Regional functional connectivity predicts distinct cognitive impairments in Alzheimer's disease spectrum

Kamalini G. Ranasinghe; Leighton B. Hinkley; Alexander J. Beagle; Danielle Mizuiri; Anne F. Dowling; Susanne M. Honma; Mariel M. Finucane; Carole Scherling; Bruce L. Miller; Srikantan S. Nagarajan; Keith A. Vossel

doi:10.1016/j.nicl.2014.07.006

Regional functional connectivity predicts distinct cognitive impairments in Alzheimer's disease spectrum

Kamalini G. Ranasinghe, Leighton B. Hinkley, Alexander J. Beagle, Danielle Mizuiri, Anne F. Dowling, Susanne M. Honma, Mariel M. Finucane, Carole Scherling, Bruce L. Miller, Srikantan S. Nagarajan, Keith A. Vossel

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

52 Scopus citations

Abstract

Understanding neural network dysfunction in neurodegenerative disease is imperative to effectively develop network-modulating therapies. In Alzheimer's disease (AD), cognitive decline associates with deficits in resting-state functional connectivity of diffuse brain networks. The goal of the current study was to test whether specific cognitive impairments in AD spectrum correlate with reduced functional connectivity of distinct brain regions. We recorded resting-state functional connectivity of alpha-band activity in 27 patients with AD spectrum - 22 patients with probable AD (5 logopenic variant primary progressive aphasia, 7 posterior cortical atrophy, and 10 early-onset amnestic/dysexecutive AD) and 5 patients with mild cognitive impairment due to AD. We used magnetoencephalographic imaging (MEGI) to perform an unbiased search for regions where patterns of functional connectivity correlated with disease severity and cognitive performance. Functional connectivity measured the strength of coherence between a given region and the rest of the brain. Decreased neural connectivity of multiple brain regions including the right posterior perisylvian region and left middle frontal cortex correlated with a higher degree of disease severity. Deficits in executive control and episodic memory correlated with reduced functional connectivity of the left frontal cortex, whereas visuospatial impairments correlated with reduced functional connectivity of the left inferior parietal cortex. Our findings indicate that reductions in region-specific alpha-band resting-state functional connectivity are strongly correlated with, and might contribute to, specific cognitive deficits in AD spectrum. In the future, MEGI functional connectivity could be an important biomarker to map and follow defective networks in the early stages of AD.

Original language	English (US)
Pages (from-to)	385-395
Number of pages	11
Journal	NeuroImage: Clinical
Volume	5
DOIs	https://doi.org/10.1016/j.nicl.2014.07.006
State	Published - 2014
Externally published	Yes

Bibliographical note

Funding Information:
We would like to thank Drs. Lennart Mucke, Katherine P. Rankin, and Joel H. Kramer for their valuable feedback on the manuscript; Dr. Gil Rabinovici and Pia Gosh for providing the amyloid imaging; Anna Karydas for her support in genotypic and CSF analysis; Adhimoolam Babu for the support and guidance in VBM analysis; and Naomi Kort for her valuable support in analyzing the MEG data. We also thank all of the study participants and their families for their generous support to our research. This study was supported by the National Institutes of Health grants ( K23 AG038357 (K.A.V.), P50 AG023501 and P01 AG19724 (B.L.M.), R21 NS76171 (S.S.N.), R01 DC010145 (S.S.N.), NS066654 (S.S.N.), NS64060 (S.S.N.), National Science Foundation grant BCS-1262297 (S.S.N.)), the John Douglas French Alzheimer’s Foundation (K.A.V.), University of California San Francisco Alzheimer’s Disease Research Center pilot project grant (K.A.V.), and a gift from the S. D. Bechtel Jr. Foundation.

