Cerebrovascular Reactivity Across the Entire Brain in Cerebral Amyloid Angiopathy

Background and Objectives Reduced cerebrovascular reactivity is proposed to be a feature of cerebral amyloid angiopathy (CAA) but has not been measured directly. Employing a global vasodilatory stimulus (hypercapnia), this study assessed the relationships between cerebrovascular reactivity and MRI markers of CAA and cognitive function. Methods In a cross-sectional study, individuals with probable CAA, mild cognitive impairment, or dementia due to Alzheimer disease and healthy controls underwent neuropsychological testing and an MRI that included a 5% carbon dioxide challenge. Cerebrovascular reactivity was compared across groups controlling for age, sex, and the presence of hypertension, and its associations with MRI markers of CAA in participants with CAA and with cognition across all participants were determined using multivariable linear regression adjusting for group, age, sex, education, and the presence of hypertension. Results Cerebrovascular reactivity data (mean +/- SD) were available for 26 participants with CAA (9 female; 74.4 +/- 7.7 years), 19 participants with mild cognitive impairment (5 female; 72.1 +/- 8.5 years), 12 participants with dementia due to Alzheimer disease (4 female; 69.4 +/- 6.6 years), and 39 healthy controls (30 female; 68.8 +/- 5.4 years). Gray and whiter matter reactivity averaged across the entire brain was lower in participants with CAA and Alzheimer disease dementia compared to healthy controls, with a predominantly posterior distribution of lower reactivity in both groups. Higher white matter hyperintensity volume was associated with lower white matter reactivity (standardized coefficient [beta], 95% CI -0.48, -0.90 to -0.01). Higher gray matter reactivity was associated with better global cognitive function (beta 0.19, 0.03-0.36), memory (beta 0.21, 0.07-0.36), executive function (beta 0.20, 0.02-0.39), and processing speed (beta 0.27, 0.10-0.45) and higher white matter reactivity was associated with higher memory (beta 0.22, 0.08-0.36) and processing speed (beta 0.23, 0.06-0.40). Conclusions Reduced cerebrovascular reactivity is a core feature of CAA and its assessment may provide an additional biomarker for disease severity and cognitive impairment.