Regional Amyloid-β Load and White Matter Abnormalities Contribute to Hypometabolism in Alzheimer’s Dementia

For the Alzheimer’s Disease Neuroimaging Initiative

Research output: Contribution to journalArticle

Abstract

We investigated the association between amyloid-β deposition and white matter (WM) integrity as a determinant of brain glucose hypometabolism across the Alzheimer’s disease (AD) spectrum. We assessed ninety-six subjects (27 cognitively normal, 49 mild cognitive impairment, and 20 AD dementia) who underwent [18F]FDG and [18F]Florbetapir positron emission tomography (PET) as well as magnetic resonance imaging (MRI) with diffusion tensor imaging. Among the regions with reduced fractional anisotropy (FA) in the AD group, we selected a voxel of interest in the angular bundle bilaterally for subsequent analyses. Using voxel-based interaction models at voxel level, we tested whether the regional hypometabolism is associated with FA in the angular bundle and regional amyloid-β deposition. In the AD patients, [18F]FDG hypometabolism in the striatum, mesiobasal temporal, orbitofrontal, precuneus, and cingulate cortices were associated with the interaction between high levels of [18F]Florbetapir standard uptake value ratios (SUVR) in these regions and low FA in the angular bundle. We found that the interaction between, rather than the independent effects of, high levels of amyloid-β deposition and WM integrity disruption determined limbic hypometabolism in patients with AD. This finding highlights a more integrative model for AD, where the interaction between partially independent processes determines the glucose hypometabolism.

Original languageEnglish (US)
Pages (from-to)4916-4924
Number of pages9
JournalMolecular Neurobiology
Volume56
Issue number7
DOIs
StatePublished - Jul 1 2019

Fingerprint

Amyloid
Alzheimer Disease
Anisotropy
Fluorodeoxyglucose F18
Glucose
Parietal Lobe
Diffusion Tensor Imaging
Gyrus Cinguli
Temporal Lobe
White Matter
Prefrontal Cortex
Positron-Emission Tomography
Magnetic Resonance Imaging
Brain

Keywords

  • Alzheimer’s disease
  • Amyloid-β (Aβ)
  • Diffusion tensor imaging (DTI)
  • Interaction
  • Positron emission tomography (PET)
  • White matter (WM)

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

For the Alzheimer’s Disease Neuroimaging Initiative. / Regional Amyloid-β Load and White Matter Abnormalities Contribute to Hypometabolism in Alzheimer’s Dementia. In: Molecular Neurobiology. 2019 ; Vol. 56, No. 7. pp. 4916-4924.
@article{8c2690a1426542e8aaa1e34c76e74584,
title = "Regional Amyloid-β Load and White Matter Abnormalities Contribute to Hypometabolism in Alzheimer’s Dementia",
abstract = "We investigated the association between amyloid-β deposition and white matter (WM) integrity as a determinant of brain glucose hypometabolism across the Alzheimer’s disease (AD) spectrum. We assessed ninety-six subjects (27 cognitively normal, 49 mild cognitive impairment, and 20 AD dementia) who underwent [18F]FDG and [18F]Florbetapir positron emission tomography (PET) as well as magnetic resonance imaging (MRI) with diffusion tensor imaging. Among the regions with reduced fractional anisotropy (FA) in the AD group, we selected a voxel of interest in the angular bundle bilaterally for subsequent analyses. Using voxel-based interaction models at voxel level, we tested whether the regional hypometabolism is associated with FA in the angular bundle and regional amyloid-β deposition. In the AD patients, [18F]FDG hypometabolism in the striatum, mesiobasal temporal, orbitofrontal, precuneus, and cingulate cortices were associated with the interaction between high levels of [18F]Florbetapir standard uptake value ratios (SUVR) in these regions and low FA in the angular bundle. We found that the interaction between, rather than the independent effects of, high levels of amyloid-β deposition and WM integrity disruption determined limbic hypometabolism in patients with AD. This finding highlights a more integrative model for AD, where the interaction between partially independent processes determines the glucose hypometabolism.",
keywords = "Alzheimer’s disease, Amyloid-β (Aβ), Diffusion tensor imaging (DTI), Interaction, Positron emission tomography (PET), White matter (WM)",
author = "{For the Alzheimer’s Disease Neuroimaging Initiative} and Schilling, {Lucas Porcello} and Pascoal, {Tharick A.} and Zimmer, {Eduardo R.} and Sulantha Mathotaarachchi and Monica Shin and {de Mello Rieder}, {Carlos Roberto} and Serge Gauthier and Andr{\'e} Palmini and Pedro Rosa-Neto and Weiner, {Michael W.} and Paul Aisen and Ronald Petersen and Jack, {Ronald Clifford R.} and William Jagust and Trojanowki, {John Q.} and Toga, {Arthur W.} and Laurel Beckett and Green, {Robert C.} and Saykin, {Andrew J.} and John Morris and Shaw, {Leslie M.} and Jeffrey Kaye and Joseph Quinn and Lisa Silbert and Betty Lind and Raina Carter and Sara Dolen and Schneider, {Lon S.} and Sonia Pawluczyk and Mauricio Beccera and Liberty Teodoro and Spann, {Bryan M.} and James Brewer and Helen Vanderswag and Adam Fleisher and Heidebrink, {Judith L.} and Lord, {Joanne L.} and Mason, {Sara S.} and Albers, {Colleen S.} and David Knopman and Kris Johnson and Doody, {Rachelle S.} and Javier Villanueva-Meyer and Munir Chowdhury and Susan Rountree and Mimi Dang and Yaakov Stern and Marek-Marsel Mesulam and Sandra Weintraub and Borna Bonakdarpour",
year = "2019",
month = "7",
day = "1",
doi = "10.1007/s12035-018-1405-1",
language = "English (US)",
volume = "56",
pages = "4916--4924",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press",
number = "7",

}

Regional Amyloid-β Load and White Matter Abnormalities Contribute to Hypometabolism in Alzheimer’s Dementia. / For the Alzheimer’s Disease Neuroimaging Initiative.

