Menardi et al. 2026; Functional dispersion within amyloid-present contexts
Chloe Chen; 17
Citation: Menardi, A., Rocca, B. L., Saglam, C., Alberti, F., Cecchin, D., Venneri, A., Cagnin, A., & Vallesi, A. (2026). Organizational principles of the cerebral cortex predict symptoms progression in the Alzheimer’s disease spectrum. NeuroImage, 121696. https://doi.org/10.1016/j.neuroimage.2026.121696
Purpose: The study aimed to understand how changes in brain functional connectivity relate to memory decline and Alzheimer’s disease progression, and to evaluate whether a multimodal framework—centered on functional gradients—can serve as an early marker of disrupted brain communication and future cognitive decline.
Methodology: Researchers analyzed 279 participants from the ADNI database with functional and structural MRI, amyloid and tau biomarkers, and detailed verbal memory assessments at baseline and two-year follow-up. Functional gradients were integrated with graph theory measures, morpho-volumetric indices, amyloid status, and regional tau burden to examine how patterns of Default Mode Network (DMN) connectivity relate to memory performance and disease progression.
Results: At baseline, functional dispersion within the DMN showed opposite relationships with memory depending on amyloid status—greater dispersion was linked to worse memory in amyloid-positive individuals but better performance in amyloid-negative individuals, with middle temporal regions showing distinct behavior. Higher dispersion predicted faster future memory decline across groups, except in tau-rich temporal regions where it appeared beneficial. Increased dispersion was also associated with later tau accumulation and structural brain changes, suggesting that altered DMN connectivity may be an early and predictive marker of cognitive decline.
Author's Note
This paper really shed light upon my previous perception that functional dispersion was a positive trait. I previously thought that increased brain activity and neuroplasticity within Alzheimer's patients or amyloid-present individuals would lead to increased hippocampus and cortex performance. In simple words, this investigation revealed the following: The greater the functional dispersion (brain activity) in amyloid-present brains, caused increased neurodegeneration occurred; the lower the functional dispersion in amyloid-present brains, caused less neurodegeneration. Yet, the greater the functional dispersion in amyloid-absent brains can result in improved memory performance.
I was intrigued by the nuance behind the Default Mode Network (DMN) and the importance of activating specific components of the brain only when necessary. The paper revealed that the DMN activated more components than necessary, resulting in an increased functional gradient. This relationship reminded me of a computer: it works perfectly fine when a few applications are open, yet when all the applications are running and hundreds of tabs are open, the computer crashes.
Figure 3B really highlights the opposite nature of dispersion and cognition as well as its interaction with MMSE. I'm really fascinated in how functional gradients can be further studied: Could functional dispersion be used as a biomarker in clinics? Can treatments reduce harmful dispersion or support beneficial compensation? How might this approach help design early interventions?
Review: This study was fun to read and informative. There are many abbreviations so its important to read the context carefully yet it was a delight to learn more about the DMN from imaging as a future biomarker rather than what I'm used to for analyzing AD (puncta quantities).