactivated, and the activation could be cognitive or pharmacological.For paired studies, the important measure is the differencein rCBF between the two SPECT studies, which indicates theeffect of activation. This avoids the problem of variation in basalvalues between individuals and the problem of the effect of anuncertain degree of cerebral atrophy upon rCBF. The semiquantitativemeasures of SPECT are adequate, and may bepreferable, for this analysis. Cognitive activation studies incontrols and in patients with AD would provide a betterunderstanding of the cerebral processes involved in cognitivefunction in normal individuals, and knowledge about the form ofdisruption of these processes in disease. Pharmacologicalactivation studies would enable direct measures of specificneurotransmitter function to be made and hence the pharmacologicalcharacterization of disease in an individual, withimplications for treatment and prognosis 19 .Another promising direction for SPECT is the study ofneurotransmitter receptors. The radioligand 123 I-QNB has beendeveloped for the measurement of muscarinic cholinergic receptorsand it has been used in the study of AD 3 . Currently it requiresa radiochemist on site to produce 123 I-QNB, and so it is notcommercially available, but the development of radioligands for