Effects of bariatric surgery on brain glucose metabolism and cognitive function: insight from dynamic FDG PET/CT study

Aim/Introduction: We aimed to evaluate the impact of bariatric surgery (RYGB) on the brain glucose metabolism and the interplay between gut hormones/metabolomics, cerebral metabolic rate of glucose (CMRGlu) and cognitive function. Materials and Methods: Thirteen morbidly obese subjects with normal glucose tolerance (BMI 46±4.9 kg/m2; HbA1c 40.1±5.9 mmol/mol; age 42.4±9.8 years) planned for RYGB surgery were recruited. Theoral glucose tolerance test (OGTT) was performed, followed by 60 minutes FDG dynamic PET study.Continuous blood samples were drawn before and at 30, 60, 90, and 120 min for glucose, insulin, GLP, VIP, GIP and C-peptide measurements. The same venous blood samples were used for calculating radioactivity concentration in plasma. Fasting blood samples for metabolomics (leptin, brain derived neurotrophic factor, BDNF) were also collected and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as an index of insulin resistance. The influx constant (Ki) and MRGlu were then quantified using the two tissue compartment Patlak approach with an imaged-derived input function (PMOD). Subsequently, the parametric CMRGlu images were created and spatially normalized in MNI space. The paired t-test and Spearman rank correlation were applied to assess changes and associations of voxel-wise CMRGlu and metabolomics. All patients underwent a battery of neuropsychiatric tests (MMSE, MoCA, Token test, TMT, etc) to assess cognitive function in several domains, before and 6 months after RYGB. Results: Six months after RYGB a significant BMI reduction (p<0.001) was achieved. Post-OGTT GLP1 was increased (p<0.01) as well as GIP (p<0.01). The HOMA- IR dropped significantly 6m after RYGB (p=0.02). Either whole brain and region-selective CMRGlu decreased 6m after surgery (15.9±4.6 to 10.5±5.1 μmol/min/100ml; p<0.01). Voxel-wise paired analysis displayed clusters of decreased CMRGlu 6m after RYGB in the widespread brain regions. In addition, we found a significant positive relationship between CMRGlu and HOMA-IR. All patients at baseline presented MMSE and MoCA scores in the normal range. However, 6 months after RYGB, the cognitive domains examined showed a trend of global improvement. MMSE score increased statistically significantly (p 0.002) as well as MoCA score (p <0.005). Conclusion: After bariatric surgery, there are several modifications of multiple factors that play a role in the so-called “intestinal-brain cross-talk”, in CMRGluand in cognitive function. CMRGluof morbidly obese subjects is abnormally enhanced in response to insulin. Bariatric surgery seems to reverse this insulin-mediated signal dysfunction and could produce significant CNS effects decreasing brain glucose over-consumption and promoting potential neuroprotective effect