Impaired visual evoked flow velocity response in cerebral amyloid angiopathy

Objective: Animal models of cerebral amyloid angiopathy (CAA) exhibit abnormal vascular reactivity. We determined whether vascular reactivity, measured by transcranial Doppler ultrasound (TCD), is reduced in humans with CAA. Methods: Cases were recruited from an established prospective study of CAA. Healthy controls were recruited from a study of normal aging. Evoked mean flow velocity increase in the posterior cerebral artery (PCA) was measured while subjects viewed a flashing alternating checkerboard stimulus. In a separate but partially overlapping cohort we measured the mean flow velocity increase in the middle cerebral artery (MCA) while subjects inhaled carbon dioxide. Results: The visual evoked mean flow velocity increase was 8.0 ± 6.1% in CAA (n = 11) compared to 17.4 ± 5.7% in controls (n = 9, p = 0.002). The PCA pulsatility index, a marker of distal vascular resistance, was higher in CAA (CAA 1.35 ± 0.35, control 1.04 ± 0.14, p = 0.03). Among CAA subjects, lower visual evoked mean flow velocity increase was associated with a higher number of hemorrhages seen on MRI (r = −0.87, p = 0.0005) and higher MRI white matter hyperintensity volume (r = −0.67, p = 0.02). The MCA response to carbon dioxide did not differ between CAA and control in 20 subjects (9 CAA, 11 control, p = 0.54). Conclusions: Cerebral amyloid angiopathy (CAA) was associated with decreased vascular reactivity in response to visual stimulation, possibly reflecting the occipital predilection of the disease. The association of posterior cerebral artery (PCA) evoked flow velocity response with elevated PCA pulsatility index and MRI markers of small vessel disease suggests that abnormal PCA evoked flow velocity in CAA is caused by pathology of the distal resistance vessels.