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Biomarkers in Dementia

Biomarkers in Dementia Fagan et al1 followed up a group of 61 normal elderly individuals (Clinical Dementia Rating [CDR] 0, ≥60 years old) for a mean time of 3 to 4 years to study cognitive decline. Individuals who progressed during the follow-up from a CDR of 0 to a CDR of 0.5 or higher were defined as converters toward very mild or mild dementia. All the other subjects were considered nonconverters. A cutoff value of 0.214 or greater for the ratio of cerebrospinal fluid (CSF) phosphorylated tau181/β-amyloid42 (ptau181/Aβ42) at baseline was adopted to predict converters and nonconverters at follow-up. The authors' conclusion is that, “CSF tau/Aβ42 ratios show strong promise as antecedent (preclinical) biomarkers that predict future dementia in cognitively normal older adults.” We would like to raise 2 objections. First, on the basis of the data reported in the article, it is possible to define the 2-by-2 chart outlined in the Table. The sensitivity, specificity, and positive and negative predictive values are 38.5%, 91.7%, 55.5%, and 84.6%, respectively. The low sensitivity and low positive predictive value do not support, in our opinion, the authors' conclusion. The same situation can be observed also for the tau/Aβ42 biomarker. Table. View LargeDownload Converters and Nonconverters in Relation to CSF ptau181/Aβ42 Ratio Second, the article does not report how many subjects, among the 13 converters (21%), had a CDR of 0.5 or a CDR of 1 and at what times. So in this group, subjects with mild cognitive impairment (MCI) are not distinguished from subjects with mild dementia. This choice is questionable because many epidemiological studies show that up to 40% of subjects with MCI reverted to a normal cognitive condition after 2 to 3 years.2 We believe that further research is necessary before suggesting the use of these biomarkers as possible predictors of progression from normal cognition/MCI to MCI/dementia in clinical practice. This issue is crucial because, taking into account the wide off-label use of cholinesterase inhibitors in MCI,3 physicians could be encouraged to prescribe these drugs for subjects classified as “positive” on the basis of CSF markers even though scientific evidence on their risk-benefit profile in MCI shows negative results.4,5 Back to top Article Information Correspondence: Dr Vanacore, National Centre of Epidemiology, Surveillance and Health Promotion, National Institute of Health, Via Giano della Bella 34, 00161 Rome, Italy (nicola.vanacore@iss.it). Financial Disclosure: None reported. References 1. Fagan AMRoe CMXiong CMintun MAMorris JCHoltzman DM Cerebrospinal fluid tau/beta-amyloid42 ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol 2007;64 (3) 343- 349PubMedGoogle ScholarCrossref 2. Panza FD’Introno AColacicco AM et al. Current epidemiology of mild cognitive impairment and other predementia syndromes. Am J Geriatr Psychiatry 2005;13 (8) 633- 644PubMedGoogle ScholarCrossref 3. Frisoni GBCanu EGeroldi CZanetti OZacchi V Drug prescription in mild cognitive impairment: the physicians' perspective in Italy. Int J Geriatr Psychiatry 2006;21 (11) 1071- 1077PubMedGoogle ScholarCrossref 4. Birks JFlicker L Donepezil for mild cognitive impairment. Cochrane Database Syst Rev 2006; (3) CD006104PubMedGoogle Scholar 5. Loy CSchneider L Galantamine for Alzheimer's disease and mild cognitive impairment. Cochrane Database Syst Rev 2006; (1) CD001747PubMedGoogle Scholar http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

Biomarkers in Dementia

Abstract

Fagan et al1 followed up a group of 61 normal elderly individuals (Clinical Dementia Rating [CDR] 0, ≥60 years old) for a mean time of 3 to 4 years to study cognitive decline. Individuals who progressed during the follow-up from a CDR of 0 to a CDR of 0.5 or higher were defined as converters toward very mild or mild dementia. All the other subjects were considered nonconverters. A cutoff value of 0.214 or greater for the ratio of cerebrospinal fluid (CSF) phosphorylated...
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Publisher
American Medical Association
Copyright
Copyright © 2007 American Medical Association. All Rights Reserved.
ISSN
0003-9942
DOI
10.1001/archneur.64.9.1356
pmid
17846281
Publisher site
See Article on Publisher Site

