July 25, 2025
Mayo Clinic researchers have found a potential noninvasive biomarker for dementia with Lewy bodies (DLB). As described in the May 2024 issue of Movement Disorders, the approach applies diffusion-weighted MRI (dMRI) with free-water mapping.
"It's a significant clinical challenge to make an early and accurate diagnosis of DLB. We need better, noninvasive biomarker tests that patients can access easily," says Shannon Y. Chiu, M.D., a neurologist at Mayo Clinic in Phoenix/Scottsdale, Arizona.
A noninvasive imaging method, dMRI assesses tissue integrity based on water diffusion changes in the brain. Previous efforts to apply dMRI to DLB yielded varying results. Most of those studies used a diffusion tensor imaging (DTI) approach to evaluate white matter microstructure. That approach has known limitations, including an inability to consider volumetric effects from extracellular free-water. Free-water mapping is a model that explicitly separates extracellular diffusing water from brain tissue.
The Mayo Clinic researchers, working with colleagues at the University of Florida, used free-water dMRI to assess 27 individuals with DLB or mild cognitive impairment with Lewy bodies. Study participants had baseline imaging and follow-up imaging after 12 or 24 months, or both.
Free-water regions of interest
Figure illustrates anterior (A), left sagittal (B) and inferior (C) views of the brain, highlighting areas where participants in the dementia with Lewy bodies study had significant free-water changes.
"We found significant longitudinal free-water increases in 12 brain regions at both 12- and 24-month follow-up," Dr. Chiu says. "We also found free-water changes from selected brain areas that were associated with clinical progression over two years." Compared with imaging performed after 12 months, free-water dMRI after 24 months showed more widespread microstructural changes in brain areas implicated in visuospatial processing, motor and cholinergic functions.
DLB is a relatively common cause of late-onset neurodegenerative dementia, accounting for up to 20% of autopsy-confirmed dementias. "Patients with DLB often get a misdiagnosis of Alzheimer's disease because we know that 50% or more patients with DLB also have coexisting Alzheimer's-related brain changes," Dr. Chiu says. Developing a noninvasive biomarker would facilitate not only accurate diagnosis but also clinical trials of potential treatments for DLB.
Dr. Chiu began her work at the University of Florida, under the supervision of David Vaillancourt, Ph.D. Dr. Vaillancourt and colleagues were the first to show elevated free-water in the posterior substantia nigra of individuals with early-stage Parkinson's disease.
Future research aims to determine the factors underlying diffusion changes in DLB. "We think it's related to neurodegeneration. But what exactly is driving it?" Dr. Chiu says. The efforts will incorporate markers of alpha-synuclein and Alzheimer's disease copathology.
As a tertiary center for DLB, Mayo Clinic has multidisciplinary physician-scientists who together care for patients and work to improve treatment. Mayo Clinic's campus in Arizona — in partnership with Banner Sun Health Research Institute — has been designated a Research Center of Excellence by the Lewy Body Dementia Association, a national patient advocacy group.
"Mayo Clinic's research efforts are intricately tied to improving patient care," Dr. Chiu says. "We hope that one day we can use dMRI and free-water mapping to determine the probability that a patient's imaging fits a diagnosis of DLB."
For more information
Chiu SY, et al. Longitudinal free-water changes in dementia with Lewy bodies. Movement Disorders. 2024;39:836.
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