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Concordance and Diagnostic Accuracy of [11C]PIB PET and Cerebrospinal Fluid Biomarkers in a Sample of Patients with Mild Cognitive Impairment and Alzheimer's Disease.
J Alzheimers Dis 2015; 45(4):1077-88JA

Abstract

BACKGROUND

Alzheimer's disease (AD) pathology can be quantified in vivo using cerebrospinal fluid (CSF) levels of amyloid-β1-42 (Aβ1-42), total-tau (t-tau), and phosphorylated tau (p-tau181p), as well as with positron emission tomography (PET) using [(11)C]Pittsburgh compound-B ([(11)C]PIB). Studies assessing concordance between these measures, however, have provided conflicting results. Moreover, it has been proposed that [(11)C]PIB PET may be of greater clinical utility in terms of identifying patients with mild cognitive impairment (MCI) who will progress to the dementia phase of AD.

OBJECTIVE

To determine concordance and classification accuracy of CSF biomarkers and [(11)C]PIB PET in a cohort of patients with MCI and AD.

METHODS

68 patients (MCI, n = 33; AD, n = 35) underwent [(11)C]PIB PET and CSF sampling. Cutoffs of >1.41 ([(11)C]PIB), <450 pg/mL-and a more lenient cutoff of 550 pg/mL-(Aβ1-42), <6.5 (Aβ1-42/p-tau181p), and 1.14 (Aβ1-42/t-tau), were used to determine concordance. Logistic regression was used to determine classification accuracy with respect to stable MCI (sMCI) versus MCI who progressed to AD (pMCI).

RESULTS

Concordance between [(11)C]PIB and Aβ1-42 was highest for sMCI (67%), followed by AD (60%) and pMCI (33%). Agreement was increased across groups using Aβ1-42 <550 pg/mL, or Aβ1-42 to tau ratios. Logistic regression showed that classification accuracy of [(11)C]PIB, between sMCI and pMCI, was superior to Aβ1-42 (73% versus 58%), Aβ1-42/t-tau (63%), and Aβ1-42/p-tau181p (65%).

CONCLUSION

In the present study, [(11)C]PIB proved a better predictor of progression to AD in patients with MCI, relative to CSF measures of Aβ1-42 or Aβ1-42/tau. Discordance between PET and CSF markers for Aβ1-42 suggests they cannot be used interchangeably, as is currently the case.

Authors+Show Affiliations

Department NVS, Centre for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Huddinge, Sweden.Department NVS, Centre for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Huddinge, Sweden Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom.Department NVS, Centre for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Huddinge, Sweden.Department NVS, Centre for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Huddinge, Sweden Department of Psychology, Stockholm University, Stockholm, Sweden.Section of Nuclear Medicine and PET, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.Department NVS, Centre for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Huddinge, Sweden Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25649653

Citation

Leuzy, Antoine, et al. "Concordance and Diagnostic Accuracy of [11C]PIB PET and Cerebrospinal Fluid Biomarkers in a Sample of Patients With Mild Cognitive Impairment and Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 45, no. 4, 2015, pp. 1077-88.
Leuzy A, Carter SF, Chiotis K, et al. Concordance and Diagnostic Accuracy of [11C]PIB PET and Cerebrospinal Fluid Biomarkers in a Sample of Patients with Mild Cognitive Impairment and Alzheimer's Disease. J Alzheimers Dis. 2015;45(4):1077-88.
Leuzy, A., Carter, S. F., Chiotis, K., Almkvist, O., Wall, A., & Nordberg, A. (2015). Concordance and Diagnostic Accuracy of [11C]PIB PET and Cerebrospinal Fluid Biomarkers in a Sample of Patients with Mild Cognitive Impairment and Alzheimer's Disease. Journal of Alzheimer's Disease : JAD, 45(4), pp. 1077-88. doi:10.3233/JAD-142952.
Leuzy A, et al. Concordance and Diagnostic Accuracy of [11C]PIB PET and Cerebrospinal Fluid Biomarkers in a Sample of Patients With Mild Cognitive Impairment and Alzheimer's Disease. J Alzheimers Dis. 2015;45(4):1077-88. PubMed PMID: 25649653.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Concordance and Diagnostic Accuracy of [11C]PIB PET and Cerebrospinal Fluid Biomarkers in a Sample of Patients with Mild Cognitive Impairment and Alzheimer's Disease. AU - Leuzy,Antoine, AU - Carter,Stephen F, AU - Chiotis,Konstantinos, AU - Almkvist,Ove, AU - Wall,Anders, AU - Nordberg,Agneta, PY - 2015/2/5/entrez PY - 2015/2/5/pubmed PY - 2016/3/10/medline KW - Alzheimer's disease KW - [${11}^C$]PIB KW - amyloid KW - cerebrospinal fluid KW - mild cognitive impairment KW - positron emission tomography KW - tau SP - 1077 EP - 88 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 45 IS - 4 N2 - BACKGROUND: Alzheimer's disease (AD) pathology can be quantified in vivo using cerebrospinal fluid (CSF) levels of amyloid-β1-42 (Aβ1-42), total-tau (t-tau), and phosphorylated tau (p-tau181p), as well as with positron emission tomography (PET) using [(11)C]Pittsburgh compound-B ([(11)C]PIB). Studies assessing concordance between these measures, however, have provided conflicting results. Moreover, it has been proposed that [(11)C]PIB PET may be of greater clinical utility in terms of identifying patients with mild cognitive impairment (MCI) who will progress to the dementia phase of AD. OBJECTIVE: To determine concordance and classification accuracy of CSF biomarkers and [(11)C]PIB PET in a cohort of patients with MCI and AD. METHODS: 68 patients (MCI, n = 33; AD, n = 35) underwent [(11)C]PIB PET and CSF sampling. Cutoffs of >1.41 ([(11)C]PIB), <450 pg/mL-and a more lenient cutoff of 550 pg/mL-(Aβ1-42), <6.5 (Aβ1-42/p-tau181p), and 1.14 (Aβ1-42/t-tau), were used to determine concordance. Logistic regression was used to determine classification accuracy with respect to stable MCI (sMCI) versus MCI who progressed to AD (pMCI). RESULTS: Concordance between [(11)C]PIB and Aβ1-42 was highest for sMCI (67%), followed by AD (60%) and pMCI (33%). Agreement was increased across groups using Aβ1-42 <550 pg/mL, or Aβ1-42 to tau ratios. Logistic regression showed that classification accuracy of [(11)C]PIB, between sMCI and pMCI, was superior to Aβ1-42 (73% versus 58%), Aβ1-42/t-tau (63%), and Aβ1-42/p-tau181p (65%). CONCLUSION: In the present study, [(11)C]PIB proved a better predictor of progression to AD in patients with MCI, relative to CSF measures of Aβ1-42 or Aβ1-42/tau. Discordance between PET and CSF markers for Aβ1-42 suggests they cannot be used interchangeably, as is currently the case. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/25649653/Concordance_and_Diagnostic_Accuracy_of_[11C]PIB_PET_and_Cerebrospinal_Fluid_Biomarkers_in_a_Sample_of_Patients_with_Mild_Cognitive_Impairment_and_Alzheimer's_Disease_ L2 - https://content.iospress.com/openurl?genre=article&amp;id=doi:10.3233/JAD-142952 DB - PRIME DP - Unbound Medicine ER -