Impaired visual evoked flow velocity response in cerebral amyloid angiopathy

Abstract

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.

Figure 1 Examples of evoked flow velocity changes in the PCA and MCA of a 77-year-old control subject (A) and a 73-year-old subject with CAA (B) A 10-Hz flashing checkerboard stimulus was viewed during the “on” period. The curves represent an average of ten 40-second epochs. The peak increase from baseline in the PCA (PCA peak response), determined after smoothing using a triangular window, was 20% in the control subject and 14% in the CAA subject. PCA = posterior cerebral artery; MCA = middle cerebral artery; CAA = cerebral amyloid angiopathy.

Figure 2 Peak PCA evoked flow velocity response to the visual stimulation task is reduced in CAA (8.0 ± 6.1%) compared to similar-aged controls (17.4 ± 5.7%) Bars indicate group means. Filled circles represent sporadic cerebral amyloid angiopathy (CAA) or control posterior cerebral artery (PCA) response. The X shows the PCA peak response from a single 42-year-old stroke-free man with hereditary CAA; this subject’s data are not included in the calculation of the sporadic CAA group mean or significance testing.

Figure 3 Posterior cerebral artery (PCA) pulsatility index is higher in those with lower PCA evoked flow velocity response to the visual stimulation task

Figure 4 PCA evoked flow velocity response to the visual stimulation task is lower in those with more MRI hemorrhages (A) and higher nWMH volume (B) Because of right-skewed distributions, the number of MRI hemorrhages and nWMH volume are plotted on a logarithmic scale and statistical testing is by Spearman correlation coefficient. PCA = posterior cerebral artery; nWMH = MRI white matter hyperintensity volume normalized to average subject head size.