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Aims: This research aimed to explore alterations in the local gyrification index (GI) and resting-state functional connectivity (RSFC) in type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment (MCI)., Methods: In this study, 126 T2DM patients with MCI (T2DM-MCI), 154 T2DM patients with normal cognition (T2DM-NC), and 167 healthy controls (HC) were recruited. All subjects underwent a battery of neuropsychological tests. A multimodal approach combining surface-based morphometry (SBM) and seed-based RSFC was used to determine the structural and functional alterations in patients with T2DM-MCI. The relationships among the GI, RSFC, cognitive ability, and clinical variables were characterized., Results: Compared with the T2DM-NC group and HC group, T2DM-MCI patients showed significantly reduced GI in the bilateral insular cortex. Decreased RSFC was found between the left insula and right precuneus, and the right superior frontal gyrus (SFG). The altered GI was correlated with T2DM duration, global cognition, and episodic memory. The mediation effects of RSFC on the association between GI and cognition were not statistically significant., Conclusion: Our results suggest that GI may serve as a novel neuroimaging biomarker to predict T2DM-related MCI and help us to improve the understanding of the neuropathological effects of T2DM-related MCI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shao, Li, Qin, Xu, Sheng, Huang, Ma, Cheng, Chen, Zhang, Zhao and Xu.)

Objective: The 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 Methods: Eighty-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., Results: No 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., Conclusion: The 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Qin, Cheng, Huang, Shao, Xu, Xu and Ye.)

Aims: This study aimed to analyze the potential association between cognition reserve (CR) components, including education, working activity, and leisure time activity, and cognitive function in subjects with white matter hyperintensities (WMH). The study also explored the role of the frontoparietal control network (FPCN) in such association., Methods: White matter hyperintensities subjects with and without cognitive impairment (CI) were evaluated with multimodal magnetic resonance imaging, neuropsychological testing, and CR survey. FPCN patterns were assessed with dorsolateral prefrontal cortex seed-based functional connectivity analysis., Results: Education was positively associated with cognitive function in WMH subjects with or without CI, whereas working activity and leisure time activity were positively associated with cognitive function only in those without CI. Similarly, education was associated with bilateral FPCN in both WMH groups, whereas working activity and leisure time activity were associated with bilateral FPCN mainly in the group without CI. Furthermore, FPCN partially mediated the association between education and cognitive function in both WMH groups., Conclusion: Education showed a positive impact on cognitive function in WMH subjects regardless of their cognitive status, whereas working activity and leisure time activity exhibited beneficial effects only in those without CI. The FPCN mediated the beneficial effect of education on cognitive function., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: The role of brain atrophy in cognitive decline related to cerebral small vessel disease (CSVD) remains unclear. This study used AccuBrain™ to identify major CSVD-related brain changes and verified the relationship between brain atrophy and different cognition domains in CSVD patients., Methods: All enrolled 242 CSVD patients and 76 healthy participants underwent magnetic resonance imaging examinations and detailed neuropsychological scale assessments were collected at the same time. The AccuBrain™ technology was applied to fully automated image segmentation, measurement, and calculation of the acquired imaging results to obtain the volumes of different brain partitions and the volume of WMH for quantitative analysis. Correlation analyses were used to estimate the relationship between MRI features and different cognitive domains. Multifactor linear regression models were performed to analyze independent predictors of MTA and cognitive decline., Results: CSVD patients exhibited multiple gray matter nucleus volume decreases in the basal ganglia regions and brain lobes, including the temporal lobe ( P = 0.019), especially in the medial temporal lobe ( p < 0.001), parietal lobe ( p = 0.013), and cingulate lobe ( p = 0.036) compare to HC. The volume of PWMH was an independent predictor of MTA for CSVD patients. Both medial temporal atrophy (MTA) and PWMH were associated with cognition impairment in CSVD-CI patients. MTA mediated the effect of PWMH on executive function in CSVD-CI patients., Conclusions: Our results showed that MTA was related to cognition impairment in CSVD patients, which might become a potential imaging marker for CSVD-CI., Competing Interests: LS is the director of BrainNow Research Institute. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sun, Huang, Cheng, Qin, Xu, Shao, Ma, Yao, Shi and Xu.)

