Dietary total antioxidant capacity and risk of prediabetes and diabetes mellitus: a systematic review and dose-response meta-analysis of 170,919 participants

BackgroundObservational studies have assessed the association between total antioxidant capacity of the diet and risk of diabetes mellitus. However, results from these studies were not entirely consistent. In the current systematic review and dose-response meta-analysis, we aimed to determine the association between dietary total antioxidant capacity (TAC) and the risk of prediabetes and diabetes mellitus.MethodsA systematic literature search of authentic electronic resources including PubMed/Medline, Embase, Scopus, ISI Web of Science and China National Knowledge Infrastructure (CNKI) was carried out to find the relevant articles published up to November 2024. Random-effects or fixed-effects models were used to aggregate the relative risks (RRs) and their 95% confidence intervals (CIs) where appropriate. Heterogeneity across the studies were determined using the Cochran’s Q test and I-square (I2) statistics.ResultsA total of 10 observational studies (five cohort, three case-control and two cross-sectional studies) were included in our meta-analysis. The pooled results indicated that higher dietary TAC was significantly associated with lower risk of prediabetes (RR = 0.58; 95% CI: 0.34–0.97; p = 0.039) and diabetes mellitus (RR = 0.71; 95% CI: 0.58–0.87, p = 0.001). In addition, dose-response analysis showed a linear trend association between dietary TAC and risk of diabetes mellitus (RR = 0.928; 95% CI: 0.842–1.023, pdose-response = 0.131, pnonlinearity = 0.078). Subgroup analyses showed the significant inverse association between dietary TAC and diabetes mellitus in mean age <50 and sample size <5,000 (RR = 0.26, 95% CI: 0.16–0.41, p < 0.001), and there was no evidence of heterogeneity (p = 0.939; I2 = 0.0%). Meanwhile, there was also an inverse association between dietary TAC and diabetes mellitus in Western countries (RR = 0.79; 95% CI: 0.68–0.92, p = 0.003), with less evidence of heterogeneity (p = 0.226; I2 = 36.7%).ConclusionOverall, higher dietary TAC was inversely associated with the risk of prediabetes and diabetes mellitus. Further well-designed prospective studies or randomized controlled trials are needed to validate the present findings.Systematic Review Register(PROSPERO), CRD42024611235

Everything of Thoughts: Defying the Law of Penrose Triangle for Thought Generation

Recent advancements in Large Language Models (LLMs) have revolutionized decision-making by breaking down complex problems into more manageable language sequences referred to as ``thoughts''. An effective thought design should consider three key perspectives: performance, efficiency, and flexibility. However, existing thought can at most exhibit two of these attributes. To address these limitations, we introduce a novel thought prompting approach called ``Everything of Thoughts'' (XoT) to defy the law of ``Penrose triangle of existing thought paradigms. XoT leverages pretrained reinforcement learning and Monte Carlo Tree Search (MCTS) to incorporate external domain knowledge into thoughts, thereby enhancing LLMs' capabilities and enabling them to generalize to unseen problems efficiently. Through the utilization of the MCTS-LLM collaborative thought revision framework, this approach autonomously produces high-quality comprehensive cognitive mappings with minimal LLM interactions. Additionally, XoT empowers LLMs to engage in unconstrained thinking, allowing for flexible cognitive mappings for problems with multiple solutions. We evaluate XoT on several challenging multi-solution problem-solving tasks, including Game of 24, 8-Puzzle, and Pocket Cube. Our results demonstrate that XoT significantly outperforms existing approaches. Notably, XoT can yield multiple solutions with just one LLM call, showcasing its remarkable proficiency in addressing complex problems across diverse domains.Comment: 17 pages, 5 figure

The Altered Reconfiguration Pattern of Brain Modular Architecture Regulates Cognitive Function in Cerebral Small Vessel Disease

