Plasma lipid signature as an indicator of the risk and rate of progression from mild cognitive impairment to Alzheimer’s disease

Background Our knowledge about the importance of lipids in progression and the rate of progression from Mild Cognitive Impairment (MCI) to AD is limited. Our objective was to determine plasma lipids that could be implicated in the progression or rate of progression from MCI to AD. Method We analyzed the plasma lipid profile of MCI patients (N = 90) by liquid chromatography coupled with mass spectrometry. The association of lipids with progression was studied by logistic regression and a Cox regression model was used to assess lipids associated with the speed of progression. We adjusted our analyses for age, sex, CSF core AD biomarkers, APOE4 status, and Mini‐Mental State Examination (MMSE). Result Forty‐seven (52%) MCI patients progressed to AD during follow‐up (58 ± 12.5 months). Regression analysis detected that presence of APOE4 allele and high levels of four lipids – two as risk factors (p = 0.002) and two as protectors (p = 0.002 and p = 0.003)– were associated with progression (AUC 0.972, p < 0.001). The effect of these lipids in separating progressive from non‐progressive patients was significant when compared with the regression model without them (AUC 0.729 vs 0.972, z = 4.595, |z|>2.575, p < 0.01). Seven lipids were associated with the rate of progression, of which two were associated with a shorter time to progression (OR 9.88, 99% CI [3.08 –31.71], p < 0.001 and OR 34.81, CI 99% [4.88 – 248.3], p < 0.001) and five with a longer time to progression (OR 0.34, 99% CI [0.135 – 0.870], p = 0.003; OR 0.164, CI 99% [0.056 – 0.479], p < 0.001; OR 0.153, 99% CI [0.056 – 0.419], p < 0.001; OR 0.148, CI 99% [0.034 – 0.644], p = 0.001; and OR 0.029, 99% CI [0.007 – 0.131], p < 0.001). Conclusion Our results suggest that lipid dysregulation could have an important role in progression and rate of progression from MCI to AD. Our data also indicate that AD lipid alterations could have clinical implications as circulating biomarkers of progression and progression speed.