Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer’s disease

Alexander N. W. Taylor; Lana Kambeitz-Ilankovic; Benno Gesierich; Lee Simon-Vermot; Nicolai Franzmeier; Miguel A.  Araque Caballero; Sophia   Meuller; Liu Hesheng; Birgit  Ertl-Wagner; Katharina Beurger; Michael Weiner; Martin Dichgans; Marco Duering; Michael Ewers

doi:10.1016/j.jalz.2016.06.2358

Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer’s disease

Alexander N. W. Taylor, Lana Kambeitz-Ilankovic, Benno Gesierich, Lee Simon-Vermot, Nicolai Franzmeier, Miguel A. Araque Caballero, Sophia Meuller, Liu Hesheng, Birgit Ertl-Wagner, Katharina Beurger, Michael Weiner, Martin Dichgans, Marco Duering, Michael Ewers

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Abstract

Introduction
White matter hyperintensities (WMHs) increase the risk of Alzheimer's disease (AD). Whether WMHs are associated with the decline of functional neural networks in AD is debated.

Method
Resting-state functional magnetic resonance imaging and WMH were assessed in 78 subjects with increased amyloid levels on AV-45 positron emission tomography (PET) in different clinical stages of AD. We tested the association between WMH volume in major atlas-based fiber tract regions of interest (ROIs) and changes in functional connectivity (FC) between the tracts' projection areas within the default mode network (DMN).

Results
WMH volume within the inferior fronto-occipital fasciculus (IFOF) was the highest among all tract ROIs and associated with reduced FC in IFOF-connected DMN areas, independently of global AV-45 PET. Higher AV-45 PET contributed to reduced FC in IFOF-connected, temporal, and parietal DMN areas.

Conclusions
High fiber tract WMH burden is associated with reduced FC in connected areas, thus adding to the effects of amyloid pathology on neuronal network function.

Original language	English
Pages (from-to)	225-235
Number of pages	11
Journal	Alzheimer's & Dementia
Volume	13
Issue number	3
DOIs	https://doi.org/10.1016/j.jalz.2016.06.2358
Publication status	Published - 15 Jul 2016
Externally published	Yes

Keywords

Alzheimer's disease
Functional connectivity
Fibre tract
resting-state fMRI
White matter hyperintensities
vascular
amyloid-beta
Resting-state fMRI
Fiber tract
Vascular
Amyloid-beta
Humans
Male
Nerve Net/diagnostic imaging
Positron-Emission Tomography
White Matter/diagnostic imaging
Neuropsychological Tests
Magnetic Resonance Imaging
Image Processing, Computer-Assisted
Aged, 80 and over
Brain Mapping
Female
Aged
Alzheimer Disease/diagnostic imaging

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Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer's diseaseFinal published version, 1.95 MBLicence: CC BY-NC-ND

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Taylor, A. N. W., Kambeitz-Ilankovic, L., Gesierich, B., Simon-Vermot, L., Franzmeier, N., Araque Caballero, M. A., Meuller, S., Hesheng, L., Ertl-Wagner, B., Beurger, K., Weiner, M., Dichgans, M., Duering, M., & Ewers, M. (2016). Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer’s disease. Alzheimer's & Dementia, 13(3), 225-235. https://doi.org/10.1016/j.jalz.2016.06.2358

@article{06333c2182b34c11b081016bfb5cec01,

title = "Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer{\textquoteright}s disease",

abstract = "IntroductionWhite matter hyperintensities (WMHs) increase the risk of Alzheimer's disease (AD). Whether WMHs are associated with the decline of functional neural networks in AD is debated.MethodResting-state functional magnetic resonance imaging and WMH were assessed in 78 subjects with increased amyloid levels on AV-45 positron emission tomography (PET) in different clinical stages of AD. We tested the association between WMH volume in major atlas-based fiber tract regions of interest (ROIs) and changes in functional connectivity (FC) between the tracts' projection areas within the default mode network (DMN).ResultsWMH volume within the inferior fronto-occipital fasciculus (IFOF) was the highest among all tract ROIs and associated with reduced FC in IFOF-connected DMN areas, independently of global AV-45 PET. Higher AV-45 PET contributed to reduced FC in IFOF-connected, temporal, and parietal DMN areas.ConclusionsHigh fiber tract WMH burden is associated with reduced FC in connected areas, thus adding to the effects of amyloid pathology on neuronal network function.",

