In this study, we assessed different components of visuospatial processing as well as some cognitive abilities that may impact it in young participants with obesity: global cognitive function, motor speed, impulsivity, response compliance, visuospatial structural ability, and visual memory, the egocentric and allocentric aspects of navigational behavior. Moreover, we investigated the differences in between individuals with obesity and normal-weight individuals in the TKP metabolites serum levels, and the relationship between TKP metabolites and spatial navigation test performances. Participants with obesity performed worse on the RCFT copy test than healthy controls, however none of the TKP metabolites predicted the test performance. Additionally, they had greater levels of the QUIN metabolite, which was a negative predictor of RRT, and DAT, whereas AFC was a negative predictor only of RPT. CRP was similarly higher in participants with obesity, and it was also a poor predictor of RRT and DAT. The visuospatial test performances are worse in participants with obesity without comorbidities than in healthy controls of a similar age range. Furthermore, QUIN and CRP may contribute to the identification of new serum biomarkers of poor visuospatial cognition in young adults with obesity.
According to literature, obesity affects cognitive function (Fergenbaum et al., 2009; Pedditizi et al., 2016) and causes a lower performance in attention and mental flexibility tests (Yau et al., 2012). Additionally, population-based longitudinal research examining changes in BMI over 28 years has shown that obesity in the early stages of life, but not in late life, as well as the distribution of adipose tissue, is associated with dementia risk (Singh-Manoux et al., 2018; Yau et al., 2012). Our findings support the notion that young individuals with obesity perform poorly on spatial navigation tests, which have been demonstrated to be impaired in the early stages of dementia (Kunz et al., 2015), when compared with their normal weight counterparts, and the findings are consistent with the existing but limited literature (Tsai et al., 2017b). Additionally, our results reveal that people with obesity participants performed worse than normal-weight participants in the RCFT copy trial, which is consistent with the literature (Boeka & Lokken, 2008). However, there was no difference between the groups in terms of RCFT immediate recall and delete recall performance. This suggests that, while memory retrieval remains unaffected, there are variations in the initial encoding of visuospatial structure information. Moreover, in the VR-Based Route-Learning Test in which we evaluated egocentric and allocentric spatial navigation, there was no difference in response times as in the reaction time test, but the performance of participants with obesity was significantly lower in terms of correct response percentages all the subtests than normal-weight participant. This may indicate that poor performance in route learning abilities in the obesity group cannot be explained by the speed-accuracy trade-off (Esmaeilzadeh et al., 2020; Salthouse, 1996). Abdominal obesity, rather than whole body adiposity, selectively affects cognitive functions (Fan et al., 2022; Kerwin et al., 2011). AFC was a negative predictor of RRT testing, which could be remedied using an egocentric strategy. Thus, abdominal fat composition may have a direct effect on egocentric strategy. Specific navigational tests that examine both allocentric and egocentric methods may be useful for distinguishing obesity-related aging from healthy aging.
Cognitive impairment and decreased brain integrity have both been related to inflammation. Furthermore, chronic low-grade inflammation, as manifested by elevated levels of circulating inflammatory markers including pro-inflammatory cytokines and the acute phase protein CRP (Reilly & Saltiel, 2017), appears to raise the risk of progressive cognitive decline (Reilly & Saltiel, 2017; Schmidt et al., 2002) However, there are not many early, non-invasive signs of neuroinflammation in people with obesity (Eagan et al., 2012; Lampe et al., 2019; Schur et al., 2015). According to studies, TKP is changed in people with obesity due to persistent systemic inflammation (Cussotto et al., 2020), and the increased circulating source of TKP metabolites may be related to adipocytes (Huang et al., 2022). Furthermore, studies have shown that KYN and TRP cross the blood-brain barrier (Heyes & Morrison, 1997) and that there is a strong correlation between KYN/TRP (r = 0.77) and QUIN (r = 0.55) concentrations in blood and CSF (Haroon et al., 2020). Additionally, even though QUIN cannot penetrate the blood-brain barrier, it may contribute to excitotoxicity by entering the brain via peripheral monocytes, which raise serum QUIN levels in Alzheimer's patients (Busse et al., 2018). A study with C57BL6 mice showed that QUIN impairs hippocampus-dependent spatial learning, and chronic QUIN also reduces functional connectivity between the prefrontal cortex and hippocampus (Latif-Hernandez et al., 2016). A similar process might play a pivotal role in people with obesity.
There were various limitations to this study. Existing research indicates that immunological function and TKP metabolite blood levels differ between sexes (Klein & Flanagan, 2016; Meier et al., 2018), but this study lacks the power to investigate its effects. Another limitation is that we evaluated only serum levels of CRP and the TKP metabolites in this study. While TNF-a and IFN-gamma elevate QUIN synergistically (Pemberton et al., 1997), QUIN stimulates the production of numerous proinflammatory cytokines and chemokines such as IL-1b at excitotoxic doses (Guillemin et al., 2003). Another important limitation may be the choice of tests. An attempt was made to create a set of tests that reflected the visualization processing as much as possible. As a result, larger studies may be valuable for confirmation analyses and exploration of a broader spectrum of immunological markers related to cognitive dysfunction in individuals with obesity.