ABSTRACT
Age is the most important risk factor for Alzheimer's disease (AD). The acceptable age range for participation in AD clinical trials is 50 to 90, and this 40-year span incorporates enormous age-related change. Clinical trial participants tend to be younger and healthier than the general population. They are also younger than the general population of AD patients. Drug development from a geroscience perspective would take greater account of effects of aging on clinical trial outcomes. The AD clinical trial pipeline has diversified beyond the canonical targets of amyloid beta protein and tau. Many of these interventions apply to age-related disorders. Anti-inflammatory agents and bioenergetic and metabolic therapies are among the well represented classes in the pipeline and are applicable to AD and non-AD age-related conditions. Drug development strategies can be adjusted to better inform outcomes of trials regarding aged individuals. Inclusion of older individuals in the multiple ascending dose trials of Phase 1, use of geriatric-related clinical outcomes and biomarkers in Phase 2, and extension of these Phase 2 learnings to Phase 3 will result in a more comprehensive understanding of AD therapies and their relationship to aging. Clinical trials can employ a more comprehensive geriatric assessment approach and biomarkers more relevant to aging at baseline and as exploratory outcomes. Greater attention to the role of aging and its influence in AD clinical trials can result in better understanding of the generalizability of clinical trial findings to the older AD population.
