Mohammed T. Abou-Saleh

ANTEMORTEM MARKERS 235predictive of subsequent conversion to AD 37 . In distinguishingbetween AD and other dementias, one study differentiated ADfrom normal ageing, depression, VaD and other causes ofcognitive impairment 38 , while in another study, no significantvolumetric differences were found between patients with subcorticalVaD and AD patients, apart from the volume of thecerebellum 39 .Positron emission tomography (PET) has been found todifferentiate between AD and VaD: in AD the typical metabolicpattern is hypometabolism in temporoparietal and frontalassociation areas, while in VaD scattered areas of hypometabolismextending over cortical and subcortical structures are seen 40 .CONCLUSIONIt is clear that a number of difficulties beset the researcherinterested in finding an antemortem marker for AD. Some of thetechniques used in this search have important limitations—inparticular, CSF measurements are influenced by a variety offactors. Diagnosis of AD, even at autopsy, may not always beaccurate, leading to heterogeneity of the patient sample. Inaddition, AD may be a heterogeneous disorder, perhaps with apresenile form, but certainly with different manifestations in themuch older age group. A marker may be present in a control withthe AD trait who has not yet developed AD, and if a marker isrelated to the severity of AD, it may not distinguish between mildcases and controls. Other dementias may overlap with AD, notonly in phenomenology but also in pathogenesis, and thereforedisplay similar markers. There are also mixed cases, wherepatients, for example, have both AD and VaD.Nevertheless, the work discussed here does suggest that somecombination of measures may ultimately correlate strongly withbiopsy diagnosis. Work in molecular and genetic biology and inbrain imaging seems particularly promising and may well tie inwith our knowledge of neurochemistry and neuropathology. Aninterdisciplinary effort to find an antemortem marker is useful notonly in leading to a better delineation of AD-related dementiasand AD subtypes, but also in providing a focus on centralpathogenic mechanisms and their possible reversal.Finally, markers may be expressed differently in differentpopulations. A genetic variant of apolipoprotein E, ApoE e4(Chapter 41) has been shown to be a risk factor for late-onset AD.Yet, in spite of relatively high frequencies of ApoE e4 in Africancountries, the prevalence of AD is very much lower than in theWestern population 41 , making it extremely important for us tounderstand the aetiology of the disease.ACKNOWLEDGEMENTSThe authors are supported by the Medical Research Council ofSouth Africa and the Provincial Administration of the WesternCape.REFERENCES1. Zubenko GS. Biological correlates of clinical heterogeneity in primarydementia. Neuropsychopharmacology 1992; 6: 77–93.2. Roth M. 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