Alzheimer’s disease (AD) is an exquisitely age-dependent disorder in which dementia symptoms follow decades of latent and prodromal disease progression. Each of the known risk or protective factors for AD alters the rate of the fundamental pathogenetic process, and thus the timing of symptom onset. New data show that APOE ĺ4, the strongest known genetic risk factor, modifies timing of disease expression but does not alter the proportion of the population susceptible, which may be near 70%. Non-steroidal anti-inflammatory drugs and post-menopausal hormone therapy appear to confer protection against AD by delaying the timing of dementia onset. Anti-oxidant vitamins may do likewise.
For each neuroprotective strategy, the timing of administration relative to staging of the disease process appears critical. Hormone therapy given at menopause or more than 10 years prior to dementia onset may be protective, but later estrogen administration offers no protection and may even add risk. NSAIDs appear to lose their effect approximately two years before dementia onset. Only for anti-oxidant vitamins does the benefit appear to sustain through the AD prodrome and beyond. Better appreciation of the influence of such timing in disease process and prevention will improve prospects for successful intervention.
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