A groundbreaking study from researchers at The University of Texas Health Science Center at San Antonio (UT Health San Antonio) has identified a new neuroimaging marker associated with cerebral small vessel disease that could help identify individuals at risk for dementia in upcoming clinical trials. This research is particularly significant for the Hispanic population, which faces a higher risk of dementia due to vascular injury compared to non-Hispanic whites.
The study focused on the marker known as the peak-width of skeletonized mean diffusivity (PSMD), which demonstrated the ability to efficiently analyze numerous brain images across multiple sites in dementia research. Claudia Satizábal, PhD, an associate professor at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases and senior author of the study, emphasized the importance of this biological validation work. “Our findings support the pursuit of larger clinical validation studies to position PSMD as a susceptibility biomarker for small vessel disease contributing to cognitive impairment and dementia,” she stated.
Published on November 21 in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, the study highlights the collaborative efforts of community participants, clinicians, and researchers at the Glenn Biggs Institute and the South Texas Alzheimer’s Disease Research Center over the past seven years. Sudha Seshadri, MD, director of the Biggs Institute and co-author of the study, praised the dedication of participants and researchers, noting their commitment even during the COVID-19 pandemic to safely conduct brain MRI scans and cognitive tests.
Understanding the Global Burden of Cognitive Impairment
The authors of the study point to a growing body of literature suggesting that cerebrovascular pathology is prevalent among adults with cognitive impairment. While vascular contributions to cognitive impairment and dementia (VCID) are significant, accurately determining the number of affected individuals is challenging due to the frequent overlap with other conditions.
Recent advances in neuroimaging have revealed a high prevalence of brain white matter damage in individuals with VCID, leading to a consensus that progressive changes in the brain related to cerebral small vessel disease (SVD) are a major mechanism behind VCID. As global life expectancy continues to rise, the incidence of age-related cognitive impairment, particularly with a vascular component, is expected to increase. The authors advocate for investigating interventions that could alleviate the burden of VCID.
“Despite the urgent need for VCID biomarkers, only a few can reliably detect and track SVD changes leading to VCID, and these have yet to receive regulatory approval for clinical trial use,” remarked Alison Luckey, PhD, a postdoctoral research fellow at the Biggs Institute and first author of the study. Currently, the most commonly used neuroimaging marker for SVD is white matter hyperintensities (WMH), although its etiology remains unclear and may encompass both vascular lesions and neurodegeneration.
The study indicates that PSMD has shown strong instrumental properties, demonstrating reliability across various users, sites, and time points. The researchers aimed to further validate PSMD by examining its association with clinically relevant aspects of VCID, such as cognitive performance.
The team studied 396 participants from the MarkVCID consortium, an initiative of the National Institute on Neurological Disorders and Stroke (NINDS) aimed at identifying and validating biomarkers for SVDs associated with VCID. Utilizing diffusion tensor imaging (DTI), the researchers derived PSMD through an automated algorithm and correlated it with a composite measure of general cognitive function, adjusting for potential confounding factors.
Their findings revealed that higher PSMD levels were associated with lower cognitive performance, independent of age, sex, education, and intracranial volume. This association was replicated in three independent samples, indicating that PSMD can explain cognitive status beyond what is accounted for by WMH, the more commonly recognized cerebrovascular marker.
The researchers concluded that PSMD possesses ideal qualities for a clinical trial biomarker, being non-invasive, fully automated, rapid, and exhibiting excellent reliability, repeatability, and reproducibility. Additional longitudinal studies to validate PSMD as a surrogate marker for cerebral small vessel diseases are currently underway.
The study included contributions from various institutions, including Boston University, Harvard Medical School, the University of California at San Francisco, and Johns Hopkins University, among others.
UT Health San Antonio is recognized as a leading research university, ranking in the top 5% globally for clinical medicine according to U.S. News & World Report. It stands at No. 12 worldwide for the impact of its discoveries, as measured by normalized citation impact, a key indicator of research influence.
This study represents a significant step forward in the quest to identify and address the risks of dementia, particularly within vulnerable populations.
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