High cognitive reserve (CR) protects against cognitive decline in individuals with white matter hyperintensities (WMH). However, the functional mechanisms remain relatively unknown. This work aimed to explore the effects of CR on the frontoparietal control network (FPCN) and cognitive function in subjects with WMH. One hundred and thirty-seven subjects with WMH and 95 control subjects without WMH underwent neuropsychological testing, CR assessments, and multimodal magnetic resonance imaging (MRI) scanning. A mixed analysis of covariance with CR level (high CR vs. low CR) and WMH status (with WMH vs. without WMH) as fixed factors was performed on the FPCN. WMH volume was negatively correlated with global cognitive function in subjects with low CR not in those with high CR, suggesting a buffering effect of high CR. An interaction between CR and WMH was detected on the right FPCN in frontal regions. Specifically, control subjects with high CR had significantly higher functional connectivity (FC) in frontal regions than control subjects with low CR, whereas this relation was inverted in WMH subjects. Correlative analyses showed positive associations of the FC with cognitive performance in both WMH subjects and control subjects, although the associations were not significant after correction for multiple comparisons. In conclusion, CR differentially regulated the FPCN in frontal regions between subjects with WMH and those without WMH. This regulation supports the flexibility of CR in regulating brain function and may underlie the effects of CR on cognitive function in WMH subjects., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To precisely prevent stroke, we evaluated three platelet function tests and their associations with clinical outcomes in ischemic stroke patients., Methods: On-treatment platelet reactivity of acute minor stroke patients taking aspirin plus clopidogrel was tested by light transmittance aggregometry (LTA), thromboelastography (TEG) and platelet function analyzer (PFA). Mann-Whitney U tests and receiver operating characteristic (ROC) curve analysis were used to assess their associations with recurrent events and clinical outcome prediction., Results: 127 acute minor stroke patients were stringently selected and followed for 13 months. Eight patients (6.3%) self-reported the recurrence and 13 (10.2%) patients self-reported bleeding. Recurrent patients displayed significantly higher on-treatment platelet reactivity when measured with LTA ( p = 0.030) and PFA ( p < 0.001). Further ROC analysis demonstrated that LTA and PFA had modest-to-fair ability to predict stroke recurrence (LTA: area under the curve [AUC], 0.765; 95% CI, 0.584-0.945, PFA: AUC, 0.832; 95% CI, 0.658-1.000). However, TEG (measured by the platelet inhibition rate) could not detect the difference between recurrent patients and non-recurrent patients ( p = 0.515) and predict recurrent events (AUC, 0.569; 95% CI, 0.368-0.770). None of the tests were associated with bleeding except for PFA ( p < 0.001), with AUC of PFA reaching 0.772 (0.726-0.818)., Conclusions: Of the three tests assessed, the predictive accuracies of PFA and LTA were satisfying for aspirin secondary prevention, while TEG's performance was poor. Only PFA could provide accurate prognostic information for bleeding.

Purpose: Combined the number, volume, and location of cerebral microbleeds (CMBs), this study aimed to explore the different features of CMBs and their correlation with cognitive ability in patients with type 2 diabetes mellitus (T2DM)., Methods: This study recruited 95 patients with T2DM and 80 healthy control (HC) individuals. AccuBrain ® , an automated tool, was used to obtain the number and volume of CMBs. The scores on global cognition and five cognitive domains were derived from a battery of cognitive tests. The logistic regression and multivariate linear regression were conducted to determine the relationship between the CMBs (number, volume, and location) and cognitive ability in patients with T2DM., Results: After adjusting for several variables, the total volume of CMBs (OR = 0.332, 95%CI: 0.133-0.825, and p = 0.018) was independent risk factor for cognitive impairment, whereas the total number of CMBs was not (OR = 0933, 95%CI: 0.794-1.097, and p = 0.400). Furthermore, the volume of CMBs in lobar regions was independently associated with working memory (β = -0.239, 95%CI: -0.565 to -0.035, and p = 0.027). However, no significant correlation between the number of CMBs (both lobar and deep/infratentorium) and any cognitive domains was observed., Conclusions: Lobar CMBs was related with cognitive impairment in patients with T2DM and might be a potential early warning signal. Compared with the counting analysis, the quantitative method offered a more sensitive and objective measurement for studying imaging features of CMBs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shao, Xu, Sheng, Qin, Ma, Luo, Lee, Shi, Huang, Cheng, Zhao and Xu.)

