Associations of plasma neuron-derived extracellular vesicles with MRI-derived parasagittal dura metrics across the cognitive continuum

Abstract Background Neuron-derived extracellular vesicles (NDEVs) have been implicated in cognitive phenotypes; however, whether their physical properties are associated with cognition and with MRI-derived markers of brain fluid clearance pathways remains unclear. We aimed to characterize plasma NDEV properties across the cognitive continuum and to examine their associations with these imaging markers. Methods This population-based study included 156 rural-dwelling older adults (aged ≥60 years; 62.8% women) from the MIND-China study. Plasma NDEV concentration and diameter were quantified using the ExoView platform. MRI-derived parasagittal dural (PSD) and cervical lymph node (LN) metrics, including structural measures and signal intensity, were assessed on three-dimensional T2 fluid-attenuated inversion recovery magnetic resonance imaging. Associations were examined using group comparisons and regression models. Results Here we show that, among the 156 participants, 37 had mild cognitive impairment and 13 had clinically diagnosed Alzheimer’s disease (AD). Larger plasma NDEVs were associated with AD and poorer cognitive function, whereas NDEV concentration was not significantly associated with AD. Greater MRI-derived PSD metrics were associated with lower plasma NDEV concentration, but not with total extracellular vesicle concentration. Conclusions Plasma NDEV size is associated with AD and poorer cognition, and MRI-derived PSD metrics are associated with plasma NDEV profiles. These findings warrant further evaluation of plasma NDEV properties as candidate biomarkers, including assessments of diagnostic accuracy and disease specificity in larger longitudinal cohorts.