Abstract WP254: Amyloid Load and Brain Atrophy in Cerebral Amyloid Angiopathy: A PiB PET-MRI Study

Introduction: Cerebral amyloid angiopathy (CAA) is a common cerebral small vessel disease characterized by vascular amyloid accumulation. Although CAA has been linked to brain atrophy, the contribution of vascular amyloid to tissue loss has not been directly quantified. We hypothesized that higher cortical amyloid would be associated with reduced gray- and white-matter volumes in CAA. Methods: We studied 47 probable CAA patients without cognitive impairment who underwent structural MRI at 1.5T and Pittsburgh compound B (PiB) PET imaging. Intracerebral hemorrhage (ICH) and cortical superficial siderosis (cSS) were identified, and lobar cerebral microbleeds (CMBs) were counted. Using FreeSurfer, we quantified cortical gray matter volume (pGMV), white matter volume (pWMV), and white matter hyperintensity volume (pWMH) as percentages of intracranial volume. Mean global cortical PiB uptake served as the index of amyloid load. Pearson correlations assessed unadjusted relationships. Separate multivariable linear regression models were built to assess the associations between PiB uptake and volumetric brain measures while adjusting for age, sex, hypertension, ICH, lobar CMB counts, cSS, and pWMH. Results: Participants had a mean age of 69.1±7, and 78.7% were male. 68.1% had ICH and 46.8% had cSS. Global cortical PiB uptake was negatively correlated with pGMV (r=-0.41, p=0.004) and with pWMV (r=-0.45, p=0.001). In adjusted models, higher PiB remained independently associated with lower pGMV (β = −0.34, 95% CI -4 to -0.05, p=0.013) and lower pWMV (β = −0.34, 95% CI -7 to -0.05 p = 0.027). Older age and male sex were also independently associated with lower pGMV (p<0.05 for both), but neither was associated with pWMV. Conclusion: Greater cortical amyloid burden is independently associated with reduced cortical gray- and white-matter volume in CAA, even in the absence of cognitive impairment. These findings extend prior observations of CAA-related atrophy by directly linking lower brain volumes to higher vascular amyloid load, supporting the view that vascular amyloid itself contributes to tissue loss in CAA beyond concomitant Alzheimer-related pathology.