Progressive Disintegration of Brain Networking from Normal Aging to Alzheimer Disease: Analysis of Independent Components of 18F-FDG PET Data

J Nucl Med. 2017 Jul;58(7):1132-1139. doi: 10.2967/jnumed.116.184309. Epub 2017 Mar 9.

Abstract

Brain connectivity has been assessed in several neurodegenerative disorders investigating the mutual correlations between predetermined regions or nodes. Selective breakdown of brain networks during progression from normal aging to Alzheimer disease dementia (AD) has also been observed. Methods: We implemented independent-component analysis of 18F-FDG PET data in 5 groups of subjects with cognitive states ranging from normal aging to AD-including mild cognitive impairment (MCI) not converting or converting to AD-to disclose the spatial distribution of the independent components in each cognitive state and their accuracy in discriminating the groups. Results: We could identify spatially distinct independent components in each group, with generation of local circuits increasing proportionally to the severity of the disease. AD-specific independent components first appeared in the late-MCI stage and could discriminate converting MCI and AD from nonconverting MCI with an accuracy of 83.5%. Progressive disintegration of the intrinsic networks from normal aging to MCI to AD was inversely proportional to the conversion time. Conclusion: Independent-component analysis of 18F-FDG PET data showed a gradual disruption of functional brain connectivity with progression of cognitive decline in AD. This information might be useful as a prognostic aid for individual patients and as a surrogate biomarker in intervention trials.

Keywords: 18F-FDG PET; Alzheimer disease; independent-component analysis; mild cognitive impairment; normal aging.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging*
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / physiopathology*
  • Brain / diagnostic imaging
  • Brain / physiopathology*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / physiopathology*
  • Connectome / methods*
  • Disease Progression
  • Fluorodeoxyglucose F18 / pharmacokinetics
  • Humans
  • Middle Aged
  • Nerve Net / diagnostic imaging
  • Nerve Net / physiopathology*
  • Positron-Emission Tomography / methods
  • Principal Component Analysis
  • Radiopharmaceuticals / pharmacokinetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Severity of Illness Index

Substances

  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18