FALLACIES IN THE PATHOLOGICAL CONFIRMATION OF THE DIAGNOSIS OF ALZHEIMERS-DISEASE

Objective-Necropsy confirmed clinical diagnostic accuracy for Alzheime r's disease is claimed to exceed 90%. This figure contains two fallaci es; it includes cases in which Alzheimer's disease exists with other d iseases affecting cognition and the studies that report these figures excluded cases without necropsy (verification bias). The effect of the se errors is estimated. Methods-Data were taken from the University of Western Ontario Dementia Study, a registry of dementia cases with cli nical and psychometric follow up to necropsy based in a university mem ory disorders clinic with secondary and tertiary referrals. Data were available on 307 patients; 200 (65%) had clinically diagnosed Alzheime r's disease, 12 (4%) vascular dementia, 47 (15%) mixed dementia, and 4 8 (16%) had other diagnoses. One hundred and ninety two of 307 cases ( 63%) died and 122 of 192 fatalities (64%) had necropsies. The patholog ical material was interpreted in two ways, allowing and disallowing co existent disease in making a diagnosis of Alzheimer's disease. In case s without necropsy, progressive cognitive loss was used as a marker fo r degenerative dementia. The outcome measures of interest were the pos itive predictive value of a clinical diagnosis of Alzheimer's disease allowing and disallowing coexistent diseases and with and without corr ection for cases that were not necropsied. Results-The clinical diagno ses differed significantly between the population who died and those w ho did not. In cases without necropsy, 22% had no dementia on follow u p, concentrated in early cases and men, showing considerable scope for verification bias. The positive predictive value of a diagnosis of Al zheimer's disease was 81% including coexistent diseases, falling to 44 % when limited to pure cases. Combined, these factors reduce the posit ive predictive value to 38% for pure Alzheimer's disease. Conclusions- Correction for dual pathology and verification bias halves the positiv e predictive value of the clinical diagnosis of Alzheimer's disease. D ata derived from necropsy studies cannot be extrapolated to the whole population. This has important implications including uncertainty abou t diagnosis and prognosis and a dilution effect in therapeutic trials in Alzheimer's disease.