Potential Implications of Slowing Disease Progression in Amyloid-Positive Early Alzheimer’s Disease: Estimates from Real-World Data - 21/11/24
, M. Georgieva 2, A. Gomez-Lievano 2, W. Ye 1, A. Zhao 2, D. Eid 2, A. Hilts 3, N. Kirson 2, T. Schilling 1Alzheimer’s Disease Neuroimaging Initiative
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Abstract |
Background |
Emerging therapies have shown promising results for slowing the progression of Alzheimer’s disease (AD). However, the potential impact of these therapies on real-world outcomes remains to be explored.
Objective |
To examine the impact of slowing AD progression on functional abilities and behavioral symptoms.
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, primary analysis) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (09/2005–03/2022, sensitivity analysis) were used.
Participants |
Individuals with mild cognitive impairment (MCI) or mild dementia, Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score 0.5–9.0 (inclusive; first visit defined as the index date), and confirmed amyloid positivity were identified in NACC. In ADNI, individuals with at least one clinical center visit with a clinical assessment of MCI or mild dementia and confirmed amyloid positivity were identified.
Measurements |
Hypothetical effects of slowing disease progression as assessed by CDR-SB on functional and behavioral outcomes including the Functional Activities Questionnaire (FAQ) score, Neuropsychiatric Inventory Questionnaire (NPI-Q) score, and the probability of complete dependence over five years were evaluated using multivariable regression among NACC participants, separately for the subgroups with MCI and mild dementia at baseline, respectively. For the ADNI sensitivity analysis, the hypothetical effects of slowing disease progression were evaluated for FAQ score using multivariable regression among the MCI participants only.
Results |
Compared with natural disease progression, slowing progression by 20% over five years for NACC participants with MCI and mild dementia, respectively, would result in 1.7-point (10.8%) and 1.6-point (12.9%) less deterioration based on FAQ; 0.5-point (20.3%) and 0.5-point (19.3%) less deterioration based on NPI-Q; 4.7 percentage-point (22.2%) and 10.1 percentage-point (21.6%) lower probability of complete dependence. Among ADNI participants, delaying disease progression by 20% or 30% over 4 years would avert deterioration based on FAQ of 1.1 points (20.4%) and 1.6 points (29.6%), respectively, compared to natural disease progression.
Conclusions |
Slowing early AD progression could result in preservation of functional and behavioral attributes and functional autonomy for longer.
Le texte complet de cet article est disponible en PDF.Key words : Alzheimer’s disease, mild cognitive impairment, beta amyloid, disease progression, clinical outcomes
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 to conduct this research. Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: ADNI_Acknowledgement_List.pdf |
Vol 11 - N° 2
P. 310-319 - mars 2024 Retour au numéro
Article précédent
- Health Economic Considerations in the Deployment of an Alzheimer’s Prevention Therapy
- Soeren Mattke, H. Jun, M. Hanson, S. Chu, J.H. Kordower, E.M. Reiman
- Impact of Differential Rates of Disease Progression in Amyloid-Positive Early Alzheimer’s Disease: Findings from a Longitudinal Cohort Analysis
- J. Chandler, M. Georgieva, Urvi Desai, N. Done, A. Gomez-Lievano, W. Ye, A. Zhao, D. Eid, A. Hilts, N. Kirson, T. Schilling
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