In: Molecular Neurobiology, Vol. 56, No. 7, 01.07.2019, p. 4916-4924.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Regional Amyloid-β Load and White Matter Abnormalities Contribute to Hypometabolism in Alzheimer’s Dementia

AU - For the Alzheimer’s Disease Neuroimaging Initiative

AU - Schilling, Lucas Porcello

AU - Pascoal, Tharick A.

AU - Zimmer, Eduardo R.

AU - Mathotaarachchi, Sulantha

AU - Shin, Monica

AU - de Mello Rieder, Carlos Roberto

AU - Gauthier, Serge

AU - Palmini, André

AU - Rosa-Neto, Pedro

AU - Weiner, Michael W.

AU - Aisen, Paul

AU - Petersen, Ronald

AU - Jack, Ronald Clifford R.

AU - Jagust, William

AU - Trojanowki, John Q.

AU - Toga, Arthur W.

AU - Beckett, Laurel

AU - Green, Robert C.

AU - Saykin, Andrew J.

AU - Morris, John

AU - Shaw, Leslie M.

AU - Kaye, Jeffrey

AU - Quinn, Joseph

AU - Silbert, Lisa

AU - Lind, Betty

AU - Carter, Raina

AU - Dolen, Sara

AU - Schneider, Lon S.

AU - Pawluczyk, Sonia

AU - Beccera, Mauricio

AU - Teodoro, Liberty

AU - Spann, Bryan M.

AU - Brewer, James

AU - Vanderswag, Helen

AU - Fleisher, Adam

AU - Heidebrink, Judith L.

AU - Lord, Joanne L.

AU - Mason, Sara S.

AU - Albers, Colleen S.

AU - Knopman, David

AU - Johnson, Kris

AU - Doody, Rachelle S.

AU - Villanueva-Meyer, Javier

AU - Chowdhury, Munir

AU - Rountree, Susan

AU - Dang, Mimi

AU - Stern, Yaakov

AU - Mesulam, Marek-Marsel

AU - Weintraub, Sandra

AU - Bonakdarpour, Borna

PY - 2019/7/1

Y1 - 2019/7/1

N2 - We investigated the association between amyloid-β deposition and white matter (WM) integrity as a determinant of brain glucose hypometabolism across the Alzheimer’s disease (AD) spectrum. We assessed ninety-six subjects (27 cognitively normal, 49 mild cognitive impairment, and 20 AD dementia) who underwent [18F]FDG and [18F]Florbetapir positron emission tomography (PET) as well as magnetic resonance imaging (MRI) with diffusion tensor imaging. Among the regions with reduced fractional anisotropy (FA) in the AD group, we selected a voxel of interest in the angular bundle bilaterally for subsequent analyses. Using voxel-based interaction models at voxel level, we tested whether the regional hypometabolism is associated with FA in the angular bundle and regional amyloid-β deposition. In the AD patients, [18F]FDG hypometabolism in the striatum, mesiobasal temporal, orbitofrontal, precuneus, and cingulate cortices were associated with the interaction between high levels of [18F]Florbetapir standard uptake value ratios (SUVR) in these regions and low FA in the angular bundle. We found that the interaction between, rather than the independent effects of, high levels of amyloid-β deposition and WM integrity disruption determined limbic hypometabolism in patients with AD. This finding highlights a more integrative model for AD, where the interaction between partially independent processes determines the glucose hypometabolism.

AB - We investigated the association between amyloid-β deposition and white matter (WM) integrity as a determinant of brain glucose hypometabolism across the Alzheimer’s disease (AD) spectrum. We assessed ninety-six subjects (27 cognitively normal, 49 mild cognitive impairment, and 20 AD dementia) who underwent [18F]FDG and [18F]Florbetapir positron emission tomography (PET) as well as magnetic resonance imaging (MRI) with diffusion tensor imaging. Among the regions with reduced fractional anisotropy (FA) in the AD group, we selected a voxel of interest in the angular bundle bilaterally for subsequent analyses. Using voxel-based interaction models at voxel level, we tested whether the regional hypometabolism is associated with FA in the angular bundle and regional amyloid-β deposition. In the AD patients, [18F]FDG hypometabolism in the striatum, mesiobasal temporal, orbitofrontal, precuneus, and cingulate cortices were associated with the interaction between high levels of [18F]Florbetapir standard uptake value ratios (SUVR) in these regions and low FA in the angular bundle. We found that the interaction between, rather than the independent effects of, high levels of amyloid-β deposition and WM integrity disruption determined limbic hypometabolism in patients with AD. This finding highlights a more integrative model for AD, where the interaction between partially independent processes determines the glucose hypometabolism.

KW - Alzheimer’s disease

KW - Amyloid-β (Aβ)

KW - Diffusion tensor imaging (DTI)

KW - Interaction

KW - Positron emission tomography (PET)

KW - White matter (WM)

UR - http://www.scopus.com/inward/record.url?scp=85056312323&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056312323&partnerID=8YFLogxK

U2 - 10.1007/s12035-018-1405-1

DO - 10.1007/s12035-018-1405-1

M3 - Article

C2 - 30414086

AN - SCOPUS:85056312323

VL - 56

SP - 4916

EP - 4924

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

IS - 7

ER -