Abstract
Vascular risk factors (e.g., obesity and hypertension) are associated with cerebral small vessel disease, Alzheimer’s disease (AD) pathology, and dementia. Reduced perfusion may reflect the impaired ability of blood vessels to regulate blood flow in reaction to varying circumstances such as hypercapnia (increased end-tidal partial pressures of CO2). It has been shown that cerebrovascular reactivity (CVR) measured with blood-oxygen-level-dependent (BOLD) MRI is correlated with cognitive performance and alterations of CVR may be an indicator of vascular disfunction leading to cognitive decline. However, the underlying mechanism of CVR alterations in BOLD signal may not be straight-forward because BOLD signal is affected by multiple physiological parameters, such as cerebral blood flow (CBF), cerebral blood volume, and oxygen metabolism. Arterial spin labeling (ASL) MRI quantitatively measures blood flow in the brain providing images of local CBF. Therefore, in this study, we measured CBF and its changes using a dynamic ASL technique during a hypercapnia challenge and tested if CBF or CVR was related to cognitive performance using the Mini-mental state examination (MMSE) score. Seventy-eight participants underwent cognitive testing and MRI including ASL during a hypercapnia challenge with a RespirAct computer-controlled gas blender, targeting 10 mmHg higher end-tidal CO2 level than the baseline while end-tidal O2 level was maintained. Pseudo-continuous ASL (PCASL) was collected during a 2-min baseline and a 2-min hypercapnic period. CVR was obtained by calculating a percent change of CBF per the end-tidal CO2 elevation in mmHg between the baseline and the hypercapnic challenge. Multivariate regression analyses demonstrated that baseline resting CBF has no significant relationship with MMSE, while lower CVR in the whole brain gray matter (β = 0.689, p = 0.005) and white matter (β = 0.578, p = 0.016) are related to lower MMSE score. In addition, region of interest (ROI) based analysis showed positive relationships between MMSE score and CVR in 26 out of 122 gray matter ROIs.
Highlights
Neurodegeneration and cerebrovascular dysfunction in the brain coexist in most cases of dementia
The regression results showed that Cerebral blood flow (CBF) in the gray matter and white matter was not associated with Mini-mental state examination (MMSE) score with (p = 0.787 in gray matter and p = 0.781 in white matter) or without (p = 0.362 in gray matter and p = 0.919 in white matter) adjustments for covariates
Our results showed that Cerebrovascular reactivity (CVR) in both gray matter and white matter of the whole brain was positively associated with cognitive performance among the subjects with an age range of 56–89 years without any significant neurologic diseases that affect cognitive decline other than mild cognitive impairment (MCI)
Summary
Neurodegeneration and cerebrovascular dysfunction in the brain coexist in most cases of dementia. They may interact with one another and can cause cognitive decline (Silvestrini et al, 2006; Kapasi et al, 2017). In the case of dynamic functional change, CBF change can be evoked for various causes such as brain activations and vasoactive challenges; it returns to its steady state baseline by cerebral auto-regulation to maintain proper brain perfusion. Cerebrovascular reactivity (CVR) may explain the connection between cognitive function and brain vascular health since CVR is an indicator of the compensatory dilatory capacity of blood flow in the brain in response to vasoactive stimuli or vasoactive challenges. CVR may be a more sensitive brain perfusion parameter compared to baseline CBF
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