RISK STRATIFICATION USING CSF BIOMARKERS IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT-AN EXPLORATORY ANALYSIS

Purpose: To examine whether biomarker levels allow for risk stratification among patients with mild cognitive impairment (MCI). Using biomarker information could be useful in targeting early interventions for these at-risk patients. 

Method: We analyzed data from the Alzheimer’s Disease Neuroimaging Initiative on MCI patients (N=163) to estimate their 2-year risk of developing Alzheimer’s disease (AD) on the basis of baseline cerebrospinal fluid (CSF) biomarkers - Aβ₄₂, t-tau and p-tau. We used receiver operating characteristic (ROC) analysis to identify the best combination of biomarkers to predict the 2-year risk of developing AD. We conducted 10-fold cross-validations to test the robustness of our result. We constructed a multi-biomarker score (S) based on the biomarkers chosen from the previous step by the following equation: S = S(β_i × biomarker A_i), where β_i denotes the estimated beta coefficients for biomarkers A_i and were obtained from the previous ROC analysis. We then calculated point estimates for transition probabilities [Pr(AD|R_j)] conditional on the quintiles of multi-biomarker score (R_j).

Result: We found that Aβ₄₂ and t-tau were the best combination among CSF biomarkers to predict overall 2-year risk of developing AD among MCI patients [area under the curve (AUC) = 0.867 vs. cross-validation AUC = 0.856]. MCI patients with baseline multi-biomarker scores in the third quintile had the highest risk of developing AD, and then the fourth, fifth, second, and first quintiles in decreasing risk. MCI patients with scores in the third quintile had a 2-year risk of 58% (95%CI, 41%-74%), compared with 9% (95%CI, 0-19%) among patients with scores in the first quintile.

Conclusion: This study informs the potential for early interventions for MCI patients at increased risk, which may be of particular value for economic evaluation of early intervention on MCI/AD patients. Our findings suggest that MCI patients with scores in the third biomarker quintile may be more likely to be the fast progressors than those in the fourth or fifth quintiles, indicating an interaction between the well-known heterogeneity in progression rate among MCI patients and biomarker levels.