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Alzheimers Res Ther. 2019 Apr 16;11(1):33. doi: 10.1186/s13195-019-0487-y.

Personalized risk for clinical progression in cognitively normal subjects-the ABIDE project.

Author information

1
Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands. i.vanmaurik@vumc.nl.
2
Department of Epidemiology and Biostatistics, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands. i.vanmaurik@vumc.nl.
3
Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
4
Brain Research Center, Amsterdam, The Netherlands.
5
Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
6
Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
7
Institutes of Neurology and Healthcare Engineering, UCL, London, UK.
8
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Barcelona, Spain and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
9
Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
10
German Center for Neurodegenerative Diseases, Bonn, Germany.
11
Department of Psychiatry, Charité Berlin, Campus Benjamin Franklin, Berlin, Germany.
12
Department of Psychiatry, University of Cologne, Cologne, Germany.
13
Department of Epidemiology and Biostatistics, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.

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 (5 years, 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.

KEYWORDS:

Biomarkers; Cerebrospinal fluid; Magnetic resonance imaging; Progression

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