Scientists at the Indiana University School of Medicine have made an important breakthrough in predicting dementia long before memory loss begins.
Their new diagnostic method can estimate a person’s stage of dementia by looking at very early changes in blood flow and energy use in the brain.
These changes can appear as early as twenty years before a clinical diagnosis, offering hope for earlier detection and better treatment options.
The findings were recently published in the journal Alzheimer’s & Dementia.
Dementia and Alzheimer’s disease take many years to fully develop. Long before a person begins to forget names, misplace objects, or struggle with daily tasks, the brain goes through silent changes.
One of the earliest signs appears to be an imbalance in how the brain uses glucose, its main source of energy, and how blood flows to important regions involved in memory, learning, and thinking. These two processes—metabolism and perfusion—are essential for healthy brain function.
The research team, led by Dr. Paul Territo and Dr. Juan Antonio K. Chong Chie, studied more than 400 adults at different stages of cognitive health. Some were completely healthy, others had early or mild cognitive impairment, and others had diagnosed Alzheimer’s disease.
Using PET scans to measure glucose metabolism and MRI scans to measure blood flow, the scientists tracked changes across 59 different brain regions. Their goal was to understand how early these disruptions begin and how they progress as dementia develops.
What they discovered was striking. The earliest changes appeared up to twenty years before a person would be clinically diagnosed with dementia. These early brain changes were also linked with inflammation, suggesting that inflammation may trigger problems in metabolism and blood flow long before memory symptoms appear.
Regions of the brain related to learning, memory, and problem-solving were the first to show signs of damage. These regions were also the least able to tolerate metabolic and vascular stress, meaning they declined faster than other parts of the brain.
To better understand these patterns, the team created a new framework that sorts patients into four stages of neuro-metabolic and vascular disruption. In the earliest stage, metabolism goes down but blood flow increases, as if the brain is trying to compensate. Later, both metabolism and blood flow decline, marking more advanced disease.
This same four-stage pattern was seen both in human patients and in animal models the researchers studied earlier. The strong alignment between the human and animal data gives scientists confidence that these early changes truly reflect the biology of Alzheimer’s disease.
Another important finding was that not all brain regions decline at the same speed. Some regions are more fragile and show damage quickly, while others remain stable for longer.
The researchers also found differences between men and women. Women progressed faster through the stages of metabolic and vascular decline than men, showing that sex may play a role in how dementia develops.
The team supported their findings by comparing brain scan results with gene signatures—patterns of genes measured from blood samples that indicate disease—and with performance on memory and thinking tests.
All three sources of data pointed to the same conclusion: early disruptions in blood flow and metabolism are reliable markers of later cognitive decline.
Dr. Territo believes this approach could help create better treatments. If medicines can improve the metabolic and vascular problems detected early in the scans, patients may see improvements in inflammation and thinking ability. This diagnostic tool may also help doctors track how well a treatment is working or identify which patients might benefit most from certain therapies.
The team’s next goal is to understand how different brain regions communicate with each other once these early changes begin. Understanding how brain circuits break down could lead to even earlier and more accurate prediction of dementia.
Reviewing the findings, this study highlights an important shift in dementia research. Traditionally, doctors diagnose Alzheimer’s disease based on the presence of amyloid plaques and tau tangles. But this research shows that blood flow and energy metabolism may change decades earlier, offering a clearer window of time for intervention.
The study suggests that inflammation may trigger a chain reaction that weakens blood vessels, lowers energy supply, and harms brain cells long before memory loss appears. By identifying these early changes, researchers may one day prevent or delay dementia much more effectively than current treatments allow.
Although more research is needed, especially to understand how brain regions influence one another, this work moves the field closer to detecting dementia before symptoms develop, opening the door to earlier and more personalized care.
If you care about dementia, please read studies that eating apples and tea could keep dementia at bay, and Olive oil: a daily dose for better brain health.
For more health information, please see recent studies what you eat together may affect your dementia risk, and time-restricted eating: a simple way to fight aging and cancer.
