Utility of Molecular and Structural Brain Imaging to Predict Progression from Mild Cognitive Impairment to Dementia

Abstract

This project compares three neuroimaging biomarkers to predict progression to dementia in subjects with mild cognitive impairment (MCI). Eighty-eight subjects with MCI and 40 healthy controls (HCs) were recruited. Subjects had a 3T magnetic resonance imaging (MRI) scan, and two positron emission tomography (PET) scans, one with Pittsburgh compound B ([¹¹C]PIB) and one with fluorodeoxyglucose ([¹⁸F]FDG). MCI subjects were followed for up to 4 y and progression to dementia was assessed on an annual basis. MCI subjects had higher [¹¹C]PIB binding potential (BP_ND) than HCs in multiple brain regions, and lower hippocampus volumes. [¹¹C]PIB BP_ND, [¹⁸F]FDG standard uptake value ratio (SUVR), and hippocampus volume were associated with time to progression to dementia using a Cox proportional hazards model. [¹⁸F]FDG SUVR demonstrated the most statistically significant association with progression, followed by [¹¹C]PIB BP_ND and then hippocampus volume. [¹¹C]PIB BP_ND and [¹⁸F]FDG SUVR were independently predictive, suggesting that combining these measures is useful to increase accuracy in the prediction of progression to dementia. Hippocampus volume also had independent predictive properties to [¹¹C]PIB BP_ND, but did not add predictive power when combined with the [¹⁸F]FDG SUVR data. This work suggests that PET imaging with both [¹¹C]PIB and [¹⁸F]FDG may help to determine which MCI subjects are likely to progress to AD, possibly directing future treatment options.