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Neuroinflammation, functional connectivity and structural network integrity in the Alzheimer's spectrum

Lookup NU author(s): Professor David BrooksORCiD


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© 2021 the Alzheimer's Association.BACKGROUND: To investigate whether neuroinflammation and β-amyloid (Aβ) deposition influence brain structural and functional connectivity in Alzheimer's spectrum, we conducted a cross-sectional multimodal imaging study and interrogated the associations between imaging biomarkers of neuroinflammation, Aβ deposition, brain connectivity and cognition. METHOD: 58 participants (25 MCI, 16 AD dementia and 17 healthy controls) were recruited and scanned with 11 C-PBR28 and 18 F-flutemetamol PET, T1-weighted, diffusion tensor and resting-state functional MRI. Brain structural and functional connectivity were assessed by global white matter integrity and functional topology metrics, while neuroinflammation and Aβ deposition were evaluated by 11 C-PBR28 and 18 F-flutemetamol uptake, respectively. Changes of the biomarkers were compared between diagnostic groups and robust regression analyses at both voxel and regional level were performed on Aβ positive patients, who were considered to be representative of Alzheimer's continuum. RESULT: Increased 11 C-PBR28 and 18 F-flutemetamol uptake, decreased FA values, impaired small-worldness and local efficiency of functional network were observed in the AD cohort. In Aβ-positive patients, cortical 11 C-PBR28 uptake correlated with decreased structural integrity and network local efficiency independent of 18 F-flutemetamol uptake and cortical thickness. Network structural integrity and cortical thickness correlated with functional metrics, including small-worldness and local efficiency, which were all associated with cognition. CONCLUSION: Our findings suggest that cortical neuroinflammation may lead to disruption of structural and functional brain network independent of amyloid deposition and cortical atrophy, which in turn can lead to cognitive impairment in AD.

Publication metadata

Author(s): Leng F, Hinz R, Gentleman S, Brooks DJ, Edison P

Publication type: Article

Publication status: Published

Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association

Year: 2021

Volume: 17

Issue: S3

Print publication date: 01/12/2021

Online publication date: 01/02/2022

Acceptance date: 02/04/2018

ISSN (print): 1552-5260

ISSN (electronic): 1552-5279

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/alz.055970

PubMed id: 35109040


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