Disruption of Functional Connectivity in Clinically Normal Older Adults Harboring Amyloid Burden
Open accessAbstract
Amyloid deposition is present in 20–50% of nondemented older adults yet the functional consequences remain unclear. The current study found that amyloid accumulation is correlated with functional disruption of the default network as measured by intrinsic activity correlations. Clinically normal participants ( n = 38, aged 60–88 years) were characterized using 11 C-labeled Pittsburgh Compound B positron emission tomography imaging to estimate fibrillar amyloid burden and, separately, underwent functional magnetic resonance imaging (fMRI). The integrity of the default network was estimated by correlating rest-state fMRI time courses extracted from a priori regions including the posterior cingulate, lateral parietal, and medial prefrontal cortices. Clinically normal participants with high amyloid burden displayed significantly reduced functional correlations within the default network relative to participants with low amyloid burden. These reductions were also observed when amyloid burden was treated as a continuous, rather than a dichotomous, measure and when controlling for age and structural atrophy. Whole-brain analyses initiated by seeding the posterior cingulate cortex, a region of high amyloid burden in Alzheimer's disease, revealed significant disruption in the default network including functional disconnection of the hippocampal formation.
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Default mode network connectivity was reported affected in subjects at risk of developing Alzheimer's disease, including patients with mild cognitive impairment, cognitively healthy elders with amyloid deposits, and midlife carriers of the APOE4 risk allele.
“Additionally, DMN connectivity was reported affected in subjects at risk of developing AD including patients with mild cognitive impairment (Rombouts et al., 2005;Sorg et al., 2007), in cognitively healthy elders with amyloid deposits (Hedden et al., 2009;Sperling et al., 2009;Sheline et al., 2010b), and in midlife carriers of APO 4 risk allele (Sheline et al., 2010a;Canuet et al., 2012).”
From Early Alterations in Functional Connectivity and White Matter Structure in a Transgenic Mouse Model of Cerebral Amyloidosis (2014) · cites this paper as Hedden et al., 2009
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Self-citationFunctional connectivity in the resting brain: a network analysis of the default mode hypothesis
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“The PCC plays a central role in the default network (Buckner et al., 2008; Fransson and Marrelec, 2008; Greicius et al., 2009).”
BackgroundReduced resting-state brain activity in the “default network” in normal aging
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“Maps of functional correlations were obtained by computing the correlation between the mean signal time course from voxels within the PCC and the time courses of all voxels across the brain using Pearson’s product moment correlation (similar to methods described by Fox et al., 2005; Vincent et al., 2006).”
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“Consistent with neuropathological observations, amyloid imaging confirms that a large proportion (20 –50%) of clinically normal older adults exhibit substantial amyloid burden (Buckner et al., 2005; Mintun et al., 2006; Johnson et al., 2007; Pike et al., 2007; Rowe et al., 2007; Aizenstein et al., 2008; Fripp et al.,…”
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- Authors
- Hedden, T., Van Dijk, K. R. A., Becker, J. A., Mehta, A., Sperling, R. A., Johnson, K. A., & Buckner, R. L.
- Affiliations
- Massachusetts General Hospital (US)
- Athinoula A. Martinos Center for Biomedical Imaging (US)
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Howard Hughes Medical Institute (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-10-07
- Volume
- 29
- Issue
- 40
- Pages
- 12686-12694
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2808119
- OpenAlex
- W1974594322
- Cited by
- 598
- References
- 15
- Citations by year
- 2026: 19 · 2025: 21 · 2024: 24 · 2023: 28 · 2022: 17 · 2021: 31 · 2020: 25 · 2019: 40 · 2018: 32 · 2017: 33 · 2016: 39 · 2015: 39 · 2014: 52 · 2013: 45 · 2012: 59
- FWCI
- 24.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Alzheimer's Association
- Massachusetts General Hospital
- University of Pittsburgh
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital
- National Institute on Aging (AG021910, R01AG021910, AG-027435-S1, R01AG027435, P50AG005134, R01AG034556)
- 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
- amyloid burden, functional connectivity, default mode network, Pittsburgh compound B, posterior cingulate cortex, hippocampal formation, functional disconnection, Alzheimer's disease, brain aging
- MeSH terms
- Aged, Aged, 80 and over, Aging, Amyloid, Brain, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Motor Cortex, Nerve Net, Visual Cortex
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