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AMOS2: Surgery does not improve executive function or memory in adolescents vs. intensive non-surgical treatment

Updated: Mar 8

Bariatric surgery, which was associated with significant weight loss, was overall no more effective than intensive non-surgical treatment, without weight loss, in improving executive function or memory in adolescents over two years, according to the outcomes of the Adolescent Morbid Obesity Surgery 2 (AMOS2) multicentre, open-label, randomised controlled trial by researchers from Sweden. The authors believe this is the first randomised data on cognitive functions and bariatric surgery. Importantly, they reported the operated adolescents had significantly greater improvement in some fundamental cognitive skills, which needs to be confirmed in future studies with larger samples.


The researchers explained that very few studies have assessed cognitive functioning and outcomes in adolescents undergoing bariatric surgery. The AMOS2 study is a randomised open-label multicentre trial assessing outcomes in adolescents with severe obesity after bariatric surgery (predominantly Roux-en-Y gastric bypass [RYGB]) and intensive non-surgical treatment with an initial eight-week low calorie diet.


Cognitive functioning was assessed with validated tests frequently used in clinical assessment at the same day as the inclusion in AMOS2 or on a day just before inclusion. For some participants the baseline assessment was done on two different days due to the high response burden in the study. The cognitive assessment was repeated at the follow-up encounters one and two years after inclusion.


For assessment of general cognitive functioning, four subtests (Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed;) from the Wechsler Intelligence Scale for Children—Fourth Edition (WISC-IV) or Wechsler Adult Intelligence Scale—Fourth Edition (WAIS-IV) were used to assess an estimated full intelligence quotient (IQ). The four subtests represent a core test from each primary index in WISC-IV and WAIS-IV.


Executive functioning was assessed with three subtests from Delis-Kaplan Executive Function System (D-KEFS), part of a subtest from NEPSY-II (A Developmental NEuroPSYchological Assessment), and one subtest from WISC-Integrated, see Table 1 for a detailed description of the subtests.


Outcomes

The researchers report the changes in cognitive functioning (verbal memory, executive functioning, fundamental cognitive skills, and estimated IQ) over two years, which were prespecified exploratory endpoints in the AMOS2-trial.


Out of 50 participants included in AMOS2, 46 (92%) adolescents participated in this study on cognitive functioning. The 46 participants (74% girls) were included in AMOS2 between October 2015 and June 2017. Two participants were enrolled before the cognitive testing was initiated in AMOS2, and two others were excluded as their knowledge of the Swedish language was insufficient.


Of the 46 adolescents with a baseline cognitive assessment, 23 were assigned to bariatric surgery, and 23 to intensive non-surgical treatment. Three of the 46 adolescents (7%) had previously been diagnosed with a mild intellectual disability and were in special education. All three were randomised to intensive non-surgical treatment. For baseline cognitive functioning, there was no significant correlation between BMI and any measure of cognitive functioning at baseline (all p>0.05). At baseline, 23/46 (50%) of the adolescents had an estimated IQ-score corresponding to a borderline intellectual functioning or lower. At the follow-ups at one and two years, the corresponding proportion was 17/43 (40%) and 11/35 (31%).


As previously report, bariatric surgery patients lost significantly more weight than participants in the non-surgical treatment arm, with a mean BMI at two years 30.06 (±5.94) vs 41.99 (±8.14), p<0.0001.


In 15/18 (83%) of assessed aspects of cognitive functioning, no significant difference between the treatment groups was found. The average difference over two years was significantly different between the groups in three sub-tests from D-KEFS assessing fundamental cognitive skills; Letter Fluency, Visual Scanning, and Word Reading, with a greater improvement in the operated adolescents compared to the adolescents undergoing intensive non-surgical treatment. One test assessing executive functioning, Category Switching, was borderline significant (p=0.050).


Results in sensitivity analyses with multiple imputation of missing data remained mostly unchanged, but a statistically significant difference was evident in Category Switching between the groups, with higher performance among the operated adolescents over follow-up (p=0.038). The results from the per-protocol analysis, where the participants were analysed as treated, were similar to the results from the analysis with multiple imputations, but then also Motor Speed, a fundamental cognitive skill test from D-KEFS, was statistically different between the groups (p=0.046) indicating greater improvement in the operated adolescents.


“The substantial proportion of adolescents with borderline general intellectual functioning or below indicates that it is important to develop current treatment options and related information, so they are more easily accessible to adolescents with cognitive challenges,” they concluded.


The study was funded by Sweden's innovation agency (VINNOVA), the Swedish Research Council, Joanna Cocozza foundation for paediatric research, the Skane University Hospital Psychology Research and Development Grant, Tore Nilsson’s Foundation, SUS Foundations and Donations and Mary von Sydow’s Foundation.


The findings were reported in the paper, ‘Cognitive functioning in adolescents with severe obesity undergoing bariatric surgery or intensive non-surgical treatment in Sweden (AMOS2): a multicentre, open-label, randomised controlled trial’, published in eClinicalMedicine. To access this paper, please click here


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