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Cited by 86Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsPsychological Testing and Assessment

A COMBINED MEASURE OF COGNITION AND FUNCTION FOR CLINICAL TRIALS: THE INTEGRATED ALZHEIMER’S DISEASE RATING SCALE (IADRS)

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Wessels, A.M., Siemers, E.R., Yu, P., Andersen, S.W., Holdridge, K.C., Sims, J.R., Sundell, K., Stern, Y. +5 more·2015·The Journal of Prevention of Alzheimer's Disease
DOI 10.14283/jpad.2015.82PMC PMC4806404
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Abstract

It is generally recognized that more sensitive instruments for the earliest stages of Alzheimer’s disease (AD) are needed. The integrated Alzheimer’s Disease Rating Scale (iADRS) combines scores from 2 widely accepted measures, the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Alzheimer’s Disease Cooperative Study – instrumental Activities of Daily Living (ADCS-iADL). Disease progression and treatment differences as measured by the iADRS were analyzed using data from solanezumab EXPEDITION, EXPEDITION2, and EXPEDITION-EXT Studies; semagacestat IDENTITY Study; and donepezil ADCS – mild cognitive impairment (ADCS-MCI) Study. Psychometric properties of the iADRS were established through principal component analysis (PCA) and estimation of contributions of subscores and individual item scores to the iADRS total score. The iADRS performed better than most composites and scales in detecting disease progression and comparably or better than individual scales in detecting treatment differences. PCA demonstrated the iADRS can be divided into two principal components primarily representing cognitive items and instrumental ADLs. Dynamic ranges of the subscales were similar across all studies, reflecting approximately equal contributions from both subscales to the iADRS total score. In item analyses, every item contributed to the total score, with varying strength of contributions by item and across data sets. The iADRS demonstrated acceptable psychometric properties and was effective in capturing disease progression from MCI through moderate AD and treatment effects across the early disease spectrum. These findings suggest the iADRS can be used in studies of mixed populations, ensuring sensitivity to treatment effects as subjects progress during studies of putative disease-modifying agents.

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Crossref · 10.14283/jpad.2015.82

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  • Diagnosing and treating people earlier in the course of AD may lead to greater clinical benefit.

    “The results of TRAILBLAZER-ALZ 2 show that diagnosing and treating people earlier in the course of AD may lead to greater clinical benefit [68,69].”

    From Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies (2023) · cites this paper as [69]

    The Introduction says trials enroll patients earlier in the AD continuum to intervene before pathological changes are severe. Results > Therapeutic Sensitivity reports a persistent difference between early-start and delayed-start treatment groups with mild AD. Neither passage evaluates earlier diagnosis or compares treatment benefit across stages of AD, so the broader claim is only partly supported. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • In the TRAILBLAZER-ALZ2 phase 3 study, donanemab treatment significantly slowed cognitive decline on the primary outcome of the integrated AD Rating Scale (iADRS) by 40% and improved all secondary clinical endpoints.

    “On 4 May 2023, Lilly announced positive results for this phase 3 study, as treatment significantly slowed cognitive decline on the primary outcome of the integrated AD Rating Scale (iADRS) by 40% and improved all secondary clinical endpoints [68,69].”

    From Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies (2023) · cites this paper as [69]

    The Results > Therapeutic Sensitivity section identifies the iADRS as a measure used to assess treatment effects, supporting the citation’s identification of the scale. But this 2015 paper analyzes solanezumab and other earlier studies, not TRAILBLAZER-ALZ2; it does not support the claimed 40% donanemab effect or improvement on all secondary endpoints. Page numbers are not provided in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Donanemab significantly slowed the clinical progression in individuals with early symptomatic AD and amyloid and tau pathology.

    “Donanemab significantly slowed the clinical progression in individuals with early symptomatic AD and amyloid and tau pathology.”

    From Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies (2023) · cites this paper as [69]

    The Results > Therapeutic Sensitivity passage reports reduced decline with solanezumab in mild AD, not donanemab. Searches for donanemab and for early symptomatic AD with amyloid and tau pathology found no passage in our copy addressing the attributed finding; page numbers were not available. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

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Cites

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Authors
Wessels, A. M., Siemers, E. R., Yu, P., Andersen, S. W., Holdridge, K. C., Sims, J. R., Sundell, K., Stern, Y., Rentz, D. M., Dubois, B., Jones, R. W., Cummings, J., & Aisen, P. S.
Affiliations
  • Eli Lilly (United States) (US)
  • Columbia University Irving Medical Center (US)
  • Brigham and Women's Hospital (US)
  • Assistance Publique – Hôpitaux de Paris (FR)
  • Royal United Hospital (GB)
  • Cleveland Clinic (US)
  • University of Southern California (US)
Corresponding author
Wessels, A.M.
ORCID
Venue
The Journal of Prevention of Alzheimer's Disease
Publisher
Elsevier BV
Published
2015
Volume
2
Issue
4
Pages
1-15
ISSN
2274-5807 (ISSN-L)
DOI
10.14283/jpad.2015.82
PMC
PMC4806404
OpenAlex
W2428090991
Cited by
86
References
4
Citations by year
2026: 6 · 2025: 11 · 2024: 18 · 2023: 14 · 2022: 12 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 8 · 2017: 4 · 2016: 2 · 2012: 1
FWCI
3.79
Type
journal article
Language
en
Open access
Locations
  • The Journal of Prevention of Alzheimer s Disease (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Columbia Academic Commons (Columbia University)
Funders
  • Eli Lilly and Company
  • National Institutes of Health (5u01ag024904-10)
  • National Institute on Aging (U01-AG-024904)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Social Sciences › Psychology › Applied Psychology › Psychological Testing and Assessment
Keywords
Alzheimer's disease, mild cognitive impairment, cognitive function, instrumental activities of daily living, disease progression, treatment effect detection, disease-modifying agents, solanezumab, semagacestat, donepezil, ADAS-Cog, psychometric properties

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