Prediction of AD dementia by biomarkers following the NIA-AA and IWG diagnostic criteria in MCI patients from three European memory clinics

Annapaola Prestia; Anna Caroli; Sara K Wade; Wiesjie M van der Flier; Rik Ossenkoppele; Bart Van Berckel; Frederik Barkhof; Charlotte E Teunissen; Anders Wall; Stephen F Carter; Michael Schöll; Il Han Choo; Agneta Nordberg; Philip Scheltens; Giovanni B Frisoni

doi:10.1016/j.jalz.2014.12.001

Prediction of AD dementia by biomarkers following the NIA-AA and IWG diagnostic criteria in MCI patients from three European memory clinics

Alzheimers Dement. 2015 Oct;11(10):1191-201. doi: 10.1016/j.jalz.2014.12.001. Epub 2015 Jan 31.

Authors

Affiliations

¹ Laboratory of Epidemiology and Neuroimaging, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
² Medical Imaging Unit, Biomedical Engineering Department, IRCCS Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
³ Department of Engineering, University of Cambridge, Cambridge, UK; Department of Decision Science, Bocconi University, Milan, Italy.
⁴ Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands; Department of Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
⁵ Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands; Department of Radiology and Nuclear Medicine and PET research, VU University Medical Center, Amsterdam, The Netherlands.
⁶ Department of Radiology and Nuclear Medicine and PET research, VU University Medical Center, Amsterdam, The Netherlands.
⁷ Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
⁸ PET-Center, Section of Nuclear Medicine & PET, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.
⁹ Karolinska Institutet, Alzheimer Neurobiology Center, Stockholm, Sweden.
¹⁰ Karolinska Institutet, Alzheimer Neurobiology Center, Stockholm, Sweden; Department of Neuropsychiatry, School of Medicine, Chosun University, Gwangju, Republic of Korea.
¹¹ Karolinska Institutet, Alzheimer Neurobiology Center, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
¹² Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
¹³ Laboratory of Epidemiology and Neuroimaging, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; Departments of Internal Medicine and Psychiatry, University Hospitals and University of Geneva, Geneve, Switzerland. Electronic address: [email protected].

PMID: 25646957
DOI: 10.1016/j.jalz.2014.12.001

Abstract

Introduction: Proposed diagnostic criteria (international working group and National Institute on Aging and Alzheimer's Association) for Alzheimer's disease (AD) include markers of amyloidosis (abnormal cerebrospinal fluid [CSF] amyloid beta [Aβ]42) and neurodegeneration (hippocampal atrophy, temporo-parietal hypometabolism on [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET), and abnormal CSF tau). We aim to compare the accuracy of these biomarkers, individually and in combination, in predicting AD among mild cognitive impairment (MCI) patients.

Methods: In 73 MCI patients, followed to ascertain AD progression, markers were measured. Sensitivity and specificity, positive (LR+) and negative (LR-) likelihood ratios, and crude and adjusted hazard ratios were computed.

Results: Twenty-nine MCI patients progressed and 44 remained stable. Positivity to any marker achieved the lowest LR- (0.0), whereas the combination Aβ42 plus FDG-PET achieved the highest LR+ (6.45). In a survival analysis, positivity to any marker was associated with 100% conversion rate, whereas negativity to all markers was associated with 100% stability.

Discussion: The best criteria combined amyloidosis and neurodegeneration biomarkers, whereas the individual biomarker with the best performance was FDG-PET.

Keywords: Alzheimer's disease; Diagnostic accuracy; Diagnostic criteria; MCI; MRI; PET.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / diagnosis
Amyloid beta-Peptides / cerebrospinal fluid*
Amyloidosis*
Atrophy
Biomarkers / cerebrospinal fluid
Disease Progression
Fluorodeoxyglucose F18
Hippocampus / pathology*
Humans
Male
Middle Aged
Positron-Emission Tomography
Predictive Value of Tests
Prognosis
Sensitivity and Specificity
tau Proteins / cerebrospinal fluid

Substances

Amyloid beta-Peptides
Biomarkers
MAPT protein, human
tau Proteins
Fluorodeoxyglucose F18