Recommendations for cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic evaluation of mild cognitive impairment.
This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-β1-42, tau, and phosphorylated tau in the diagnostic evaluation of patients with mild cognitive impairment (MCI). The recommendations were developed by a multidisciplinary working group and based on the available evidence and consensus from focused group discussions for 1) prediction of clinical progression to Alzheimer's disease (AD) dementia, 2) cost-effectiveness, 3) interpretation of results, and 4) patient counseling. The working group recommended using CSF AD biomarkers in the diagnostic workup of MCI patients, after prebiomarker counseling, as an add-on to clinical evaluation to predict functional decline or conversion to AD dementia and to guide disease management. Because of insufficient evidence, it was uncertain whether CSF AD biomarkers outperform imaging biomarkers. Furthermore, the working group provided recommendations for interpretation of ambiguous CSF biomarker results and for pre- and post-biomarker counseling.
Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Sanna-Kaisa
SK
Herukka
Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Anja Hviid
AH
Simonsen
Department of Geriatric Medicine, Karolinska University Hospital, Huddinge, Sweden.
Niels
N
Andreasen
Neurochemistry Laboratory, Faculty of Medicine, CHUC-Coimbra University Hospital, CNC, CNC.IBILI-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Ines
I
Baldeiras
Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Maria
M
Bjerke
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Kaj
K
Blennow
Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
Sebastiaan
S
Engelborghs
Geneva Neuroscience Center, University Hospitals and University of Geneva, Geneva, Switzerland; IRCCS Fatebenefratelli, Brescia, Italy.
Giovanni B
GB
Frisoni
Department of Neurodegenerative Disorders, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland.
Tomasz
T
Gabryelewicz
IRCCS Fatebenefratelli, Brescia, Italy.
Samantha
S
Galluzzi
Alzheimer Centre Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
Ron
R
Handels
Center for Cognitive Impairments, Department of Neurology, University Medical Center Ljubljana, Ljubljana, Slovenia.
Milica G
MG
Kramberger
Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland.
Agnieszka
A
Kulczyńska
Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic i Universitari, IDIBAPS, Barcelona, Spain; Beta Brain Research Center, Fundació Pasqual Maragall, Barcelona, Spain.
Jose Luis
JL
Molinuevo
Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland; Department of Biochemical Diagnostics, University Hospital in Białystok, Białystok, Poland.
Barbara
B
Mroczko
Department of NVS, Center for Alzheimer Research, Translational Alzheimer Neurobiology, Karolinska Institutet, Huddinge, Sweden.
Agneta
A
Nordberg
Neurochemistry Laboratory, Faculty of Medicine, CHUC-Coimbra University Hospital, CNC, CNC.IBILI-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Catarina Resende
CR
Oliveira
Department of Neurology, University of Ulm, Ulm, Germany.
Markus
M
Otto
Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland.
Juha O
JO
Rinne
Center for Cognitive Impairments, Department of Neurology, University Medical Center Ljubljana, Ljubljana, Slovenia.
Uroš
U
Rot
Department of Neurology, Hacettepe University Hospitals, Ankara, Turkey.
Esen
E
Saka
Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Hilkka
H
Soininen
Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Hanne
H
Struyfs
Neuropathology Laboratory, Neurological Institute C. Besta, Milan, Italy.
Silvia
S
Suardi
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; Department of Neurology, Alzheimer Centre, VUMC, Amsterdam, The Netherlands.
Pieter Jelle
PJ
Visser
Department NVS, Karolinska Institutet, Center for Alzheimer Research, Division of Neurogeriatrics, Huddinge, Sweden.
Bengt
B
Winblad
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Henrik
H
Zetterberg
Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Electronic address: gunhild.waldemar.01@regionh.dk.
Gunhild
G
Waldemar
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D060825:Cognitive Dysfunction / Q000175:diagnosis*; D006801:Humans; D016239:MEDLINE / Q000706:statistics & numerical data; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
Alzheimer's disease; Biomarkers; CSF; Diagnostics; GRADE; Mild cognitive impairment; Recommendations