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BARICO: Bariatric surgery leads to cognitive improvement in approximately 40% of participants

In a study including 133 adults with severe obesity who underwent bariatric surgery, cognitive function, inflammatory biomarkers, comorbidities, physical activity, and depressive symptoms were still improved two years after bariatric surgery, researchers from the Netherlands report. The cohort study included participants from the Bariatric Surgery Rijnstate and Radboudumc Neuroimaging and Cognition in Obesity (BARICO) study.



The investigators explained that obesity is inversely associated with gray matter (GM) volume and white matter (WM) integrity and positively associated with WM hyperintensities (WMH). These brain changes might be induced by reduced cerebral blood flow (CBF), which often coincides with obesity. Cognitive functions, particularly domains of executive function, attention and episodic and working memory, are associated with obesity, corresponding to changes in hippocampus and prefrontal regions.


Previous studies have shown bariatric surgery induced weight loss is associated with improved brain function and structure. However, the authors stated that the results are “contradictory, underlying mechanisms remain largely unknown, and it is uncertain whether outcomes are long-lasting.” It has also being hypothesised that the imbalance of adipokines and proinflammatory cytokines may be involved, as they impair CBF and therewith cause neurodegeneration, which may be reversible after bariatric surgery.


Cognition was assessed at baseline and six and 24 months after surgery using neuropsychological tests. MRI scans were obtained at baseline and 24 months after BS. At all time points, blood samples and anthropometric data (body weight, waist circumference (WC), BMI, and percentage total body weight loss (TBWL)) were collected. Only participants who completed measurements at all time points were included. Blood pressure was measured in sitting position, with fasting blood samples collected at all time points.


To examine the association of surgery with cognition, the researchers calculated the 20% change index (assuming that participants show clinically meaningful and significant cognitive improvement if their postoperative test score is 20% higher than the preoperative test score) 24 months after surgery.


Outcomes

Overall, mean body weight, BMI, WC, ad blood pressure were significantly lower six and 24 months after surgery. From six to 24 months, percentage TBWL was significantly higher. Compared with baseline, medication use for comorbidities was significantly lower 24 months after surgery (eg. antihypertensive use, 48 patients (36.1%) vs 22 patients (16.7%).


Several cognitive domains significantly improved at six and 24 months after surgery, the baseline cohort had a median (IQR) MOCA score of 27 (26.0-29.0). Based on the 20% change index, 15 participants (11.3%) showed improvements in working memory, 42 participants (31.6%) showed improvements in episodic memory, 32 participants (24.1%) showed improvements in in verbal fluency, 51 participants (40.2%) showed improvements in ability to shift attention and 52 participants (42.9%) showed improvements in global cognition.


According to the BDI score at baseline, 71 participants (54.6%) experienced minimal depressive symptoms, 55 participants (42.3%) experienced mild depressive symptoms and four participants (3.1%) experienced moderate depressive symptoms. At 24 months after BS, 12 participants (9.4%) had mild depressive symptoms and two participants (1.6%) had moderate depressive symptoms. Additionally, the Baecke score was significantly higher six months after surgery and remained stable up to 24 months (mean [SD] Baecke score: baseline, 7.64 [1.29]; six months, 8.36 [1.23]; 24 months, 8.19 [1.35]; p<0.001).


Brain changes were observed after BS (Table 3). GM volume, GM cortical thickness, and GM CBF were significantly lower 2 years after BS. Several other ROIs, including amygdala, caudate nucleus, putamen, insula, cingulate gyrus, and occipital, parietal, and temporal cortex exhibited significantly lower volumes after BS. No volumetric changes were observed in hippocampus, nucleus accumbens, frontal cortex, or WM. Cortical thickness of all ROIs was significantly lower after BS, except thickness of the temporal cortex, which was significantly larger (mean [SD] thickness: 2.724 [0.101] mm vs 2.761 [0.007] mm; P = .007). Moreover, after BS, CBF was lower in several cortical and subcortical regions, including caudate nucleus, putamen, insula, and frontal and occipital cortex. CBF in temporal cortex, parietal cortex, and nucleus accumbens did not change after BS.


Regarding sCOV, the caudate nucleus showed a higher sCOV, while temporal cortex showed lower sCOV after BS (median [IQR] sCOV: 4.41% [3.83%-5.18%] vs 3.97% [3.71%-4.59%]; P = .02). sCOV of all other ROIs remained stable over time. MSMD was significantly lower, whereas WMH volume did not change after BS.


Circulating markers were analysed before and after surgery and after six months, high-sensitivity C-reactive protein (hs-CRP), leptin, serum amyloid A, tumour necrosis factor–α, interleukin-1β (IL-1β), IL-6, and plasminogen activator inhibitor-1 were significantly lower, whereas adiponectin and neurofilament light chain (NFL) were significantly higher compared with baseline. hs-CRP and IL-6 were still lower at 24 months (eg, mean [SD] hs-CRP: baseline, 4.77 [5.80] μg/mL vs 0.80 [1.09] μg/mL; p<0.001), while leptin, serum amyloid A, and tumour necrosis factor–α did not change at 24 months compared with six months after surgery.


They also reported that plasminogen activator inhibitor-1 returned to baseline levels by 24 months after surgery. IL-1β was higher 24 months after surgery vs. six-month follow-up but remained significantly lower compared with baseline. At 24 months after BS, adiponectin was higher, while NFL remained stable compared with the six-month follow-up. brain-derived neurotrophic factor (BDNF) was significantly higher at 24 months after surgery.


“Altogether, these results provide new information on longer-term outcomes associated with bariatric surgery-induced weight loss in cognition and brain structure and perfusion, although exact underlying mechanisms remain unsolved,” the study authors write. “Future studies should include control groups and other mechanisms to clarify cognition and brain changes after bariatric surgery. Such studies can contribute to development of strategies to reduce risk of obesity and neurodegenerative diseases.”


The findings were published in the paper, ‘Long-Term Brain Structure and Cognition Following Bariatric Surgery’, published in JAMA Network Open. To access this paper, please click here

 

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