Objectives: We used functional MRI (fMRI), transcranial Doppler ultrasound, and visual evoked potentials (VEPs) to determine the nature of blood flow responses to functional brain activity and carbon dioxide (CO 2 ) inhalation in patients with cerebral amyloid angiopathy (CAA), and their association with markers of CAA severity.Methods: In a cross-sectional prospective cohort study, fMRI, transcranial Doppler ultrasound CO 2 reactivity, and VEP data were compared between 18 patients with probable CAA (by Boston criteria) and 18 healthy controls, matched by sex and age. Functional MRI consisted of a visual task (viewing an alternating checkerboard pattern) and a motor task (tapping the fingers of the dominant hand).Results: Patients with CAA had lower amplitude of the fMRI response in visual cortex compared with controls (p 5 0.01), but not in motor cortex (p 5 0.22). In patients with CAA, lower visual cortex fMRI amplitude correlated with higher white matter lesion volume (r 5 20.66, p 5 0.003) and more microbleeds (r 5 20.78, p , 0.001). VEP P100 amplitudes, however, did not differ between CAA and controls (p 5 0.45). There were trends toward reduced CO 2 reactivity in the middle cerebral artery (p 5 0.10) and posterior cerebral artery (p 5 0.08).Conclusions: Impaired blood flow responses in CAA are more evident using a task to activate the occipital lobe than the frontal lobe, consistent with the gradient of increasing vascular amyloid severity from frontal to occipital lobe seen in pathologic studies. Reduced fMRI responses in CAA are caused, at least partly, by impaired vascular reactivity, and are strongly correlated with other neuroimaging markers of CAA severity. Neurology ® 2013;81:1659-1665 GLOSSARY BOLD 5 blood oxygen level-dependent; CAA 5 cerebral amyloid angiopathy; CO 2 5 carbon dioxide; DEF 5 dynamic end-tidal forcing; DSM-IV 5 Diagnostic and Statistical Manual of Mental Disorders, 4th edition; fMRI 5 functional MRI; ICH 5 intracerebral hemorrhage; PETCO 2 5 partial pressure of end-tidal carbon dioxide; VEP 5 visual evoked potential; WMH 5 white matter hyperintensity.Cerebral amyloid angiopathy (CAA) is best recognized clinically as a cause of frequent recurrent intracerebral hemorrhages (ICHs) and microbleeds, reflecting loss of vascular integrity due to b-amyloid deposition.1 However, accumulating evidence suggests that impaired vascular reactivity is another feature of CAA. In a mouse model of severe CAA, there was decreased vasodilation in response to whisker barrel stimulation and to carbon dioxide (CO 2 ) inhalation, a vasodilatory stimulus.2 In a small study of patients with probable CAA, posterior cerebral artery flow velocity responses were lower than controls when viewing a visual stimulus, but middle cerebral artery flow velocity responses to CO 2 inhalation were relatively preserved.3 It was not clear whether the differential responses observed in the visual and CO 2 experiments were due to the different arteries tested, the different types of vasodilatory stimulus used, or wer...