ADCOMS: a composite clinical outcome for prodromal Alzheimer's disease trials
Open accessAbstract
BACKGROUND: Development of new therapies for Alzheimer's disease (AD) is increasingly focused on more mildly affected populations, and requires new assessment and outcome strategies. Patients in early stages of AD have mild cognitive decline and no, or limited, functional impairment. To respond to these assessment challenges, we developed a measurement approach based on established scale items that exhibited change in previous amnestic Mild Cognitive Impairment (aMCI) trials. METHODS: Partial least squares regression with a longitudinal clinical decline model identified items from commonly used clinical scales with the highest combined sensitivity to change over time in aMCI and weighted these items according to their relative contribution to detecting clinical progression in patients' early stages of AD. The resultant AD Composite Score (ADCOMS) was assessed for its ability to detect treatment effect in aMCI/prodromal AD (pAD) clinical trial populations. RESULTS: ADCOMS consists of 4 Alzheimer's Disease Assessment Scale-cognitive subscale items, 2 Mini-Mental State Examination items, and all 6 Clinical Dementia Rating-Sum of Boxes items. ADCOMS demonstrated improved sensitivity to clinical decline over individual scales in pAD, aMCI and in mild AD dementia. ADCOMS also detected treatment effects associated with the use of cholinesterase inhibitors in these populations. Improved sensitivity predicts smaller sample size requirements when ADCOMS is used in early AD trials. CONCLUSIONS: ADCOMS is proposed as new standard outcome for pAD and mild AD dementia trials, and is progressing in a CAMD-sponsored qualification process for use in registration trials of pAD.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
AD Composite Score has been a useful measure of cognitive outcome in trials concerning early-stage Alzheimer disease with limited cognitive deficits.
“AD Composite Score (ADCOMS), which combines scores on items derived from the AD Assessment Scale–cognitive subscale (ADAS-cog), clinical dementia rating (CDR) score, and Mini-Mental Status Examination (MMSE), has been a useful measure of cognitive outcome in trials concerning early-stage AD with limited cognitive deficits [38].”
From Clinical trials of new drugs for Alzheimer disease (2020) · cites this paper as [38]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.005 · Cited by 18,657 · see citing works
Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., Gamst, A., Holtzman, D. M., Jagust, W. J., Petersen, R. C., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.008 · Cited by 10,152 · see citing works
A Randomized, Double-Blind, Study of Rofecoxib in Patients with Mild Cognitive Impairment
on behalf of the Rofecoxib Protocol 078 study group, Thal, L. J., Ferris, S. H., Kirby, L., Block, G. A., Lines, C. R., Yuen, E., Assaid, C., Nessly, M. L., Norman, B. A., et al. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300690 · Cited by 402 · see citing works
Flagged first, then by citations
Research works printed but not linked: 12
- [3]Dubois B, Feldman HH, Jacova C, et al Revising the definition of Alzheimer's disease: a new lexicon. Lancet Neurol 2010; 9: 1118– 27. 10.1016/S1474-4422(10)70223-4 20934914 · DOI · Paper page
- [4]Hampel H, Frank R, Broich K et al Biomarkers for Alzheimer's disease: academic, industry and regulatory perspectives. Nat Rev Drug Discov 2010; 9: 560– 74. 10.1038/nrd3115 20592748 · DOI
- [6]Diniz BS, Yassuda MS, Nunes PV, et al Mini-mental State Examination performance in mild cognitive impairment subtypes. Int Psychogeriatr 2007; 19: 647– 56. 10.1017/S104161020700542X 17502007 · DOI
- [7]Cano SJ, Posner HB, Moline ML, et al The ADAS-cog in Alzheimer's disease clinical trials: psychometric evaluation of the sum and its parts. J Neurol Neurosurg Psychiatry 2010; 81: 1363– 8. 10.1136/jnnp.2009.204008 20881017 · DOI
- [8]Petersen RC, Thomas RG, Grundman M, et al Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med 2005; 352: 2379– 88. 10.1056/NEJMoa050151 15829527 · DOI · Paper page
- [9]Doody RS, Ferris SH, Salloway S, et al Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial. Neurology 2009; 72: 1555– 61. 10.1212/01.wnl.0000344650.95823.03 19176895 · DOI
- [11]Romero K, de Mars M, Frank D, et al The Coalition Against Major Diseases: developing tools for an integrated drug development process for Alzheimer's and Parkinson's diseases. Clin Pharmacol Ther 2009; 86: 365– 7. 10.1038/clpt.2009.165 19763117 · DOI
- [12]Jelic V, Kivipelto M, Winblad B Clinical trials in mild cognitive impairment: lessons for the future. J Neurol Neurosurg Psychiatry 2006; 77: 429– 38. 10.1136/jnnp.2005.072926 16306154 PMC2077499 · DOI
- [13]Aisen PS, Schneider LS, Sano M, et al High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA 2008; 300: 1774– 83. 10.1001/jama.300.15.1774 18854539 PMC2684821 · DOI
- [14]Rogers SL, Farlow MR, Doody RS, et al A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group. Neurology 1998; 50: 136– 45. 10.1212/WNL.50.1.136 9443470 · DOI · Paper page
- [15]Harrison J, Minassian SL, Jenkins L, et al A neuropsychological test battery for use in Alzheimer disease clinical trials. Arch Neurol 2007; 64: 1323– 9. 10.1001/archneur.64.9.1323 17846273 · DOI
- [16]Lasser R, Ostrowitzki S, Scheltens P, et al Efficacy and safety of gantenerumab from the phase 3 SCarlet RoAD trial, a study of ganenerumab in patients with prodromal AD. J Prev Alzheimer Dis 2015; 2: 275– 6.
