Study Shows 40% of Participants Sustain Cognitive Improvement After Surgery-Induced Weight Loss

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Sustained cognitive improvement is likely a result of lower inflammation, remission of comorbidities, higher physical activity, and better mood.

Key Takeaways:

  1. Cognitive Enhancement Following Bariatric Surgery (BS): Following BS, participants experienced improvements in various cognitive domains—including working memory, episodic memory, verbal fluency, and attention shifting, as well as overall global cognition—and these enhancements were observed at both the 6-month and 24-month marks after surgery. Notably, participants also reported an overall reduction in depressive symptoms over the same period.
  2. Brain Structural Changes Post-BS: MRI scans had revealed significant alterations in brain structure following BS. Specifically, reductions in gray matter volume and cortical thickness were observed after 24 months, which indicates potential structural adaptations in response to weight loss; however, certain brain regions (eg, hippocampus, nucleus accumbens, and frontal cortex) did not show volumetric changes.
  3. Metabolic Effects Following Surgery: In addition to cognitive and structural changes, BS was associated with metabolic improvements. Participants showed reductions in inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α, along with increases in neuroprotective factors like adiponectin and neurofilament light chain.

In order to reduce potential obesity-induced consequences to the brain, long-term weight loss solutions are important. Bariatric surgery (BS) is a method that can contribute to rapid, sustainable weight loss as well as a reduction in comorbidities; however, results are often contradictory due to underlying mechanisms—which remain relatively unknown—and the uncertainty of whether or not outcomes are long-lasting. Authors of a study published in JAMA Network Open aimed to strengthen the understanding of the impact of BS to further contribute to the development of treatment strategies for dementia and obesity.

The cohort study included participants from the Bariatric Surgery Rijnstate and Radboudumc Neuroimaging and Cognition in Obesity (BARICO) study. Patients aged 35 to 55 years with severe obesity (body mass index [BMI] of >40 or >35 with comorbidities) who underwent BS to induce weight loss were included in the study. Individuals were excluded from enrollment if they had neurological or severe psychiatric illnesses, were pregnant, received treatment with antibiotics, probiotics, or prebiotics.

In addition, magnetic resonance imaging (MRI) scans were obtained at baseline and 24 months following BS. MRI imaging was used to examine brain volume (total cerebral gray matter [GM] and white matter [WM] volumes which are normalized by intracranial volume), cortical thickness (global measures and overall mean cortical thickness), and subcortical volumes (hippocampus, amygdala, caudate nucleus, putamen, and nucleus accumbens); output WMH volume as well as global WM mean diffusivity; and arterial spin labeling, which included cerebral blood flow (CBF), and spatial coefficient of variation (sCOV) within the overall GM and different regions of interests (ROIs).

Each participant’s cognition was assessed prior to BS (baseline) and again with the use of neuropsychological tests at both 6 and 24 months following BS, in which overall cognitive performance, episodic memory, flexibility, and verbal fluency were assessed. Patients filled out standardized online questionnaires that assessed their depressive symptoms over the past 2 weeks (range: 0-63) with higher scores indicating greater depressive symptoms, and physical activity and the amount of time spent on different activities (range: 3-15) with higher scores indicated greater physical activity.

Woman stepping onto an electronic scale -- Image credit: Siam | stock.adobe.com

Image credit: Siam | stock.adobe.com

A total of 133 participants were included in the study. According to the authors, mean body weight, BMI, WC, and blood pressure were significantly lower at 6 and 24 months after BS; however, from 6 to 24 months, percentage total body weight loss was noticeably higher.

Additionally, several cognitive domains had improved at 6 and 24 months after BS. At baseline, the cohort had a median cognitive score of 27 (range: 26.0-29.0). Notably, participants demonstrated improvements in working memory (n = 15; 11.3%), episodic memory (n = 42; 31.6%), verbal fluency (n = 32; 24.1%), the ability to shift attention (n = 51; 40.2%), and global cognition (n = 52; 42.9%). Further, the BDI score at baseline indicates that 71 participants (54.6%) had experienced minimal depressive symptoms, 55 (42.3%) had mild symptoms, and 4 (3.1%) had moderate symptoms; however, at 24 months after BS, 12 participants (9.4%) had mild depressive symptoms and 2 (1.6%) had moderate symptoms. In addition, the Baecke score was noticeably higher 6 months after surgery and remained stable up to 24 months (mean [SD] Baecke score: baseline, 7.64 [1.29]; 6 months, 8.36 [1.23]; 24 months, 8.19 [1.35]; P < .001).

The study authors noted that brain changes were observed after BS, with GM volume, GM cortical thickness, and GM CBF all significantly lower after 24 months. Other ROIs—amygdala, caudate nucleus, putamen, insula, cingulate gyrus, as well as occipital, parietal, and temporal cortex—had exhibited much lower volumes following BS. There were no observed volumetric changes in hippocampus, nucleus accumbens, frontal cortex, or WM. In addition, cortical thickness for all ROIs was significantly lower following BS; however, the temporal cortex was shown to be much larger (mean [SD] thickness: 2.724 [0.101] mm vs 2.761 [0.007] mm; P = .007). Further, after BS, CBF was lower in multiple cortical and subcortical regions—caudate nucleus, putamen, insula, as well as frontal and occipital cortex—but CBF in temporal cortex, parietal cortex, and nucleus accumbens did not change post-BS.

After 6 months, high-sensitivity C-reactive protein, serum amyloid A, tumor necrosis factor–α, interleukin-1β (IL-1β), IL-6, and plasminogen activator inhibitor-1 were noticeably lower, whereas adiponectin and neurofilament light chain (NFL) were significantly higher compared with baseline levels.

Limitations of the study include the lack of control group and the exclusion of cortical surface and curvature when analyzing the MRI scans. The study authors note that there was an unequal sex distribution among participants (less than 20% of participants were male); however, the investigators note that the sex distribution in the study represents the general BS population.

Although the results indicate a cognitive improvement after 24 months among participants who received BS, according to the study author. They suggest that future research that includes control groups as well as other mechanisms to better clarify cognition and brain changes post-BS should be conducted.

Reference

Custers E, Vreeken D, Kleemann R, et al. Long-Term Brain Structure and Cognition Following Bariatric Surgery. JAMA Netw Open. 2024;7(2):e2355380. doi:10.1001/jamanetworkopen.2023.55380

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