Background: Cerebral small vessel disease (SVD) is a common cause of cognitive dysfunction. However, little is known whether the altered reconfiguration pattern of brain modular architecture regulates cognitive dysfunction in SVD.Methods: We recruited 25 cases of SVD without cognitive impairment (SVD-NCI) and 24 cases of SVD with mild cognitive impairment (SVD-MCI). According to the Framingham Stroke Risk Profile, healthy controls (HC) were divided into 17 subjects (HC-low risk) and 19 subjects (HC-high risk). All individuals underwent resting-state functional magnetic resonance imaging and cognitive assessments. Graph-theoretical analysis was used to explore alterations in the modular organization of functional brain networks. Multiple regression and mediation analyses were performed to investigate the relationship between MRI markers, network metrics and cognitive performance.Results: We identified four modules corresponding to the default mode network (DMN), executive control network (ECN), sensorimotor network and visual network. With increasing vascular risk factors, the inter- and intranetwork compensation of the ECN and a relatively reserved DMN itself were observed in individuals at high risk for SVD. With declining cognitive ability, SVD-MCI showed a disrupted ECN intranetwork and increased DMN connection. Furthermore, the intermodule connectivity of the right inferior frontal gyrus of the ECN mediated the relationship between periventricular white matter hyperintensities and visuospatial processing in SVD-MCI.Conclusions: The reconfiguration pattern of the modular architecture within/between the DMN and ECN advances our understanding of the neural underpinning in response to vascular risk and SVD burden. These observations may provide novel insight into the underlying neural mechanism of SVD-related cognitive impairment and may serve as a potential non-invasive biomarker to predict and monitor disease progression

Effects of Combined Intervention of rTMS and Neurotransmitter Drugs on the Brain Functional Networks in Patients with Cognitive Impairment

Alzheimer’s disease (AD) causes extensive neural network dysfunction. Memantine and donepezil are commonly used as monotherapy or in combination with non-drug interventions, such as repetitive transcranial magnetic stimulation (rTMS), for its treatment. However, no studies have reported any differences between the effects of combined neurotransmitter and rTMS interventions versus rTMS alone on the brain networks of patients with cognitive impairment. Therefore, it is crucial to explore the advantages of different intervention methods to guide clinical practice. We used resting-state functional magnetic resonance imaging (rs-fMRI) to investigate the impact of neurotransmitter superimposed rTMS and rTMS alone on the brain functional network of patients with cognitive impairment. We divided patients with cognitive impairment who had received rTMS into two groups based on whether they received neurotransmitters: the combined intervention group and the rTMS-alone intervention group. We conducted rs-fMRI scans and comprehensively assessed cognitive function in these patients. To examine the effects of the superimposed interventions, we utilized independent component analysis to evaluate the functional connectivity of brain networks in these patients. Compared to the rTMS-alone intervention group, co-intervention of neurotransmitter drugs and rTMS exhibited potential for cognitive enhancement via the reconstructed inter-network connectivity of the cerebellum and the enhanced intra-network connectivity of the frontal-parietal regions in these patients with cognitive impairment. We hypothesized that the combination of neurotransmitter drugs and rTMS intervention could have greater clinical benefits than rTMS intervention alone, leading to improved cognitive function in patients with cognitive impairment.</jats:p

Magnetic Resonance Imaging Biomarkers of Punding in Parkinson&rsquo;s Disease

Punding is a rare condition triggered by dopaminergic therapy in Parkinson&rsquo;s disease (PD), characterized by a complex, excessive, repetitive, and purposeless abnormal movement, and its pathogenesis remains unclear. We aimed to assess the brain structure alterations related to punding by using multipametric magnetic resonance imaging (MRI). Thirty-eight PD patients (19 with punding and 19 without punding) from the Parkinson&rsquo;s Progression Marker Initiative (PPMI) were included in this study. Cortical thickness was assessed with FreeSurfer, and the integrity of white matter fiber tracts and network topologies were analyzed by using FMRIB Software Library (FSL) and Pipeline for Analyzing braiN Diffusion imAges (PANDA). PD patients with punding showed a higher apathy score and more severe cortical atrophy in the left superior parietal, right inferior parietal, and right superior frontal gyrus, and worse integrity of the right cingulum cingulate tract compared to those without punding. On the other hand, no significant difference in structural network topologies was detected between the two groups. These data suggest that the specific area of destruction may be an MRI biomarker of punding risk, and these findings may have important implications for understanding the neural mechanisms of punding in PD

The Enhanced Interhemispheric Functional Connectivity in the Striatum Is Related to the Cognitive Impairment in Individuals With White Matter Hyperintensities

