A novel neuroimaging marker, peak-width of skeletonized mean diffusivity (PSMD), shows potential in identifying individuals at risk of developing dementia, according to a study led by researchers at The University of Texas Health Science Center at San Antonio (UT Health San Antonio). The study, published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, highlights the relevance of PSMD, particularly for the Hispanic population, which faces a higher risk of dementia due to vascular injury. This advancement could significantly improve the efficiency of multi-site dementia studies.
PSMD as a VCID Biomarker
Claudia Satizábal, PhD, associate professor at the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases at UT Health San Antonio, emphasized the importance of the findings, stating that the biological validation supports larger clinical studies to position PSMD as a risk biomarker of small vessel disease contributing to cognitive impairment and dementia. The research is a result of a collaboration between community participants, patients, clinicians, and researchers at the Glenn Biggs Institute and the South Texas Alzheimer's Disease Research Center.
The Growing Concern of Cognitive Impairment
With increasing life expectancy, the global burden of age-related cognitive impairment, including vascular etiology, is set to rise. Cerebrovascular pathology is increasingly recognized as a significant factor in cognitive impairment. Slow progressive changes in the brain related to cerebral small vessel disease (SVD) are a major mechanism involved in vascular contributions to cognitive impairment and dementia (VCID). Alison Luckey, PhD, postdoctoral research fellow with the Biggs Institute, noted the pressing need for VCID biomarkers, as only a few can reliably detect and track SVD changes leading to VCID, and none have yet been approved for clinical trials.
Validating PSMD
The study focused on validating PSMD, which had previously demonstrated excellent instrumental properties. Researchers aimed to establish its biological validity by associating it with clinically meaningful aspects of VCID, such as cognitive performance. The team studied 396 participants from the MarkVCID consortium. PSMD was derived from diffusion tensor imaging (DTI) using an automated algorithm and related to a composite measure of general cognitive function using linear regression models.
The study found that higher PSMD was associated with lower general cognition, independent of factors like age, sex, education, and intracranial volume. These findings were replicated across three independent samples. Furthermore, PSMD explained cognitive status beyond what could be accounted for by white matter hyperintensities (WMH), the more commonly used cerebrovascular marker.
Implications for Clinical Trials
The researchers concluded that PSMD possesses ideal qualities for use in clinical trials targeting dementias. Its non-invasive nature, full automation, speed, and excellent reliability make it a promising tool. Additional longitudinal validation studies are underway to further assess PSMD as a surrogate marker for cerebral small vessel diseases.
