Comparing the brain MRIs of people with and without dementia, researchers have identified an accurate ‘signature’ that may signal a person’s risk of developing the disease five to 10 years before symptoms appear. The novel biomarker could provide an early diagnosis, allowing therapeutic interventions to slow the disease’s progress.
With the world’s population aging, there’s a push towards finding ways to reduce the public health burden of dementia. Research has added to our understanding of the risk factors that contribute to the condition, which includes its most common type, Alzheimer’s disease, and evolved to recognize it involves complex, mixed underlying pathologies.
Identifying a biomarker or signature of dementia that can be applied to large at-risk populations has obvious advantages for diagnosis and treatment. This prompted researchers from the University of Texas Health Science Center at San Antonio (UT Health San Antonio), in collaboration with UC Davis and Boston University, to sift through thousands of brain MRIs to identify an accurate dementia biomarker that appears five-to-10 years before symptoms do.
“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,” said Claudia Satizabal, lead and corresponding author of the study.
The researchers analyzed the brain MRIs of 1,146 participants from the ongoing, longitudinal Framingham Heart Study (FHS) and 513 participants from the UC Davis Alzheimer’s Disease Research Center (UCD-ADRC). The Californian cohort included 44% representation of Black and Hispanic participants, whereas the Massachusetts (FHS) cohort was predominantly non-Hispanic white. Both were aged 70 to 74, on average, at the time of the MRI studies.
“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 Sudha Seshadri, a study co-author.
The researchers were looking specifically for differences in the thickness of the brain’s cortical gray matter, comparing those participants with dementia to age- and sex-matched participants known to remain cognitively normal for at least 10 years after their MRI. The cortex, the brain’s outer layer, is gray-matter-rich and divided into numerous functional areas, including those responsible for memory, reasoning, senses, and language.
The researchers found that results were consistent across populations. In general, thicker ribbons of cortical gray matter correlated with a reduced risk of all-cause and Alzheimer’s disease dementia. Thinner ribbons correlated with an increased risk. They also observed significant associations between this dementia signature and cognitive function. Greater cortical thickness was associated with better measures of episodic memory and general cognitive function in the Massachusetts group and better episodic memory and executive function in the California group.
“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,” Satizabal said. “Although more studies are needed to validate this biomarker, we’re off to a good start. The relationship between thinning and dementia risk behaved the same way in different races and ethnic groups.”
Interestingly, the researchers found that cortical thickness wasn’t associated with genetics, which could be a good thing.
“We looked at APOE4, which is a main genetic factor related to dementia, and it was not related to gray matter thickness at all,” said Satizabal. “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.”
MRI is a relatively simple, non-invasive way to measure this dementia signature.
“A high proportion of people going to the neurologist get their MRI done, so this thickness value might be something that a neuroradiologist derives,” Seshadri said. “A person’s gray matter thickness might be analyzed as a percentile of the thickness of healthy people for that age.”
The researchers plan to explore risk factors that may be related to cortical thinning, including cardiovascular risk factors, diet, genetics, and exposure to environmental pollutants. They say that the novel signature could be used to develop and evaluate therapeutics and would assist clinical trial researchers by identifying participants who are ‘on track’ to develop dementia but don’t have symptoms yet.
The study was published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Source: UT Health San Antonio