title: Cost-effectiveness of cerebrospinal biomarkers for the diagnosis of Alzheimer's disease.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Ivey Business School, Western University, 1255 Western Road, London, ON, N6G 0N1, Canada.|School of Medicine, University College Cork, College Road, Cork, T12 YN60, Ireland.
authors.forename: Spencer A W
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, ON, N6A 5A5, Canada.|Stroke, Dementia & Heart Disease Laboratory, Western University, London, ON, N6A 5A5, Canada.|Department of Anatomy & Cell Biology, Western University, London, ON, N6A 5A5, Canada.
authors.forename: Luciano A
authors.initials: LA
authors.lastname: Sposato
authors.affiliation: Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, ON, N6A 5A5, Canada.|Department of Biostatistics and Epidemiology, Schulich School of Medicine and Dentistry, Western University, London, ON, N6A 5C1, Canada.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Hachinski
authors.affiliation: Ivey Business School, Western University, 1255 Western Road, London, ON, N6G 0N1, Canada. lcipriano@ivey.uwo.ca.|Department of Biostatistics and Epidemiology, Schulich School of Medicine and Dentistry, Western University, London, ON, N6A 5C1, Canada. lcipriano@ivey.uwo.ca.
authors.forename: Lauren E
authors.identifier: http://orcid.org/0000-0001-5568-4516
authors.initials: LE
authors.lastname: Cipriano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000191:economics* / Q000453:epidemiology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003362:Cost-Benefit Analysis; D003661:Decision Support Techniques; D006801:Humans; D008279:Magnetic Resonance Imaging; D008390:Markov Chains; D008875:Middle Aged; D008962:Models, Theoretical; D015995:Prevalence; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers
keywords: Alzheimer’s disease; Cerebrospinal fluid biomarkers; Cost-effectiveness analysis; Neuroimaging