Background: We previously created a serum-based algorithm that yielded excellent diagnostic accuracy in Alzheimer’s disease. The current project was designed to refine that algorithm by reducing the number of serum proteins and by including clinical labs. The link between the biomarker risk score and neuropsychological performance was also examined. Methods: Serum-protein multiplex biomarker data from 197 patients diagnosed with Alzheimer’s disease and 203 cognitively normal controls from the Texas Alzheimer’s Research Consortium were analyzed. The 30 markers identified as the most important from our initial analyses and clinical labs were utilized to create the algorithm. Results: The 30-protein risk score yielded a sensitivity, specificity, and AUC of 0.88, 0.82, and 0.91, respectively. When combined with demographic data and clinical labs, the algorithm yielded a sensitivity, specificity, and AUC of 0.89, 0.85, and 0.94, respectively. In linear regression models, the biomarker risk score was most strongly related to neuropsychological tests of language and memory. Conclusions: Our previously published diagnostic algorithm can be restricted to only 30 serum proteins and still retain excellent diagnostic accuracy. Additionally, the revised biomarker risk score is significantly related to neuropsychological test performance.

1.
Alzheimer’s Association: 2008 Alzheimer’s disease facts and figures. Alzheimers Dement 2008;4:110–133.
2.
O’Bryant S, Xiao G, Barber R, Reisch J, Doody R, Fairchild T, Adams P, Waring S, Diaz-Arrastia R, Texas Alzheimer’s Research Consortium: A serum protein-based algorithm for the detection of Alzheimer’s disease. Arch Neurol 2010;67:1077–1081.
3.
Schneider P, Hampel H, Buerger K: Biological marker candidates of Alzheimer’s disease in blood, plasma, and serum. CNS Neurosci Ther 2009;15:358–374.
4.
Thal LJ, et al: The role of biomarkers in clinical trials for Alzheimer disease. Alzheimer Dis Assoc Disord 2006;20:6–15.
5.
Ray S, et al: Classification and prediction of clinical Alzheimer’s diagnosis based on plasma signaling proteins. Nat Med 2007;13:1359–1362.
6.
Booij BB, et al: A gene expression pattern in blood for the early detection of Alzheimer’s disease. J Alzheimers Dis 2011;23:109–119.
7.
Rye PD, et al: A novel blood test for the early detection of Alzheimer’s disease. J Alzheimers Dis 2011;23:121–129.
8.
O’Bryant SE, et al: A serum protein-based algorithm for the detection of Alzheimer disease. Arch Neurol 2010;67:1077–1081.
9.
Mueller SG, et al: Ways toward an early diagnosis in Alzheimer’s disease: The Alzheimer’s Disease Neuroimaging Initiative (ADNI). Alzheimers Dement 2005;1:55–66.
10.
Waring S, O’Bryant SE, Reisch JS, Diaz-Arrastia R, Knebl J, Doody R, Texas Alzheimer’s Research Consortium: The Texas Alzheimer’s Research Consortium longitudinal research cohort: Study design and baseline characteristics. Texas Pub Health J 2008;60:9–13.
11.
O’Bryant SE, et al: Brain-derived neurotrophic factor levels in Alzheimer’s disease. J Alzheimers Dis 2009;17:337–341.
12.
McKhann D, Drockman D, Folstein M, et al: Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group. Neurology 1984;34:939–944.
13.
Wechsler D: Wechsler Memory Scale, ed 3. San Antonio, The Psychological Corporation, 1997.
14.
Lezak MD, Howieson DB, Loring DW: Neuropsychological Assessment, ed 4. Oxford, Oxford University Press, 2004.
15.
Strauss E, Sherman EMS, Spreen O: A Compendium of Neuropsychological Tests: Administration, Norms, and Commentary, ed 3. Oxford, Oxford University Press, 2006.
16.
Yesavage JA, Brink TL, Rose TL, et al: Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 1983;17:37–49.
17.
Folstein MF, Folstein SE, McHugh PR: ‘Mini-Mental State’: A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198.
18.
Morris JC: The Clinical Dementia Rating (CDR): current version and scoring rules (see comment). Neurology 1993;43:2412–2414.
19.
