Early functional network alterations in asymptomatic elders at risk for Alzheimer’s disease

Abstract

Amyloid-β (Aβ) deposition is known to starts decades before the onset of clinical symptoms of Alzheimer’s disease (AD), however, the detailed pathophysiological processes underlying this preclinical period are not well understood. This study aimed to investigate functional network alterations in cognitively intact elderly individuals at risk for AD, and assessed the association between these network alterations and changes in Aβ deposition, glucose metabolism, and brain structure. Forty-five cognitively normal elderly subjects, who were classified into Aβ-positive (CN+) and Aβ-negative (CN−) groups using 11C-Pittsburgh compound B PET, underwent resting state magnetoencephalography measurements, 18F-fluorodeoxyglucose PET (FDG-PET) and structural MRI. Results demonstrated that in the CN+ group, functional connectivity (FC) within the precuneus was significantly decreased, whereas it was significantly enhanced between the precuneus and the bilateral inferior parietal lobules in the low-frequency bands (theta and delta). These changes were suggested to be associated with local cerebral Aβ deposition. Most of Aβ+ individuals in this study did not show any metabolic or anatomical changes, and there were no significant correlations between FC values and FDG-PET or MRI volumetry data. These results demonstrate that functional network alterations, which occur in association with Aβ deposition, are detectable using magnetoencephalography before metabolic and anatomical changes are seen.

Alterations in resting-state network dynamics along the Alzheimer’s disease continuum: a combined MEG-PET/MR approach

“…Such voxel-based comparison of each patient's FDG-PET data with that of those of the healthy elders' group was not performed in the present study due to (i) the low number of healthy elders and the need to have a large group of healthy subjects (>50) to increase the sensitivity/specificity of such highly multivariate FDG-PET analyses 93 , and (ii) because of the high-resolution and MRI-based correction for attenuation of our FDG-PET data, which complicate the use of FDG-PET data available in large database (e.g., ADNI). Furthermore, a previous study has shown that healthy elders at risk for AD (i.e., with Aβ-positive defined by using C-Pittsburgh compound B PET), contrary to healthy elders with Aβ-negative, presented an increase in rsFC between the precuneus and the bilateral inferior parietal lobules in theta and delta frequency bands 94 . This finding suggests an association between these electrophysiological rsFC changes and local cerebral amyloid deposition 94 .…”

“…Furthermore, a previous study has shown that healthy elders at risk for AD (i.e., with Aβ-positive defined by using C-Pittsburgh compound B PET), contrary to healthy elders with Aβ-negative, presented an increase in rsFC between the precuneus and the bilateral inferior parietal lobules in theta and delta frequency bands 94 . This finding suggests an association between these electrophysiological rsFC changes and local cerebral amyloid deposition 94 . Further research should investigate the dynamic resting-state changes in healthy elders at risk of developing AD in order to clarify the relation with AD pathology.…”

The relationship between physical activity, apolipoprotein E ε4 carriage, and brain health

“…Early loss of inhibitory neurons in preclinical AD leads to a state of increased hyperexcitability and hypersynchrony [13][14][15], which has been found to augment amyloid release and produce neurotoxic effects [16,17]. We hypothesize that PA exerts a neuroprotective effect that will be associated with reduced network synchrony in both groups, in opposition to the state of synaptic hyperexcitability that characterizes preclinical and prodromal AD [18][19][20][21][22]. Then, once we have identified the functional connectivity (FC) patterns that are influenced by PA level, we will explore if there are any associations between these FC patterns and structural integrity (gray and white matter), cognition, and mood.…”

The relationship between physical activity, apolipoprotein E ε4 carriage and brain health

“…Artifact-free data were segmented in 4 seconds epochs. Then MEG time series were filtered into delta (2-4Hz), theta (4-8Hz), alpha (8-12Hz) and beta (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). This procedure has been reported in detailed in (22).…”

“…Early loss of inhibitory neurons in preclinical AD leads to a state of increased hyperexcitability and hypersynchrony (13)(14)(15), which has been found to augment amyloid release and produce neurotoxic effects (16,17). We hypothesize that PA exerts a neuroprotective effect that will be associated with reduced network synchrony in both groups, in opposition to the state of synaptic hyperexcitability that characterizes preclinical and prodromal AD (18)(19)(20)(21)(22). Then, once we have identified the functional connectivity (FC) patterns that are influenced by PA level, we will explore if there are any associations between these FC patterns and structural integrity (grey and white matter), cognition, and mood.…”