Amyloid-β deposition predicts oscillatory slowing of magnetoencephalography signals and a reduction of functional connectivity over time in cognitively unimpaired adults
(2025) In Brain Communications 7(1).- Abstract
With the ongoing developments in the field of anti-amyloid therapy for Alzheimer’s disease, it is crucial to better understand the longitudinal associations between amyloid-β deposition and altered network activity in the living human brain. We included 110 cognitively unimpaired individuals (67.9 ± 5.7 years), who underwent [18F]flutemetamol (amyloid-β)-PET imaging and resting-state magnetoencephalography (MEG) recording at baseline and 4-year follow-up. We tested associations between baseline amyloid-β deposition and MEG measures (oscillatory power and functional connectivity). Next, we examined the relationship between baseline amyloid-β deposition and longitudinal MEG measures, as well as between baseline MEG measures and... (More)
With the ongoing developments in the field of anti-amyloid therapy for Alzheimer’s disease, it is crucial to better understand the longitudinal associations between amyloid-β deposition and altered network activity in the living human brain. We included 110 cognitively unimpaired individuals (67.9 ± 5.7 years), who underwent [18F]flutemetamol (amyloid-β)-PET imaging and resting-state magnetoencephalography (MEG) recording at baseline and 4-year follow-up. We tested associations between baseline amyloid-β deposition and MEG measures (oscillatory power and functional connectivity). Next, we examined the relationship between baseline amyloid-β deposition and longitudinal MEG measures, as well as between baseline MEG measures and longitudinal amyloid-β deposition. Finally, we assessed associations between longitudinal changes in both amyloid-β deposition and MEG measures. Analyses were performed using linear mixed models corrected for age, sex and family. At baseline, amyloid-β deposition in orbitofrontal-posterior cingulate regions (i.e. early Alzheimer’s disease regions) was associated with higher theta (4–8 Hz) power (β = 0.17, P < 0.01) in- and lower functional connectivity [inverted Joint Permutation Entropy (JPEinv) theta, β = −0.24, P < 0.001] of these regions, lower whole-brain beta (13–30 Hz) power (β = −0.13, P < 0.05) and lower whole-brain functional connectivity (JPEinv theta, β = −0.18, P < 0.001). Whole-brain amyloid-β deposition was associated with higher whole-brain theta power (β = 0.17, P < 0.05), lower whole-brain beta power (β = −0.13, P < 0.05) and lower whole-brain functional connectivity (JPEinv theta, β = −0.21, P < 0.001). Baseline amyloid-β deposition in early Alzheimer’s disease regions also predicted future oscillatory slowing, reflected by increased theta power over time in early Alzheimer’s disease regions and across the whole brain (β = 0.11, β = 0.08, P < 0.001), as well as decreased whole-brain beta power over time (β = −0.04, P < 0.05). Baseline amyloid-β deposition in early Alzheimer’s disease regions also predicted a reduction in functional connectivity between these regions and the rest of the brain over time (JPEinv theta, β = −0.07, P < 0.05). Baseline whole-brain amyloid-β deposition was associated with increased whole-brain theta power over time (β = 0.08, P < 0.01). Baseline MEG measures were not associated with longitudinal amyloid-β deposition. Longitudinal changes in amyloid-β deposition in early Alzheimer’s disease regions were associated with longitudinal changes in functional connectivity of early Alzheimer’s disease regions (JPEinv theta, β = −0.19, P < 0.05) and the whole brain [corrected amplitude envelope correlations alpha (8–13 Hz), β = −0.22, P < 0.05]. Finally, longitudinal changes in whole-brain amyloid-β deposition were associated with longitudinal changes in whole-brain relative theta power (β = 0.21, P < 0.05). Disruptions of oscillatory power and functional connectivity appear to represent early functional consequences of emerging amyloid-β deposition in cognitively unimpaired individuals. These findings suggest a role for neurophysiology in monitoring disease progression and potential treatment effects in pre-clinical Alzheimer’s disease.
(Less)
- author
- organization
- publishing date
- 2025
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer’s disease, longitudinal, neurophysiology, PET
- in
- Brain Communications
- volume
- 7
- issue
- 1
- article number
- fcaf018
- publisher
- Oxford University Press
- external identifiers
-
- pmid:40008329
- scopus:85219542455
- ISSN
- 2632-1297
- DOI
- 10.1093/braincomms/fcaf018
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain.
