Amyloid Deposition Is Associated with Impaired Default Network Function in Older Persons without Dementia

Sperling, Reisa A.; LaViolette, Peter S.; O’Keefe, Kelly; O’Brien, Jacqueline; Rentz, Dorene M.; Pihlajamäki, Maija; Marshall, Gad A.; Hyman, Bradley T.; Selkoe, Dennis J.; Hedden, Trey; Buckner, Randy L.; Becker, J. Alex; Johnson, Keith A.

doi:10.1016/j.neuron.2009.07.003

Cited by 886 publications

(839 citation statements)

References 74 publications

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“…The authors reported that high levels of Ab deposition were associated with an aberrant default network fMRI activity pattern that was similar to the pattern of dysfunction reported in AD. These findings indicated that Ab pathology is linked to neural dysfunction in the brain regions that serve memory function, thereby supporting the hypothesis that cognitively intact older individuals with evidence of Ab pathology may be in early stages of AD (Sperling et al, 2009) (see Figure 3C).…”

Section: Impact Of Multimodality Neuroimaging On Alzheimer's Diseasesupporting

confidence: 72%

“…It is becoming more common to acquire multimodality neuroimaging data that include PET and fMRI, as well as other types of MR (and optical) outcomes (Apkarian et al, 2005;Catana et al, 2008;Dougherty et al, 2008;Herzog et al, 2011;Huppert et al, 2008;Newberg et al, 2005;Rabiner et al, 2011;Sperling et al, 2009;Tong et al, 2011). Combined fMRI and PET brain imaging will become even more commonplace with the increased availability of combined PET/MR imaging systems.…”

Section: Multimodality Imagingmentioning

confidence: 99%

“…The authors concluded that there was a phase of increased MTL activation early in the course of prodromal AD that was followed by a subsequent decrease with disease progression. This work was one of several timely fMRI studies that probed memory function in AD at that time (see Sperling et al, 2009).…”

Section: Animal Imagingmentioning

confidence: 99%

“…Images are shown for control and mild cognitive impairment (MCI) subjects who are PiB(-) and PiB( + ), relative to a PiB( + ) AD subject. (B) Variation in FDG metabolism across PiB(-) and PiB( + ) CON subjects; (C) Areas of strong association between functional magnetic resonance imaging (fMRI) activity during a memory task and amyloid deposition in posterior cingulate/precuneus (PPC), for CON and AD subjects that involve areas of the default network (higher PiB associated with increasingly aberrant MR response) (Sperling et al, 2009). (D) Hippocampal gray matter volume loss in PiB( + ) MCI subjects, relative to PiB(-) MCI subjects.…”

Section: Impact Of Multimodality Neuroimaging On Alzheimer's Diseasementioning

confidence: 99%

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Molecular Brain Imaging in the Multimodality Era

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2012

J Cereb Blood Flow Metab

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Multimodality molecular brain imaging encompasses in vivo visualization, evaluation, and measurement of cellular/molecular processes. Instrumentation and software developments over the past 30 years have fueled advancements in multimodality imaging platforms that enable acquisition of multiple complementary imaging outcomes by either combined sequential or simultaneous acquisition. This article provides a general overview of multimodality neuroimaging in the context of positron emission tomography as a molecular imaging tool and magnetic resonance imaging as a structural and functional imaging tool. Several image examples are provided and general challenges are discussed to exemplify complementary features of the modalities, as well as important strengths and weaknesses of combined assessments. Alzheimer's disease is highlighted, as this clinical area has been strongly impacted by multimodality neuroimaging findings that have improved understanding of the natural history of disease progression, early disease detection, and informed therapy evaluation.

