Functional connectivity fingerprints in Alzheimer's Disease

A new study led by Sara Stampacchia, in collaboration with Enrico Amico (previously Mip:Lab, EPFL and now University of Birmingham, UK), Valentina Garibotto (Nuclear Medicine and Molecular Imaging, Geneva University Hospital - HUG), and the Geneva Memory Centre (HUG), and published in Communications Biology, investigates whether brain "fingerprints"—unique patterns of brain connectivity—remain distinct even in the presence of Alzheimer’s disease (AD). Just as every person has a unique fingerprint, this new method has revealed that functional connectivity of the brain is also highly individual, just as a fingerprint.

Stampacchia and colleagues used fMRI data from two distinct cohorts: healthy elderly individuals without signs of AD pathology and patients with cognitive decline due to AD, ranging from mild cognitive impairment to dementia. They aimed to explore whether unique brain signatures – brain fingerprints - persist throughout AD progression.

The findings reveal that brain connectivity patterns remain sufficiently distinct and unique, allowing to identify individuals even for advanced AD. However, these patterns undergo significant changes as the disease progresses. Similarly to young individuals, healthy elderlies show the greatest variability in brain regions associated with higher cognitive functions, while in AD patients there is a "reconfiguration" of the fingerprint, with a shift toward lower-order brain functions (such as sensory-motor processing) and between functional system connections in key resting-state networks.

These findings are important for several reasons. First, despite sharing the same diagnosis and pathophysiology, individual AD patients exhibit variability between each other that is comparable to that seen in healthy individuals. This suggests that the diagnosis/disease explains only a portion of each individual’s variability. Additionally, the results indicate that this variability may be driven by cognitive functions that are not typically considered, such as sensory-motor processing, which could merit more attention in the design of rehabilitation protocols. Finally, these findings highlight the importance of focusing on individual variability in Alzheimer’s research. Tracking the evolution of each person’s brain functional network over time could lead to the development of personalized models of disease progression, improve predictions of disease trajectories, and enhance treatment strategies, thereby advancing personalized medicine in the management of Alzheimer’s disease.

In ongoing work, we aim to evaluate whether functional connectivity remains distinct in individuals with Parkinson’s Disease and to explore potential differences in patterns of individual variability between PD patients with and without hallucinations (see Bernasconi et al., 2023, Albert et al., 2024).