Keywords

Alzheimer's disease spectrum
Logopenic variant PPA
Magnetoencephalography (MEG)
Network dysfunction
Posterior cortical atrophy
Resting-state functional connectivity

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title = "Regional functional connectivity predicts distinct cognitive impairments in Alzheimer's disease spectrum",

abstract = "Understanding neural network dysfunction in neurodegenerative disease is imperative to effectively develop network-modulating therapies. In Alzheimer's disease (AD), cognitive decline associates with deficits in resting-state functional connectivity of diffuse brain networks. The goal of the current study was to test whether specific cognitive impairments in AD spectrum correlate with reduced functional connectivity of distinct brain regions. We recorded resting-state functional connectivity of alpha-band activity in 27 patients with AD spectrum - 22 patients with probable AD (5 logopenic variant primary progressive aphasia, 7 posterior cortical atrophy, and 10 early-onset amnestic/dysexecutive AD) and 5 patients with mild cognitive impairment due to AD. We used magnetoencephalographic imaging (MEGI) to perform an unbiased search for regions where patterns of functional connectivity correlated with disease severity and cognitive performance. Functional connectivity measured the strength of coherence between a given region and the rest of the brain. Decreased neural connectivity of multiple brain regions including the right posterior perisylvian region and left middle frontal cortex correlated with a higher degree of disease severity. Deficits in executive control and episodic memory correlated with reduced functional connectivity of the left frontal cortex, whereas visuospatial impairments correlated with reduced functional connectivity of the left inferior parietal cortex. Our findings indicate that reductions in region-specific alpha-band resting-state functional connectivity are strongly correlated with, and might contribute to, specific cognitive deficits in AD spectrum. In the future, MEGI functional connectivity could be an important biomarker to map and follow defective networks in the early stages of AD.",

keywords = "Alzheimer's disease spectrum, Logopenic variant PPA, Magnetoencephalography (MEG), Network dysfunction, Posterior cortical atrophy, Resting-state functional connectivity",

author = "Ranasinghe, {Kamalini G.} and Hinkley, {Leighton B.} and Beagle, {Alexander J.} and Danielle Mizuiri and Dowling, {Anne F.} and Honma, {Susanne M.} and Finucane, {Mariel M.} and Carole Scherling and Miller, {Bruce L.} and Nagarajan, {Srikantan S.} and Vossel, {Keith A.}",

note = "Funding Information: We would like to thank Drs. Lennart Mucke, Katherine P. Rankin, and Joel H. Kramer for their valuable feedback on the manuscript; Dr. Gil Rabinovici and Pia Gosh for providing the amyloid imaging; Anna Karydas for her support in genotypic and CSF analysis; Adhimoolam Babu for the support and guidance in VBM analysis; and Naomi Kort for her valuable support in analyzing the MEG data. We also thank all of the study participants and their families for their generous support to our research. This study was supported by the National Institutes of Health grants ( K23 AG038357 (K.A.V.), P50 AG023501 and P01 AG19724 (B.L.M.), R21 NS76171 (S.S.N.), R01 DC010145 (S.S.N.), NS066654 (S.S.N.), NS64060 (S.S.N.), National Science Foundation grant BCS-1262297 (S.S.N.)), the John Douglas French Alzheimer{\textquoteright}s Foundation (K.A.V.), University of California San Francisco Alzheimer{\textquoteright}s Disease Research Center pilot project grant (K.A.V.), and a gift from the S. D. Bechtel Jr. Foundation. ",

year = "2014",

doi = "10.1016/j.nicl.2014.07.006",

language = "English (US)",

volume = "5",

pages = "385--395",

journal = "NeuroImage: Clinical",

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T1 - Regional functional connectivity predicts distinct cognitive impairments in Alzheimer's disease spectrum

AU - Ranasinghe, Kamalini G.

AU - Hinkley, Leighton B.

AU - Beagle, Alexander J.

AU - Mizuiri, Danielle

AU - Dowling, Anne F.

AU - Honma, Susanne M.

AU - Finucane, Mariel M.

AU - Scherling, Carole

AU - Miller, Bruce L.

AU - Nagarajan, Srikantan S.

AU - Vossel, Keith A.

