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Randomized Controlled Trial
. 2016 Sep;87(9):993-9.
doi: 10.1136/jnnp-2015-312383. Epub 2016 Mar 23.

ADCOMS: a composite clinical outcome for prodromal Alzheimer's disease trials

Jinping Wang  1 , Veronika Logovinsky  1 , Suzanne B Hendrix  2 , Stephanie H Stanworth  2 , Carlos Perdomo  1 , Lu Xu  1 , Shobha Dhadda  1 , Ira Do  1 , Martin Rabe  1 , Johan Luthman  1 , Jeffrey Cummings  3 , Andrew Satlin  1
Affiliations
Randomized Controlled Trial

ADCOMS: a composite clinical outcome for prodromal Alzheimer's disease trials

Jinping Wang et al. J Neurol Neurosurg Psychiatry. 2016 Sep.

Abstract

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.

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Figures

Figure 1
Figure 1
Variable importance of projection plot of partial least squares model fitted using the pooled-MCI (amnestic mild cognitive impairment) data set. MMSE, Mini-Mental State Exam; ADAS-cog, Alzheimer's Disease Assessment Scale-cognitive subscale; CDR-SB, Clinical Dementia Rating, sum of boxes.
See this image and copyright information in PMC

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