Barry J. Goldlist MD, FRCPC, FACP
The first five international conferences on Alzheimer's Disease were meant for scientists, as there was essentially nothing available for clinical use. This year's meeting was quite different. The recent licensing of donepezil in Canada and the United States will soon be followed by numerous new drugs, many of which will have novel modes of action. The importance of Canadian research in this field was highlighted by the active participation in the program of Howard Feldman (Vancouver), Serge Gauthier (Montreal) and Ken Rockwood (Halifax). One of the keynote presentations was by Peter St. George Hyslop, Director of the Centre for Research in Neurodegenerative Disorders at the University of Toronto.
The meeting still emphasized basic science, particularly in the area of molecular genetics and molecular biology, but there were more than enough sessions for clinicians and clinical investigators. One interesting symposium concerned itself with the design of clinical trials for demonstrating disease course-altering effects (rather than just symptomatic improvement). It seems that for the immediate future, staggered start and withdrawal design will be the standard. The theory is that if a drug truly alters the disease course, patients starting the active drug later (i.e. placebo changed to active drug) will never achieve the same benefit as the group started on active drug (i.e. active drug to active drug). Similarly, early withdrawal patients (i.e. active drug changed to placebo) would have a better end result than patients never on active drug (placebo to placebo). Preliminary evidence was presented that suggested a new drug, propentofylline, might have such an effect. This drug is not a cholinesterase inhibitor such as donepezil, but rather is felt to be a microglial cell modulator, and thus inhibits some of the inflammatory response seen in various dementias.
Farther from clinical applicability, but still exciting was a round table discussion entitled "Beyond Cholinesterase Inhibitors: Toward the Next Generation of AD Therapeutics." Presentations on possible therapeutic interventions, such as modulating b-amyloidogenesis, inhibiting neurofibrillary degeneration or using muscarinic agonists. It seems quite likely that the 7th International Symposium in the year 2000 will be even more exciting for clinicians.