- id
- 3919996e-ec9f-4440-8f4a-99813f000643
- date added to LUP
- 2025-07-04 08:54:32
- date last changed
- 2025-07-05 03:00:11
@article{3919996e-ec9f-4440-8f4a-99813f000643,
abstract = {{<p>With the ongoing developments in the field of anti-amyloid therapy for Alzheimer’s disease, it is crucial to better understand the longitudinal associations between amyloid-β deposition and altered network activity in the living human brain. We included 110 cognitively unimpaired individuals (67.9 ± 5.7 years), who underwent [<sup>18</sup>F]flutemetamol (amyloid-β)-PET imaging and resting-state magnetoencephalography (MEG) recording at baseline and 4-year follow-up. We tested associations between baseline amyloid-β deposition and MEG measures (oscillatory power and functional connectivity). Next, we examined the relationship between baseline amyloid-β deposition and longitudinal MEG measures, as well as between baseline MEG measures and longitudinal amyloid-β deposition. Finally, we assessed associations between longitudinal changes in both amyloid-β deposition and MEG measures. Analyses were performed using linear mixed models corrected for age, sex and family. At baseline, amyloid-β deposition in orbitofrontal-posterior cingulate regions (i.e. early Alzheimer’s disease regions) was associated with higher theta (4–8 Hz) power (β = 0.17, P < 0.01) in- and lower functional connectivity [inverted Joint Permutation Entropy (JPE<sub>inv</sub>) theta, β = −0.24, P < 0.001] of these regions, lower whole-brain beta (13–30 Hz) power (β = −0.13, P < 0.05) and lower whole-brain functional connectivity (JPE<sub>inv</sub> theta, β = −0.18, P < 0.001). Whole-brain amyloid-β deposition was associated with higher whole-brain theta power (β = 0.17, P < 0.05), lower whole-brain beta power (β = −0.13, P < 0.05) and lower whole-brain functional connectivity (JPE<sub>inv</sub> theta, β = −0.21, P < 0.001). Baseline amyloid-β deposition in early Alzheimer’s disease regions also predicted future oscillatory slowing, reflected by increased theta power over time in early Alzheimer’s disease regions and across the whole brain (β = 0.11, β = 0.08, P < 0.001), as well as decreased whole-brain beta power over time (β = −0.04, P < 0.05). Baseline amyloid-β deposition in early Alzheimer’s disease regions also predicted a reduction in functional connectivity between these regions and the rest of the brain over time (JPE<sub>inv</sub> theta, β = −0.07, P < 0.05). Baseline whole-brain amyloid-β deposition was associated with increased whole-brain theta power over time (β = 0.08, P < 0.01). Baseline MEG measures were not associated with longitudinal amyloid-β deposition. Longitudinal changes in amyloid-β deposition in early Alzheimer’s disease regions were associated with longitudinal changes in functional connectivity of early Alzheimer’s disease regions (JPE<sub>inv</sub> theta, β = −0.19, P < 0.05) and the whole brain [corrected amplitude envelope correlations alpha (8–13 Hz), β = −0.22, P < 0.05]. Finally, longitudinal changes in whole-brain amyloid-β deposition were associated with longitudinal changes in whole-brain relative theta power (β = 0.21, P < 0.05). Disruptions of oscillatory power and functional connectivity appear to represent early functional consequences of emerging amyloid-β deposition in cognitively unimpaired individuals. These findings suggest a role for neurophysiology in monitoring disease progression and potential treatment effects in pre-clinical Alzheimer’s disease.</p>}},
author = {{Scheijbeler, Elliz P. and de Haan, Willem and Coomans, Emma M. and den Braber, Anouk and Tomassen, Jori and ten Kate, Mara and Konijnenberg, Elles and Collij, Lyduine E. and van de Giessen, Elsmarieke and Barkhof, Frederik and Visser, Pieter Jelle and Stam, Cornelis J. and Gouw, Alida A.}},
issn = {{2632-1297}},
keywords = {{Alzheimer’s disease; longitudinal; neurophysiology; PET}},
language = {{eng}},
number = {{1}},
publisher = {{Oxford University Press}},
series = {{Brain Communications}},
title = {{Amyloid-β deposition predicts oscillatory slowing of magnetoencephalography signals and a reduction of functional connectivity over time in cognitively unimpaired adults}},
url = {{http://dx.doi.org/10.1093/braincomms/fcaf018}},
doi = {{10.1093/braincomms/fcaf018}},
volume = {{7}},
year = {{2025}},
}