The role of vascular reactivity in Alzheimer’s disease and its link with cognition

Vascular damage, like cerebral amyloid angiopathy (CAA), is a comorbidity in the majority of Alzheimer’s disease (AD) patients. Vascular reactivity has been introduced as a novel marker for vascular damage in CAA. It is measured as the blood oxygen level dependent (BOLD) response in the visual cortex after visual stimulation. It may detect underlying vascular factors early in the disease, like in patients with subjective (SCI) or mild cognitive impairment (MCI). In these stages, SCI patients start to experience subjective cognitive complaints, whereas these can be objectified in MCI patients. The aim of this study is to measure and compare vascular reactivity in memory clinic patients and controls, and explore its association with cognition. We performed 3T MRI in 43 controls, 17 SCI, 20 MCI, and 12 AD patients and obtained 3D T1-weighted images, FLAIR, and visually stimulated BOLD fMRI scans. The main independent variable was patient group. Dependent variables were three vascular...Show moreVascular damage, like cerebral amyloid angiopathy (CAA), is a comorbidity in the majority of Alzheimer’s disease (AD) patients. Vascular reactivity has been introduced as a novel marker for vascular damage in CAA. It is measured as the blood oxygen level dependent (BOLD) response in the visual cortex after visual stimulation. It may detect underlying vascular factors early in the disease, like in patients with subjective (SCI) or mild cognitive impairment (MCI). In these stages, SCI patients start to experience subjective cognitive complaints, whereas these can be objectified in MCI patients. The aim of this study is to measure and compare vascular reactivity in memory clinic patients and controls, and explore its association with cognition. We performed 3T MRI in 43 controls, 17 SCI, 20 MCI, and 12 AD patients and obtained 3D T1-weighted images, FLAIR, and visually stimulated BOLD fMRI scans. The main independent variable was patient group. Dependent variables were three vascular reactivity parameters time-to-peak, time-to-baseline, and amplitude of the BOLD response. Univariate linear models were performed to comparedifferences in vascular reactivity between memory clinic patients and controls, and separate patient groups and controls. Linear regression analyses were performed to explore the association between vascular reactivity and cognition. All analyses were corrected for age, gender, gray matter volume, white matter hyperintensities, and CAA. BOLD amplitudes were smaller in dementia and MCI (ps < .001), but not SCI patients (p = .77).Time-to-peak and time-to-baseline showed no differences between groups (ps > .07). Lower amplitude of the BOLD response was associated with poorer performance of global cognitive, memory, executive, and language functioning (ps < .04). Our findings demonstrate that dementia and MCI are associated with lower vascular reactivity, reflected as amplitude of the BOLD response. In our sample, lower vascular reactivity is also associated with poorer cognitive functioning. These results indicate that impaired vascular reactivity plays a key role early in dementia and is an independent contributor to cognitive decline. Potentially, vascular reactivity could be used as a marker for amyloid-beta and as an alternative way to quantify vascular damage. Ultimately, it could aid in the development of interventions focused on amyloid-beta removal and could serve as a marker for disease progression.Show less

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The role of vascular reactivity in Alzheimer’s disease and its link with cognition