Researchers have found a biomarker that can detect dementia far earlier than its onset. According to research, thinning of specific brain regions may be an early predictor of dementia risk, appearing 5-10 years before the development of obvious symptoms. The hippocampus, a region connected with memory and learning, is a particularly interesting area of study.
According to researchers at The University of Texas Health Science Center at San Antonio (UT Health San Antonio), a ribbon of brain tissue known as cortical gray matter thins in people who develop dementia, and this appears to be an accurate biomarker of the disease five to ten years before symptoms appear.
The researchers collaborated with colleagues from the University of California, Davis, and Boston University to undertake an MRI brain imaging study that was published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. They looked at 1,000 Framingham Heart Study individuals from Massachusetts and 500 from a California cohort. The California volunteers comprised 44% Black and Hispanic people, whereas the Massachusetts cohort was primarily non-Hispanic White. At the time of the MRI scans, both cohorts had an average age of 70 to 74 years.
The big interest in this paper is that, if we can replicate it in additional samples, cortical gray matter thickness will be a marker we can use to identify people at high risk of dementia.
Claudia Satizabal
“The big interest in this paper is that, if we can replicate it in additional samples, cortical gray matter thickness will be a marker we can use to identify people at high risk of dementia,” said study lead author Claudia Satizabal, PhD, of UT Health San Antonio’s Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. “By detecting the disease early, we are in a better time window for therapeutic interventions and lifestyle modifications, and to do better tracking of brain health to decrease individuals’ progression to dementia.”
Repeating the Framingham findings in the more-diverse California cohort “gives us confidence that our results are robust,” Satizabal said.
Sifting MRIs for a pattern
While dementias can affect different brain regions, Alzheimer’s disease and frontotemporal dementia impact the cortex, and Alzheimer’s is the most common type of dementia.
The study compared participants with and without dementia at the time of MRI. “We went back and examined the brain MRIs done 10 years earlier, and then we mixed them up to see if we could discern a pattern that reliably distinguished those who later developed dementia from those who did not,” said co-author Sudha Seshadri, MD, director of the Glenn Biggs Institute at UT Health San Antonio and senior investigator with the Framingham Heart Study.
“This kind of study is only possible when you have longitudinal follow-up over many years as we did at Framingham and as we are building in San Antonio,” Seshadri said in a statement. “The people who had the research MRI scans while they were well and kept coming back to be studied are the selfless heroes who make such valuable discoveries, such prediction tools possible.”
The findings were consistent across populations. In general, thicker ribbons were associated with better outcomes and thinner ribbons with poorer outcomes. “Although more studies are needed to validate this biomarker, we’re off to a good start,” he said. “The relationship between thinning and dementia risk behaved the same way in different races and ethnic groups.”
Applications
Clinical trial researchers could use the thinning biomarker to minimize cost by selecting participants who haven’t yet developed any disease but are on track for it, Seshadri said. They would be at greatest need to try investigational medications, she said.
The biomarker would also be useful to develop and evaluate therapeutics, Seshadri noted.
Future directions
Satizabal stated that the team intends to investigate potential risk factors associated with the thinning. These include cardiovascular risk factors, food, genetics, and exposure to environmental pollution, she explained.
“We looked at APOE4, which is a main genetic factor related to dementia, and it was not related to gray matter thickness at all,” Satizabal said in a statement. “We think this is good, because if thickness is not genetically determined, then there are modifiable factors such as diet and exercise that can influence it.”
