Perivascular spaces mediate a relationship between diabetes and other cerebral small vessel disease markers in cerebrovascular and neurodegenerative diseases

Type 2 diabetes mellitus (T2DM) and hypertension are risk factors for cerebral small vessel disease (SVD); however, few studies have characterised their relationships with MRI-visible perivascular spaces (PVS). MRI was used to quantify deep (d) and periventricular (p) white matter hyperintensities (WMH), lacunes, PVS in the white matter (wmPVS) or basal ganglia (bgPVS), and diffusion metrics in white matter. Patients with T2DM had greater wmPVS volume and there were greater wmPVS volumes in patients with T2DM and hypertension together. Counterfactual moderated mediation models found indirect effects of T2DM on volumes of other SVD and diffusion markers that were mediated by wmPVS: pWMH, dWMH, periventricular lacunes, and deep lacunes, and progression of deep lacunes over 1 year, in patients with hypertension, but not in patients without hypertension. Studying the regulation of cortical perivascular fluid dynamics may reveal mechanisms that mediate the impact of T2DM on cerebral small vessels.

Automated summary

Type 2 diabetes mellitus (T2DM) and hypertension are risk factors for cerebral small vessel disease (SVD), and their relationships with MRI-visible perivascular spaces (PVS) were investigated. T2DM patients had greater volumes of PVS in the white matter, and those with T2DM and hypertension had even greater volumes. Mediation models revealed indirect effects of T2DM on other SVD markers mediated by PVS in patients with hypertension. Understanding the regulation of cortical perivascular fluid dynamics may elucidate mechanisms linking T2DM to cerebral small vessel damage.