Long-Term Brain Structure and Cognition Following Bariatric Surgery

Abstract

Importance: Weight loss induced by bariatric surgery (BS) is associated with improved cognition and changed brain structure; however, previous studies on the association have used small cohorts and short follow-up periods, making it difficult to determine long-term neurological outcomes associated with BS.

Objective: To investigate long-term associations of weight loss after BS with cognition and brain structure and perfusion.

Design, setting, and participants: This cohort study included participants from the Bariatric Surgery Rijnstate and Radboudumc Neuroimaging and Cognition in Obesity study. Data from participants with severe obesity (body mass index [BMI; calculated as weight in kilograms divided by height in meters squared] >40, or BMI >35 with comorbidities) eligible for Roux-en-Y gastric bypass and aged 35 to 55 years were enrolled from a hospital specialized in BS (Rijnstate Hospital, Arnhem, the Netherlands). Participants were recruited between September 2018 and December 2020 with follow-up till March 2023. Data were collected before BS and at 6 and 24 months after BS. Data were analyzed from March to November 2023.

Exposure: Roux-en-Y gastric bypass.

Main outcomes and measures: Primary outcomes included body weight, BMI, waist circumference, blood pressure, medication use, cognitive performance (20% change index of compound z-score), brain volumes, cortical thickness, cerebral blood flow (CBF), and spatial coefficient of variation (sCOV). Secondary outcomes include cytokines, adipokines, depressive symptoms (assessed using the Beck Depression Inventory), and physical activity (assessed using the Baecke Questionnaire).

Results: A total of 133 participants (mean [SD] age, 46.8 [5.7] years; 112 [84.2%] female) were included. Global cognition was at least 20% higher in 52 participants (42.9%) at 24 months after BS. Compared with baseline, at 24 months, inflammatory markers were lower (mean [SD] high-sensitivity C-reactive protein: 4.77 [5.80] μg/mL vs 0.80 [1.09] μg/mL; P < .001), fewer patients used antihypertensives (48 patients [36.1%] vs 22 patients [16.7%]), and patients had lower depressive symptoms (median [IQR] BDI score: 9.0 [5.0-13.0] vs 3.0 [1.0-6.0]; P < .001) and greater physical activity (mean [SD] Baecke score: 7.64 [1.29] vs 8.19 [1.35]; P < .001). After BS, brain structure and perfusion were lower in most brain regions, while hippocampal and white matter volume remained stable. CBF and sCOV did not change in nucleus accumbens and parietal cortex. The temporal cortex showed a greater thickness (mean [SD] thickness: 2.724 [0.101] mm vs 2.761 [0.007] mm; P = .007) and lower sCOV (median [IQR] sCOV: 4.41% [3.83%-5.18%] vs 3.97% [3.71%-4.59%]; P = .02) after BS.

Conclusions and relevance: These findings suggest that BS was associated with health benefits 2 years after surgery. BS was associated with improved cognition and general health and changed blood vessel efficiency and cortical thickness of the temporal cortex. These results may improve treatment options for patients with obesity and dementia.

Figure 1.. Plasma Concentrations of Adipokines and Cytokines Among Patients Who Underwent Bariatric Surgery

Repeated measures analysis of variance were conducted to assess changes in circulating factors over time. Significant changes over time are indicated by P values. Complete data for all parameters on both time points were available for 110 participants. For illustrative purposes 3 extreme high SAA values (111.49 µg/mL, 401.25, and 50.70 µg/mL) at baseline are not shown. Individual values for every plasma marker are presented in eTable 4 in Supplement 1. hs-CRP indicates high sensitive C-reactive protein; SAA, serum amyloid A; TNF-α, tumor necrosis factor α. Dots indicate individual data points; bars, medians; bars, IQRs; and whiskers, ranges.

Figure 2.. Plasma Concentrations of Cytokines and Brain-Associated Blood-Based Biomarkers Among Patients Who Underwent Bariatric Surgery

Repeated measures analysis of variance were conducted to assess changes in circulating factors over time. Significant changes over time are indicated by P values. Complete data for all parameters on both time points were available for 110 participants, except for interleukin-1β (IL-1β), for which data from 111 participants were available. For illustrative purposes 3 extreme high IL-1β values (7.59 pg/mL, 12.75 pg/mL, and 3.94 pg/mL) at baseline are not shown. At the 2 year time point, 2 extreme high IL-1β values (5.12 and 3.26 pg/mL) was not included for illustrative purposes. Individual values for every plasma marker are presented in eTable 4 in Supplement 1. BDNF indicates brain derived neurotrophic factor; NFL = neurofilament light chain; PAI-1 plasminogen activator inhibitor-1. Dots indicate individual data points; bars, medians; bars, IQRs; and whiskers, ranges.