Alzheimer's centennial legacy: origins, landmarks and the current status of knowledge concerning cognitive aspects.

This review commemorates 100 years of research into Alzheimer's disease and, by happy coincidence, the publication of 100 papers in Brain on the topic. The first part of the review traces the evolution of concepts and landmarks in the modern history of Alzheimer's disease. It highlights the continuing role of careful clinico-pathological studies which have set the stage for each major leap forwards, such as the emergence of the cholinergic hypothesis, and the realistation that subjects pass through an amnestic prodrome which is thought to reflect dysfunction of the hippocampal formation before the onset of full blown dementia. The contribution of structural and functional imaging is briefly described. The important contribution of publications in Brain is illustrated throughout the first section. The second part attempts to review the current status of our knowledge concerning behavioural, neuropsychological and neuropsychiatric aspects of the disease, emphasizing areas of continuing controversy.