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 0-470-84641-0THE GENETICS OF ALZHEIMER’S DISEASE 22125. Burt DB, Loveland KA, Chen Y-W et al. Aging in adults withDown’s syndrome: report from a longitudinal study. Am J MentRetard 1995; 100: 262–70.26. Devenny DA, Silverman WP, Hill AL et al. Normal ageing in adultswith Down’s syndrome: a longitudinal study. J Intellect Disabil Res1996; 40: 208–21.27. Oliver C, Crayton L, Holland AJ et al. A four-year prospective studyof age-related cognitive change in adults with Down’s syndrome.Psychol Med 1998; 28: 1365–77.28. Zigman W, Schupf N, Haveman M, Silerman W. The epidemiologyof Alzheimer’s disease in intellectual disability: results and recommendationsfrom an international conference. J Intellect Disabil Res1997; 41: 76–80.29. Rumble B, Retallack R, Hilbich C et al. Amyloid A4 protein and itsprecursor in Down’s syndrome and Alzheimer’s disease. N Engl JMed 1989; 320: 1446–52.30. Potter H. Alzheimer’s disease, Down’s syndrome, and chromosomesegregation. Lancet 1996; 348: 66.31. Schupf N, Kapell D, Lee JH et al. Increased risk of Alzheimer’s diseasein mothers of adults with Down’s syndrome. Lancet 1994; 344: 353–6.32. Prasher VP, Chowdbury TA, Rowe BR, Bain SC. ApoE genotypeand Alzheimer’s disease in adults with Down syndrome: metaanalysis.Am J Ment Retard 1997; 102: 103–10.33. Farrer MJ, Crayton L, Davies GE et al. Allelic variability in D21S11,but not APP or APOE, is associated with cognitive decline in Downsyndrome. NeuroReport 1997; 8: 1645–9.34. Mann DMA. Association between Alzheimer’s disease and Downsyndrome: neuropathological observations. In Berg JM, Karlinsky H,Holland AJ, eds, Alzheimer Disease, Down Syndrome, and TheirRelationship, Oxford University Press: Oxford, 1993; 71–92.International Criteria for Alzheimer’s Disease and Their Problems—ICD-10, DSM-IV and NINCDS–ADRDAKenneth RockwoodDalhousie University, Halifax, Nova Scotia, CanadaDementia often comes to attention when an elderly person’scognition or behaviour no longer conforms to what is expected.Given inherent variability in people and their circumstances, intheir past and present performance, in how this matters, in theexpectation of changes with age, it is no surprise that howdementia is described, whether it is attributed to Alzheimer’sdisease (AD), and what that is taken to mean will vary withinand across societies 1 . Comparing three sets of commonly-usedcriteria for AD shows that while each conceptualizes dementiasimilarly, differences in their literal application can give highlyvariable results. Such specious variability distracts from theimportant task of better understanding heterogeneity in diseaseexpression—especially in the presence of medical and psychiatricco-morbidity.THE THREE SETS OF CRITERIAThe criteria of the National Institute of Neurological andCommunicative Disorders and Stroke, and the Alzheimer’s Diseaseand Related Disorders Association (NINCDS–ADRDA) 2 requirea clinical examination to produce evidence of dementia, defined asprogressive deficits in memory and other areas of cognition (notablylanguage, motor skills and perception) that occurs without adisturbance of consciousness, and in the absence of ‘‘systemicdisorders other than brain diseases that in and of themselves couldaccount for the deficits’’. The criteria also require that the onset bebetween ages 40 and 90, the initial examination include astandardized cognitive test, and the deficits be ‘‘confirmed byneuropsychological tests’’. ‘‘Exclusion of causes of dementia otherthan Alzheimer’s’’ allows a diagnosis of probable AD, withneuropathological confirmation required to make the diagnosisdefinitive. Possible AD exists when ‘‘atypical’’ features or other comorbidillnesses exist.The 10th International Classification of Diseases (ICD-10)has both clinical guidelines 3 and research criteria 4 for Mentaland Behavioural Disorders. AD is classed as a dementia,defined as progressive impairment, in the absence of cloudingof consciousness, of multiple higher cortical functions, specifiedas: memory, thinking, orientation, comprehension, calculation,learning capacity, language and judgement. Interestingly, thecriteria also note that non-cognitive features (‘‘deterioration inemotional control, social behaviour, or motivation’’) canaccompany or even precede dementia. The diagnosis is oneof exclusion; only insidious onset and slow deterioration arecited as characteristic of AD. Subtypes include early and lateonset, and ‘‘atypical or mixed’’. The research criteria specifymild, moderate and severe stages, based chiefly on the extentof memory loss, although the impact on daily activities isnoted.The fourth edition of the Diagnostic and Statistical Manual ofMental Disorders (DSM-IV) of the American Psychiatric Associationdefines dementia as ‘‘multiple cognitive deficits that includememory impairment and at least one of . . . aphasia, apraxia,agnosia, or a disturbance in executive functioning’’, provided thatsuch deficits cause impairment, ‘‘occupational or social functioning’’and represent a decline 5 . The criteria for ‘‘Dementia of theAlzheimer’s Type’’ emphasize the need to rule out otherconditions, and to exclude the syndrome if it exists only in thesetting of delirium. Subtypes include early and late onset, andeach of coincident delirium, delusions, and depressed mood. Theaccompanying text emphasizes insidious onset and gradualdecline, notes that (but does not specify how) ‘‘cultural background’’should be taken into account, and, while recognizingdifferences in levels of disability, provides no specific criteria forstaging.PROBLEMS WITH CURRENT CRITERIADespite cross-national studies of their individual reliability andvalidity 6 variability in diagnostic criteria can have profound