Loss of intranetwork and internetwork resting state functional connections with Alzheimer’s disease progression
Open accessAbstract
Alzheimer's disease (AD) is the most common cause of dementia. Much is known concerning AD pathophysiology but our understanding of the disease at the systems level remains incomplete. Previous AD research has used resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) to assess the integrity of functional networks within the brain. Most studies have focused on the default-mode network (DMN), a primary locus of AD pathology. However, other brain regions are inevitably affected with disease progression. We studied rs-fcMRI in five functionally defined brain networks within a large cohort of human participants of either gender (n = 510) that ranged in AD severity from unaffected [clinical dementia rating (CDR) 0] to very mild (CDR 0.5) to mild (CDR 1). We observed loss of correlations within not only the DMN but other networks at CDR 0.5. Within the salience network (SAL), increases were seen between CDR 0 and CDR 0.5. However, at CDR 1, all networks, including SAL, exhibited reduced correlations. Specific networks were preferentially affected at certain CDR stages. In addition, cross-network relations were consistently lost with increasing AD severity. Our results demonstrate that AD is associated with widespread loss of both intranetwork and internetwork correlations. These results provide insight into AD pathophysiology and reinforce an integrative view of the brain's functional organization.
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Some preclinical AD data has indicated altered rsfMRI FC resulting in a loss of connectivity in the default mode network and salience network, and this finding correlates with Aβ plaque accumulation, resulting in decreased connectivity between the precuneus and hippocampus.
“Some preclinical AD data has indicated altered rsfMRI FC (Sheline and Raichle, 2013) resulting in a loss of connectivity in the default mode network and salience network (Brier et al., 2012) and this finding correlates with Aβ plaque accumulation, resulting in decreased connectivity between the precuneus and hippocampus (Sheline et al., 2010).”
From Early stage alterations in white matter and decreased functional interhemispheric hippocampal connectivity in the 3xTg mouse model of Alzheimer’s disease. (2019) · cites this paper as Brier et al., 2012
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- Authors
- Brier, M. R., Thomas, J. B., Snyder, A. Z., Benzinger, T. L., Zhang, D., Raichle, M. E., Holtzman, D. M., Morris, J. C., & Ances, B. M.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-06-27
- Volume
- 32
- Issue
- 26
- Pages
- 8890-8899
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3458508
- OpenAlex
- W1979631864
- Cited by
- 595
- References
- 17
- Citations by year
- 2026: 28 · 2025: 39 · 2024: 36 · 2023: 44 · 2022: 47 · 2021: 54 · 2020: 63 · 2019: 42 · 2018: 35 · 2017: 37 · 2016: 36 · 2015: 50 · 2014: 45 · 2013: 32 · 2012: 6
- FWCI
- 21.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- Bristol-Myers Squibb
- Pfizer
- Avid Radiopharmaceuticals
- Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. Louis
- National Institute on Aging (P 50 AG05681, P50AG005681, P01 AG0 3991, P01AG003991, P01AG026276)
- National Institute of Mental Health (K23MH081786)
- National Institute of Nursing Research (R01NR012657, R01NR012907)
- National Institute of General Medical Sciences (T32GM007200)
- National Institute of Neurological Disorders and Stroke (P30NS057105, P30NS048056, P50NS006833, NS 06833)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, resting-state functional connectivity, default mode network, salience network, functional brain networks, disease progression, Clinical Dementia Rating
- MeSH terms
- Aged, Alzheimer Disease, Brain, Brain Mapping, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Nerve Net, Neural Pathways, Oxygen, Psychiatric Status Rating Scales, Rest, Statistics as Topic, Cohort Studies, Disease Progression
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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