Demonstration of the iADRS as an integrated measure of global disease severity in early symptomatic Alzheimer’s disease using Rasch measurement theory (RMT)
Year: 2023
Type: article
Abstract: Background As an outcome measure in Alzheimer’s disease (AD) clinical trials, the integrated Alzheimer’s Disease Rating Scale (iADRS) assesses the impact of cognitive loss on the ability to perform daily activities. The iADRS integrates items from the ADAS‐Cog13 and the ADCS‐iADL, providing a measure of global AD severity. The present work evaluated integration of cognitive and functional items within the iADRS using RMT, a psychometric approach that models individual items and responses on to a single measurement continuum representing a latent construct (i.e., disease severity). Method RMT was performed using RUMM2030 using data from the Phase 2, placebo‐controlled TRAILBLAZER‐ALZ study designed to evaluate the safety and efficacy of donanemab in participants with early symptomatic AD. Data from 245 participants were pooled across treatment arms and timepoints (7 timepoints over 18 months). Result The iADRS person separation index (PSI) was 0.89, indicating good reliability and ability to differentiate between levels of impairment. Results also indicated good item‐person targeting, with items covering the range of disease severity (mean = ‐1.27, SE = 0.67). The hierarchy of items along the iADRS measurement continuum (Figure 1) reflected observed patterns of clinical decline. Delayed episodic memory impairments preceded broader impairments in immediate memory and memory‐dependent iADLs, including talking about recent experiences (reading, television); more widespread deficits in iADL functioning (telephone use, meal preparation) emerged next, followed by multi‐domain cognitive impairments in orientation and language. While cognition (specifically memory) was impaired earlier than function, cognitive and functional items demonstrated similar rates of decline along the disease severity continuum. Conclusion Model fit and item placement provide support for integration of cognitive and functional items within the iADRS. Placement of items along a single continuum revealed a mixture of cognitive and functional items sensitive to impairment across the spectrum of mild symptomatic disease, and demonstrated how items work together to provide improved coverage of disease‐related impairments. The findings provide further support for the use of the iADRS in clinical trials as an integrated assessment of global disease progression in early symptomatic AD.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.082362
Institution: Eli Lilly (United States)
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4390191810