Table 2.

Barriers and challenges to developing clinical trials in Lewy body dementia

Category	Barriers and challenges
Trial focus	- Need for both disease-modifying and symptomatic trials - Lack of studies focusing on the breadth of LBD symptoms, including non-cognitive outcomes
Study population	- Delays in LBD diagnosis - Heterogeneity of clinical symptomatology - Co-morbidities (e.g., cerebrovascular disease) - Concomitant medication use (e.g., cholinesterase inhibitors, antipsychotics, parkinsonian medications)
Recruitment and retention	- Cognitively impaired population - Lack of under-represented minorities in studies - Complex and long assessment batteries - Study procedures (e.g., lumbar puncture, imaging) - Caregivers with high degrees of burden and stress - Long travel distances to study centers - Retention of older adults with combined cognitive, behavioral, and motor symptoms
Selection of outcome measures	- Lack of LBD-specific outcome measures - Existing outcome measures designed more for use in AD trials - Optimal outcome for different symptoms is uncertain - Existing outcome measures often lack validated measurement properties for LBD (e.g., inter-rater reliability, sensitivity to change)
Study execution	- Medication effects on attention and alertness - Cognitive fluctuations, which may affect test performance - “On” and “off” timing in individuals with Parkinson’s disease
Biomarkers	- Lack of biomarkers of progression - Lack of established α-synuclein biomarkers (imaging, biofluid) - Biomarkers in DLB criteria focus on diagnosis rather than clinical trial use - Lack of biomarker standardization - Lack of availability or access to some biomarker studies (e.g., dopaminergic imaging, polysomnography, cardiac MIBG)

Abbreviations: AD Alzheimer’s disease, LBD Lewy body dementia