Amyloid-β deposition predicts oscillatory slowing of magnetoencephalography signals and a reduction of functional connectivity over time in cognitively unimpaired adults

Elliz P Scheijbeler; Willem de Haan; Emma M Coomans; Anouk den Braber; Jori Tomassen; Mara Ten Kate; Elles Konijnenberg; Lyduine E Collij; Elsmarieke van de Giessen; Frederik Barkhof; Pieter Jelle Visser; Cornelis J Stam; Alida A Gouw

doi:10.1093/braincomms/fcaf018

Amyloid-β deposition predicts oscillatory slowing of magnetoencephalography signals and a reduction of functional connectivity over time in cognitively unimpaired adults

Brain Commun. 2025 Jan 20;7(1):fcaf018. doi: 10.1093/braincomms/fcaf018. eCollection 2025.

Authors

Elliz P Scheijbeler^{1

2

3}, Willem de Haan^{1

2}, Emma M Coomans^{4

5}, Anouk den Braber^{1

2

4

5

6}, Jori Tomassen^{1

2}, Mara Ten Kate^{1

2

4

5}, Elles Konijnenberg^{1

2}, Lyduine E Collij^{4

5

7}, Elsmarieke van de Giessen^{4

5}, Frederik Barkhof^{4

5

8}, Pieter Jelle Visser^{1

2

9}, Cornelis J Stam³, Alida A Gouw³

Affiliations

¹ Alzheimer Center Amsterdam, Department of Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081 HV Amsterdam, The Netherlands.
² Amsterdam Neuroscience, Neurodegeneration, 1081 HV Amsterdam, The Netherlands.
³ Department of Clinical Neurophysiology & MEG Center, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081 HV Amsterdam, The Netherlands.
⁴ Department of Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam UMC, 1081 HV Amsterdam, The Netherlands.
⁵ Amsterdam Neuroscience, Brain Imaging, 1081 HV Amsterdam, The Netherlands.
⁶ Department of Biological Psychology, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.
⁷ Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, 202 13 Malmö, Sweden.
⁸ Queen Square Institute of Neurology and Centre for Medical Image Computing, University College London, WC1N 3BG London, UK.
⁹ Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, 6229 ET Maastricht, The Netherlands.

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 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_inv) 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_inv 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_inv 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_inv 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_inv 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.

Keywords: Alzheimer’s disease; PET; longitudinal; neurophysiology.