keywords = "Alzheimer's disease, Functional connectivity, Fibre tract, resting-state fMRI, White matter hyperintensities, vascular, amyloid-beta, Resting-state fMRI, Fiber tract, Vascular, Amyloid-beta, Humans, Male, Nerve Net/diagnostic imaging, Positron-Emission Tomography, White Matter/diagnostic imaging, Neuropsychological Tests, Magnetic Resonance Imaging, Image Processing, Computer-Assisted, Aged, 80 and over, Brain Mapping, Female, Aged, Alzheimer Disease/diagnostic imaging",

author = "Taylor, {Alexander N. W.} and Lana Kambeitz-Ilankovic and Benno Gesierich and Lee Simon-Vermot and Nicolai Franzmeier and {Araque Caballero}, {Miguel A.} and Sophia Meuller and Liu Hesheng and Birgit Ertl-Wagner and Katharina Beurger and Michael Weiner and Martin Dichgans and Marco Duering and Michael Ewers",

note = "Funding Information: Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.ucla.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found in “Additional Authors” supplemental material and at http://adni.loni.ucla.edu/wpcontent/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf. This work was supported by grants of the LMUexcellent Initiative (ADDMe), Alzheimer's Forschung Initiative (AFI) and the European Commission (PCIG12-GA-2012-334259, VASCAMY) to M.E.; the Vascular Dementia Research Foundation to Martin Dichgans; Merck, Avid, the Veterans Administration (VA) and Department of Defense (DOD) to M.W.W.; grant numbers 2U01AG024904, W81XWH-13-1-0259, W81XWH-12-2-0012, R01 AG10897, 1P41 EB015904, P01 AG19724, R01 AG032306, R01A G03879, ADNI 2-12-233036, 20110506, R01 MH098062-01 from the following sources: National Institutes of Health/National Institutes Alzheimer's/National Institute of Mental Health, Department of Defense, gs12:Alzheimer's Association, gs13:Alzheimer's Drug Discovery Foundation, to M.W.W.; travel expenses for lectures from the United Leukodystrophy Foundation, the European Stroke Conference, and Kenes International to M.D. Publisher Copyright: {\textcopyright} 2016 The Authors",

year = "2016",

month = jul,

day = "15",

doi = "10.1016/j.jalz.2016.06.2358",

language = "English",

volume = "13",

pages = "225--235",

journal = "Alzheimer's & Dementia",

issn = "1552-5260",

publisher = "Elsevier",

number = "3",

}

Taylor, ANW, Kambeitz-Ilankovic, L, Gesierich, B, Simon-Vermot, L, Franzmeier, N, Araque Caballero, MA, Meuller, S, Hesheng, L, Ertl-Wagner, B, Beurger, K, Weiner, M, Dichgans, M, Duering, M & Ewers, M 2016, 'Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer’s disease', Alzheimer's & Dementia, vol. 13, no. 3, pp. 225-235. https://doi.org/10.1016/j.jalz.2016.06.2358

TY - JOUR

T1 - Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer’s disease

AU - Taylor, Alexander N. W.

AU - Kambeitz-Ilankovic, Lana

AU - Gesierich, Benno

AU - Simon-Vermot, Lee

AU - Franzmeier, Nicolai

AU - Araque Caballero, Miguel A.