N1 - Funding Information: We would like to thank Drs. Lennart Mucke, Katherine P. Rankin, and Joel H. Kramer for their valuable feedback on the manuscript; Dr. Gil Rabinovici and Pia Gosh for providing the amyloid imaging; Anna Karydas for her support in genotypic and CSF analysis; Adhimoolam Babu for the support and guidance in VBM analysis; and Naomi Kort for her valuable support in analyzing the MEG data. We also thank all of the study participants and their families for their generous support to our research. This study was supported by the National Institutes of Health grants ( K23 AG038357 (K.A.V.), P50 AG023501 and P01 AG19724 (B.L.M.), R21 NS76171 (S.S.N.), R01 DC010145 (S.S.N.), NS066654 (S.S.N.), NS64060 (S.S.N.), National Science Foundation grant BCS-1262297 (S.S.N.)), the John Douglas French Alzheimer’s Foundation (K.A.V.), University of California San Francisco Alzheimer’s Disease Research Center pilot project grant (K.A.V.), and a gift from the S. D. Bechtel Jr. Foundation.

PY - 2014

Y1 - 2014

N2 - Understanding neural network dysfunction in neurodegenerative disease is imperative to effectively develop network-modulating therapies. In Alzheimer's disease (AD), cognitive decline associates with deficits in resting-state functional connectivity of diffuse brain networks. The goal of the current study was to test whether specific cognitive impairments in AD spectrum correlate with reduced functional connectivity of distinct brain regions. We recorded resting-state functional connectivity of alpha-band activity in 27 patients with AD spectrum - 22 patients with probable AD (5 logopenic variant primary progressive aphasia, 7 posterior cortical atrophy, and 10 early-onset amnestic/dysexecutive AD) and 5 patients with mild cognitive impairment due to AD. We used magnetoencephalographic imaging (MEGI) to perform an unbiased search for regions where patterns of functional connectivity correlated with disease severity and cognitive performance. Functional connectivity measured the strength of coherence between a given region and the rest of the brain. Decreased neural connectivity of multiple brain regions including the right posterior perisylvian region and left middle frontal cortex correlated with a higher degree of disease severity. Deficits in executive control and episodic memory correlated with reduced functional connectivity of the left frontal cortex, whereas visuospatial impairments correlated with reduced functional connectivity of the left inferior parietal cortex. Our findings indicate that reductions in region-specific alpha-band resting-state functional connectivity are strongly correlated with, and might contribute to, specific cognitive deficits in AD spectrum. In the future, MEGI functional connectivity could be an important biomarker to map and follow defective networks in the early stages of AD.

AB - Understanding neural network dysfunction in neurodegenerative disease is imperative to effectively develop network-modulating therapies. In Alzheimer's disease (AD), cognitive decline associates with deficits in resting-state functional connectivity of diffuse brain networks. The goal of the current study was to test whether specific cognitive impairments in AD spectrum correlate with reduced functional connectivity of distinct brain regions. We recorded resting-state functional connectivity of alpha-band activity in 27 patients with AD spectrum - 22 patients with probable AD (5 logopenic variant primary progressive aphasia, 7 posterior cortical atrophy, and 10 early-onset amnestic/dysexecutive AD) and 5 patients with mild cognitive impairment due to AD. We used magnetoencephalographic imaging (MEGI) to perform an unbiased search for regions where patterns of functional connectivity correlated with disease severity and cognitive performance. Functional connectivity measured the strength of coherence between a given region and the rest of the brain. Decreased neural connectivity of multiple brain regions including the right posterior perisylvian region and left middle frontal cortex correlated with a higher degree of disease severity. Deficits in executive control and episodic memory correlated with reduced functional connectivity of the left frontal cortex, whereas visuospatial impairments correlated with reduced functional connectivity of the left inferior parietal cortex. Our findings indicate that reductions in region-specific alpha-band resting-state functional connectivity are strongly correlated with, and might contribute to, specific cognitive deficits in AD spectrum. In the future, MEGI functional connectivity could be an important biomarker to map and follow defective networks in the early stages of AD.

KW - Alzheimer's disease spectrum

KW - Logopenic variant PPA

KW - Magnetoencephalography (MEG)

KW - Network dysfunction

KW - Posterior cortical atrophy

KW - Resting-state functional connectivity

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EP - 395

JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

ER -

Regional functional connectivity predicts distinct cognitive impairments in Alzheimer's disease spectrum

Abstract

Bibliographical note

Keywords

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