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Advantages
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Large number of treated subjects
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Targeted intervention
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Easier to identify (no biomarker required)
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Evidenced pathophysiological mechanisms (biomarkers)
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Larger benefit at the individual level
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Disadvantages
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Cost of intervention (necessity of large intervention in terms of subject number and duration to obtain a benefit at the population level)
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Limited number of subjects
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Frail population
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Necessity of biomarkers (availability, acceptability, standardization)
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Diagnostic uncertainty
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Cost of biomarkers (for example, amyloid imaging)
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Variability of size effect
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Strength of evidence is highly dependent on the validity of pathophysiological hypothesis
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Proposal for future treatment strategies
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Symptomatic treatments for clinical (mild to severe) stages of Alzheimer’s disease
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Tailored intervention for prodromal and very mild Alzheimer’s disease
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Prevention (multidomain intervention)
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This kind of targeted prevention study using expensive treatment interventions and outcome measures could serve as proof of concept to stimulate cheaper interventions
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Biomarkers could be considered as outcome for evaluating the impact on disease-relevant pathophysiology
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