Impact of early intervention and disease modification in patients with predementia Alzheimer’s disease: a Markov model simulation
David Budd1, Leah C Burns2, Zhenchao Guo2, Gilbert L’Italien2,3, Pablo Lapuerta1
1Bristol-Myers Squibb, Princeton, NJ, USA; 2Bristol-Myers Squibb, Wallingford, CT, USA; 3Yale University School of Medicine, New Haven, CT, USA
Background: Early screenings involving biomarkers and use of potential disease-modifying therapies (DMTs) may have significant humanistic implications for treatment strategies in Alzheimer’s disease.
Methods: Markov models simulated transitions of patient cohorts beginning in predementia, a hypothetical early stage of Alzheimer’s disease marked by objective cognitive impairment/memory complaints without functional impairment, and followed for 10 years. Hypothetical cohorts of 10,000 patients included those who were treated with standard of care (donepezil) upon reaching mild–moderate Alzheimer’s disease, a DMT in predementia, and a DMT in mild-moderate Alzheimer’s disease. Transition probabilities were based on data from the Alzheimer’s Disease Neuroimaging Initiative and published clinical data, and estimated for the hypothetical DMT. In each disease stage (predementia, mild, moderate, or severe), time was computed and costs were estimated using literature review and published data, and published data provided mortality rates. The impact of screening was evaluated using positive predictive value (patients identified as predementia truly at risk for transition to dementia).
Results: Earlier treatment yielded modest gains in total life-years; however, the distribution was skewed towards milder disease. Assuming a 25% reduction in the annual risk of progression, treating predementia patients with DMT increased life-years in predementia to mild states on average from 3.2 to 4.2, while life-years spent in moderate-to-severe Alzheimer’s disease decreased from 2.6 to 2.2. Average time in the community increased from 4.4 to 5.4 years, while time in long-term care declined from 1.3 to 0.9 years. This impact grows as the advantage of the novel agent increases. Screening accuracy had significant implications for cost-effectiveness.
Conclusion: If screening can accurately identify predementia patients at risk for progression, earlier treatment with DMTs has the potential benefit to patients of prolonging time in milder disease, reducing time spent with more severe disease, increasing time in the community, and reducing time in long-term care.
Keywords: Alzheimer’s disease, Markov model, disease-modifying therapy, donepezil, standard of care, predementia
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]
Readers of this article also read:
Causative factors for formation of toxic islet amyloid polypeptide oligomer in type 2 diabetes mellitus
Jeong HR, An SSA
Published Date: 19 November 2015
Carr ME, Tortella BJ
Published Date: 3 September 2015
Mutations in presenilin 2 and its implications in Alzheimer’s disease and other dementia-associated disorders
Cai Y, An SSA, Kim SY
Published Date: 14 July 2015
Published Date: 12 December 2014
Prozorova GF, Pozdnyakov AS, Kuznetsova NP, Korzhova SA, Emel’yanov AI, Ermakova TG, Fadeeva TV, Sosedova LM
Published Date: 16 April 2014
Ashwanikumar N, Kumar NA, Nair SA, Kumar GS
Published Date: 15 November 2012
Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS
Published Date: 27 July 2012
Particle size reduction to the nanometer range: a promising approach to improve buccal absorption of poorly water-soluble drugs
Rao S, Song Y, Peddie F, Evans AM
Published Date: 20 June 2011
Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant
Published Date: 14 July 2010
Characterization of complexation of poly (N-isopropylacrylamide-co-2-(dimethylamino) ethyl methacrylate) thermoresponsive cationic nanogels with salmon sperm DNA
Jim Moselhy, Tasnim Vira, Fei-Fei Liu, et al
Published Date: 24 August 2009