AU - Meuller, Sophia

AU - Hesheng, Liu

AU - Ertl-Wagner, Birgit

AU - Beurger, Katharina

AU - Weiner, Michael

AU - Dichgans, Martin

AU - Duering, Marco

AU - Ewers, Michael

N1 - Funding Information: Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.ucla.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found in “Additional Authors” supplemental material and at http://adni.loni.ucla.edu/wpcontent/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf. This work was supported by grants of the LMUexcellent Initiative (ADDMe), Alzheimer's Forschung Initiative (AFI) and the European Commission (PCIG12-GA-2012-334259, VASCAMY) to M.E.; the Vascular Dementia Research Foundation to Martin Dichgans; Merck, Avid, the Veterans Administration (VA) and Department of Defense (DOD) to M.W.W.; grant numbers 2U01AG024904, W81XWH-13-1-0259, W81XWH-12-2-0012, R01 AG10897, 1P41 EB015904, P01 AG19724, R01 AG032306, R01A G03879, ADNI 2-12-233036, 20110506, R01 MH098062-01 from the following sources: National Institutes of Health/National Institutes Alzheimer's/National Institute of Mental Health, Department of Defense, gs12:Alzheimer's Association, gs13:Alzheimer's Drug Discovery Foundation, to M.W.W.; travel expenses for lectures from the United Leukodystrophy Foundation, the European Stroke Conference, and Kenes International to M.D. Publisher Copyright: © 2016 The Authors

PY - 2016/7/15

Y1 - 2016/7/15

N2 - IntroductionWhite matter hyperintensities (WMHs) increase the risk of Alzheimer's disease (AD). Whether WMHs are associated with the decline of functional neural networks in AD is debated.MethodResting-state functional magnetic resonance imaging and WMH were assessed in 78 subjects with increased amyloid levels on AV-45 positron emission tomography (PET) in different clinical stages of AD. We tested the association between WMH volume in major atlas-based fiber tract regions of interest (ROIs) and changes in functional connectivity (FC) between the tracts' projection areas within the default mode network (DMN).ResultsWMH volume within the inferior fronto-occipital fasciculus (IFOF) was the highest among all tract ROIs and associated with reduced FC in IFOF-connected DMN areas, independently of global AV-45 PET. Higher AV-45 PET contributed to reduced FC in IFOF-connected, temporal, and parietal DMN areas.ConclusionsHigh fiber tract WMH burden is associated with reduced FC in connected areas, thus adding to the effects of amyloid pathology on neuronal network function.

AB - IntroductionWhite matter hyperintensities (WMHs) increase the risk of Alzheimer's disease (AD). Whether WMHs are associated with the decline of functional neural networks in AD is debated.MethodResting-state functional magnetic resonance imaging and WMH were assessed in 78 subjects with increased amyloid levels on AV-45 positron emission tomography (PET) in different clinical stages of AD. We tested the association between WMH volume in major atlas-based fiber tract regions of interest (ROIs) and changes in functional connectivity (FC) between the tracts' projection areas within the default mode network (DMN).ResultsWMH volume within the inferior fronto-occipital fasciculus (IFOF) was the highest among all tract ROIs and associated with reduced FC in IFOF-connected DMN areas, independently of global AV-45 PET. Higher AV-45 PET contributed to reduced FC in IFOF-connected, temporal, and parietal DMN areas.ConclusionsHigh fiber tract WMH burden is associated with reduced FC in connected areas, thus adding to the effects of amyloid pathology on neuronal network function.

KW - Alzheimer's disease

KW - Functional connectivity

KW - Fibre tract

KW - resting-state fMRI

KW - White matter hyperintensities

KW - vascular

KW - amyloid-beta

KW - Resting-state fMRI

KW - Fiber tract

KW - Vascular

KW - Amyloid-beta

KW - Humans

KW - Male

KW - Nerve Net/diagnostic imaging

KW - Positron-Emission Tomography

KW - White Matter/diagnostic imaging

KW - Neuropsychological Tests

KW - Magnetic Resonance Imaging

KW - Image Processing, Computer-Assisted

KW - Aged, 80 and over

KW - Brain Mapping

KW - Female

KW - Aged

KW - Alzheimer Disease/diagnostic imaging

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U2 - 10.1016/j.jalz.2016.06.2358

DO - 10.1016/j.jalz.2016.06.2358

M3 - Article

C2 - 27432800

SN - 1552-5260

VL - 13

SP - 225

EP - 235

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

IS - 3

ER -

Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer’s disease

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Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer’s disease

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