Impact of Differential Rates of Disease Progression in Amyloid-Positive Early Alzheimer’s Disease: Findings from a Longitudinal Cohort Analysis - 21/11/24
, N. Done 2, A. Gomez-Lievano 2, W. Ye 1, A. Zhao 2, D. Eid 2, A. Hilts 3, N. Kirson 2, T. Schilling 1
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Abstract |
Background |
There is limited literature regarding the impact of differential rates of disease progression on longitudinal outcomes in individuals with early Alzheimer’s disease (AD) and confirmed brain amyloid pathology.
Objectives |
To describe the underlying characteristics and long-term outcomes associated with different rates of disease progression among amyloid-positive individuals with early symptomatic AD.
Design |
Retrospective observational study.
Setting |
Data from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) in the United States (06/2005-11/2021).
Participants |
Individuals with a clinical assessment of mild cognitive impairment or dementia and Clinical Dementia Rating® Dementia Staging Instrument Sum of Boxes (CDR-SB) score 0.5–9.0 (inclusive; first visit defined as the index date) and confirmed amyloid positivity. Participants were stratified into No Progression (change ≤0), Slower Progression (0< change <2.0 points), Median Progression (2.0-point change), and Faster Progression (change >2.0 points) cohorts based on the observed distribution of changes in CDR-SB score between the index and first subsequent visit.
Measurements |
For each cohort, the functional and neuropsychiatric outcomes were described at index and each subsequent visit for up to five years, and least-square (LS) mean changes from baseline were estimated using linear mixed-effects models adjusting for baseline demographic and clinical characteristics.
Results |
Among 1,263 participants included in the analysis, the mean±standard deviation (SD) age at index was 72.7±9.7 years and 55.3% were males. Demographic characteristics and comorbidity profiles at index were similar across cohorts. However, at index, the Faster Progression (N=279) cohort had higher CDR-SB and Functional Assessment Questionnaire (FAQ) scores compared with the No Progression (N=474), Slower Progression (N=297), and Median Progression (N=213) cohorts. Adjusting for baseline characteristics, at year 5 after index the FAQ score increased by 23.6 points for Faster Progression cohort and 10.4, 15.8, and 19.2 points for the No, Slower, and Median Progression cohorts, respectively. The corresponding increases in Neuropsychiatric Inventory Questionnaire (NPI-Q) scores were 6.7 points for the Faster Progression cohort, and by 1.3, 3.1, and 8.3 points, for the No, Slower, and Median Progression cohorts, respectively.
Conclusions |
Despite similar demographic and clinical profiles at baseline, amyloid-positive individuals with greater deterioration based on CDR-SB early in the AD trajectory continue to experience worse functional and behavioral outcomes over time than those with more gradual deterioration in this metric.
Le texte complet de cet article est disponible en PDF.Key words : Amyloid-positive, disease progression, disease trajectory, early Alzheimer’s disease
Plan
| Disclosures: JMC, WY, and TS are employees of Eli Lilly and Company and hold stock or stock options in Eli Lilly and Company. MG, UD, NK, ND, AZ, DE, AGL, and AH are employees of Analysis Group, Inc., which received consulting fees from the study sponsor for this research. Prior presentations: Preliminary results from this study were presented as a poster presentation at the Clinical Trials on Alzheimer’s Disease (CTAD) 15th Annual Conference, held from November 29 - December 2, 2022, in San Francisco, CA. |
Vol 11 - N° 2
P. 320-328 - mars 2024 Retour au numéro
Article précédent
- Potential Implications of Slowing Disease Progression in Amyloid-Positive Early Alzheimer’s Disease: Estimates from Real-World Data
- J. Chandler, N. Done, Urvi Desai, M. Georgieva, A. Gomez-Lievano, W. Ye, A. Zhao, D. Eid, A. Hilts, N. Kirson, T. Schilling, Alzheimer’s Disease Neuroimaging Initiative
- Validation, Deployment, and Real-World Implementation of a Modular Toolbox for Alzheimer’s Disease Detection and Dementia Risk Reduction: The AD-RIDDLE Project
- K. Malzbender, P. Barbarino, P. Barkman Ferrell, A. Bradshaw, A.J. Brookes, C. Díaz, W.M. van der Flier, J. Georges, O. Hansson, M. Hartmanis, L. Jönsson, R. Krishnan, T. MacLeod, F. Mangialasche, P. Mecocci, C. Minguillon, L. Middleton, S. Pla, S.P. Sardi, M. Schöll, M. Suárez-Calvet, W. Weidner, P.J. Visser, H. Zetterberg, N. Bose, A. Solomon, Miia Kivipelto, AD-RIDDLE Consortium
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