Functional magnetic resonance imaging detection of vascular reactivity in cerebral amyloid angiopathy

Abstract

Objective In addition to its role in hemorrhagic stroke, advanced cerebral amyloid angiopathy (CAA) is also associated with ischemic lesions and vascular cognitive impairment. We used functional MRI techniques to identify CAA-associated vascular dysfunction. Methods Functional MRI was performed on 25 nondemented subjects with probable CAA (mean ± standard deviation age 70.2±7.8) and 12 healthy elderly controls (age 75.3±6.2). Parameters measured were reactivity to visual stimulation (quantified as blood oxygen level-dependent [BOLD] response amplitude, time to peak response, and time to return to baseline after stimulus cessation) and resting absolute cerebral blood flow in the visually activated region (measured by arterial spin labeling). Results CAA subjects demonstrated reduced response amplitude (percent change in BOLD signal 0.65±0.28 vs 0.89±0.14, p<0.01), prolonged time to peak (11.1±5.1 vs 6.4±1.8 sec, p<0.001) and prolonged time to baseline (16.5±6.7 vs 11.6±3.1 sec, p<0.001) relative to controls. These differences were independent of age, sex, and hypertension in multivariable analysis and were also present in secondary analyses excluding nonresponsive voxels or voxels containing chronic blood products. Within the CAA group, longer time to peak correlated with overall volume of white matter T2 hyperintensity (Pearson correlation 0.53, p=0.007). Absolute resting blood flow in visual cortex, in contrast, was essentially identical between the groups (44.0±12.6 vs 45.0±10.0 ml/100g/min, p=0.8). Interpretation Functional MRI identifies robust differences in both amplitude and timing of the response to visual stimulation in advanced CAA. These findings point to potentially powerful approaches for identifying the mechanistic links between vascular amyloid deposits, vascular dysfunction, and CAA-related brain injury.

Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy

“…0.30 for all comparisons). DISCUSSION Our data confirm 2 previous pilot studies suggesting decreased brain task-related blood flow reactivity in CAA, 3,4 and provide new evidence to suggest that the physiologic basis of the reduced signal is impaired vasodilation, not decreased metabolic activity. Additionally, our data are the first to suggest there is a gradient of increasingly impaired vasodilation from anterior (frontal) to posterior (occipital) brain regions that matches the known distribution of vascular amyloid deposition in CAA as identified pathologically 17 and on PET amyloid imaging.…”

“…To further ensure that we studied patients without significant occipital lobe neuronal dysfunction, we excluded patients with hemorrhages in the occipital pole, visual field defects, or poor visual acuity, and observed patients during the experiment to ensure that they attended well to the task. Two previous studies have found decreased occipital visual taskrelated blood flow responses in CAA and suggested they were caused by decreased vascular reactivity 3,4 ; however, the present study is the first to directly show neurovascular decoupling in patients with CAA.…”

“…PET amyloid imaging was not done in the present study; future studies should investigate whether regions of impaired vascular reactivity correlate with regions of increased amyloid deposition. We analyzed the amplitude of the BOLD fMRI response as our prespecified outcome; however, there is evidence that time to peak response is prolonged in CAA, 4 and additional studies are needed to fully characterize the nature of abnormal blood flow responses in CAA, including which features best differentiate CAA from controls and which are most sensitive to change over time.…”

“…3 Finally, a recent study showed reduced functional MRI (fMRI) activation in CAA with a smaller amplitude and longer time to peak of the blood oxygen level-dependent (BOLD) signal in response to a visual stimulation task. 4 We hypothesized that patients with CAA would exhibit impaired vasodilation in posterior brain arteries leading to reduced CO 2 reactivity and lower blood flow responses to occipital lobe metabolic activity with preserved visual evoked potentials (VEPs). These hypotheses were tested in a prospective crosssectional study of patients with CAA and matched controls.…”

Ischemic brain injury in cerebral amyloid angiopathy

“…longer BOLD time to peak in patients were related to greater WMH volume, independent of age, sex, and hypertension, [88][89][90] providing a possible mechanism for subcortical ischemic injury. The authors hypothesize that impaired vasoreactivity in CAA might cause a mismatch between perfusion and metabolic demand, thereby inducing ischemic damage.…”