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Randomized Controlled Trial
. 2025 Sep;12(8):100261.
doi: 10.1016/j.tjpad.2025.100261. Epub 2025 Jul 1.

The Alzheimer's Disease Cooperative Study - Activities of Daily Living dependence score: revision and validation of an algorithm evaluating patient dependence across the spectrum of AD severity

Julie M Chandler  1 , Claire J Lansdall  2 , Wenyu Ye  3 , Fiona McDougall  4 , Mark Belger  5 , Balazs Toth  6 , Xiaojuan Mi  7 , Kaycee M Sink  8 , Alexandra S Atkins  9
Affiliations
Randomized Controlled Trial

The Alzheimer's Disease Cooperative Study - Activities of Daily Living dependence score: revision and validation of an algorithm evaluating patient dependence across the spectrum of AD severity

Julie M Chandler et al. J Prev Alzheimers Dis. 2025 Sep.

Abstract

Background: Increasing dependence on informal and formal caregivers in Alzheimer's disease (AD) contributes to high societal cost. Treatments that delay time to increased dependence/care needs would be clinically meaningful, but these outcomes are rarely collected in early AD clinical trials. The 2015 ADCS-ADL dependence algorithm was created to estimate level of dependence in AD.

Objectives: To revise the original dependence algorithm to improve accuracy of dependence scores (DS) across AD severity, including early symptomatic AD.

Design: Secondary data analysis SETTING: Community cohort; randomized clinical trial PARTICIPANTS: 14,000 participants enrolled across GERAS-EU observational study and 12 AD clinical trials.

Measurements: Three-phase algorithm revision: 1) reassess ADCS-ADL items to identify those appropriate for assessing dependence; 2) (a) assign individual item responses to degrees of assistance and (b) to operationalize assignment of DS based on extent of total assistance needed; and 3) validate revised algorithm in multiple datasets across AD severity from mild cognitive impairment due to AD to moderate-severe AD.

Results: The revised DS (0-6) algorithm classified most participants with early symptomatic AD as independent or moderately independent (DS<3) at baseline. With disease progression over time, the proportion of participants who were mildly to fully dependent (DS≥3) increased across AD severity. Increased DS was associated with incremental worsening of clinical outcomes.

Conclusions: The revised ADCS-ADL DS algorithm provides a supplementary approach to evaluate the impact of emerging treatments on independence/care needs in AD and may be useful in clinical trials where the ADCS-ADL has been collected.

Clinical trial registration information: EXPEDITION 1 NCT00905372; EXPEDITION 2 NCT00904683; EXPEDITION 3 NCT01900665; AMARANTH NCT02245737; TRAILBLAZER-ALZ NCT03367403; TRAILBLAZER-ALZ 2 NCT04437511; GRADUATE I NCT03444870; GRADUATE II NCT03443973; CREAD NCT02670083; CREAD 2, NCT03114657; TAURIEL NCT03289143; LAURIET NCT03828747.

Keywords: Alzheimer’s Disease Cooperative Study-Activities of Daily Living scale; Alzheimer’s disease; Care partner; Dependence.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Julie M. Chandler was an employee of Eli Lilly and Company during the work for this manuscript. Wenyu Ye, Mark Belger, and Alexandra S. Atkins are employees and minor shareholders of Eli Lilly and Company. Xiaojuan Mi is an employee of TechData Services Company. Claire J. Lansdall is an employee and minor shareholder of F. Hoffmann-La Roche AG. Fiona McDougall and Balazs Toth are employees Genentech, Inc., a member of the Roche Group, and minor shareholders of F. Hoffmann-La Roche AG. Kaycee M. Sink was an employee of Genentech, Inc., a member of the Roche Group, during the work for this manuscript. At the time of publication, she is a full-time employee of Cogstate, Inc., which had no role in the study. Kaycee M. Sink is a minor shareholder of F. Hoffmann-La Roche AG.

Figures

Fig 1
Fig. 1
Distribution of dependence by disease severity* at Baseline and 18 Months: GERAS-EU. *Disease severity was defined using baseline MMSE. Abbreviations: AD=Alzheimer’s disease; DL=Dependence level; MMSE=Mini-Mental State Examination.
Fig. 2
Fig. 2
Revised ADCS-ADL Dependence Score algorithm (0-6 levels) showing distributions at Baseline and over 18 Months by severity* *Disease severity was defined using baseline MMSE or CDR-GS. Abbreviations: AD=Alzheimer’s disease; CDR-GS=Clinical Dementia Rating Scale – Global Score; DL=Dependence level; MCI=Mild cognitive impairment due to AD; MMSE=Mini-Mental State Examination; NA=Not available.
See this image and copyright information in PMC

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