Testing the Clinical Dementia Rating Sum of Boxes as an Outcome for Dementia with Lewy Bodies Clinical Trials.

INTRODUCTION

Dementia with Lewy bodies (DLB), a common cause of dementia, has no FDA-approved therapies, and clinical trials to date have had limited ability to demonstrate efficacy. The lack of validated DLB-specific clinical trial outcomes may hinder these efforts. Here, we test whether the Clinical Dementia Rating (CDR) and other commonly used clinical evaluation tools for Alzheimer's disease (AD) and Parkinson's disease (PD) could potentially be used as outcome measures in future DLB clinical trials.

METHODS

A retrospective, cross-sectional chart review of 600 patients (359 AD, 241 DLB) who completed a comprehensive clinical, cognitive, functional, and behavioral evaluation over a 10-year period was carried out. Performance of the CDR, its sum of boxes (CDR-SB), and other AD and PD evaluation measures were assessed for stage-wide performance from mild cognitive impairment (CDR 0.5) to moderate-severe dementia (CDR 2).

RESULTS

The CDR and CDR-SB characterize important differences between AD and DLB across different cross-sectional stages of disease severity, with the greatest differences seen at the CDR 0.5 stage. DLB showed greater deficits in commonly used AD functional and behavioral measures at the CDR 0.5 stage, while more DLB-specific measures showed significant differences from AD across the entire disease spectrum. The patient version of the Quick Dementia Rating System showed greater stage-wide impairment in DLB than AD, supporting its use as a patient-reported outcome. The Montreal Cognitive Assessment showed greater stage-wide impairment in AD than in DLB patients, suggesting lack of sensitivity as an outcome measure for DLB clinical trials.

CONCLUSION

Improved study design and selection of appropriate outcome measures in DLB clinical trials can facilitate demonstration of efficacy. While the CDR-SB could work on a DLB clinical trial, the field would be most advanced by the development of a DLB-specific global rating instrument.