Early brain activity changes in healthy adults, linked to Alzheimer’s proteins, predict cognitive decline.
In our latest study published in open access by Nature Neuroscience, we have discovered how early changes in brain activity—linked to the buildup of amyloid-beta and tau proteins—could predict the onset of cognitive decline in Alzheimer’s disease, years before symptoms like memory loss appear. These findings pave the way for early detection and intervention in individuals at risk of developing the disease.
This research was in collaboration with the Villeneuve lab also at McGill.
Amyloid-beta and tau proteins have long been associated with Alzheimer’s disease. Amyloid-beta tends to accumulate early in the aging brain, while tau follows later, leading to neurodegenerative changes. Until now, the exact relationship between the early buildup of these proteins and brain activity was poorly understood.
“Our goal was to contribute to a better understanding of whether early changes in brain activity are related to the accumulation of these proteins, even in people who are symptom-free,” said the study’s lead author, Prof. Sylvain Baillet. “We did observe such alterations in brain activity. Consistent with predictions from animal models, we found that amyloid-beta was related to a form of acceleration in brain activity, while a synergy between amyloid and tau led to a considerable slowing of brain activity.”
We conducted short magnetoencephalography (MEG) brain scans on participants, following them over a period of three to four years. We discovered that the early changes in brain activity were stronger in those participants who eventually developed memory or attention deficits. This means that even before symptoms like memory loss or attention deficits become obvious, the brain is already showing signs of dysfunction, which in principle could be detected by a rapid MEG scan of only five minutes.
One further interesting finding from our study is that the brain activity changes we observed early on, when amyloid-beta and tau proteins first started accumulating, predicted later brain activity changes in more advanced stages of Alzheimer’s. To show this, we retrieved data from two independent studies involving patients with early Alzheimer’s or mild cognitive impairment (MCI). We then verified that the predictions from our model, based on asymptomatic participants, could accurately predict the brain activity seen in those more advanced cases.
This suggests that the way amyloid-beta and tau interact with brain activity early on may help forecast later disease progression. Again, these findings were obtained using independent datasets, showing that our predictions held true across different groups and methods (see figure below).
The significance of this finding lies in its potential for early detection. Brain activity changes could serve as an early warning system; by identifying these subtle shifts in brain function, we might be able to predict who is at higher risk for developing cognitive problems later on. This could open the door to earlier interventions, including treatments against amyloid deposits that are currently emerging, and more specific therapies before Alzheimer’s symptoms fully emerge.
As a next step, we are continuing to follow participants from the PREVENT-AD cohort, a unique group of individuals at risk of developing Alzheimer’s. Over nearly ten years, these participants have undergone follow-up MEG scans, amyloid and tau PET imaging, and in-depth cognitive testing.
Our goal now is to refine how well we can predict cognitive decline and Alzheimer’s symptoms from short MEG scans, potentially up to a decade before they appear. We also want to emphasize that the PREVENT-AD datasets will be released to all researchers, encouraging replication and novel findings.
We foresee that AD research community stands to benefit from this data-sharing effort. We are deeply grateful to the participants for their dedication and involvement in this research, which has made these insights possible.
We believe our study highlights the importance of understanding how the disease begins, offering hope for more targeted and effective treatment strategies.
This research was led in collaboration with Prof Sylvia Villeneuve’s group, also at McGill.
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