Disrupted Intrinsic Networks Link Amyloid-β Pathology and Impaired Cognition in Prodromal Alzheimer's Disease
Open accessAbstract
Amyloid-β pathology (Aβ) and impaired cognition characterize Alzheimer's disease (AD); however, neural mechanisms that link Aβ-pathology with impaired cognition are incompletely understood. Large-scale intrinsic connectivity networks (ICNs) are potential candidates for this link: Aβ-pathology affects specific networks in early AD, these networks show disrupted connectivity, and they process specific cognitive functions impaired in AD, like memory or attention. We hypothesized that, in AD, regional changes of ICNs, which persist across rest- and cognitive task-states, might link Aβ-pathology with impaired cognition via impaired intrinsic connectivity. Pittsburgh compound B (PiB)-positron emission tomography reflecting in vivo Aβ-pathology, resting-state fMRI, task-fMRI, and cognitive testing were used in patients with prodromal AD and healthy controls. In patients, default mode network's (DMN) functional connectivity (FC) was reduced in the medial parietal cortex during rest relative to healthy controls, relatively increased in the same region during an attention-demanding task, and associated with patients' cognitive impairment. Local PiB-uptake correlated negatively with DMN connectivity. Importantly, corresponding results were found for the right lateral parietal region of an attentional network. Finally, structural equation modeling confirmed a direct influence of DMN resting-state FC on the association between Aβ-pathology and cognitive impairment. Data provide evidence that disrupted intrinsic network connectivity links Aβ-pathology with cognitive impairment in early AD.
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The correlation between disruption of functional connectivity and Aβ pathology has recently been described in AD, but this study is the first to show that this association is present already at the very earliest preclinical stages of AD when Aβ fibrils are just starting to accumulate.
“This correlation between the disruption of functional connectivity and Aβ pathology has recently been described in AD32, 33, but to our knowledge the present study is the first to show that this association is present already at the very earliest preclinical stages of AD when Aβ fibrils are just starting to accumulate.”
From Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity (2017) · cites this paper as [33]
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- Authors
- Koch, K., Myers, N. E., Göttler, J., Pasquini, L., Grimmer, T., Förster, S., Manoliu, A., Neitzel, J., Kurz, A., Förstl, H., Riedl, V., Wohlschläger, A. M., Drzezga, A., & Sorg, C.
- Affiliations
- TUM Klinikum (DE)
- Klinik und Poliklinik für Nuklearmedizin (DE)
- Corresponding author
- Koch, Kathrin
- ORCID
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-07-04
- Volume
- 25
- Issue
- 12
- Pages
- 4678-4688
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- PMC
- PMC4635914
- OpenAlex
- W2136388544
- Cited by
- 97
- References
- 67
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 11 · 2020: 9 · 2019: 10 · 2018: 7 · 2017: 13 · 2016: 13 · 2015: 8 · 2014: 2
- FWCI
- 6.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cerebral Cortex (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Funders
- Wellcome Trust
- 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
- prodromal Alzheimer's disease, amyloid-beta pathology, resting-state networks, default mode network, functional connectivity, cognitive impairment, Pittsburgh compound B, resting-state fMRI, attentional networks, medial parietal cortex, amyloid PET, memory impairment
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Aniline Compounds, Attention, Brain Mapping, Cognition, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Thiazoles, Amyloid beta-Peptides, Positron-Emission Tomography, Cognitive Dysfunction
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