The impact of bariatric surgery on cerebral vascular reactivity

Obesity is associated with cognitive dysfunction, and is a primary precursor for several life threatening diseases, including Alzheimer's disease, dementia, and stroke. The exact mechanism responsible for these aforementioned conditions remains incompletely understood; however, given the mounting evidence of peripheral vascular dysfunction, we hypothesize that the dynamic dilation capacity of the cerebral vasculature in response to a challenge like CO 2 inhalation is an important contributor. Bariatric surgery is an effective long‐term weight loss strategy, with dramatic improvements in hyperlipidemia and diabetes. Remarkably, these favorable improvements also translate into meaningful clinical outcomes, including improvements in neurocognitive function, Alzheimer's disease risk, and stroke events. That bariatric surgery is also associated with favorable improvements in peripheral vascular function (i.e. flow‐mediated dilation) further supports the hypothesis that improvement in neurocognitive function is vascular in origin. To test this hypothesis, we evaluated middle cerebral artery (MCA) dilation in response to a hypercapnic challenge (5% CO 2 , 21% O 2 , N 2 balance) using magnetic resonance imaging (MRI). To establish our technique, we first assessed the change in MCA cross‐sectional area (CSA) during hypercapnia in young, healthy normal weight adults (n=7, age 24 ± 5 years, BMI 23.1 ± 1.9 kg/m 2 ). Then, to assess the effects of obesity on cerebral vascular reactivity, we compared the change in MCA CSA in normal weight, age‐matched middle‐aged adults (n=10, age: 48 ± 6 years, BMI: 22.8 ± 1.9 kg/m 2 ) and obese bariatric surgery candidates (n=5, age: 51 ± 10 years, BMI: 43.0 ± 3.1 kg/m 2 ). Lastly, to assess the effects of bariatric surgery, we examined the change in MCA CSA at 2 weeks and 12 weeks after sleeve gastrectomy (obese subjects). As expected, the hypercapnic challenge caused a significant increase in end‐tidal CO 2 , respiration rate and heart rate (P ET CO 2 : 42 ± 4 to 50 ± 2 mmHg; RR: 9 ± 3 to 12 ± 4 breaths/min, HR: 59 ± 13 to 62 ± 12 bpm, p<0.001) across all individuals (pooled data) with no differential responses between groups (p>0.5). In young adults, MCA CSA increased significantly with hypercapnic challenge (6.0 ± 1.1 to 6.7 ± 1.0 mm 2 , p = 0.019). In contrast, MCA CSA failed to increase significantly (6.8 ± 1.4 to 7.0 ± 1.4 mm, p=0.46) in middle‐aged adults, demonstrating an age‐dependent response. Remarkably, in obese subjects, MCA CSA decreased from 6.9 ± 0.7 to 6.7 ± 1.2 mm 2 (p=0.66) during hypercapnia, with 3 out of 5 subjects exhibiting vasoconstriction. Following bariatric surgery, MCA CSA increased significantly with hypercapnia at 2 weeks (+0.7 ± 0.4 mm 2 ; +11.7 ± 3.2 %; p=0.04; all 5 subjects exhibited dilation to CO 2 inhalation) and remained above pre‐surgery values at 12 weeks (+0.3 ± 0.5 mm 2 ; + 4.3 ± 3.0 %; p=0.31). We interpret these data to support the hypothesis that obesity impairs cerebral vascular reactivity, and improvements in neurovascular function following bariatric surgery may be mediated, at least in part, through improvements in cerebral vascular function. Support or Funding Information This research was funded by UTSW Center for Translational Medicine Grant 5UL1TR001105. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .