The effect of APOE ε4 allele on cholinesterase inhibitors in patients with alzheimer disease: Evaluation of the feasibility of resting state functional connectivity magnetic resonance imaging

Liang Wang, Jonathan Day, Catherine M. Roe, Matthew R. Brier, Jewell B. Thomas, Tammie L. Benzinger, John C. Morris, Beau M. Ances

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

This work is to determine whether apolipoprotein E (APOE) genotype modulates the effect of cholinesterase inhibitor (ChEI) treatment on resting state functional connectivity magnetic resonance imaging (rs-fcMRI) in patients with Alzheimer disease (AD). We retrospectively studied very mild and mild AD participants who were treated (N=25) or untreated (N=19) with ChEIs with respect to rs-fcMRI measure of 5 resting state networks (RSNs): default mode, dorsal attention (DAN), control (CON), salience (SAL), and sensory motor. For each network, a composite score was computed as the mean of Pearson correlations between pairwise time courses extracted from areas comprising this network. The composite scores were analyzed as a function of ChEI treatment and APOE ε4 allele. Across all participants, significant interactions between ChEI treatment and APOE ε4 allele were observed for all 5 RSNs. Within APOE ε4 carriers, significantly greater composite scores were observed in the DAN, CON, and SAL for treated compared with untreated participants. Within APOE ε4 noncarriers, treated and untreated participants did not have significantly different composite scores for all RSNs. These data suggest that APOE genotype affects the response to ChEI using rs-fcMRI. Rs-fcMRI may be useful for assessing the therapeutic effect of medications in AD clinical trials.

Original languageEnglish
Pages (from-to)122-127
Number of pages6
JournalAlzheimer disease and associated disorders
Volume28
Issue number2
DOIs
StatePublished - 2014

Keywords

  • Alzheimer disease (AD)
  • Apolipoprotein E (APOE)
  • Cholinesterase inhibitor
  • Functional magnetic resonance imaging (fMRI)
  • Resting state functional connectivity

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