Gray matter network disruptions and regional amyloid beta in cognitively normal adults

Mara ten Kate, Pieter Jelle Visser, Hovagim Bakardjian, Frederik Barkhof, Sietske A.M. Sikkes, Wiesje M. van der Flier, Philip Scheltens, Harald Hampel, Marie Odile Habert, Bruno Dubois, Betty M. Tijms, C. Audrain, A. Auffret, H. Bakardjian, F. Baldacci, B. Batrancourt, I. Benakki, H. Benali, H. Bertin, A. Bertrand & 31 others L. Boukadida, F. Cacciamani, V. Causse, E. Cavedo, S. Cherif Touil, P. A. Chiesa, O. Colliot, G. Dalla Barba, M. Depaulis, A. Dos Santos, B. Dubois, M. Dubois, S. Epelbaum, B. Fontaine, H. Francisque, G. Gagliardi, A. Genin, R. Genthon, P. Glasman, F. Gombert, M. O. Habert, H. Hampel, H. Hewa, M. Houot, N. Jungalee, A. Kas, M. Kilani, V. La Corte, F. Le Roy, S. Lehericy, INSIGHT-preAD study group

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The accumulation of amyloid plaques is one of the earliest pathological changes in Alzheimer's disease (AD) and may occur 20 years before the onset of symptoms. Examining associations between amyloid pathology and other early brain changes is critical for understanding the pathophysiological underpinnings of AD. Alterations in gray matter networks might already start at early preclinical stages of AD. In this study, we examined the regional relationship between amyloid aggregation measured with positron emission tomography (PET) and gray matter network measures in elderly subjects with subjective memory complaints. Single-subject gray matter networks were extracted from T1-weigthed structural MRI in cognitively normal subjects (n = 318, mean age 76.1 ± 3.5, 64% female, 28% amyloid positive). Degree, clustering, path length and small world properties were computed. Global and regional amyloid load was determined using [18F]-Florbetapir PET. Associations between standardized uptake value ratio (SUVr) values and network measures were examined using linear regression models. We found that higher global SUVr was associated with lower clustering (ß = -0.12, p < 0.05), and small world values (ß = -0.16, p < 0.01). Associations were most prominent in orbito- and dorsolateral frontal and parieto-occipital regions. Local SUVr values showed less anatomical variability and did not convey additional information beyond global amyloid burden. In conclusion, we found that in cognitively normal elderly subjects, increased global amyloid pathology is associated with alterations in gray matter networks that are indicative of incipient network breakdown towards AD dementia.

Original languageEnglish
Article number67
JournalFrontiers in Aging Neuroscience
Volume10
Issue numberFEB
DOIs
Publication statusPublished - 15 Mar 2018

