Latest Trends in Outcome Measures in Dementia and Mild Cognitive Impairment Trials.

Disease modification trials in dementia and mild cognitive impairment (MCI) have not met with success. One potential criticism of these trials is the lack of sensitive outcome measures. A large number of outcome measures have been employed in dementia and MCI trials. This review aims to describe and analyze the utility of cognitive/clinical outcome measures in Alzheimer's disease (AD) and MCI trials. Methods: A PubMed search was conducted using relevant MeSH terms and exploded keywords. The search was confined to English language publications of human studies from the last five years which describe the latest trends in the use of outcome measures. Results: Despite broad use, the outcome measures employed are heterogeneous, with little data on correlations between scales. Another problem is that most studies are over-reliant on clinician/researcher assessment and cognitive outcomes, and there is a definite lack of stakeholder input. Finetuning of the paradigm is also required for people with early-stage disease, mild to moderate disease, and advanced dementia, as the outcome measures in these subgroups have varying relevance. Disease modification/prevention is an appropriate goal in early disease, whereas palliation and freedom from discomfort are paramount in later stages. The outcome measures selected must be suitable for and sensitive to these particular care goals. Although there is a shift to enrich MCI cohorts using a biomarker-based approach, the clinical relevance of such outcome measures remains uncertain. Conclusions: Outcome measures in dementia/MCI trials remain inhomogeneous and diverse, despite extensive use. Outcome measures fall within several paradigms, including cognitive, functional, quality-of-life, biomarker-based, and patient-reported outcome measures. The success of future disease-modifying trials is reliant to a large extent on the selection of outcome measures which combine all outcomes of clinical relevance as well as clinical meaning. Outcome measures should be tied to the type and stage of dementia and to the specific interventions employed.