Amyloid Plaques Disrupt Resting State Default Mode Network Connectivity in Cognitively Normal Elderly

Important functional connections within the default mode network (DMN) are disrupted in Alzheimer's disease (AD), likely from amyloid-beta (Aβ) plaque-associated neuronal toxicity. Here, we sought to determine if pathological effects of Aβ amyloid plaques could be seen, even in the absence of a...

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Published in	Biological psychiatry (1969) Vol. 67; no. 6; pp. 584 - 587
Main Authors	Sheline, Yvette I., Raichle, Marcus E., Snyder, Abraham Z., Morris, John C., Head, Denise, Wang, Suzhi, Mintun, Mark A.
Format	Journal Article
Language	English
Published	New York, NY Elsevier Inc 15.03.2010 Elsevier
Subjects	Adult and adolescent clinical studies Aged Aged, 80 and over Alzheimer Disease - metabolism Alzheimer Disease - pathology Alzheimer's disease amyloid Amyloid beta-Peptides - metabolism Aniline Compounds Biological and medical sciences Brain - blood supply Brain - diagnostic imaging Brain - pathology Brain Mapping - methods Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Female fMRI Geriatric Assessment hippocampus Humans Image Processing, Computer-Assisted - methods Longitudinal Studies Magnetic Resonance Imaging - methods Male Medical sciences Nerve Net - blood supply Nerve Net - diagnostic imaging Nerve Net - pathology Neurology Organic mental disorders. Neuropsychology Oxygen - blood PIB Positron-Emission Tomography - methods precuneus Psychiatric Status Rating Scales Psychiatric/Mental Health Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Rest - physiology resting state Statistics as Topic Thiazoles fMRI resting state amyloid hippocampus precuneus PIB Alzheimer's disease Human Nervous system diseases Alzheimer disease Central nervous system Nuclear magnetic resonance imaging Encephalon Cerebral disorder Rest Central nervous system disease Medical imagery Degenerative disease Amyloid Elderly Hippocampus Functional imaging
Online Access	Get full text
ISSN	0006-3223 1873-2402 1873-2402
DOI	10.1016/j.biopsych.2009.08.024

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Abstract	Important functional connections within the default mode network (DMN) are disrupted in Alzheimer's disease (AD), likely from amyloid-beta (Aβ) plaque-associated neuronal toxicity. Here, we sought to determine if pathological effects of Aβ amyloid plaques could be seen, even in the absence of a task, by examining functional connectivity in cognitively normal participants with and without preclinical amyloid deposition. Participants with Alzheimer's disease (AD) ( n = 35) were compared with 68 cognitively normal participants who were further subdivided by positron emission tomography (PET) Pittsburgh Compound-B (PIB) imaging into those without evidence of brain amyloid (PIB−) and those with brain amyloid (PIB+) deposition. Resting state functional magnetic resonance imaging (fMRI) demonstrated that, compared with the PIB− group, the PIB+ group differed significantly in functional connectivity of the precuneus to hippocampus, parahippocampus, anterior cingulate, dorsal cingulate, gyrus rectus, superior precuneus, and visual cortex. These differences were in the same regions and in the same direction as differences found in the AD group. Thus, before any manifestations of cognitive or behavioral changes, there were differences in resting state connectivity in cognitively normal subjects with brain amyloid deposition, suggesting that early manifestation of Aβ toxicity can be detected using resting state fMRI.
