Certain areas of the brain in individuals with Alzheimer’s exhibit more frequent reorganizations during rest compared to those without the condition––and this regular reshuffling in healthy individuals can sometimes indicate who might develop the disease in the future, a recent study from the University of Michigan and Columbia University reports.

The brain’s capacity to rearrange its regions is termed neural flexibility, states Eleanna Varangis, assistant professor at the U-M School of Kinesiology and lead author of the publication in the Journal of Alzheimer’s Disease.

“Our brain continually organizes and reorganizes regions into various functional networks to ensure it has the necessary resources for a range of cognitive tasks,” Varangis noted, who also participates in the Michigan Concussion Center. “We discovered that in Alzheimer’s disease, the brain has a tendency to reorganize more frequently.”

“In general, our study implies we might utilize information regarding how our brain arranges itself into functional networks to potentially help determine whether an individual has Alzheimer’s disease.”

It is estimated that 1 in 10 men and 1 in 5 women will experience Alzheimer’s disease in their lifetime, making early intervention essential for preserving independence. Functional brain imaging has shown promise as an initial biomarker of disease risk, according to Varangis.

This research, supported by the National Institutes of Health and the Brain & Behavior Research Foundation, utilized functional MRI data gathered while participants were awake but at rest to analyze neural flexibility in the brains of 862 older adults in the Alzheimer’s Disease Neuroimaging Initiative, categorized into three groups: cognitively normal; mild cognitive impairment; and individuals with Alzheimer’s disease.

Varangis and team aimed to resolve two queries: whether the brain damage caused by Alzheimer’s disease leads to alterations in neural flexibility; and whether neural flexibility could assist in predicting who in the cognitively normal group might transition to Alzheimer’s disease.

The researchers discovered that neural flexibility was notably elevated in the Alzheimer’s cohort compared to the cognitively normal group across all brain regions and in six specific networks. Additionally, the mild cognitive impairment group showed significantly higher neural flexibility than the cognitively normal group in the visual network. Among the 617 healthy participants at baseline, 8.6% progressed to dementia over the subsequent 11 years, aligning with national dementia prevalence estimates in older adults. Increased neural flexibility in the visual network correlated with a transition to Alzheimer’s disease.

“Although this effect was modest, it suggests that activity in these visual areas might provide insights regarding the risk for Alzheimer’s disease years ahead of formal diagnosis,” Varangis explained. “As cognitive impairment is generally viewed as the primary symptom of Alzheimer’s disease, it was somewhat unexpected, yet not entirely surprising, that this sensory network predicted conversion to Alzheimer’s.”

“In typical Alzheimer’s progression, the brain pathology related to the disease usually does not impact sensory regions until later stages. It is possible that these areas exhibit greater flexibility because they are among the less affected, healthier regions of the brain.”

The findings challenged the researchers’ assumptions because, generally, flexibility and adaptability are perceived positively, Varangis noted.

“However, once we observe the onset of the disease process, it may be that if we are merely resting and demonstrating this frequent reassignment of brain regions to varied functions, then parts of the brain might not be functioning as they ideally should,” she added.

Valuing that this is an experimental method, Varangis emphasizes that it remains far from a diagnostic solution.

“The bright side is that many believe neurodegenerative diseases lead to a general deceleration of brain function over time,” she remarked. “Yet, these discoveries also illustrate the brain’s dynamic nature, suggesting that even as individuals undergo cognitive changes or decline, there remains substantial flexibility in our brains to adapt, which I find to be a beacon of hope and resilience.”

Co-authors include: Jun Liu, Yuqi Miao, Xi Zhu, Yaakov Stern, Seonjoo Lee, all affiliated with Columbia University. This work was financed by grants from the National Institutes of Health [R01AG062578 (PI: Lee), NIH K01MH122774] and a Brain & Behavior Research Foundation NARSAD Young Investigator Grant (PI: Zhu).