Universität zu Köln

van Maurik, Ingrid S., Slot, Rosalinde E. R., Verfaillie, Sander C. J., Zwan, Marissa D., Bouwman, Femke H., Prins, Niels D., Teunissen, Charlotte E., Scheltens, Philip ORCID: 0000-0002-1046-6408, Barkhof, Frederik ORCID: 0000-0003-3543-3706, Wattjes, Mike P., Molinuevo, Jose Luis, Rami, Lorena, Wolfsgruber, Steffen, Peters, Oliver, Jessen, Frank, Berkhof, Johannes and van der Flier, Wiesje M. (2019). Personalized risk for clinical progression in cognitively normal subjects-the ABIDE project. Alzheimers Res. Ther., 11. LONDON: BMC. ISSN 1758-9193

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Abstract

Background: Biomarkers such as cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) have predictive value for progression to dementia in patients with mild cognitive impairment (MCI). The pre-dementia stage takes far longer, and the interpretation of biomarker findings is particular relevant for individuals who present at a memory clinic, but are deemed cognitively normal. The objective of the current study is to construct biomarker-based prognostic models for personalized risk of clinical progression in cognitively normal individuals presenting at a memory clinic. Methods: We included 481 individuals with subjective cognitive decline (SCD) from the Amsterdam Dementia Cohort. Prognostic models were developed by Cox regression with patient characteristics, MRI, and/or CSF biomarkers to predict clinical progression to MCI or dementia. We estimated 5- and 3-year individualized risks based on patient-specific values. External validation was performed on Alzheimer's Disease Neuroimaging Initiative (ADNI) and an European dataset. Results: Based on demographics only (Harrell's C=0.70), 5- and 3-year progression risks varied from 6% [3-11] and 4% [2-8] (age 55, MMSE 30) to 38% [29-49] and 28% [21-37] (age 70, MMSE 27). Normal CSF biomarkers strongly decreased progression probabilities (Harrell's C=0.82). By contrast, abnormal CSF markedly increased risk (5years, 96% [56-100]; 3 years, 89% [44-99]). The CSF model could reclassify 58% of the individuals with an intermediate risk (35-65%) based on the demographic model. MRI measures were not retained in the models. Conclusion: The current study takes the first steps in a personalized approach for cognitively normal individuals by providing biomarker-based prognostic models.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code van Maurik, Ingrid S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Slot, Rosalinde E. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Verfaillie, Sander C. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zwan, Marissa D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bouwman, Femke H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Prins, Niels D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Teunissen, Charlotte E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Scheltens, Philip UNSPECIFIED orcid.org/0000-0002-1046-6408 UNSPECIFIED Barkhof, Frederik UNSPECIFIED orcid.org/0000-0003-3543-3706 UNSPECIFIED Wattjes, Mike P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Molinuevo, Jose Luis UNSPECIFIED UNSPECIFIED UNSPECIFIED Rami, Lorena UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolfsgruber, Steffen UNSPECIFIED UNSPECIFIED UNSPECIFIED Peters, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Jessen, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Berkhof, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Flier, Wiesje M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-150682
DOI:	10.1186/s13195-019-0487-y
Journal or Publication Title:	Alzheimers Res. Ther.
Volume:	11
Date:	2019
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1758-9193
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ALZHEIMERS ASSOCIATION WORKGROUPS; CEREBROSPINAL-FLUID BIOMARKERS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; MEMORY DECLINE; DISEASE; DEMENTIA; IMPAIRMENT; CRITERIA; RECOMMENDATIONS Multiple languages Clinical Neurology; Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15068