Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that profoundly impacts patients and public health. It manifests through cognitive decline such as memory loss and functional impairment, leading to a loss of independence and the need for full-time care. The number of patients with dementia worldwide is expected to exceed 150 million by 2050. The disease not only affects individuals but also significantly impacts families, caregivers, and society. Family members often become primary caregivers leading to emotional, physical, and financial strains.

Clinical trials in AD represent a critical frontier in the search for effective treatments and interventions, however, the field faces several challenges and complexities. As an example, with increased intervention targeting early-stage AD, the choice of specific and sensitive clinical endpoints to capture subtle cognitive and functional changes, and understanding their applicability in clinical practice, are becoming critical. Currently, there is a lack of definitive evidence of how trial outcome measures correlate with changes in disease progression and treatment response which creates ambiguity around their clinical relevance. Addressing this uncertainty would benefit patients, caregivers, primary care providers, and regulators, by improving our comprehension of how trial endpoints relate to everyday clinical assessments.

Presently, clinical trials in AD employ a variety of assessment tools, with considerable variability in the endpoints selected. This review will cover what constitutes clinically meaningful changes in early-stage AD, the most frequently used assessment tools, and discuss those measures in relation to disease progression and treatment efficacy.