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Cited by 12Dementia and Cognitive Impairment ResearchFunctional Brain Connectivity StudiesAlzheimer's disease research and treatments

Amyloid associated intermittent network disruptions in cognitively intact older subjects: structural connectivity matters

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Mueller, Susanne G., Weiner, Michael W.·2017·Frontiers in Aging Neuroscience
DOI 10.3389/fnagi.2017.00418PMC PMC5742224
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Abstract

Observations in animal models suggest that amyloid can cause network hypersynchrony in the early preclinical phase of Alzheimer’s disease (AD). The aim of this study was a) to obtain evidence of paroxysmal hypersynchrony in cognitively intact subjects (CN) with increased brain amyloid load from task-free fMRI exams using a dynamic analysis approach, b) to investigate if and how hypersynchrony interferes with memory performance and c) to describe its relationship with gray and white matter connectivity. Florbetapir-F18 PET and task-free 3T functional and structural MRI were acquired in 47 CN (age =70.6±6.6), 17 were amyloid pos (florbetapir SUVR >1.11). A parcellation scheme encompassing 382 regions of interest was used to extract regional gray matter volumes, FA-weighted fiber tracts and regional BOLD signals. Graph analysis was used to characterize the gray matter atrophy profile and the white matter connectivity of each subject. The fMRI data was processed using a combination of sliding windows, graph and hierarchical cluster analysis. Each activity cluster was characterized by identifying strength dispersion (difference between pos and neg strength) their maximal and minimal pos and neg strength rois and by investigating their distribution and association with memory performance and gray and white matter connectivity using spearman rank correlations (FDR p<0.05). The cluster analysis identified 8 different activity clusters. Cluster 8 was characterized by the largest strength dispersion indicating hypersynchrony. Its duration/subject was positively correlated with amyloid load (r=0.42, p = 0.03) and negatively with memory performance (CVLT delayed recall r=-0.39 p = 0.04). The assessment of the regional strength distribution indicated a functional disconnection between mesial temporal structures and the rest of the brain. White matter connectivity was increased in left lateral and mesial temporal lobe and was positively correlated with strength dispersion in the cross-modality analysis suggesting that it enables widespread hypersynchrony. In contrast, precuneus, gray matter connectivity was decreased in the right fusiform gyrus and negatively correlated with high degrees of strength dispersion suggesting that progressing gray matter atrophy could prevent the generation of paroxysmal hypersynchrony in later stages of the disease.

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  • Callosal white matter degeneration may contribute to functional disruption of functional networks such as the default mode network.

    “our findings support the possibility that callosal white matter degeneration contribute to functional disruption of functional networks such as the default mode network (Chhatwal et al., 2013; Mueller and Weiner, 2017; Taylor et al., 2017)”

    From White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease (2018) · cites this paper as Mueller and Weiner, 2017

    The Discussion (page not provided) suggests that impaired structural connectivity could alter widespread functional connectivity as neurodegeneration progresses. It does not identify callosal white matter degeneration as the cause or establish this relationship specifically for the default mode network. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Mueller, S. G., & Weiner, M. W.
Affiliations
San Francisco VA Medical Center (US)
Corresponding author
Mueller, Susanne G.
ORCID
Venue
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Published
2017-12-19
Volume
9
Pages
418-418
ISSN
1663-4365 (ISSN-L)
DOI
10.3389/fnagi.2017.00418
PMC
PMC5742224
OpenAlex
W2779422732
Cited by
12
References
4
Citations by year
2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2
FWCI
1.12
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Aging Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • National Institutes of Health (R01 AG010897)
  • University of California, San Francisco (REAC/CTSI 37785-525205)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
amyloid, Alzheimer's disease, gray matter atrophy, white matter connectivity, medial temporal lobe, memory performance, functional disconnection, strength dispersion, graph analysis, florbetapir PET

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