Document Detail

Cholinergic enhancement of functional networks in older adults with mild cognitive impairment.
MedLine Citation:
PMID:  23447373     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: The importance of the cholinergic system for cognitive function has been well documented in animal and human studies. The objective of this study was to elucidate the cognitive and functional connectivity changes associated with enhanced acetylcholine levels. We hypothesized that older adults with mild memory deficits would show behavioral and functional network enhancements with an acetylcholinesterase inhibitor treatment (donepezil) when compared to a placebo control group.
METHODS: We conducted a 3-month, double-blind, placebo-controlled study on the effects of donepezil in 27 older adults with mild memory deficits. Participants completed a delayed recognition memory task. Functional magnetic resonance imaging (fMRI) scans were collected at baseline prior to treatment and at 3-month follow-up while subjects were on a 10mg daily dose of donepezil or placebo.
RESULTS: Donepezil treatment significantly enhanced the response time for face and scene memory probes when compared to the placebo group. A group-by-visit interaction was identified for the functional network connectivity of the left fusiform face area (FFA) with the hippocampus and inferior frontal junction, such that the treatment group showed increased connectivity over time when compared to the placebo group. Additionally, the enhanced functional network connectivity of the FFA and hippocampus significantly predicted memory response time at 3-month follow-up in the treatment group.
INTERPRETATION: These findings suggest that increased cholinergic transmission improves goal-directed neural processing and cognitive ability and may serve to facilitate communication across functionally-connected attention and memory networks. Longitudinal fMRI is a useful method for elucidating the neural changes associated with pharmacological modulation and is a potential tool for monitoring intervention efficacy in clinical trials.
Judy Pa; Anne S Berry; Mariana Compagnone; Jacqueline Boccanfuso; Ian Greenhouse; Michael T Rubens; Julene K Johnson; Adam Gazzaley
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-06-17
Journal Detail:
Title:  Annals of neurology     Volume:  73     ISSN:  1531-8249     ISO Abbreviation:  Ann. Neurol.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-07-22     Completed Date:  2013-09-23     Revised Date:  2014-06-17    
Medline Journal Info:
Nlm Unique ID:  7707449     Medline TA:  Ann Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  762-73     Citation Subset:  IM    
Copyright Information:
© 2013 American Neurological Association.
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MeSH Terms
Aged, 80 and over
Brain / drug effects,  physiopathology*
Cholinesterase Inhibitors / therapeutic use*
Double-Blind Method
Indans / therapeutic use
Longitudinal Studies
Middle Aged
Mild Cognitive Impairment / drug therapy*,  physiopathology,  psychology*
Nerve Net / drug effects,  physiology*
Photic Stimulation / methods
Piperidines / therapeutic use
Reaction Time / drug effects,  physiology
Up-Regulation / drug effects,  physiology*
Grant Support
Reg. No./Substance:
0/Cholinesterase Inhibitors; 0/Indans; 0/Piperidines; 8SSC91326P/donepezil

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