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

J Alzheimers Dis. 2017;60(3):939-947. doi: 10.3233/JAD-161284.

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 (BPND) than HCs in multiple brain regions, and lower hippocampus volumes. [11C]PIB BPND, [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 BPND and then hippocampus volume. [11C]PIB BPND 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 BPND, 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.

Keywords: Alzheimer’s disease; PET; mild cognitive impairment; prognosis; volumetric MRI.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aniline Compounds
  • Apolipoproteins E / genetics
  • Benzothiazoles
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Brain / pathology
  • Cognitive Dysfunction / diagnostic imaging*
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / metabolism*
  • Cognitive Dysfunction / pathology
  • Dementia / diagnostic imaging*
  • Dementia / genetics
  • Dementia / metabolism*
  • Dementia / pathology
  • Disease Progression
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Kaplan-Meier Estimate
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Organ Size
  • Positron-Emission Tomography
  • Prognosis
  • Proportional Hazards Models
  • Radiopharmaceuticals
  • Thiazoles

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Aniline Compounds
  • Apolipoproteins E
  • Benzothiazoles
  • Radiopharmaceuticals
  • Thiazoles
  • Fluorodeoxyglucose F18