A Shift in Brain Connectivity Reveals Early Risk of Alzheimer’s

Researchers have observed an intriguing phenomenon in cognitively healthy older adults: a shift in how their brain connects its different regions. This change, characterized by a decrease in local connections and an increase in long-range connections, could indicate an early risk of developing Alzheimer’s disease.

The study involved 86 adults aged 65 to 80, all cognitively normal. Participants underwent brain imaging exams and blood tests to detect markers associated with the disease. Among them, some had amyloid deposits—a protein linked to Alzheimer’s—or carried the APOE4 gene, known to increase the risk of the disease.

The results show that individuals with amyloid deposits or carriers of the APOE4 gene have reduced local connectivity in a brain region called the inferior frontal cortex. Conversely, their long-range connectivity is stronger in areas such as the superior motor area, the inferior frontal gyrus, and the anterior insula. These regions play a key role in cognitive functions like attention, movement control, and emotion regulation.

Another blood marker, the neurofilament light chain, also revealed links to brain connectivity. Participants with high levels of this marker, which signals neuronal damage, had weaker local connectivity in regions such as the insula and the cingulate cortex. At the same time, their long-range connectivity was increased in areas like the precuneus, the putamen, and the thalamus, all of which are involved in essential cognitive processes.

This shift from weakened local connectivity to strengthened long-range connectivity may reflect the brain’s attempt to compensate for early disease-related damage. However, this reorganization could also indicate a loss of specialization in neural networks, which, in the long term, could impair cognitive performance. Indeed, researchers noted that these changes in long-range connectivity were associated with poorer performance on tests of memory, processing speed, and executive functions.

These findings suggest that the way the brain organizes and communicates could be an early indicator of vulnerability to Alzheimer’s disease, long before the first symptoms appear. This type of functional marker could, in the future, help identify at-risk individuals and monitor disease progression non-invasively.

Legal Attributions

Study Citation

DOI: https://doi.org/10.1007/s11357-026-02333-5

Title: A local-to-distant shift in dynamic brain connectivity marks early Alzheimer’s risk

Journal: GeroScience

Publisher: Springer Science and Business Media LLC

Authors: Andrea Coca-Pulido; Patricio Solis-Urra; Oren Contreras-Rodríguez; Carles Biarnés; Marcos Olvera-Rojas; Shivangi Jain; Anuradha Sehrawat; Yijun Chen; Yolanda García-Rivero; Manuel Gomez-Rio; Kirk I. Erickson; Jose Mora-Gonzalez; Irene Esteban-Cornejo