Donepezil Enhances Frontal Functional Connectivity in Alzheimer's Disease: A Pilot Study

Ludovica Griffanti; Gordon K. Wilcock; Natalie Voets; Guendalina Bonifacio; Clare E. MacKay; Mark Jenkinson; Giovanna Zamboni

doi:10.1159/000450546

Donepezil Enhances Frontal Functional Connectivity in Alzheimer's Disease: A Pilot Study

Ludovica Griffanti, Gordon K. Wilcock, Natalie Voets, Guendalina Bonifacio, Clare E. MacKay, Mark Jenkinson, Giovanna Zamboni

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

Abstract

Background: We have previously shown that increased resting-state functional magnetic resonance imaging (fMRI)-based functional connectivity (FC) within the frontal resting-state networks in Alzheimer's disease (AD) patients reflects residual, possibly compensatory, function. This suggests that symptomatic treatments should aim to enhance FC specifically in these networks. Methods: 18 patients with probable AD underwent brain MRI and neuropsychological assessment at baseline and after 12 weeks of treatment with donepezil. We tested if changes in cognitive performance after treatment correlated with changes in FC in resting-state networks known to be altered in AD. Results: We found increases in FC in the orbitofrontal network that correlated with cognitive improvement after treatment. The increased FC was greatest in patients who responded most to treatment. Conclusion: This 'proof of concept' study suggests that changes in network-specific FC might be a biomarker of pharmacological intervention efficacy in AD.

Original language	English
Pages (from-to)	518-528
Number of pages	11
Journal	Dementia and Geriatric Cognitive Disorders Extra
Volume	6
Issue number	3
DOIs	https://doi.org/10.1159/000450546
Publication status	Published or Issued - 9 Sept 2016
Externally published	Yes

Keywords

Alzheimer's disease
Cholinesterase inhibitors
Donepezil
Functional connectivity
Functional magnetic resonance imaging
Resting-state networks

ASJC Scopus subject areas

Cognitive Neuroscience
Psychiatry and Mental health

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10.1159/000450546

Cite this

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title = "Donepezil Enhances Frontal Functional Connectivity in Alzheimer's Disease: A Pilot Study",

abstract = "Background: We have previously shown that increased resting-state functional magnetic resonance imaging (fMRI)-based functional connectivity (FC) within the frontal resting-state networks in Alzheimer's disease (AD) patients reflects residual, possibly compensatory, function. This suggests that symptomatic treatments should aim to enhance FC specifically in these networks. Methods: 18 patients with probable AD underwent brain MRI and neuropsychological assessment at baseline and after 12 weeks of treatment with donepezil. We tested if changes in cognitive performance after treatment correlated with changes in FC in resting-state networks known to be altered in AD. Results: We found increases in FC in the orbitofrontal network that correlated with cognitive improvement after treatment. The increased FC was greatest in patients who responded most to treatment. Conclusion: This 'proof of concept' study suggests that changes in network-specific FC might be a biomarker of pharmacological intervention efficacy in AD.",

keywords = "Alzheimer's disease, Cholinesterase inhibitors, Donepezil, Functional connectivity, Functional magnetic resonance imaging, Resting-state networks",

author = "Ludovica Griffanti and Wilcock, {Gordon K.} and Natalie Voets and Guendalina Bonifacio and MacKay, {Clare E.} and Mark Jenkinson and Giovanna Zamboni",

note = "Publisher Copyright: {\textcopyright} 2016 The Author(s) Published by S. Karger AG, Basel.",

year = "2016",

month = sep,

day = "9",

doi = "10.1159/000450546",

language = "English",

volume = "6",

pages = "518--528",

journal = "Dementia and Geriatric Cognitive Disorders Extra",

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T1 - Donepezil Enhances Frontal Functional Connectivity in Alzheimer's Disease

T2 - A Pilot Study

AU - Griffanti, Ludovica

AU - Wilcock, Gordon K.

AU - Voets, Natalie

AU - Bonifacio, Guendalina

AU - MacKay, Clare E.

AU - Jenkinson, Mark

AU - Zamboni, Giovanna

PY - 2016/9/9

Y1 - 2016/9/9

N2 - Background: We have previously shown that increased resting-state functional magnetic resonance imaging (fMRI)-based functional connectivity (FC) within the frontal resting-state networks in Alzheimer's disease (AD) patients reflects residual, possibly compensatory, function. This suggests that symptomatic treatments should aim to enhance FC specifically in these networks. Methods: 18 patients with probable AD underwent brain MRI and neuropsychological assessment at baseline and after 12 weeks of treatment with donepezil. We tested if changes in cognitive performance after treatment correlated with changes in FC in resting-state networks known to be altered in AD. Results: We found increases in FC in the orbitofrontal network that correlated with cognitive improvement after treatment. The increased FC was greatest in patients who responded most to treatment. Conclusion: This 'proof of concept' study suggests that changes in network-specific FC might be a biomarker of pharmacological intervention efficacy in AD.

AB - Background: We have previously shown that increased resting-state functional magnetic resonance imaging (fMRI)-based functional connectivity (FC) within the frontal resting-state networks in Alzheimer's disease (AD) patients reflects residual, possibly compensatory, function. This suggests that symptomatic treatments should aim to enhance FC specifically in these networks. Methods: 18 patients with probable AD underwent brain MRI and neuropsychological assessment at baseline and after 12 weeks of treatment with donepezil. We tested if changes in cognitive performance after treatment correlated with changes in FC in resting-state networks known to be altered in AD. Results: We found increases in FC in the orbitofrontal network that correlated with cognitive improvement after treatment. The increased FC was greatest in patients who responded most to treatment. Conclusion: This 'proof of concept' study suggests that changes in network-specific FC might be a biomarker of pharmacological intervention efficacy in AD.

KW - Alzheimer's disease

KW - Cholinesterase inhibitors

KW - Donepezil

KW - Functional connectivity

KW - Functional magnetic resonance imaging

KW - Resting-state networks

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JO - Dementia and Geriatric Cognitive Disorders Extra

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IS - 3

ER -

Donepezil Enhances Frontal Functional Connectivity in Alzheimer's Disease: A Pilot Study

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

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