The year 2005 marks the centenary of the discovery of Treponema pallidum by Schaudinn and Hoffmann, an important milestone in a long process that culminated in the cure of general paralysis of the insane, probably the most frequent type of dementia up to the first half of the 20th century. Reflections on the process that achieved the virtual eradication of general paralysis of the insane may be important in developing approaches to manage Alzheimer disease, today's most prevalent type of dementia. Both for general paralysis of the insane and Alzheimer disease, it took time for them to be recognized as frequent causes of dementia. The hypothesis of the syphilitic origin of general paralysis of the insane instigated heated debates during the 19th century, even surpassing those between proponents of the amyloid cascade versus the tau protein hypotheses for Alzheimer disease. The results of the management of general paralysis of the insane warrant special reflection. Penicillin therapy arrests the disease, but many patients did not regain their previous cognitive performance. The treatment, to be completely efficient, must be accomplished in the phase of early syphilis or in the latent period, thereby preventing the evolution to general paralysis of the insane. The same probably will be true for Alzheimer disease-to be completely successful, treatment should be given before the disease has begun to damage the brain.