AbstractList	Important functional connections within the default mode network (DMN) are disrupted in Alzheimer's disease (AD), likely from amyloid-beta (Aβ) plaque-associated neuronal toxicity. Here, we sought to determine if pathological effects of Aβ amyloid plaques could be seen, even in the absence of a task, by examining functional connectivity in cognitively normal participants with and without preclinical amyloid deposition. Participants with Alzheimer's disease (AD) ( n = 35) were compared with 68 cognitively normal participants who were further subdivided by positron emission tomography (PET) Pittsburgh Compound-B (PIB) imaging into those without evidence of brain amyloid (PIB−) and those with brain amyloid (PIB+) deposition. Resting state functional magnetic resonance imaging (fMRI) demonstrated that, compared with the PIB− group, the PIB+ group differed significantly in functional connectivity of the precuneus to hippocampus, parahippocampus, anterior cingulate, dorsal cingulate, gyrus rectus, superior precuneus, and visual cortex. These differences were in the same regions and in the same direction as differences found in the AD group. Thus, before any manifestations of cognitive or behavioral changes, there were differences in resting state connectivity in cognitively normal subjects with brain amyloid deposition, suggesting that early manifestation of Aβ toxicity can be detected using resting state fMRI. Important functional connections within the default mode network (DMN) are disrupted in Alzheimer's disease (AD), likely from amyloid-beta (Abeta) plaque-associated neuronal toxicity. Here, we sought to determine if pathological effects of Abeta amyloid plaques could be seen, even in the absence of a task, by examining functional connectivity in cognitively normal participants with and without preclinical amyloid deposition. Participants with Alzheimer's disease (AD) (n = 35) were compared with 68 cognitively normal participants who were further subdivided by positron emission tomography (PET) Pittsburgh Compound-B (PIB) imaging into those without evidence of brain amyloid (PIB-) and those with brain amyloid (PIB+) deposition. Resting state functional magnetic resonance imaging (fMRI) demonstrated that, compared with the PIB- group, the PIB+ group differed significantly in functional connectivity of the precuneus to hippocampus, parahippocampus, anterior cingulate, dorsal cingulate, gyrus rectus, superior precuneus, and visual cortex. These differences were in the same regions and in the same direction as differences found in the AD group. Thus, before any manifestations of cognitive or behavioral changes, there were differences in resting state connectivity in cognitively normal subjects with brain amyloid deposition, suggesting that early manifestation of Abeta toxicity can be detected using resting state fMRI. Important functional connections within the default mode network (DMN) are disrupted in Alzheimer's disease (AD), likely from amyloid-beta (Abeta) plaque-associated neuronal toxicity. Here, we sought to determine if pathological effects of Abeta amyloid plaques could be seen, even in the absence of a task, by examining functional connectivity in cognitively normal participants with and without preclinical amyloid deposition.BACKGROUNDImportant functional connections within the default mode network (DMN) are disrupted in Alzheimer's disease (AD), likely from amyloid-beta (Abeta) plaque-associated neuronal toxicity. Here, we sought to determine if pathological effects of Abeta amyloid plaques could be seen, even in the absence of a task, by examining functional connectivity in cognitively normal participants with and without preclinical amyloid deposition.Participants with Alzheimer's disease (AD) (n = 35) were compared with 68 cognitively normal participants who were further subdivided by positron emission tomography (PET) Pittsburgh Compound-B (PIB) imaging into those without evidence of brain amyloid (PIB-) and those with brain amyloid (PIB+) deposition.METHODSParticipants with Alzheimer's disease (AD) (n = 35) were compared with 68 cognitively normal participants who were further subdivided by positron emission tomography (PET) Pittsburgh Compound-B (PIB) imaging into those without evidence of brain amyloid (PIB-) and those with brain amyloid (PIB+) deposition.Resting state functional magnetic resonance imaging (fMRI) demonstrated that, compared with the PIB- group, the PIB+ group differed significantly in functional connectivity of the precuneus to hippocampus, parahippocampus, anterior cingulate, dorsal cingulate, gyrus rectus, superior precuneus, and visual cortex. These differences were in the same regions and in the same direction as differences found in the AD group.RESULTSResting state functional magnetic resonance imaging (fMRI) demonstrated that, compared with the PIB- group, the PIB+ group differed significantly in functional connectivity of the precuneus to hippocampus, parahippocampus, anterior cingulate, dorsal cingulate, gyrus rectus, superior precuneus, and visual cortex. These differences were in the same regions and in the same direction as differences found in the AD group.Thus, before any manifestations of cognitive or behavioral changes, there were differences in resting state connectivity in cognitively normal subjects with brain amyloid deposition, suggesting that early manifestation of Abeta toxicity can be detected using resting state fMRI.CONCLUSIONSThus, before any manifestations of cognitive or behavioral changes, there were differences in resting state connectivity in cognitively normal subjects with brain amyloid deposition, suggesting that early manifestation of Abeta toxicity can be detected using resting state fMRI. BackgroundImportant functional connections within the default mode network (DMN) are disrupted in Alzheimer's disease (AD), likely from amyloid-beta (Aβ) plaque-associated neuronal toxicity. Here, we sought to determine if pathological effects of Aβ amyloid plaques could be seen, even in the absence of a task, by examining functional connectivity in cognitively normal participants with and without preclinical amyloid deposition. MethodsParticipants with Alzheimer's disease (AD) ( n = 35) were compared with 68 cognitively normal participants who were further subdivided by positron emission tomography (PET) Pittsburgh Compound-B (PIB) imaging into those without evidence of brain amyloid (PIB−) and those with brain amyloid (PIB+) deposition. ResultsResting state functional magnetic resonance imaging (fMRI) demonstrated that, compared with the PIB− group, the PIB+ group differed significantly in functional connectivity of the precuneus to hippocampus, parahippocampus, anterior cingulate, dorsal cingulate, gyrus rectus, superior precuneus, and visual cortex. These differences were in the same regions and in the same direction as differences found in the AD group. ConclusionsThus, before any manifestations of cognitive or behavioral changes, there were differences in resting state connectivity in cognitively normal subjects with brain amyloid deposition, suggesting that early manifestation of Aβ toxicity can be detected using resting state fMRI.
