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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / cerebrospinal fluid
  • Brain / diagnostic imaging
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / diagnosis*
  • Cognitive Dysfunction / diagnostic imaging
  • Dementia / cerebrospinal fluid
  • Dementia / diagnosis
  • Dementia / diagnostic imaging
  • Disease Progression*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Precision Medicine
  • Risk Factors


  • Biomarkers