The online version of this article (doi:10.1186/s13195-017-0243-0) contains supplementary material, which is available to authorized users.
Accurate and timely diagnosis of Alzheimer’s disease (AD) is important for prompt initiation of treatment in patients with AD and to avoid inappropriate treatment of patients with false-positive diagnoses.
Using a Markov model, we estimated the lifetime costs and quality-adjusted life-years (QALYs) of cerebrospinal fluid biomarker analysis in a cohort of patients referred to a neurologist or memory clinic with suspected AD who remained without a definitive diagnosis of AD or another condition after neuroimaging. Parametric values were estimated from previous health economic models and the medical literature. Extensive deterministic and probabilistic sensitivity analyses were performed to evaluate the robustness of the results.
At a 12.7% pretest probability of AD, biomarker analysis after normal neuroimaging findings has an incremental cost-effectiveness ratio (ICER) of $11,032 per QALY gained. Results were sensitive to the pretest prevalence of AD, and the ICER increased to over $50,000 per QALY when the prevalence of AD fell below 9%. Results were also sensitive to patient age (biomarkers are less cost-effective in older cohorts), treatment uptake and adherence, biomarker test characteristics, and the degree to which patients with suspected AD who do not have AD benefit from AD treatment when they are falsely diagnosed.
The cost-effectiveness of biomarker analysis depends critically on the prevalence of AD in the tested population. In general practice, where the prevalence of AD after clinical assessment and normal neuroimaging findings may be low, biomarker analysis is unlikely to be cost-effective at a willingness-to-pay threshold of $50,000 per QALY gained. However, when at least 1 in 11 patients has AD after normal neuroimaging findings, biomarker analysis is likely cost-effective. Specifically, for patients referred to memory clinics with memory impairment who do not present neuroimaging evidence of medial temporal lobe atrophy, pretest prevalence of AD may exceed 15%. Biomarker analysis is a potentially cost-saving diagnostic method and should be considered for adoption in high-prevalence centers.
Additional file 1: Cost-effectiveness of cerebrospinal biomarkers for Alzheimer’s diagnosis: supplemental Methods, Results, figures and tables as referenced in the text. (DOCX 91 kb)13195_2017_243_MOESM1_ESM.docx
Alzheimer’s Association. Alzheimer’s disease facts and figures. Alzheimers Dement. 2014;10:e47–92. CrossRef
McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev. 2006;2:CD003154.
López-Bastida J, Hart W, García-Pérez L, Linertová R. Cost-effectiveness of donepezil in the treatment of mild or moderate Alzheimer’s disease. J Alzheimers Dis. 2009;16:399–407. PubMed
Bloudek LM, Spackman DE, Blankenburg M, Sullivan SD. Review and meta-analysis of biomarkers and diagnostic imaging in Alzheimer’s disease. J Alzheimer’s Dis. 2011;26:627–45. CrossRef
Hornberger J, Michalopoulos S, Dai M, Andrade P, Dilla T, Happich M. Cost-effectiveness of florbetapir-PET in Alzheimer’s disease: a Spanish societal perspective. J Ment Health Policy Econ. 2015;18:63–73. PubMed
Valcárcel-Nazco C, Perestelo-Pérez L, Molinuevo JL, Mar J, Castilla I, Serrano-Aguilar P. Cost-effectiveness of the use of biomarkers in cerebrospinal fluid for Alzheimer’s disease. J Alzheimers Dis. 2014;42:777–88. PubMed
Gold MR, Siegel JE, Russell LB, Weinstein MC, editors. Cost-effectiveness in health and medicine. 1st ed. London: Oxford University Press; 1996.
Arias E. United States life tables, 2009. Natl Vital Stat Rep. 2014;62(7).
Bloudek LM, Spackman DE, Veenstra DL, Sullivan SD. CDR state transition probabilities in Alzheimer’s disease with and without cholinesterase inhibitor intervention in an observational cohort. J Alzheimer’s Dis. 2011;24:599–607.
APA Work Group on Alzheimer’s Disease and other Dementias. American Psychiatric Association practice guideline for the treatment of patients with Alzheimer’s disease and other dementias, second edition. Am J Psychiatry. 2007;164(12 Suppl):1–56.
Winslow BT, Onysko MK, Stob CM, Hazlewood KA. Treatment of Alzheimer disease. Am Fam Physician. 2011;83:1403–12. PubMed
Mucha L, Wang SS, Cuffel B, McRae T, Mark TL, del Valle M. Comparison of cholinesterase inhibitor utilization patterns and associated health care costs in Alzheimer’s disease. J Manag Care Pharm. 2008;14:451–61. PubMed
Michalowsky B, Eichler T, Thyrian JR, Hertel J, Wucherer D, Hoffmann W, et al. Healthcare resource utilization and cost in dementia: are there differences between patients screened positive for dementia with and those without a formal diagnosis of dementia in primary care in Germany? Int Psychogeriatr. 2016;28:359–69. CrossRefPubMed
Oyebode JR, Parveen S. Psychosocial interventions for people with dementia: an overview and commentary on recent developments. Dementia (London). doi: 10.1177/1471301216656096.
Centers for Medicare & Medicaid Services. Medicare fee-for-service payment schedule. 2009. https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/FeeScheduleGenInfo/index.html?redirect=/feeschedulegeninfo/. Accessed 16 July 2014.
Lassman D, Hartman M, Washington B, Andrews K, Catlin A. US health spending trends by age and gender: selected years 2002–10. Health Aff (Millwood). 2014;33:815–22. CrossRef
MetLife. 2012 MetLife market survey of long-term care costs. New York: Author; 2012. https://www.metlife.com/mmi/research/2012-market-survey-long-term-care-costs.html#keyfindings. Accessed 16 July 2014.
Centers for Disease Control and Prevention (CDC). Health Data Interactive (HDI): mortality and life expectancy: mortality by underlying and multiple cause, ages 18+: US, 1981–2010. Atlanta: CDC; 2014. http://www.healthdata.gov/dataset/health-data-interactive-hdi. Accessed 19 Aug 2014.
Malouf R, Birks J. Donepezil for vascular cognitive impairment. Cochrane Database Syst Rev. 2004;1:CD004395.
Ritchie C, Smailagic N, Noel-Storr AH, Takwoingi Y, Flicker L, Mason SE, et al. Plasma and cerebrospinal fluid amyloid beta for the diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev. 2014;6:CD008782.
Consumer Reports. Evaluating prescription drugs used to treat Alzheimer’s disease. 2012. http://www.consumerreports.org/cro/2012/07/evaluating-drugs-to-treat-alzheimer-s-disease/index.htm. Accessed 16 July 2014.
- Cost-effectiveness of cerebrospinal biomarkers for the diagnosis of Alzheimer’s disease
Spencer A. W. Lee
Luciano A. Sposato
Lauren E. Cipriano
- BioMed Central