Cerebrovascular reactivity to carbon dioxide (CVR-CO2) is impaired in conditions affecting cerebral vasculature. Obesity increases the risk of Alzheimer’s disease (AD). The hippocampus plays a prominent role in cognition and it is one of the earliest brain structures affected during the progression of AD. It remains uncertain how obesity affects cerebral vasculature in AD vulnerable regions. We examined the relationship between body mass index and neocortical and hippocampal vasoreactivity. Our pulsed ASL sequence combined a flow-sensitive alternating inversion-recovery labeling scheme with balanced steady-state free precession to optimize spatial resolution and lower sensitivity to susceptibility artifacts. Cerebral blood flow (CBF) measurements were done during rest and rebreathing challenge designed to increased CO2 level. In obese women (BMI≥30, n=36) hippocampal vasoreactivity was 80% lower than in their non-obese peers. No relationship was observed in men or with respect to cortical vasoreactivity.
Cerebrovascular reactivity to carbon dioxide (CVR-CO2) can be considered a measure of vascular health and it is impaired in conditions affecting cerebral vasculature 1,2. Vascular risk factors in general and obesity in particular increase the risk of neurodegenerative diseases like Alzheimer’s disease (AD) 3. The hippocampus plays a prominent role in cognition and it is one of the earliest brain structures affected during the progression of AD 4. However it remains uncertain how obesity affects cerebral vasculature in AD vulnerable regions. We investigated the effects of obesity on hippocampal and cortical vasoreactivity in a group of cognitively healthy adult and elderly.
Study subjects. Two hundred sixty two men (n=101) and woman (n=161). Mean age of the whole group was 69.3 ± 6.8 years, education 16.9 ± 2.3 years. All underwent medical (including body mass index (BMI)) and cognitive examination.
Arterial spin labeling. We used a pulsed ASL sequence combining a flow-sensitive alternating inversion-recovery labeling scheme with balanced steady-state free precession (bSSFP) readout 5,6. The bSSFP readout was chosen in preference to echo planar imaging because of its higher spatial resolution and lower sensitivity to susceptibility artifacts. To optimize hippocampal sampling, perfusion data were acquired using one oblique slice passing through the left and right hippocampus and middle temporal gyrus.
Cerebral blood flow (CBF) sampling. Hippocampal and cortical regions of interest (ROI) were defined directly on high-resolution ASL images (to minimize partial volume errors), using an in-house-developed software (https://wp.nyu.edu/firevoxel/). Cortical ROI was defined on the same slice as hippocampal ROIs and encompassed temporal, parietal and in some cases also occipital cortex.
Vasoreactivity. To estimate CVR-CO2 CO2 level was increased using a re-breathing protocol 7,8. Subjects were asked to breathe through a mouthpiece and a respiratory tube. The rebreathing apparatus included a HEPA bacterial/viral filter and a standard gas-anesthesia tube of 35 mm diameter and a custom-adjusted length. Nose was clamped to force inspiration of partially exhaled air. Oxygen saturation, heart rate and CO2 content in the expired air were monitored during image acquisition using Medrad Veris system. The CVR-CO2 response to an increase in blood CO2 was calculated as:
CVR-CO2= ((CBFCO2 -CBFrest) / CBFrest)*100) / ΔCO2.
where: CBFCO2 indicates CBF calculated during the session when subjects breathed through a respiratory tube, CBFrest indicates CBF calculated during the imaging session without the tube; ΔCO2 indicates the difference in end tidal CO2 between the two sessions.
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