Establishing the Clinical Meaningfulness of Cognitive Measures for Huntington's Disease

Addressing cognitive decline in Huntington's disease (HD) is a priority for clinical trials. Yet, cognitive measures are undervalued in endpoint strategies due to unclear relevance to clinically meaningful outcomes such as everyday function. This thesis developed a framework for substantiating clinically meaningful cognitive effects in HD trials. Using this framework, I conducted studies demonstrating the relevance of cognitive effects to everyday life. I interviewed patients and caregivers to identify meaningful cognitive symptoms and assess the relevance of cognitive measures to important outcomes. I also established thresholds for cognitive change that translate to meaningful everyday changes. This empirical framework supports the clinical meaningfulness of cognitive measures for HD trials, significantly advancing endpoint methodology.