Clinical correlates of perfusion and diffusion MRI metrics in cognitively unimpaired older adults

Cerebral small vessel disease (CSVD) is associated with vascular risk factors (VRFs) and early executive function (EF) decline. Because periventricular white matter (PVWM) is the most weakly perfused brain region, it may be particularly sensitive to early manifestations of CSVD. Among 101 cognitively unimpaired adults, we assessed the cross-sectional correlations of arterial spin-labeled derived absolute and relative cerebral blood flow (CBF and rCBF, respectively) and diffusion tensor imaging (DTI) metrics in normal-appearing WM (NA-WM) and normal-appearing PVWM (NA-PVWM) with VRFs and EF, and evaluated the mediation and moderation relationships between these variables in amyloid β negative (Aβ-) subjects. CBF, rCBF, and DTI metrics were significantly different in NA-PVWM compared to NA-WM (<i>p</i> < 0.001). In multivariate analysis of the Aβ- group, NA-PVWM rCBF was associated with VRFs (<i>p</i> = 0.012), while NA-PVWM rCBF (<i>p</i> = 0.035) and mean diffusivity (MD) in NA-WM (<i>p</i> = 0.022) and NA-PVWM (<i>p</i> = 0.029) were associated with EF. The association between VRF and EF was not mediated by rCBF and/or MD. However, increased MD was significantly associated with poorer EF for NA-PVWM CBF ⩽16.3 mL/100 g/min and NA-PVWM rCBF ⩽0.35. NA-PVWM rCBF is associated with VRFs and EF and might be an early biomarker for CSVD, especially in the absence of amyloid pathology.