ObjectiveThe cognitive performance of individuals with white matter hyperintensities (WMH) tends to vary considerably. This study aimed to explore the relationship of the synchronous spontaneous activities in homotopic areas across hemispheres, named as voxel-mirrored homotopic connectivity (VMHC), with the cognitive performance of individuals with WMH.Materials and MethodsEighty-two WMH subjects without cognitive impairment (CI), 56 WMH subjects with CI, and 92 healthy subjects (HS) underwent neuropsychological tests and multimodal magnetic resonance imaging scans. VMHC maps were analyzed among the three groups. Correlative analyses were performed between VMHC values and cognitive function.ResultsNo significant difference in WMH volume, brain volume, or gray matter atrophy rate was shown between WMH subjects with and without CI. In contrast, those with CI displayed lower VMHC in the bilateral cuneus and calcarine and higher VMHC in the lentiform nucleus and caudate nucleus (LNCN) than those without CI. Furthermore, the VMHC in the LNCN was negatively associated with the global function and the memory function in WMH subjects.ConclusionThe enhanced VMHC in the LNCN was associated with the development of CI in individuals with WMH. This finding may contribute to the exploration of surrogate markers for the CI caused by WMH.</jats:sec

Abstract WP489: Disrupted Functional and Structural Connectivity Within Default Mode Network Contribute to WMH Related Cognitive Impairment

Aims: The prevalence of white matter hyperintensities (WMH) rises dramatically with aging. Both the progression of WMH and default mode network (DMN) have been proven to be closely associated with cognitive function. Thus, we hypothesized that changes in functional connectivity (FC) and structural connectivity (SC) of the DMN contributed to WMH related cognitive impairment. Methods: A total of 116 subjects were enrolled from the Cerebral Small Vessel Disease Register in Drum Tower Hospital of Nanjing University, and were distributed across three categories according to Fazekas rating scale: WMH I(n=57), WMH II(n=34), and WMH III (n=25). The clinical and neuropsychological data were collected, and all participants underwent 3D T1 weighted images, T2 weighted images, 3D fluid attenuated inversion recovery (FLAIR) images, diffusion tensor images (DTI), and diffusion weighted imaging (DWI). The alterations of FC and SC within the DMN were further explored in these subjects. Results: The study found that age and hypertension were risk factors for WMH progression. Subjects with a larger WMH burden displayed higher DMN FC in the medial frontal gyrus (MFG), while lower DMN FC in the thalamus. After adjustment for age, gender, and education, the increasing FC between the MFG, posterior cingulate cortex (PCC), and ascending mean diffusivity (MD) of the white matter tracts between the hippocampus and PCC were independent indicators of worse performance in memory. Moreover, the decreasing FC between the thalamus, PCC, and ascending MD of the white matter tracts between the thalamus and PCC were independent risk factors for a slower processing speed. Conclusion: The changes in FC and SC within the DMN attributed to WMH progression were responsible for the cognitive impairment. </jats:p

Altered morphological connectivity mediated white matter hyperintensity-related cognitive impairment

White matter hyperintensities (WMH) are widely observed in older adults and are closely associated with cognitive impairment. However, the underlying neuroimaging mechanisms of WMH-related cognitive dysfunction remain unknown. This study recruited 61 WMH individuals with mild cognitive impairment (WMH-MCI, n = 61), 48 WMH individuals with normal cognition (WMH-NC, n = 48) and 57 healthy control (HC, n = 57) in the final analyses. We constructed morphological networks by applying the Kullback-Leibler divergence to estimate interregional similarity in the distributions of regional gray matter volume. Based on morphological networks, graph theory was applied to explore topological properties, and their relationship to WMH-related cognitive impairment was assessed. There were no differences in small-worldness, global efficiency and local efficiency. The nodal local efficiency, degree centrality and betweenness centrality were altered mainly in the limbic network (LN) and default mode network (DMN). The rich-club analysis revealed that WMH-MCI subjects showed lower average strength of the feeder and local connections than HC (feeder connections: P = 0.034; local connections: P = 0.042). Altered morphological connectivity mediated the relationship between WMH and cognition, including language (total indirect effect: −0.010; 95 % CI: −0.024, −0.002) and executive (total indirect effect: −0.010; 95 % CI: −0.028, −0.002) function. The altered topological organization of morphological networks was mainly located in the DMN and LN and was associated with WMH-related cognitive impairment. The rich-club connection was relatively preserved, while the feeder and local connections declined. The results suggest that single-subject morphological networks may capture neurological dysfunction due to WMH and could be applied to the early imaging diagnostic protocol for WMH-related cognitive impairment