Neurological Impact of Weight Reduction and Fitness Interventions

This study will test how significant weight loss through bariatric surgery, combined with a personalised exercise program, affects brain inflammation. Th investigators want to understand the connection between obesity-related body inflammation, metabolic issues, and brain inflammation and function.

This randomised controlled trial aims to evaluate the effects of marked weight loss, via bariatric surgery, combined with a personalised exercise intervention on markers of brain inflammation. This study will allow the investigators to explore the link between excessive adiposity-induced systemic chronic inflammation, metabolic abnormalities, and neuroinflammation. The investigators hypothesise that bariatric surgery, i.e., marked weight loss, and exercise will result in attenuated neuroinflammation (as measured by neuroimaging), improvements in cognitive function, improvements in immune-inflammatory markers, and improvements in cardiometabolic biomarkers at 12 months compared to control. This study is a parallel group, randomised controlled trial. A 1:1 allocation ratio will be applied to either the intervention group (bariatric surgery and usual care with exercise) or control group (bariatric surgery and usual care). Participants in both arms will be followed over a period of 12 months after surgery. A comprehensive set of evaluations will be performed prior to the surgery, with follow-up in-person evaluations at 6 weeks and 3, 4.5, 6, and 12 months. The primary objective is to evaluate the effect of bariatric surgery and exercise on neuroinflammation compared to control at 12-months. This will be assessed via a novel neuroimaging technique. Secondary and exploratory objectives are to evaluate the effect of bariatric surgery and exercise on brain structure, cognition, immune-inflammatory markers, cardiometabolic markers, psychosocial factors, diet, and physical functioning compared to control. The investigators would also like to explore within-group differences for all the above from baseline to 12-months.

Inclusion Criteria: * 18-80 years of age. * Eligible for bariatric surgery. * Willingness to provide informed consent and willingness to participate and comply with the study requirements Exclusion Criteria: * Unable to undertake MRI due to size restrictions i.e., shoulder width more than 70 cm. * History or clinical manifestation of any other significant metabolic, hematologic, pulmonary, cardio- vascular, gastrointestinal, neurologic, immune, hepatic, renal, urologic, muscular, and joint disorders, or cancer that, in the opinion of the investigator, would make the candidate ineligible for the study. For example, significant joint pain could interfere with adherence to the exercise program. * Have objectively assessed cognitive impairment as assessed by the Montreal Cognitive Assessment (MoCA) i.e., total score less than 26. * Non-MRI-compatible implanted devices or implants. * Inability to exercise via supine ergometer. * Claustrophobia. * Psychiatric or behavioural problems (history of drug and alcohol abuse, eating disorder). * Breastfeeding or pregnant women, or those intending to become pregnant before the scheduled end of the intervention. * Unwilling to be assigned at random to the exercise or control intervention. * Unwilling or unable to adhere to the rigors of the exercise intervention or evaluation schedule over the entire one-year period. * Concurrent participation in any other interventional study.