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Section: Impact Of Multimodality Neuroimaging On Alzheimer's Diseasesupporting

confidence: 72%

Section: Multimodality Imagingmentioning

confidence: 99%

Section: Animal Imagingmentioning

confidence: 99%

Section: Impact Of Multimodality Neuroimaging On Alzheimer's Diseasementioning

confidence: 99%

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Molecular Brain Imaging in the Multimodality Era

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2012

J Cereb Blood Flow Metab

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“…The default mode network (DMN) and other resting‐state networks, that is, regions with synchronized fMRI activity, have been studied as markers for AD progression (Binnewijzend et al., 2012; Filippini et al., 2009; Sheline et al., 2010). Functional brain connectivity changes in healthy adults are related to amyloid depositions (Hedden et al., 2009; Sperling et al., 2009), and carriers of the APOE‐ε4 allele show increased co‐activation with the DMN in young adults (Bookheimer et al., 2000; Filippini et al., 2009), indicating that functional connectivity is sensitive to AD‐related alterations of the brain. This study extends these previous findings, using a large sample from a population imaging study, combined with comprehensive AD‐related cognitive assessment and genotyping.…”

Section: Introductionmentioning

confidence: 99%

Functional brain network centrality is related to APOE genotype in cognitively normal elderly

et al. 2018

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IntroductionAmyloid plaque deposition in the brain is an early pathological change in Alzheimer's disease (AD), causing disrupted synaptic connections. Brain network disruptions in AD have been demonstrated with eigenvector centrality (EC), a measure that identifies central regions within networks. Carrying an apolipoprotein (APOE)‐ε4 allele is a genetic risk for AD, associated with increased amyloid deposition. We studied whether APOE‐ε4 carriership is associated with EC disruptions in cognitively normal individuals.MethodsA total of 261 healthy middle‐aged to older adults (mean age 56.6 years) were divided into high‐risk (APOE‐ε4 carriers) and low‐risk (noncarriers) groups. EC was computed from resting‐state functional MRI data. Clusters of between‐group differences were assessed with a permutation‐based method. Correlations between cluster mean EC with brain volume, CSF biomarkers, and psychological test scores were assessed.ResultsDecreased EC in the visual cortex was associated with APOE‐ε4 carriership, a genetic risk factor for AD. EC differences were correlated with age, CSF amyloid levels, and scores on the trail‐making and 15‐object recognition tests.ConclusionOur findings suggest that the APOE‐ε4 genotype affects brain connectivity in regions previously found to be abnormal in AD as a sign of very early disease‐related pathology. These differences were too subtle in healthy elderly to use EC for single‐subject prediction of APOE genotype.

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Effect ofAPOEε4 Status on Intrinsic Network Connectivity in Cognitively Normal Elderly Subjects

Jones²,

et al. 2011

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ObjectiveTo examine default mode and salience network functional connectivity as a function of APOE ε4 status in a group of cognitively normal age-, sex-, and education-matched older adults.DesignCase-control study.SubjectsFifty-six cognitively normal APOE ε4 carriers and 56 age-, sex- and education-matched cognitively normal APOE ε4 noncarriers.Main Outcome MeasureAlterations in in-phase default mode and salience network connectivity in APOE ε4 carriers compared with APOE ε4 noncarriers ranging from 63 to 91 years of age.ResultsA posterior cingulate seed revealed decreased in-phase connectivity in regions of the posterior default mode network that included the left inferior parietal lobe, left middle temporal gyrus, and bilateral anterior temporal lobes in the ε4 carriers relative to APOE ε4 noncarriers. An anterior cingulate seed showed greater in-phase connectivity in the salience network including the cingulate gyrus, medial prefrontal cortex, bilateral insular cortex, striatum, and thalamus in APOE ε4 carriers vs noncarriers. There were no groupwise differences in brain anatomy.ConclusionsThe observation of functional alterations in default mode and salience network connectivity in the absence of structural changes between APOE ε4 carriers and noncarriers suggests that alterations in connectivity may have the potential to serve as an early biomarker.

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Amyloid Deposition Is Associated with Impaired Default Network Function in Older Persons without Dementia

Cited by 886 publications

References 74 publications

Molecular Brain Imaging in the Multimodality Era

Molecular Brain Imaging in the Multimodality Era

Functional brain network centrality is related to APOE genotype in cognitively normal elderly

Effect ofAPOEε4 Status on Intrinsic Network Connectivity in Cognitively Normal Elderly Subjects

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