Abstract WMP78: Microstructural Alterations And Vascular Dysfunction In Cerebral Amyloid Angiopathy

Abstract

Background: Cerebral amyloid angiopathy (CAA) causes impaired vascular reactivity to physiologic stimuli that mediates CAA-related white matter hyperintensities (WMH) but its relationship to microstructural changes has not yet been tested. We hypothesized that the degree of vascular dysfunction would be associated with alterations in white matter microstructure in patients with CAA. Methods: Fifty-five non-demented probable CAA patients underwent high-resolution structural MRI including Diffusion-Weighted Imaging (DWI) and functional MRI (fMRI). WMH volume was quantified and expressed as percent of total intracranial volume (pWMH). Vascular reactivity was measured as the amplitude of the blood-oxygenation-level-dependent response (BOLD_Amp) to a visual stimulus. Peak Width of Skeletonized Mean Diffusivity (PSMD) was calculated from DWI and used as a marker of microstructural integrity. Results: Patients had a mean age of 69.3±7.4 years and 36 (65%) had intracerebral hemorrhage (ICH). The mean PSMD was [(3.92±0.8) х 10–4 mm2/s] and the mean BOLD_Amp was 1.15±0.2%. Neither PSMD nor BOLD_Amp differed between patients with ICH and those without (p>0.2 for all comparisons). PSMD significantly correlated with older age (r=0.335, p=0.012), with higher pWMH (r=0.792, p<0.001) and with lower BOLD_Amp (r= –0.5, p<0.001). PSMD showed a trend to increase more in patients with hypertension (HT) than without ([(4.09±0.8) х 10–4 mm2/s] vs. ([(3.74±0.8) х 10–4 mm2/s], p=0.097). BOLD_Amp also correlated with pWMH (r= –0.409, p=0.002). In a linear regression analysis, decrease in BOLD_Amp was independently associated with increased PSMD corrected for age, sex, HTN, ICH and pWMH (β= –0.91, 95%CI (–1.77)-(–0.05), p=0.037). pWMH was also associated with PSMD in this model (β=1.22, 95%CI 0.89-1.54, p<0.001). Conclusion: This study supports the view that vascular dysfunction in CAA is closely linked with CAA-related global ischemic injury including MRI-visible white matter injury as well as microstructural tissue disruption.