Predicting progression to dementia in persons with mild cognitive impairment using cerebrospinal fluid markers

Ron L H Handels; Stephanie J B Vos; Milica G Kramberger; Vesna Jelic; Kaj Blennow; Mark van Buchem; Wiesje van der Flier; Yvonne Freund-Levi; Harald Hampel; Marcel Olde Rikkert; Ania Oleksik; Zvezdan Pirtosek; Philip Scheltens; Hilkka Soininen; Charlotte Teunissen; Magda Tsolaki; Asa K Wallin; Bengt Winblad; Frans R J Verhey; Pieter Jelle Visser

doi:10.1016/j.jalz.2016.12.015

Predicting progression to dementia in persons with mild cognitive impairment using cerebrospinal fluid markers

Alzheimers Dement. 2017 Aug;13(8):903-912. doi: 10.1016/j.jalz.2016.12.015. Epub 2017 Feb 17.

Authors

Ron L H Handels¹, Stephanie J B Vos², Milica G Kramberger³, Vesna Jelic⁴, Kaj Blennow⁵, Mark van Buchem⁶, Wiesje van der Flier⁷, Yvonne Freund-Levi⁸, Harald Hampel⁹, Marcel Olde Rikkert¹⁰, Ania Oleksik⁶, Zvezdan Pirtosek³, Philip Scheltens¹¹, Hilkka Soininen¹², Charlotte Teunissen¹³, Magda Tsolaki¹⁴, Asa K Wallin¹⁵, Bengt Winblad⁴, Frans R J Verhey², Pieter Jelle Visser¹⁶

Affiliations

¹ Department of Psychiatry and Neuropsychology, Alzheimer Centre Limburg, School for Mental Health and Neurosciences, Maastricht University, Maastricht, The Netherlands. Electronic address: ron.handels@maastrichtuniversity.nl.
² Department of Psychiatry and Neuropsychology, Alzheimer Centre Limburg, School for Mental Health and Neurosciences, Maastricht University, Maastricht, The Netherlands.
³ Department of Neurology, Ljubljana University Medical Centre, Ljubljana, Slovenia.
⁴ Division of Clinical Geriatrics, Department of NVS, Karolinska Institutet, Center for Alzheimer Research, Division of Neurogeriatrics, Huddinge, Sweden.
⁵ Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
⁶ Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands.
⁷ Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands; Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
⁸ Division of Clinical Geriatrics, Department of NVS, Karolinska Institutet, Center for Alzheimer Research, Division of Neurogeriatrics, Huddinge, Sweden; Department of Psychiatry, Tiohundra AB Norrtälje Hospital, Stockholm Sweden.
⁹ AXA Research Fund & UPMC Chair, Paris, France; Sorbonne Universités Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du cerveau et de la moelle (ICM), Département de Neurologie, Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Boulevard de l'hôpital, Paris, France.
¹⁰ Department of Geriatrics, Radboudumc Alzheimer Centre, Donders Institute for Brain Cognition and Behavior, Radboud University Medical Centre, Nijmegen, The Netherlands.
¹¹ Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
¹² Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Neurocenter-Neurology, Kuopio University Hospital, Kuopio, Finland.
¹³ Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, VU University Medical Centre, Amsterdam, The Netherlands.
¹⁴ Memory and Dementia Outpatient Clinic, 3rd Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
¹⁵ Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
¹⁶ Department of Psychiatry and Neuropsychology, Alzheimer Centre Limburg, School for Mental Health and Neurosciences, Maastricht University, Maastricht, The Netherlands; Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.

PMID: 28216393
DOI: 10.1016/j.jalz.2016.12.015

Abstract

Introduction: We aimed to determine the added value of cerebrospinal fluid (CSF) to clinical and imaging tests to predict progression from mild cognitive impairment (MCI) to any type of dementia.

Methods: The risk of progression to dementia was estimated using two logistic regression models based on 250 MCI participants: the first included standard clinical measures (demographic, clinical, and imaging test information) without CSF biomarkers, and the second included standard clinical measures with CSF biomarkers.

Results: Adding CSF improved predictive accuracy with 0.11 (scale from 0-1). Of all participants, 136 (54%) had a change in risk score of 0.10 or higher (which was considered clinically relevant), of whom in 101, it was in agreement with their dementia status at follow-up.

Discussion: An individual person's risk of progression from MCI to dementia can be improved by relying on CSF biomarkers in addition to recommended clinical and imaging tests for usual care.

Keywords: Alzheimer's disease; Conversion; Dementia; Mild cognitive impairment; Predict; Prognosis; Progression; Reclassification; Risk; Risk prediction model.

Publication types

Multicenter Study

MeSH terms

Aged
Aged, 80 and over
Biomarkers / cerebrospinal fluid
Cognitive Dysfunction / cerebrospinal fluid*
Cognitive Dysfunction / diagnostic imaging
Dementia / cerebrospinal fluid*
Dementia / diagnostic imaging
Disease Progression
Educational Status
Female
Follow-Up Studies
Humans
Logistic Models
Magnetic Resonance Imaging
Male
Mental Status and Dementia Tests
Middle Aged
Prognosis
Risk Assessment
Temporal Lobe / diagnostic imaging

Substances

Biomarkers