Cerebrovascular reactivity in cerebral amyloid angiopathy, Alzheimer disease, and mild cognitive impairment

Abstract

Objective: To assess cerebrovascular reactivity in response to a visual task in participants with cerebral amyloid angiopathy (CAA), Alzheimer disease (AD), and mild cognitive impairment (MCI) using fMRI.

Methods: This prospective cohort study included 40 patients with CAA, 22 with AD, 27 with MCI, and 25 healthy controls. Each participant underwent a visual fMRI task using a contrast-reversing checkerboard stimulus. Visual evoked potentials (VEPs) were used to compare visual cortex neuronal activity in 83 participants. General linear models using least-squares means, adjusted for multiple comparisons with the Tukey test, were used to estimate mean blood oxygen level-dependent (BOLD) signal change during the task and VEP differences between groups.

Results: After adjustment for age and hypertension, estimated mean BOLD response amplitude was as follows: CAA 1.88% (95% confidence interval [CI] 1.60%-2.15%), AD 2.26% (1.91%-2.61%), MCI 2.15% (1.84%-2.46%), and control 2.65% (2.29%-3.00%). Only patients with CAA differed from controls (p = 0.01). In the subset with VEPs, group was not associated with prolonged latencies or lower amplitudes. Lower BOLD amplitude response was associated with higher white matter hyperintensity (WMH) volumes in CAA (for each 0.1% lower BOLD response amplitude, the WMH volume was 9.2% higher, 95% CI 6.0%-12.4%) but not other groups (p = 0.002 for interaction) when controlling for age and hypertension.

Conclusions: Mean visual BOLD response amplitude was lowest in participants with CAA compared to controls, without differences in VEP latencies and amplitudes. This suggests that the impaired visual BOLD response is due to reduced vascular reactivity in CAA. In contrast to participants with CAA, the visual BOLD response amplitude did not differ between those with AD or MCI and controls.

Figure 1. BOLD signal change across all groups

Blood oxygen level–dependent (BOLD) signal change in the 200 most active voxels in response to a visual stimulus was 29% lower in participants with cerebral amyloid angiopathy (CAA) compared to healthy controls after adjustment for age and hypertension (p = 0.01). There were no differences between participants with mild cognitive impairment (MCI) (p = 0.17) or Alzheimer disease (AD) (p = 0.39) and healthy controls. Error bars represent SD.

Figure 2. BOLD activation across all groups

Voxel-wise comparisons of blood oxygen level–dependent (BOLD) activation between patients with (A) cerebral amyloid angiopathy (CAA), (B) Alzheimer disease (AD), or (C) mild cognitive impairment (MCI) compared to healthy controls. The greatest volume of impaired visual cortex activation compared to healthy controls was in CAA, followed by AD and then MCI. Models were adjusted for age and hypertension. Significance was determined by a z statistic >2.3 (p < 0.05) and was cluster corrected for multiple comparisons.

Figure 3. Association of visual BOLD response amplitude with WMH volume

Estimated percent increase in white matter hyperintensities (WMH) per 0.1% decrease in visual blood oxygen level–dependent (BOLD) response is graphed for each group. The association between visual BOLD response amplitude and WMH volume varied by group (interaction p = 0.002). AD = Alzheimer disease; CAA = cerebral amyloid angiopathy; CI = confidence interval; MCI = mild cognitive impairment.