Resting-state BOLD networks versus task-associated functional MRI for distinguishing Alzheimer's disease risk groups

To assess the ability of resting state functional magnetic resonance imaging to distinguish known risk factors for Alzheimer's disease, we evaluated 17 cognitively normal individuals with a family history of AD and at least one copy of the apolipoprotein e4 allele compared to 12 individuals who were not carriers of the APOE4 gene and did not have a family history of AD

Adam S. Fleisher; Ayesha Sherzai; Curtis Taylor; Jessica B.S. Langbaum; Kewei Chen; Richard B. Buxton


Scholarcy highlights

  • Functional imaging has been demonstrated to be able to distinguish people at risk for Alzheimer's disease prior to any clinical manifestations of neurodegeneration in young and middle aged individuals(Bookheimer et al, 2000; Fleisher et al, 2005; Fleisher et al, 2008; Reiman et al, 1996; Reiman et al, 2004)
  • This has proven useful for understanding functional brain pathways, it is not clear that these activation techniques will be practical for use as biomarkers to identify individuals predisposed to developing dementia or useful as outcome measures in preventative drug studies. functional magnetic resonance imaging activation studies suffer from intra and inter-subject variability, scanner variability, are dependent on task performance, and often involve lengthy scan times with complex study designs that are hard to standardize, and are difficult to perform in cognitively impaired individuals. fMRI evaluation of the resting state of the brain may be a sufficient and relevant target for studies of pre-clinical dementia
  • This study supports recent reports that that resting state blood oxygenation level dependent fMRI can identify differences based on risk for AD In comparison with encoding-associated BOLD activations and deactivations, evaluation of network connectivity of low frequency fluctuations more readily detected variability associated with AD risk and provided superior effect sizes for distinguishing risk groups
  • Overall our findings suggest that abnormalities in resting state networks may represent early functional impairment associated with risk for AD
  • Resting state BOLD fMRI is a viable candidate for a biomarker of preclinical dementia, and potentially a valuable tool in dementia prediction, prognosis, and preventative treatment development in AD
  • There were no significant differences in the total volumes of deactivated regions between risk groups
  • A recent study showed increased default mode network BOLD signal and encoding associated hippocampal signal in young APOE4 carriers, indicating that resting state fMRI may be a sensitive technique for identifying patterns associated with risk for AD many decades prior to development of AD pathology or clinical symptoms(Filippini et al, 2009)
  • Use of resting state blood oxygenation level dependent functional magnetic resonance imaging may be a more sensitive marker of preclinical functional reorganization in those at risk for Alzheimer's disease, potentially representing underlying early AD pathology, as compared to activation and deactivation task-associated fMRI

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