Abstract

Fagan et al1 followed up a group of 61 normal elderly individuals (Clinical Dementia Rating [CDR] 0, ≥60 years old) for a mean time of 3 to 4 years to study cognitive decline. Individuals who progressed during the follow-up from a CDR of 0 to a CDR of 0.5 or higher were defined as converters toward very mild or mild dementia. All the other subjects were considered nonconverters. A cutoff value of 0.214 or greater for the ratio of cerebrospinal fluid (CSF) phosphorylated tau181/β-amyloid42 (ptau181/Aβ42) at baseline was adopted to predict converters and nonconverters at follow-up. The authors' conclusion is that, “CSF tau/Aβ42 ratios show strong promise as antecedent (preclinical) biomarkers that predict future dementia in cognitively normal older adults.” We would like to raise 2 objections. First, on the basis of the data reported in the article, it is possible to define the 2-by-2 chart outlined in the Table. The sensitivity, specificity, and positive and negative predictive values are 38.5%, 91.7%, 55.5%, and 84.6%, respectively. The low sensitivity and low positive predictive value do not support, in our opinion, the authors' conclusion. The same situation can be observed also for the tau/Aβ42 biomarker. Table. View LargeDownload Converters and Nonconverters in Relation to CSF ptau181/Aβ42 Ratio Second, the article does not report how many subjects, among the 13 converters (21%), had a CDR of 0.5 or a CDR of 1 and at what times. So in this group, subjects with mild cognitive impairment (MCI) are not distinguished from subjects with mild dementia. This choice is questionable because many epidemiological studies show that up to 40% of subjects with MCI reverted to a normal cognitive condition after 2 to 3 years.2 We believe that further research is necessary before suggesting the use of these biomarkers as possible predictors of progression from normal cognition/MCI to MCI/dementia in clinical practice. This issue is crucial because, taking into account the wide off-label use of cholinesterase inhibitors in MCI,3 physicians could be encouraged to prescribe these drugs for subjects classified as “positive” on the basis of CSF markers even though scientific evidence on their risk-benefit profile in MCI shows negative results.4,5 Back to top Article Information Correspondence: Dr Vanacore, National Centre of Epidemiology, Surveillance and Health Promotion, National Institute of Health, Via Giano della Bella 34, 00161 Rome, Italy (nicola.vanacore@iss.it). Financial Disclosure: None reported. References 1. Fagan AMRoe CMXiong CMintun MAMorris JCHoltzman DM Cerebrospinal fluid tau/beta-amyloid42 ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol 2007;64 (3) 343- 349PubMedGoogle ScholarCrossref 2. Panza FD’Introno AColacicco AM et al. Current epidemiology of mild cognitive impairment and other predementia syndromes. Am J Geriatr Psychiatry 2005;13 (8) 633- 644PubMedGoogle ScholarCrossref 3. Frisoni GBCanu EGeroldi CZanetti OZacchi V Drug prescription in mild cognitive impairment: the physicians' perspective in Italy. Int J Geriatr Psychiatry 2006;21 (11) 1071- 1077PubMedGoogle ScholarCrossref 4. Birks JFlicker L Donepezil for mild cognitive impairment. Cochrane Database Syst Rev 2006; (3) CD006104PubMedGoogle Scholar 5. Loy CSchneider L Galantamine for Alzheimer's disease and mild cognitive impairment. Cochrane Database Syst Rev 2006; (1) CD001747PubMedGoogle Scholar

Journal

Archives of NeurologyAmerican Medical Association

Published: Sep 1, 2007

References