Experts identify 'critical window' when early signs of neurodegeneration become visible on imaging
Researchers have identified an ideal window of time when adults should undergo neuroimaging to identify potential biomarkers indicative of neurodegeneration.
The new data, published in Proceedings of the National Academy of Sciences, suggests that people between the ages of 40 and 59 should undergo both functional MRI (fMRI) and electroencephalography (EEG). During this time, changes related to insulin resistance in different parts of the brain can be more readily identified. What’s more, experts believe the changes can be reversed before they progress into cognitive decline.
“This study demonstrates that brain aging follows a specific progression, with the first stage occurring in middle age and coinciding with increased insulin resistance,” lead author Mujica-Parodi, director of the Laboratory for Computational Neurodiagnostics (LCNeuro) and professor of biomedical engineering in the Laufer Center for Physical and Quantitative Biology, and colleagues explained. “Moreover, we show that brain areas that age fastest are also those most vulnerable to neuronal insulin resistance."
For their work, the team analyzed four fMRI datasets, which included more than 19,000 participants ranging in age from 30s to 90s. Changes of metabolic, vascular and inflammatory biomarkers implicated in dysregulated glucose control were compared to determine their effect on aging over time.
The team observed that neural changes occur in an S-shaped statistical curve with transition points that are obvious on imaging. This refutes prior data that suggested age-related degradation happens in a linear manner.
The first changes were seen around age 44, accelerating most rapidly around 67. The team identified the primary driver as neuronal insulin resistance—a metabolic change that preceded both vascular and inflammatory changes. A secondary gene expression analysis further validated this finding, the researchers noted.
Encouragingly, the group also identified the neuronal ketone transporter MCT2 as a potential protective factor that could slow and, in some cases, reverse the changes observed. This is likely due to neurons’ ability to metabolize ketones as energy sources without insulin.
This finding motivated a separate international study, which revealed that ketones can effectively stabilize neurodegeneration in brain networks most vulnerable to aging—a promising finding in the fight to slow cognitive decline among the aging population. These benefits were most pronounced in people ages 40 to 59.
The team believes their findings signal a window of opportunity for spotting and potentially reversing brain aging.
“This represents a paradigm shift in how we think about brain aging prevention,” noted first author Botond Antal, postdoctoral associate in biomedical engineering at Stony Brook. “Rather than waiting for cognitive symptoms, which may not appear until substantial damage has occurred, we can potentially identify people at risk through neurometabolic markers and intervene during this critical window.”
There is the possibility that these findings could lead to new screening guidelines that could change how imaging is utilized and would put greater emphasis on identifying the effects of insulin resistance in the brain, not just the blood.
Learn more about the findings here.
In addition to her background in journalism, Hannah also has patient-facing experience in clinical settings, having spent more than 12 years working as a registered rad tech. She began covering the medical imaging industry for Innovate Healthcare in 2021.