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Editorial
March 2000

Methods for Discerning Disease-Modifying Effects in Alzheimer Disease Treatment Trials

Arch Neurol. 2000;57(3):312-314. doi:10.1001/archneur.57.3.312

TREATMENTS SUCH as cholinesterase inhibitors, vitamin E, and ginkgo biloba have been shown to have clear but small effect sizes on clinical measures of dementia in randomized controlled trials for Alzheimer disease (AD). For each of these treatments, plausible mechanistic arguments, such as antioxidant effects or alteration of amyloid protein processing, have been proposed as to how they may retard the progression of disease. However, let's face it: we can argue until our plaques become dense-cored and we still don't know whether the observed effects are purely symptomatic or in fact represent a change in a fundamental aspect of the progressive neuropathology of AD itself. As attractive as these mechanisms may be, the innate slow and variable rate of progression of untreated AD requires additional methods to demonstrate more than a symptomatic treatment effect.

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