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.
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.
Departments of *Neurology §Radiology ¶Bioengineering ‡The Charles F. and Joanne Knight Alzheimer's Disease Research Center ∥The Hope Center, Washington University in St Louis †Saint Louis College of Pharmacy, Saint Louis, MO.
Liang
L
Wang
Jonathan
J
Day
Catherine M
CM
Roe
Matthew R
MR
Brier
Jewell B
JB
Thomas
Tammie L
TL
Benzinger
John C
JC
Morris
Beau M
BM
Ances
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000077265:Donepezil; D005240:Feasibility Studies; D005260:Female; D059907:Functional Neuroimaging; D005702:Galantamine / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000187:drug effects* / Q000503:physiopathology; D048448:Phenylcarbamates / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D000068836:Rivastigmine
D053327:Apolipoprotein E4; D002800:Cholinesterase Inhibitors; D007189:Indans; D048448:Phenylcarbamates; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D000068836:Rivastigmine