Mohammed T. Abou-Saleh

Principles and Practice of Geriatric Psychiatry.Editors: Professor John R. M. Copeland, Dr Mohammed T. Abou-Saleh and Professor Dan G. BlazerCopyright & 2002 John Wiley & Sons LtdPrint ISBN 0-471-98197-4 Online ISBN 0-470-84641-0MINOR COGNITIVE IMPAIRMENT 307Alzheimer’s Disease: One or Several?C. Holmes and A. MannInstitute of Psychiatry, London, UKThe current research diagnostic criteria for psychiatric illness,DSM-IV 1 and ICD-10 2 have evolved from a clinically descriptiveexercise to an operationally defined procedure with a sharpdemarcation between disease categories. In studies of dementia,diagnostic criteria with a hierarchical approach to diagnosis havealso been widely adopted, in which the probability of a diagnosticsubtype of dementia being present in a subject is also specified 3–5 .Subjects who fulfil clinical diagnostic criteria for probable diseaseare considered to have a purer form of the disease than thosefulfilling the possible diagnostic category alone. This categoricalapproach aims to maximize differences between cases so that theyare cleanly diagnosed. Thus, the presence of a delirium excludesthe diagnosis of dementia, and the presence of cerebrovasculardisease debars the diagnosis of probable Alzheimer’s disease(AD). So widespread is the use of these diagnostic criteria that it isnow almost impossible to practise clinical psychiatry, let alone getresearch findings published, without reference to them.Clearly, this approach has its uses. It enables psychiatrists fromdifferent cultures to know, within the restraints of the diagnosticcriteria, what collection of phenomenology or associated pathologythey are talking about. An expertise (and associated researchprojects) can be developed within these diagnostic categories.However, there are problems with such an approach and theseare particularly clear in the area of dementia research. Thus, acategorical approach to diagnosis can lead to the exclusion of alarge and interesting group of patients who do not fall into neatdivisions. Such an approach emphasizes research into differencesrather than similarities, between diagnostic categories. Finally, theassumption that clinical diagnostic categories have biologicalmeaning is questionable.In dementing illness, mixed pathologies are common. Indeed,the presence of vascular or Lewy body pathology, in the absenceof other pathology, is relatively rare 6 . The reasons why variouspathologies coexist could give important clues to the aetiology ofboth. However, for example, examination of patients fulfillingNINCDS–ADRDA diagnostic criteria for probable AD will leadto the exclusion of patients who have vascular risk factors, and sotheir importance in the development of AD pathology will beunderestimated 7 . Common risk factors that are likely to beimportant in the development of AD and vascular disease havebeen recently reviewed 8 , with associations found between AD andatherosclerosis, smoking, type 2 diabetes and high cholesterol.The mechanisms of such a link are not yet established. Doesvascular disease play a part in the promotion of AD pathology orits presentation? Do common factors, such as insulin resistance,oxidative stress or cytokine activation, underlie both pathologies?Clearly, the examination of mixed cases in research studies wouldbe beneficial in understanding common aetiological mechanisms.The separation of some diagnostic categories lends an emphasisto differences where in fact greater similarities exist. Dementia anddelirium, like the common subgroups of dementia, often coexistand also share many similar clinical and biological features. Thisfinding is, ironically, emphasized by the demarcation of onesubgroup of dementia, dementia with Lewy bodies, which hasclinical characteristics such as prominent attentional deficits,hallucinations and fluctuating cognition that can make differentiationfrom delirium, particularly in initial presentation, verydifficult. Rather than emphasize differences, another approachwould be to accept the clinical similarities and to examine in moredetail common epidemiological factors and pathological mechanismsof action, such as acetylcholine depletion and cytokineactivation 9 .The adoption of clinical diagnostic criteria often presumes thata group of individuals, having reconciled a number of differentopinions of varying political strength, have been able to define asingle biological entity on the basis of its clinical features. Clearly,this is highly unlikely. Indeed, in dementia research (where we arefortunate in having generally agreed neuropathological hallmarksby which this hypothesis can be tested) it can be seen that theapplication of clinical research diagnostic criteria to a communitybasedsample of patients with dementia suggests that, while theyare efficient in identifying pathology per se, they are notably lessefficient when other pathologies are present 6 .In summary, whilst clinical diagnostic criteria have their uses,they also have their limitations. A broader perspective is needed,which can encompass research into the common aetiologicalmechanisms that explain the existence of common clinical orpathological phenomena across, and between, different clinicaldiagnostic categories.REFERENCES1. American Psychiatric Association. Diagnostic and Statistical Manual ofMental Disorders, 4th edn (DSM-IV). Washington, DC: APA, 1994.2. World Health Organization. The ICD-10 Classification of Mental andBehavioural Disorders. Geneva: WHO, 1992.3. McKhann G, Drachman D, Folstein M et al. Clinical diagnosis ofAlzheimer’s disease. Report of the NINCDS–ADRDA work groupunder the auspices of Department of Health and Human Services TaskForce on Alzheimer’s Disease. Neurology: 1984; 34: 939–44.4. Roman GC, Tatemichi TK, Erkinjuntti T et al. Vascular dementia:diagnostic criteria for research studies. Report of the NINDS–AIRENInternational Workshop. Neurology 1993; 43: 250–60.5. McKeith IG, Galasko D, Kosaka K et al. Consensus guidelines for theclinical and pathologic diagnosis of dementia with Lewy bodies (DLB):report of the consortium on DLB international workshop. Neurology1996; 47: 1113–24.6. Holmes C, Cairns N, Lantos P, Mann A. Validity of current clinicalcriteria for Alzheimer’s disease, vascular dementia and dementia withLewy bodies. Br J Psychiat 1999; 174: 45–50.7. Prince MJ. Vascular risk factors and atherosclerosis as risk factors forcognitive decline and dementia. J Psychosom Res 1995; 39(5): 525–30.8. Stewart R. Cardiovascular factors in Alzheimer’s Disease. J NeurolNeurosurg Psychiat 1998; 65: 143–7.9. Eikelenboom P, Hoogendijk WJ. Do delirium and Alzheimer’sdementia share specific pathogenetic mechanisms? Dement GeriatCogn Disord 1999; 10(5): 319–24.