Associations in Alzheimer’s disease between intracranial vascular metrics from 4D‐flow MRI and β‐amyloid and tau PET

Abstract

AbstractBackgroundCerebrovascular disease (CVD), has been linked with dementia stages of Alzheimer’s disease (AD); however, the question of whether CVD is associated with underlying AD pathophysiology remains unresolved. This work investigated the relationship between advanced MRI based cerebrovascular markers with AD biomarkers of β‐amyloid deposition and neurofibrillary tau tangles in subjects spanning the AD clinical spectrum.MethodSubjects: Study groups are summarized in figure 1. MRI: Whole brain 4D‐Flow data were acquired on a 3.0T system using a 32‐channel head coil. From 4D‐Flow images, intracranial blood flow, trans‐capillary pulse wave delay, and low frequency oscillations (LFOs) were estimated. Trans‐capillary pulse wave delay was defined as the cardiac pulse wave transit time from intracranial arteries‐to‐capillaries‐to‐veins and was measured from cardiac wave time‐to‐upstroke differences in arteries and veins. White matter hyperintensity (WMH) lesion volumes were segmented from T2‐FLAIR images using the Lesion Segmentation Toolbox in SPM12. PET: Four groups were established based on clinical diagnosis and biomarker positivity. Subjects were classified as cognitively normal (CN) or impaired (IM) (MCI or dementia) based on a clinical consensus review. Amyloid (A) (+/‐) was determined using a previously established global PiB DVR threshold >1.19 and tau (T) (+/‐) was determined using a previously established entorhinal cortex MK‐6240 SUVR threshold >1.27. Pairwise statistical differences were assessed using ANOVA followed by post‐hoc analysis (P<0.05 significance).ResultTrans‐capillary pulse wave delay was significantly longer in controls (A‐/T‐/CN) when compared with AD biomarker confirmed groups (fig 2 b) (P<0.001). Low frequency flow range and LFOs were significantly lower and diminished in A+T+ groups both cognitively normal and impaired (fig 3 P<0.001; fig 4 P=0.027, P=0.046, P=0.046). Linear regression analysis showed a weak correlation between trans‐capillary pulse wave delay and PiB and MK‐6240 (R2=0.12, R2=0.04), and between LFOs and PiB and MK‐6240 (R2=0.07, R2=0.03) (fig 5). No significant AT biomarker group differences were observed across other modalities such as traditional cardiovascular and cerebrovascular metrics, including WMH lesion volumes (fig 1).ConclusionAlthough more traditional measures of CVD were not related to biomarker groups, 4D‐Flow MRI based vascular markers suggest significant intracranial vascular stiffness and reduced autoregulation‐related vasomotion in AD biomarker positive subjects during preclinical AD.