Related Experiment Video
Updated: May 25, 2026
The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease
Published on: October 13, 2016
Test sequence of CSF and MRI biomarkers for prediction of AD in subjects with MCI
Stephanie Vos1, Ineke van Rossum, Leah Burns
1Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, The Netherlands. s.vos@maastrichtuniversity.nl
Abstract:
Our aim was to identify the best diagnostic test sequence for predicting Alzheimer's disease (AD)-type dementia in subjects with mild cognitive impairment (MCI) using cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) biomarkers. We selected 153 subjects with mild cognitive impairment from a multicenter memory clinic-based cohort. We tested the CSF beta amyloid (Aβ)1-42/tau ratio using enzyme-linked immunosorbent assay (ELISA) and hippocampal volumes (HCVs) using the atlas-based learning embeddings for atlas propagation (LEAP) method. Outcome measure was progression to AD-type dementia in 2 years. At follow-up, 48 (31%) subjects converted to AD-type dementia. In multivariable analyses, CSF Aβ1-42/tau and HCV predicted AD-type dementia regardless of apolipoprotein E (APOE) genotype and cognitive scores. Test sequence analyses showed that CSF Aβ1-42/tau increased predictive accuracy in subjects with normal HCV (p < 0.001) and abnormal HCV (p = 0.025). HCV increased predictive accuracy only in subjects with normal CSF Aβ1-42/tau (p = 0.014). Slope analyses for annual cognitive decline yielded similar results. For selection of subjects for a prodromal AD trial, the best balance between sample size and number of subjects needed to screen was obtained with CSF markers. These results provide further support for the use of CSF and magnetic resonance imaging biomarkers to identify prodromal AD.
Insights
Identifying Alzheimer's disease (AD) progression in mild cognitive impairment (MCI) is crucial. Cerebrospinal fluid (CSF) biomarkers and magnetic resonance imaging (MRI) hippocampal volumes effectively predict AD dementia, guiding clinical trial selection.
Area of Science:
- Neurology
- Biomarker Discovery
- Neuroimaging
Background:
- Mild cognitive impairment (MCI) is a transitional stage preceding Alzheimer's disease (AD) dementia.
- Accurate prediction of AD progression in MCI is vital for early intervention and clinical trial enrollment.
- Cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) biomarkers show promise for predicting AD dementia.
Purpose of the Study:
- To determine the optimal sequence of diagnostic tests for predicting Alzheimer's disease (AD)-type dementia in individuals with mild cognitive impairment (MCI).
- To evaluate the predictive value of CSF beta-amyloid (Aβ)1-42/tau ratio and hippocampal volumes (HCVs) for AD dementia progression.
- To assess the utility of these biomarkers in selecting participants for prodromal AD clinical trials.
Main Methods:
- A cohort of 153 MCI subjects from a multicenter memory clinic were analyzed.
- CSF Aβ1-42/tau ratio was measured using ELISA, and HCVs were quantified using the LEAP method.
- Progression to AD dementia within 2 years was the primary outcome measure.
Main Results:
- 48 (31%) subjects progressed to AD dementia within 2 years.
- CSF Aβ1-42/tau and HCV independently predicted AD dementia, irrespective of APOE genotype or cognitive scores.
- CSF Aβ1-42/tau improved prediction in both normal and abnormal HCV groups; HCV improved prediction only in the normal CSF Aβ1-42/tau group.
Conclusions:
- Combined CSF and MRI biomarkers enhance the prediction of AD dementia in MCI.
- CSF markers offer the best balance for subject selection in prodromal AD trials.
- These findings support the use of CSF and MRI biomarkers for identifying prodromal AD.
