Prenatal exposure to undernutrition is associated with a specific lipid profile predicting future brain aging

Abstract

Prenatal adversity affects cognitive and brain aging. Both lipid and leptin concentrations may be involved. We investigated if prenatal undernutrition is associated with a specific blood lipid profile and/or leptin concentrations, and if these relate to cognitive function and brain aging. 801 plasma samples of members of the Dutch famine birth cohort were assessed for lipidomics and leptin at age 58. Cognitive performance was measured with a Stroop task at 58, and MRI-based BrainAGE was derived in a subsample at 68. Out of 259 lipid signals, a signature of five identified individuals who were undernourished prenatally. These five lipids were not associated with cognitive performance, but three were predictive of BrainAGE. Leptin was not associated with prenatal famine exposure, Stroop performance, or BrainAGE. In conclusion, prenatal undernutrition was associated with an altered lipid profile predictive of BrainAGE 10 years later, demonstrating the potential of lipid profiles as early biomarkers for accelerated brain aging.

Fig. 1. Random forest variable importance plot showing the relative importance to classification of the top 30 lipids and receiver operating curve showing the sensitivity, specificity and area under the curve of the model.

A Variable importance plot of lipids responsible for driving classification of prenatal famine exposed versus non-exposed individuals. B ROC curve showing diagnostic ability of random forest model.

Fig. 2. Plots showing the performance and the lipids responsible for driving the random forest model of BrainAGE.

A Scatter plot of actual BrainAGE against predicted BrainAGE in an independent test set. B Variable importance plot of lipids responsible for driving the random forest model used to generate the predictions in A.