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Lookup NU author(s): Emeritus Professor David Brooks
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. INTRODUCTION: Microglial responses are an integral part of Alzheimer's disease (AD) pathology and are associated with amyloid beta (Aβ) deposition. This study aimed to investigate the effects of Aβ and microglial responses on global cognitive impairment. METHODS: In this longitudinal study, 28 patients with mild cognitive impairment and 11 healthy controls underwent 11C-PK11195 and 11C-Pittsburgh compound B positron emission tomography (PET), structural magnetic resonance imaging scans, and global cognitive ratings at baseline and 2-year follow-up. Correlations between PET uptake and global cognition were assessed. Additionally, the mediation effect of the microglial response on the association between Aβ load and global cognition was assessed. RESULTS: Aβ load and the microglial response were both independently detrimental to global cognitive performance at baseline; however, at 2-year follow-up the association between Aβ load and global cognitive ratings was partially mediated by the microglial response. DISCUSSION: As AD progresses, the associated microglial response partially mediates the detrimental effect of aggregated Aβ on cognition. Highlights: This was a longitudinal study of amyloid beta (Aβ), microglial responses, and global cognitive performance. Aβ and microglial responses both affect cognition in early Alzheimer's disease. Microglial response partially mediates the effect of Aβ on cognition in later stages.
Author(s): Madsen LS, Ismail R, Parbo P, Kjeldsen PL, Schaldemose JL, Hansen KV, Gottrup H, Aanerud J, Eskildsen SF, Brooks DJ
Publication type: Article
Publication status: Published
Journal: Alzheimer's and Dementia
Year: 2024
Volume: 20
Issue: 11
Pages: 8028-8037
Print publication date: 01/11/2024
Online publication date: 11/10/2024
Acceptance date: 07/09/2024
Date deposited: 22/10/2024
ISSN (print): 1552-5260
ISSN (electronic): 1552-5279
Publisher: John Wiley and Sons Inc.
URL: https://doi.org/10.1002/alz.14298
DOI: 10.1002/alz.14298
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