Peak Width of Skeletonized Mean Diffusivity (PSMD) and cognition in healthy adults

Abstract

Objective: The "Peak Width of Skeletonized Mean Diffusivity" (PSMD) has been shown to be a promising DTI marker to assess white matter integrity, which is highly associated with cognitive health. There are few papers that have investigated associations between PSMD and cognition, in particular only two longitudinal studies. The first aim of this work was to investigate associations between PSMD and cognition in cognitively healthy adults in a cross-sectional study. The main aim of the work was to longitudinally investigate whether PSMD changes are related to cognitive changes over time. In addition, associations between PSMD, age, gender, vascular risk factors, white matter hyperintensities, and brain volume were investigated. Methods: A total of 326 healthy adults aged 38-87 years were included in the cross-sectional study. MRI-based PSMD values were calculated together with measurements of total brain volume and WMH volumes. Cognitive performance was assessed in four domains: Memory, visual-practical skills, executive functions, and a composite score for global cognition. In a subgroup of 61 participants with complete longitudinal data, longitudinal changes in PSMD, WMH volume, and cognitive performance were examined. Results: In the cross-sectional analysis with 326 participants, PSMD showed a strong positive correlation with age, with a steeper increase observed in participants aged ≥ 60 years. In this age group, men also had significantly higher PSMD levels than women. In addition, PSMD was positively associated with the volume of WMH. In the cross-sectional analysis, higher PSMD levels were also significantly associated with lower performance in visual-practical skills and executive functions. The longitudinal analysis (n = 61) also revealed an increase in PSMD over time. The increase in PSMD correlated positively with the increase in WMH volume. However, an increase in PSMD over time did not correlate with changes in any of the cognitive domains analyzed. Conclusion: Our results confirm that PSMD-defined white matter integrity decreases with age and increasing damage from WMH. Associations with cognition were only detectable cross-sectionally, but not longitudinally. This may be due to the small number of cases in our longitudinal data and further studies with the same objective should aim for larger study populations and longer follow-up times.

Date of Award	2025
Original language	English
Awarding Institution	Medical University Graz
Supervisor	Stephan Seiler (Supervisor) & Christian Enzinger (Co-supervisor)