Cited by
Sorted by citations
Lecanemab in early Alzheimer's disease
van Dyck, C. H., Swanson, C. J., Aisen, P., Bateman, R. J., Chen, C., Gee, M., Kanekiyo, M., Li, D., Reyderman, L., Cohen, S., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2212948 · Cited by 5,678 · see citing works
Self-citationA critical appraisal of amyloid-β-targeting therapies for Alzheimer disease
Panza, F., Lozupone, M., Logroscino, G., & Imbimbo, B. P. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-018-0116-6 · Cited by 965 · see citing works
Swanson, C. J., Zhang, Y., Dhadda, S., Wang, J., Kaplow, J., Lai, R. Y. K., Lannfelt, L., Bradley, H., Rabe, M., Koyama, A., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00813-8 · Cited by 847 · see citing works
“ADCOMS, a score generated from 12 items collected with 3 well-established clinical scales [21], was employed as a sensitive measure of clinical decline in early Alzheimer’s disease intended to aid in driving response-adaptive subject allocation.”
MethodAlzheimer's disease drug development pipeline: 2019
Cummings, J., Lee, G., Ritter, A., Sabbagh, M., & Zhong, K. (2019) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.05.008 · Cited by 762 · see citing works
Self-citationThe amyloid hypothesis in Alzheimer disease: new insights from new therapeutics
Karran, E., & De Strooper, B. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00391-w · Cited by 742 · see citing works
Clinical trials of new drugs for Alzheimer disease
Huang, L.-K., Chao, S.-P., & Hu, C.-J. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-019-0609-7 · Cited by 702 · see citing works
Alzheimer’s disease drug development pipeline: 2022
Cummings, J., Lee, G., Nahed, P., Kambar, M. E. Z. N., Zhong, K., Fonseca, J., & Taghva, K. (2022) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12295 · Cited by 665 · see citing works
Tolar, M., Abushakra, S., Hey, J. A., Porsteinsson, A., & Sabbagh, M. (2020) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00663-w · Cited by 354 · see citing works
Shi, M., Chu, F., Zhu, F., & Zhu, J. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.870517 · Cited by 275 · see citing works
Alzheimer’s Disease: Key Insights from Two Decades of Clinical Trial Failures
Kim, C. K., Lee, Y. R., Ong, L., Gold, M., Kalali, A., & Sarkar, J. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-215699 · Cited by 241 · see citing works
New approaches to symptomatic treatments for Alzheimer’s disease
Cummings, J. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00424-9 · Cited by 226 · see citing works
Self-citationCummings, J., Ritter, A., & Zhong, K. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179901 · Cited by 176 · see citing works
Self-citationAmyloid‐β immunotherapy for alzheimer disease: Is it now a long shot?
Panza, F., Lozupone, M., Seripa, D., & Imbimbo, B. P. (2019) · Annals of Neurology · doi:10.1002/ana.25410 · Cited by 178 · see citing works
DEFINING DISEASE MODIFYING THERAPY FOR ALZHEIMER’S DISEASE
Cummings, J., & Fox, N. (2017) · The Journal of Prevention of Alzheimer's Disease · doi:10.14283/jpad.2017.12 · Cited by 139 · see citing works
Self-citationEbell, M. H., Barry, H. C., Baduni, K., & Grasso, G. (2024) · The Annals of Family Medicine · doi:10.1370/afm.3050 · Cited by 100 · see citing works
Expectations and clinical meaningfulness of randomized controlled trials
Petersen, R. C., Aisen, P. S., Andrews, J. S., Atri, A., Matthews, B. R., Rentz, D. M., Siemers, E. R., Weber, C. J., & Carrillo, M. C. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.12959 · Cited by 95 · see citing works
BACE inhibitors in clinical development for the treatment of Alzheimer’s disease
Panza, F., Lozupone, M., Solfrizzi, V., Sardone, R., Piccininni, C., Dibello, V., Stallone, R., Giannelli, G., Bellomo, A., Greco, A., et al. (2018) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2018.1531706 · Cited by 92 · see citing works
The dynamics of biomarkers across the clinical spectrum of Alzheimer's disease
Hadjichrysanthou, C., Evans, S., Bajaj, S., Siakallis, L. C., McRae-McKee, K., de Wolf, F., Anderson, R. M., & Initiative, T. A. D. N. (2020) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00636-z · Cited by 86 · see citing works
“The second is the AD Composite Score (ADCOMS) (0 to 1.97) [38], which has been developed to detect a related clinical decline in amnestic MCI due to AD, and prodromal and mild AD.”
