The effects of APOE on the functional architecture of the resting brain

Trachtenberg, Aaron J.; Filippini, Nicola; Ebmeier, Klaus P.; Smith, Stephen M.; Karpe, Fredrik; Mackay, Clare E.

doi:10.1016/j.neuroimage.2011.07.059

Cited by 126 publications

(104 citation statements)

References 45 publications

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“…Heightened LIM connectivity has been reported in early onset, non-ADAD patients [29], and in individuals with subjective memory impairment [53]. The effect of APOEε4 carriage on LIM connectivity, however, lacks consensus [54][55][56]. Since LIM hyperconnectivity in early onset AD patients was shown to correlate positively with memory performance, it is likely that increased connectivity in this network contributes to preserving function in the face of medial temporal lobe pathology [29].…”

Section: Connectivity Changes Outside the Dmnmentioning

confidence: 99%

IC‐P‐033: Resting‐State Network Dysfunction in Alzheimer’s Disease: A Systematic Review and Meta‐Analysis

Badhwar

Tam

Dansereau

et al. 2016

Alzheimer's & Dementia

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Introduction: We performed a systematic review and meta-analysis of the Alzheimer's disease (AD) literature to examine consistency of functional connectivity alterations in AD dementia and mild cognitive impairment, using resting-state functional magnetic resonance imaging. Methods: Studies were screened using a standardized procedure. Multiresolution statistics were performed to assess the spatial consistency of findings across studies. Results: Thirty-four studies were included (1363 participants, average 40 per study). Consistent alterations in connectivity were found in the default mode, salience, and limbic networks in patients with AD dementia, mild cognitive impairment, or in both groups. We also identified a strong tendency in the literature toward specific examination of the default mode network. Discussion: Convergent evidence across the literature supports the use of resting-state connectivity as a biomarker of AD. The locations of consistent alterations suggest that highly connected hub regions in the brain might be an early target of AD.

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Section: Connectivity Changes Outside the Dmnmentioning

confidence: 99%

IC‐P‐033: Resting‐State Network Dysfunction in Alzheimer’s Disease: A Systematic Review and Meta‐Analysis

Badhwar

Tam

Dansereau

et al. 2016

Alzheimer's & Dementia

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“…Research probing the relationship between APOE e4 and amyloid across the lifespan found that despite no episodic memory performance difference, e4 carriers showed accelerated deposition of amyloid, with 10% of the population defined as amyloid positive by halfway through the fifth decade (Jack et al, 2015). This may also be the route by which APOE e4 impacts functional connectivity (Sheline et al, 2010), demonstrated in the earlier research of Trachtenberg et al (2012a;2012b). These changes may be particularly relevant for executive attention, which requires communication between multiple processing regions.…”

Section: Discussionmentioning

confidence: 88%

“…Recent research, however, has found overlapping patterns of task-related functional activity in mid-age e2 and e4 carriers, compared to an e3 group, during both a Stroop task, and an episodic memory task (Trachtenberg et al, 2012a). Both genotype groups also showed differences in resting-state activity compared to an e3 group (Trachtenberg et al, 2012b). This calls into question how the assumed dichotomy in APOE associated cognitive ageing manifests, and highlights APOE e2 as a crucial area for future research.…”

Section: Introductionmentioning

confidence: 96%

“…In light of recent research (Trachtenberg et al, 2012a;Trachtenberg et al, 2012b), it is unclear whether e2 carriers will show equal or advantaged performance compared to homozygous e3 carriers. This study took an exploratory look at the e2 effects on attentional control mechanisms, to provide the foundation for future work establishing the profile of this genotype in midadulthood.…”

Section: Introductionmentioning

confidence: 99%

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The APOE paradox: do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline

Lancaster

Tabet

Rusted

2016

Neurobiology of Aging

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Article (Accepted Version) http://sro.sussex.ac.uk Lancaster, Claire, Tabet, Naji and Rusted, Jennifer (2016) The APOE paradox: how do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline. Neurobiology of Aging, This version is available from Sussex Research Online: http://sro.sussex.ac.uk/62415/ This document is made available in accordance with publisher policies and may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the URL above for details on accessing the published version. Copyright and reuse:Sussex Research Online is a digital repository of the research output of the University.Copyright and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable, the material made available in SRO has been checked for eligibility before being made available.Copies of full text items generally can be reproduced, displayed or performed and given to third parties in any format or medium for personal research or study, educational, or not-for-profit purposes without prior permission or charge, provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. AbstractPossession of an APOE e4 allele is an established risk factor for Alzheimer's disease, while the less commonly studied e2 variant is premised to offer some protection. This research explores the purported deleterious-protective dichotomy of APOE variants on attentional control in mid-adulthood. 66 volunteers, aged 45-55 years, completed three tasks that provided complementary measures of attentional control: prospective memory, sustained attention and inhibition. Performance was compared between e2 carriers, e4 carriers and e3 homozygotes (the population norm). Carriers of the e4 allele showed subtle disadvantages, compared to the e3 group, in accuracy of Stroop task and prospective memory performance. Contrary to expectations, e2 carriers showed performance disadvantages in sustained attention. The finding of detrimental effects in attentional control for both e4 and e2 complicates the current model that proposes opposing effects of these variants on later-life cognition. Future research is needed to understand how cognitive differences develop with increasing age, and the physiological mechanisms that underpin these changes.

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“…The APOE epsilon 4 (APOE e4) allele is not only an important risk factor for AD and cardiovascular diseases, 27,105 but is also associated with functional brain changes [106][107][108] that can correlate with behavioral performance. 109 Glucose hypometabolism has been associated with the presence of the APOE e4 allele in non-demented older adults.…”

Section: Cardiovascular Risk Factors and Cognitive Declinementioning

confidence: 99%

The link between cardiovascular risk, Alzheimer's disease, and mild cognitive impairment: support from recent functional neuroimaging studies

Ferreira

Tamashiro-Duran

Squarzoni

et al. 2014

Rev. Bras. Psiquiatr.

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Objective: To review functional neuroimaging studies about the relationship between cardiovascular risk factors (CVRFs), Alzheimer's disease (AD), and mild cognitive impairment (MCI). Methods: We performed a comprehensive literature search to identify articles in the neuroimaging field addressing CVRF in AD and MCI. We included studies that used positron emission tomography (PET), single photon emission computerized tomography (SPECT), or functional magnetic resonance imaging (fMRI). Results: CVRFs have been considered risk factors for cognitive decline, MCI, and AD. Patterns of AD-like changes in brain function have been found in association with several CVRFs (both regarding individual risk factors and also composite CVRF measures). In vivo assessment of AD-related pathology with amyloid imaging techniques provided further evidence linking CVRFs and AD, but there is still limited information resulting from this new technology. Conclusion: There is a large body of evidence from functional neuroimaging studies supporting the hypothesis that CVRFs may play a causal role in the pathophysiology of AD. A major limitation of most studies is their cross-sectional design; future longitudinal studies using multiple imaging modalities are expected to better document changes in CVRF-related brain function patterns and provide a clearer picture of the complex relationship between aging, CVRFs, and AD.

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The effects of APOE on the functional architecture of the resting brain

Cited by 126 publications

References 45 publications

IC‐P‐033: Resting‐State Network Dysfunction in Alzheimer’s Disease: A Systematic Review and Meta‐Analysis

IC‐P‐033: Resting‐State Network Dysfunction in Alzheimer’s Disease: A Systematic Review and Meta‐Analysis

The APOE paradox: do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline

The link between cardiovascular risk, Alzheimer's disease, and mild cognitive impairment: support from recent functional neuroimaging studies

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