Abstract 16: Functional Magnetic Resonance Imaging as a Predictor of Cognitive Impairment in Cerebral Amyloid Angiopathy

Abstract

Background: Cerebral Amyloid Angiopathy (CAA) emerged as an important contributor to cognitive impairment (CI) in elderly. Multiple lines of evidence suggest the presence of vascular dysfunction in CAA but its relationship to CI has not been tested. We hypothesized that the degree of vascular dysfunction identified by functional magnetic resonance imaging (fMRI) is a predictor of subsequent development of CI in patients with CAA. Methods: Thirty nondemented probable CAA patients diagnosed with Boston criteria were prospectively enrolled. They underwent high-resolution structural MRI and fMRI at baseline and cognitive assessment both at baseline and follow up. Structural MRI markers (microbleed counts, superficial siderosis, enlarged perivascular spaces, cortical microinfarcts) and FreeSurfer based volumetric analyses (cortical thickness, white matter hyperintensity volume) were obtained. An fMRI measure of vascular reactivity to visual stimulation, time-to-peak [TTP] of blood oxygen level-dependent [BOLD] response, was the main physiologic marker of interest. Main outcome measure was the development of CI defined based on structured cognitive assessments. Results: Patients had a mean age of 69.1±7.6 years. During a median follow-up of 23 months, 13 patients (43.3%) developed CI. Patients who developed CI did not differ from the patients without CI in terms of age, sex, risk factors and structural MRI markers (all p>0.2). Patients with CI trended towards fewer years of education (16±2.8 years vs 18±2.8 years, p=0.069). Baseline TTP of BOLD response was significantly higher in patients with incident CI as compared to patients without CI (12.7 ± 5.8 vs 7.8 ± 2.9, p=0.005). In a cox regression analysis, higher TTP was independently associated with future CI risk, after adjusting for age, sex, WMH volumes and education years (hazard ratio: 1.23; 95% CI: 1.06-1.42; p=0.006). Conclusion: The severity of baseline vascular dysfunction is associated with future CI in CAA. Unlike markers of parenchymal injury that are typically irreversible, vascular dysfunction might be reversible making our findings potentially relevant to future therapeutic development efforts.