Ivnik R, Malec JF, Smith GE, Tangalos EG, Petersen RC, Kokmen E, Kurkland LT: Mayo’s Older Americans Normative Studies: WAIS-R norms for age 56 to 97. Clin Neuropsychol 1992;6:1–30.
20.
Ivnik RJ, Malec JF, Smith GE, Tangalos EG, Petersen RC: Neuropsychological tests’ norms above age 55 COWAT, BNT, MAE Token, WRAT-R Reading, AMNART, STROOP, TMT and JLO. Clin Neuropsychol 1996;10:262–278.
21.
Tulsky D, Zhu J, Ledbetter M: WAIS-III – WMS-III Technical Manual. San Antonio, The Psychological Corporation, 1997.
22.
Hobson V, Hall JR, Harvey M, Cullum CM, Lacritz L, Massman PJ, Waring SC, O’Bryant SE: An examination of the Boston Naming Test: calculation of an ‘estimated’ 60-item score from 30- and 15-item scores in a cognitively impaired population. Int J Geriatr Psychiatry 2011;26:351–355.
23.
Dickstein DL, et al: Role of vascular risk factors and vascular dysfunction in Alzheimer’s disease. Mt Sinai J Med 2010;77:82–102.
24.
Piazza F, et al: Increased tissue factor pathway inhibitor and homocysteine in Alzheimer’s disease. Neurobiol Aging 2010, E-pub ahead of print.
25.
Okereke OI, et al: A profile of impaired insulin degradation in relation to late-life cognitive decline: a preliminary investigation. Int J Geriatr Psychiatry 2009;24:177–182.
26.
van Oijen M, et al: Plasma Abeta(1–40) and Abeta(1–42) and the risk of dementia: a prospective case-cohort study. Lancet Neurol 2006;5:655–660.
27.
R Development Core Team: R: A language and environment for statistical computing. 2009. www.R-project.org.
28.
Breiman L: Random forests. Machine Learn 2001;45:5–32.
29.
Graff-Radford NR, et al: Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease (erratum appears in Arch Neurol 2007;64:1246). Arch Neurol 2007;64:354–362.
30.
Anonymous, Consensus report of the Working Group on: ‘Molecular and Biochemical Markers of Alzheimer’s Disease’. The Ronald and Nancy Reagan Research Institute of the Alzheimer’s Association and the National Institute on Aging Working Group (see comment) (erratum appears in Neurobiol Aging 1998;19:285). Neurobiol Aging 1998;19:109–116.
31.
O’Bryant SE, Lucas JA: Estimating the predictive value of the Test of Memory Malingering: an illustrative example for clinicians. Clin Neuropsychol 2006;20:533–540.
32.
Vemuri P, et al: Alzheimer’s disease diagnosis in individual subjects using structural MR images: validation studies. NeuroImage 2008;39:1186–1197.
33.
Zhang D, et al: Multimodal classification of Alzheimer’s disease and mild cognitive impairment. NeuroImage 2011;55:856–867.
34.
Brys M, et al: Magnetic resonance imaging improves cerebrospinal fluid biomarkers in the early detection of Alzheimer’s disease. J Alzheimers Dis 2009;16:351–362.
35.
O’Bryant SE, et al: Decreased C-reactive protein levels in Alzheimer disease. J Geriatr Psychiatry Neurol 2010;23:49–53.
36.
In’t Veld BA: Ruitenberg A, Hofman A, Launer LJ, van Duijn CM, Stijnen T, et al: Nonsteroidal antiinflammatory drugs and the risk of Alzheimer’s disease. New Engl J Med 2001;345:1515–1521.
37.
Anthony JC, et al: Reduced prevalence of AD in users of NSAIDs and H2 receptor antagonists: the Cache County study. Neurology 2000;54:2066–2071.
38.
Etminan M, Gill S, Samii A: Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer’s disease: systematic review and meta-analysis of observational studies. BMJ 2003;327:128.
39.
Aisen PS, et al: Neither rofecoxib nor naproxen slows cognitive decline in people with mild-to-moderate Alzheimer’s disease. Evidence-Based Healthcare 2003;7:200–201.
40.
Thal LJ, et al: A randomized, double-blind, study of rofecoxib in patients with mild cognitive impairment. Neuropsychopharmacology 2005;30:1204–1215.
41.
Adapt Research Group, et al: Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial. Neurology 2007;68:1800–1808.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.