Research evaluation and diagnosis of probable Alzheimer's disease over thelast two decades: I

Objective: To describe the experience of a research clinic diagnosing AD du ring the last two decades, with special emphasis on patients who meet the N ational Institute of Neurological and Communicative Disorders and Stroke-Al zheimer's Disease and Related Disorders Association criteria for probable A D, their patterns of clinical presentation, and neuropathologic outcomes. B ackground: Probable AD has a heterogeneous clinical presentation, and can o ccur in the context of complicating factors. There are few reports, and non e with this large of a sample, about the pattern of presentation, the natur e of comorbidities, and the sensitivity and specificity of diagnosis. Resul ts: The AD Research Center of Pittsburgh examined 1139 patients with probab le AD between April 1983 and February 2000. Of these 1139 probable AD patie nts, 29 (2.5%) had slow progression, 27 (2%) had rapid progression, 70 (6%) had an atypical presentation, and 85 (7%) had coexistent cerebrovascular d isease. Confluent periventricular white matter lesions were found in 348 (3 0.5%) patients with probable AD. The overall sensitivity for the diagnosis of AD was 97% and the specificity 80%. However, the accuracy for the diagno sis of AD varied over the years: from 1983 to 1989, the sensitivity was 94% and specificity 52%, and from 1990 to 2000, the sensitivity was 98% and sp ecificity 88%. Conclusion: Although the diagnosis of probable AD has been u sed to indicate the presence of a homogeneous clinical entity, these patien ts can vary in presentation, onset, or clinical course. This finding is of particular importance for the understanding of the pathophysiologic basis o f the disease, and for the better identification of responders to dementia treatments. Although the sensitivity for the diagnosis of AD remained above 90% over the last two decades, the specificity increased, reflecting progr essive improvement in the diagnosis of other dementing disorders.