Abstract
We tested the claim that inter-individual CBF variability in Alzheimer’s disease (AD) is substantially reduced after correction for arterial carbon dioxide tension (PaCO2). Specifically, we tested whether the variability of CBF in brain of patients with AD differed significantly from brain of age-matched healthy control subjects (HC). To eliminate the CO2-induced variability, we developed a novel and generally applicable approach to the correction of CBF for changes of PaCO2 and applied the method to positron emission tomographic (PET) measures of CBF in AD and HC groups of subjects. After correction for the differences of CO2 tension, the patients with AD lost the inter-individual CBF variability that continued to characterize the HC subjects. The difference (ΔK1) between the blood-brain clearances (K1) of water (the current measure of CBF) and oxygen (the current measure of oxygen clearance) was reduced globally in AD and particularly in the parietal, occipital, and temporal lobes. We then showed that oxygen gradients calculated for brain tissue were similar in AD and HC, indicating that the low residual variability of CBF in AD may be due to low functional demands for oxidative metabolism of brain tissue rather than impaired delivery of oxygen.
Highlights
DELIVERY OF OXYGEN AFTER LOSS OF VARIABILITY To understand how the loss of Cerebral blood flow (CBF) variability related to functional demands in the Alzheimer’s disease (AD) patients, we tested whether the dependence of oxygen consumption on oxygen delivery to the brain ( K 1) was affected in brain of the patients with AD
GENERAL CO2 CORRECTION METHOD The method presented here is a practical approach to the correction of CBF data for changes of PaCO2 that relates individual measures to the normocapnic mean for an individual or a group
In studies analyzed by general linear model (GLM) statistics, PaCO2 variation can be factored out as a covariate, but the procedure considers only the influence on the statistics, not the magnitude of the corrected flow
Summary
Cerebral blood flow (CBF) measures vary greatly among healthy individuals at rest (Ito et al, 2004; Aanerud et al, 2012) Some of this inter-individual variability may arise from intra-individual temporal fluctuations in CBF regulation, such as arterial CO2 tension changes or varying functional demands within each subject. The method as presented has broad applicability to CBF measurements, regardless of modality, including non-invasive measures of CO2 (for example with a finger monitor) We used this novel approach to determine how much of the CBF variability remained after the reactivity due to variations of PaCO2 was eliminated in a group of healthy individuals and a group of patients with AD. DELIVERY OF OXYGEN AFTER LOSS OF VARIABILITY To understand how the loss of CBF variability related to functional demands in the AD patients, we tested whether the dependence of oxygen consumption on oxygen delivery to the brain ( K 1) was affected in brain of the patients with AD
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