Neuroinflammation and Functional Connectivity in Alzheimer's Disease: Interactive Influences on Cognitive Performance.
Tsvetanov, Kamen A.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Society for Neuroscience
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Passamonti, L., Tsvetanov, K. A., Jones, S., Bevan-Jones, W., Arnold, R., Borchert, R., Mak, E., et al. (2019). Neuroinflammation and Functional Connectivity in Alzheimer's Disease: Interactive Influences on Cognitive Performance.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 39 (36), 7218-7226. https://doi.org/10.1523/jneurosci.2574-18.2019
Neuroinflammation is a key part of the etio-pathogenesis of Alzheimer’s disease. We test the relationship between neuroinflammation and the disruption of functional connectivity in large-scale networks, and their joint influence on cognitive impairment. We combined [11C]PK11195 positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI) in 28 humans (12 females/16 males) with clinical diagnosis of probable Alzheimer’s disease or mild cognitive impairment with positive PET biomarker for amyloid, and 14 age-, sex-, and education-matched healthy humans (8 females/6 males). Source-based ‘inflammetry’ was used to extract principal components of [11C]PK11195 PET signal variance across all participants. rs-fMRI data were pre-processed via independent component analyses to classify neuronal and non-neuronal signals. Multiple linear regression models identified sources of signal co-variance between neuroinflammation and brain connectivity profiles, in relation to group and cognitive status. Patients showed significantly higher [11C]PK11195 binding relative to controls, in a distributed spatial pattern including the hippocampus, medial, and inferior temporal cortex. Patients with enhanced loading on this [11C]PK11195 binding distribution displayed diffuse abnormal functional connectivity. The expression of a stronger association between such abnormal connectivity and higher levels of neuroinflammation correlated with worse cognitive deficits. Our study suggests that neuroinflammation relates to the pathophysiological changes in network function that underlie cognitive deficits in Alzheimer’s disease. Neuroinflammation, and its association with functionally-relevant reorganisation of brain networks, is proposed as a target for emerging immuno-therapeutic strategies aimed at preventing or slowing the emergence of dementia.
Hippocampus, Cerebral Cortex, Humans, Alzheimer Disease, Inflammation, Amides, Isoquinolines, Radiopharmaceuticals, Positron-Emission Tomography, Magnetic Resonance Imaging, Cognition, Aged, Aged, 80 and over, Middle Aged, Female, Male, Connectome
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
British Academy (pf160048)
Wellcome Trust (088324/Z/09/Z)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
WELLCOME TRUST (103838/Z/14/Z)
External DOI: https://doi.org/10.1523/jneurosci.2574-18.2019
This record's URL: https://www.repository.cam.ac.uk/handle/1810/291854
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