Cite this

ten Kate, Mara ; Visser, Pieter Jelle ; Bakardjian, Hovagim ; Barkhof, Frederik ; Sikkes, Sietske A.M. ; van der Flier, Wiesje M. ; Scheltens, Philip ; Hampel, Harald ; Habert, Marie Odile ; Dubois, Bruno ; Tijms, Betty M. ; Audrain, C. ; Auffret, A. ; Bakardjian, H. ; Baldacci, F. ; Batrancourt, B. ; Benakki, I. ; Benali, H. ; Bertin, H. ; Bertrand, A. ; Boukadida, L. ; Cacciamani, F. ; Causse, V. ; Cavedo, E. ; Cherif Touil, S. ; Chiesa, P. A. ; Colliot, O. ; Dalla Barba, G. ; Depaulis, M. ; Dos Santos, A. ; Dubois, B. ; Dubois, M. ; Epelbaum, S. ; Fontaine, B. ; Francisque, H. ; Gagliardi, G. ; Genin, A. ; Genthon, R. ; Glasman, P. ; Gombert, F. ; Habert, M. O. ; Hampel, H. ; Hewa, H. ; Houot, M. ; Jungalee, N. ; Kas, A. ; Kilani, M. ; La Corte, V. ; Le Roy, F. ; Lehericy, S. ; INSIGHT-preAD study group. / Gray matter network disruptions and regional amyloid beta in cognitively normal adults. In: Frontiers in Aging Neuroscience. 2018 ; Vol. 10, No. FEB.
@article{b8fbeca8adcc445495bbb5a2e07ff077,
title = "Gray matter network disruptions and regional amyloid beta in cognitively normal adults",
abstract = "The accumulation of amyloid plaques is one of the earliest pathological changes in Alzheimer's disease (AD) and may occur 20 years before the onset of symptoms. Examining associations between amyloid pathology and other early brain changes is critical for understanding the pathophysiological underpinnings of AD. Alterations in gray matter networks might already start at early preclinical stages of AD. In this study, we examined the regional relationship between amyloid aggregation measured with positron emission tomography (PET) and gray matter network measures in elderly subjects with subjective memory complaints. Single-subject gray matter networks were extracted from T1-weigthed structural MRI in cognitively normal subjects (n = 318, mean age 76.1 ± 3.5, 64{\%} female, 28{\%} amyloid positive). Degree, clustering, path length and small world properties were computed. Global and regional amyloid load was determined using [18F]-Florbetapir PET. Associations between standardized uptake value ratio (SUVr) values and network measures were examined using linear regression models. We found that higher global SUVr was associated with lower clustering ({\ss} = -0.12, p < 0.05), and small world values ({\ss} = -0.16, p < 0.01). Associations were most prominent in orbito- and dorsolateral frontal and parieto-occipital regions. Local SUVr values showed less anatomical variability and did not convey additional information beyond global amyloid burden. In conclusion, we found that in cognitively normal elderly subjects, increased global amyloid pathology is associated with alterations in gray matter networks that are indicative of incipient network breakdown towards AD dementia.",
keywords = "Alzheimer's disease, Amyloid beta, Graph theory, Gray matter network, MRI, PET, Subjective memory complaints",
author = "{ten Kate}, Mara and Visser, {Pieter Jelle} and Hovagim Bakardjian and Frederik Barkhof and Sikkes, {Sietske A.M.} and {van der Flier}, {Wiesje M.} and Philip Scheltens and Harald Hampel and Habert, {Marie Odile} and Bruno Dubois and Tijms, {Betty M.} and C. Audrain and A. Auffret and H. Bakardjian and F. Baldacci and B. Batrancourt and I. Benakki and H. Benali and H. Bertin and A. Bertrand and L. Boukadida and F. Cacciamani and V. Causse and E. Cavedo and {Cherif Touil}, S. and Chiesa, {P. A.} and O. Colliot and {Dalla Barba}, G. and M. Depaulis and {Dos Santos}, A. and B. Dubois and M. Dubois and S. Epelbaum and B. Fontaine and H. Francisque and G. Gagliardi and A. Genin and R. Genthon and P. Glasman and F. Gombert and Habert, {M. O.} and H. Hampel and H. Hewa and M. Houot and N. Jungalee and A. Kas and M. Kilani and {La Corte}, V. and {Le Roy}, F. and S. Lehericy and {INSIGHT-preAD study group}",
year = "2018",
month = "3",
day = "15",
doi = "10.3389/fnagi.2018.00067",
language = "English",
volume = "10",
journal = "Frontiers in Aging Neuroscience",
issn = "1663-4365",
publisher = "Frontiers Media S.A.",
number = "FEB",

}

ten Kate, M, Visser, PJ, Bakardjian, H, Barkhof, F, Sikkes, SAM, van der Flier, WM, Scheltens, P, Hampel, H, Habert, MO, Dubois, B, Tijms, BM, Audrain, C, Auffret, A, Bakardjian, H, Baldacci, F, Batrancourt, B, Benakki, I, Benali, H, Bertin, H, Bertrand, A, Boukadida, L, Cacciamani, F, Causse, V, Cavedo, E, Cherif Touil, S, Chiesa, PA, Colliot, O, Dalla Barba, G, Depaulis, M, Dos Santos, A, Dubois, B, Dubois, M, Epelbaum, S, Fontaine, B, Francisque, H, Gagliardi, G, Genin, A, Genthon, R, Glasman, P, Gombert, F, Habert, MO, Hampel, H, Hewa, H, Houot, M, Jungalee, N, Kas, A, Kilani, M, La Corte, V, Le Roy, F, Lehericy, S & INSIGHT-preAD study group 2018, 'Gray matter network disruptions and regional amyloid beta in cognitively normal adults' Frontiers in Aging Neuroscience, vol. 10, no. FEB, 67. https://doi.org/10.3389/fnagi.2018.00067

Gray matter network disruptions and regional amyloid beta in cognitively normal adults. / ten Kate, Mara; Visser, Pieter Jelle; Bakardjian, Hovagim; Barkhof, Frederik; Sikkes, Sietske A.M.; van der Flier, Wiesje M.; Scheltens, Philip; Hampel, Harald; Habert, Marie Odile; Dubois, Bruno; Tijms, Betty M.; Audrain, C.; Auffret, A.; Bakardjian, H.; Baldacci, F.; Batrancourt, B.; Benakki, I.; Benali, H.; Bertin, H.; Bertrand, A.; Boukadida, L.; Cacciamani, F.; Causse, V.; Cavedo, E.; Cherif Touil, S.; Chiesa, P. A.; Colliot, O.; Dalla Barba, G.; Depaulis, M.; Dos Santos, A.; Dubois, B.; Dubois, M.; Epelbaum, S.; Fontaine, B.; Francisque, H.; Gagliardi, G.; Genin, A.; Genthon, R.; Glasman, P.; Gombert, F.; Habert, M. O.; Hampel, H.; Hewa, H.; Houot, M.; Jungalee, N.; Kas, A.; Kilani, M.; La Corte, V.; Le Roy, F.; Lehericy, S.; INSIGHT-preAD study group.