Author	Sheline, Yvette I. Wang, Suzhi Snyder, Abraham Z. Morris, John C. Head, Denise Raichle, Marcus E. Mintun, Mark A.
AuthorAffiliation	1 Department of Psychiatry, Washington University School of Medicine St Louis, MO 2 Department of Radiology, Washington University School of Medicine St Louis, MO 3 Department of Neurology, Washington University School of Medicine St Louis, MO 4 Department of Psychology, Washington University School of Medicine St Louis, MO
AuthorAffiliation_xml	– name: 3 Department of Neurology, Washington University School of Medicine St Louis, MO – name: 4 Department of Psychology, Washington University School of Medicine St Louis, MO – name: 1 Department of Psychiatry, Washington University School of Medicine St Louis, MO – name: 2 Department of Radiology, Washington University School of Medicine St Louis, MO
Author_xml	– sequence: 1 givenname: Yvette I. surname: Sheline fullname: Sheline, Yvette I. email: yvette@npg.wustl.edu organization: Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri – sequence: 2 givenname: Marcus E. surname: Raichle fullname: Raichle, Marcus E. organization: Department of Radiology, Washington University School of Medicine, St. Louis, Missouri – sequence: 3 givenname: Abraham Z. surname: Snyder fullname: Snyder, Abraham Z. organization: Department of Radiology, Washington University School of Medicine, St. Louis, Missouri – sequence: 4 givenname: John C. surname: Morris fullname: Morris, John C. organization: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri – sequence: 5 givenname: Denise surname: Head fullname: Head, Denise organization: Department of Psychology, Washington University School of Medicine, St. Louis, Missouri – sequence: 6 givenname: Suzhi surname: Wang fullname: Wang, Suzhi organization: Department of Radiology, Washington University School of Medicine, St. Louis, Missouri – sequence: 7 givenname: Mark A. surname: Mintun fullname: Mintun, Mark A. organization: Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri
BackLink	http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22504753$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/19833321$$D View this record in MEDLINE/PubMed
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Snippet	Important functional connections within the default mode network (DMN) are disrupted in Alzheimer's disease (AD), likely from amyloid-beta (Aβ)... BackgroundImportant functional connections within the default mode network (DMN) are disrupted in Alzheimer's disease (AD), likely from amyloid-beta (Aβ)... Important functional connections within the default mode network (DMN) are disrupted in Alzheimer's disease (AD), likely from amyloid-beta (Abeta)...
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SubjectTerms	Adult and adolescent clinical studies Aged Aged, 80 and over Alzheimer Disease - metabolism Alzheimer Disease - pathology Alzheimer's disease amyloid Amyloid beta-Peptides - metabolism Aniline Compounds Biological and medical sciences Brain - blood supply Brain - diagnostic imaging Brain - pathology Brain Mapping - methods Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Female fMRI Geriatric Assessment hippocampus Humans Image Processing, Computer-Assisted - methods Longitudinal Studies Magnetic Resonance Imaging - methods Male Medical sciences Nerve Net - blood supply Nerve Net - diagnostic imaging Nerve Net - pathology Neurology Organic mental disorders. Neuropsychology Oxygen - blood PIB Positron-Emission Tomography - methods precuneus Psychiatric Status Rating Scales Psychiatric/Mental Health Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Rest - physiology resting state Statistics as Topic Thiazoles
Title	Amyloid Plaques Disrupt Resting State Default Mode Network Connectivity in Cognitively Normal Elderly
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