The milestones of AD have been defined (see Table 1).Some of these could be targeted for treatment with agood chance of alleviating symptoms and a positivepotential impact on the cost of care. 1 Results of just one study by the Alzheimer Disease CooperativeStudy (ADCS) group, showing delayed loss ofautonomy and even death in moderate to severe stagesof AD by using alpha-tocopherol, influenced clinicalpractice to use vitamin E in all stages of AD, at least inthe US. 2 This practice changed because a meta-analysis of clinical studies using high doses of tocopherolsuggested a higher mortality. Symptomatic domains in dementia include cognition,activities of daily living (ADL) and behavior. In manypatients, early changes in mood and anxiety precede theformal diagnosis of AD. Cognitive and functional ADLdecline are relatively linear over time, whereas neuro-psychiatric symptoms peak midway into the disease andimprove spontaneously through the severe stage as motorskills become impaired; at this stage, patients may exhibitParkinson-like physical signs. 3 These natural fluctuations in the intensity of symptomatic domains through thestages of AD have an impact on trial design andoutcomes (see Table 2)

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