In: Frontiers in Aging Neuroscience, Vol. 10, No. FEB, 67, 15.03.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Gray matter network disruptions and regional amyloid beta in cognitively normal adults

AU - ten Kate, Mara

AU - Visser, Pieter Jelle

AU - Bakardjian, Hovagim

AU - Barkhof, Frederik

AU - Sikkes, Sietske A.M.

AU - van der Flier, Wiesje M.

AU - Scheltens, Philip

AU - Hampel, Harald

AU - Habert, Marie Odile

AU - Dubois, Bruno

AU - Tijms, Betty M.

AU - Audrain, C.

AU - Auffret, A.

AU - Bakardjian, H.

AU - Baldacci, F.

AU - Batrancourt, B.

AU - Benakki, I.

AU - Benali, H.

AU - Bertin, H.

AU - Bertrand, A.

AU - Boukadida, L.

AU - Cacciamani, F.

AU - Causse, V.

AU - Cavedo, E.

AU - Cherif Touil, S.

AU - Chiesa, P. A.

AU - Colliot, O.

AU - Dalla Barba, G.

AU - Depaulis, M.

AU - Dos Santos, A.

AU - Dubois, B.

AU - Dubois, M.

AU - Epelbaum, S.

AU - Fontaine, B.

AU - Francisque, H.

AU - Gagliardi, G.

AU - Genin, A.

AU - Genthon, R.

AU - Glasman, P.

AU - Gombert, F.

AU - Habert, M. O.

AU - Hampel, H.

AU - Hewa, H.

AU - Houot, M.

AU - Jungalee, N.

AU - Kas, A.

AU - Kilani, M.

AU - La Corte, V.

AU - Le Roy, F.

AU - Lehericy, S.

AU - INSIGHT-preAD study group

PY - 2018/3/15

Y1 - 2018/3/15

N2 - The accumulation of amyloid plaques is one of the earliest pathological changes in Alzheimer's disease (AD) and may occur 20 years before the onset of symptoms. Examining associations between amyloid pathology and other early brain changes is critical for understanding the pathophysiological underpinnings of AD. Alterations in gray matter networks might already start at early preclinical stages of AD. In this study, we examined the regional relationship between amyloid aggregation measured with positron emission tomography (PET) and gray matter network measures in elderly subjects with subjective memory complaints. Single-subject gray matter networks were extracted from T1-weigthed structural MRI in cognitively normal subjects (n = 318, mean age 76.1 ± 3.5, 64% female, 28% amyloid positive). Degree, clustering, path length and small world properties were computed. Global and regional amyloid load was determined using [18F]-Florbetapir PET. Associations between standardized uptake value ratio (SUVr) values and network measures were examined using linear regression models. We found that higher global SUVr was associated with lower clustering (ß = -0.12, p < 0.05), and small world values (ß = -0.16, p < 0.01). Associations were most prominent in orbito- and dorsolateral frontal and parieto-occipital regions. Local SUVr values showed less anatomical variability and did not convey additional information beyond global amyloid burden. In conclusion, we found that in cognitively normal elderly subjects, increased global amyloid pathology is associated with alterations in gray matter networks that are indicative of incipient network breakdown towards AD dementia.

AB - The accumulation of amyloid plaques is one of the earliest pathological changes in Alzheimer's disease (AD) and may occur 20 years before the onset of symptoms. Examining associations between amyloid pathology and other early brain changes is critical for understanding the pathophysiological underpinnings of AD. Alterations in gray matter networks might already start at early preclinical stages of AD. In this study, we examined the regional relationship between amyloid aggregation measured with positron emission tomography (PET) and gray matter network measures in elderly subjects with subjective memory complaints. Single-subject gray matter networks were extracted from T1-weigthed structural MRI in cognitively normal subjects (n = 318, mean age 76.1 ± 3.5, 64% female, 28% amyloid positive). Degree, clustering, path length and small world properties were computed. Global and regional amyloid load was determined using [18F]-Florbetapir PET. Associations between standardized uptake value ratio (SUVr) values and network measures were examined using linear regression models. We found that higher global SUVr was associated with lower clustering (ß = -0.12, p < 0.05), and small world values (ß = -0.16, p < 0.01). Associations were most prominent in orbito- and dorsolateral frontal and parieto-occipital regions. Local SUVr values showed less anatomical variability and did not convey additional information beyond global amyloid burden. In conclusion, we found that in cognitively normal elderly subjects, increased global amyloid pathology is associated with alterations in gray matter networks that are indicative of incipient network breakdown towards AD dementia.

KW - Alzheimer's disease

KW - Amyloid beta

KW - Graph theory

KW - Gray matter network

KW - MRI

KW - PET

KW - Subjective memory complaints

UR - http://www.scopus.com/inward/record.url?scp=85043985409&partnerID=8YFLogxK

U2 - 10.3389/fnagi.2018.00067

DO - 10.3389/fnagi.2018.00067

M3 - Article

VL - 10

JO - Frontiers in Aging Neuroscience

JF - Frontiers in Aging Neuroscience

SN - 1663-4365

IS - FEB

M1 - 67

ER -