InfluentialAnti-amyloid-β protein agents for the treatment of Alzheimer’s disease: an update on emerging drugs
Lozupone, M., Solfrizzi, V., D’Urso, F., Di Gioia, I., Sardone, R., Dibello, V., Stallone, R., Liguori, A., Ciritella, C., Daniele, A., et al. (2020) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2020.1808621 · Cited by 77 · see citing works
Assunção, S. S., Sperling, R. A., Ritchie, C., Kerwin, D. R., Aisen, P. S., Lansdall, C., Atri, A., & Cummings, J. (2022) · Alzheimer's Research & Therapy · doi:10.1186/s13195-022-00984-y · Cited by 71 · see citing works
Self-citationPersonalized risk for clinical progression in cognitively normal subjects-the ABIDE project
Initiative, F. T. A. D. N., van Maurik, I. S., Slot, R. E. R., Verfaillie, S. C. J., Zwan, M. D., Bouwman, F. H., Prins, N. D., Teunissen, C. E., Scheltens, P., Barkhof, F., et al. (2019) · Alzheimer's Research & Therapy · doi:10.1186/s13195-019-0487-y · Cited by 47 · see citing works
Building clinically relevant outcomes across the Alzheimer's disease spectrum
Rentz, D. M., Wessels, A. M., Annapragada, A. V., Berger, A., Edgar, C. J., Gold, M., Miller, D. S., Randolph, C., Ryan, J. M., Wunderlich, G., et al. (2021) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12181 · Cited by 38 · see citing works
Alzheimer’s Disease Clinical Trials: Moving Toward Successful Prevention
Rafii, M. S., & Aisen, P. S. (2019) · CNS Drugs · doi:10.1007/s40263-018-0598-1 · Cited by 36 · see citing works
Conrado, D. J., Duvvuri, S., Geerts, H., Burton, J., Biesdorf, C., Ahamadi, M., Macha, S., Hather, G., Francisco Morales, J., Podichetty, J., et al. (2020) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1782 · Cited by 21 · see citing works
Immunotherapeutic approaches for Alzheimer’s disease: Exploring active and passive vaccine progress
Bhadane, P., Roul, K., Belemkar, S., & Kumar, D. (2024) · Brain Research · doi:10.1016/j.brainres.2024.149018 · Cited by 15 · see citing works
Niidome, T., Ishikawa, Y., Ogawa, T., Nakagawa, M., & Nakamura, Y. (2024) · Folia Pharmacologica Japonica · doi:10.1254/fpj.24005 · Cited by 14 · see citing works
Setbacks and Opportunities in Disease-Modifying Therapies in Alzheimer Disease
Forester, B. P., Patrick, R. E., & Harper, D. G. (2020) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2019.2332 · Cited by 9 · see citing works
- Authors
- Wang, J., Logovinsky, V., Hendrix, S. B., Stanworth, S. H., Perdomo, C., Xu, L., Dhadda, S., Do, I., Rabe, M., Luthman, J., Cummings, J., & Satlin, A.
- Affiliations
- Eisai (United States) (US)
- Cleveland Clinic (US)
- Corresponding author
- Cummings, Jeffrey
- ORCID
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2016-03-23
- Volume
- 87
- Issue
- 9
- Pages
- 993-999
- ISSN
- 0022-3050 (ISSN-L)
- 1468-330X
- PMC
- PMC5013117
- OpenAlex
- W2306039713
- Cited by
- 160
- References
- 3
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 21 · 2023: 16 · 2022: 22 · 2021: 16 · 2020: 18 · 2019: 16 · 2018: 12 · 2017: 9 · 2016: 3
- FWCI
- 11.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health (K01AG030514, P30AG010129, U01 AG024904)
- U.S. Department of Defense (W81XWH-12-2-0012)
- 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
- prodromal Alzheimer's disease, mild cognitive impairment, composite endpoints, Alzheimer's Disease Assessment Scale, Clinical Dementia Rating, Mini-Mental State Examination, partial least squares regression, sensitivity to change, cholinesterase inhibitors, sample size requirements
- MeSH terms
- Aged, Alzheimer Disease, Female, Humans, Male, Psychiatric Status Rating Scales, Biomarkers, Least-Squares Analysis, Amyloid beta-Peptides, Disease Progression, Cognitive Dysfunction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