Aims: This study aimed to investigate the relationships of impaired cerebrovascular reactivity (CVR) and abnormal functional connectivity (FC) with white matter hyperintensity (WMH)-related cognitive decline., Methods: A total of 233 WMH subjects were recruited and categorized into WMH-I ( n = 106), WMH-II ( n = 72), and WMH-III ( n = 55) groups according to Fazekas visual rating scale. All participants underwent neuropsychological tests and multimodal MRI scans, including 3D-T1, and resting-state functional magnetic resonance imaging (rs-fMRI). The alterations of CVR maps and FC were further explored., Results: Subjects with a higher WMH burden displayed a lower CVR in the left medial occipital gyrus (MOG). The FC analysis using MOG as a seed revealed that the FC of the left insula, left inferior parietal lobule, and thalamus changed abnormally as WMH aggravated. After adjusting for age, gender, and education years, the serial mediation analysis revealed that periventricular white matter hyperintensity contributes indirectly to poorer Mini-Mental State Examination (MMSE) scores (indirect effect: β = -0.1248, 95% CI: -0.4689, -0188), poorer Montreal Cognitive Assessment (MoCA) (indirect effect: β = -0.1436, 95% CI: -0.4584, -0.0292) scores, and longer trail making tests A (TMT-A) (indirect effect: β = 0.1837, 95% CI: 0.0069, 0.8273) times, specifically due to the lower CVR of the left MOG and the higher FC of the left insula-MOG., Conclusion: The CVR decline of the left MOG and the abnormal FC of the left insula-MOG attributed to WMH progression were responsible for the poor general cognition (MMSE and MoCA) and information processing speed (TMT-A). The left MOG may act as a connection, which is involved in the processing of cognitive biases by connecting with the left insula-cortical regions in WMH individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Qin, Chu, Xu, Ni, Ma, Shao, Huang, Zhang, Zhang and Xu.)

Background: Stimulating superficial brain regions highly associated with the hippocampus by repetitive transcranial magnetic stimulation (rTMS) may improve memory of Alzheimer's disease (AD) spectrum patients., Objective: We recruited 16 amnesic mild cognitive impairment (aMCI) and 6 AD patients in the study. All the patients were stimulated to the left angular gyrus, which was confirmed a strong link to the hippocampus through neuroimaging studies, by the neuro-navigated rTMS for four weeks., Methods: Automated fiber quantification using diffusion tensor imaging metrics and graph theory analysis on functional network were employed to detect the neuroplasticity of brain networks., Results: After neuro-navigated rTMS intervention, the episodic memory of aMCI patients and Montreal Cognitive Assessment score of two groups were significantly improved. Increased FA values of right anterior thalamic radiation among aMCI patients, while decreased functional network properties of thalamus subregions were observed, whereas similar changes not found in AD patients. It is worth noting that the improvement of cognition was associated with the neuroplasticity of thalamic system., Conclusion: We speculated that the rTMS intervention targeting left angular gyrus may be served as a strategy to improve cognitive impairment at the early stage of AD patients, supporting by the neuroplasticity of thalamic system.

Aims: We aimed to determine whether preprocedural renal function affects the outcome of acute ischemic stroke (AIS) patients with mechanical thrombectomy (MT) and whether this effect is modified by the onset-to-reperfusion time (OTR) and mediated by collateral status., Methods: Eligible patients with anterior circulation large vessel occlusion (LVO) who underwent MT between August 2018 and August 2020 were reviewed. The main outcome was good functional outcome [defined as modified Rankin Scale (mRS) of 0-2] at 3 months. Multivariable logistic regression analyses were conducted to explore the relationship between renal function and good functional outcome. A moderation analysis and the Johnson-Neyman technique were performed to assess the interaction between renal function and OTR to predict the outcome of AIS patients with MT., Results: Among 100 enrolled patients, 36 (36%) exhibited good functional outcome. A decreased preprocedural estimated glomerular filtration rate (pre-eGFR) was significantly associated with worse functional outcome [adjusted OR, 1.059 (1.012-1.108); p, 0.014], and this effect was partly mediated by collateral circulation. An interaction between OTR and pre-eGFR on functional outcome was observed (P for interaction, 0.22), and pre-eGFR only had a significant effect on functional outcome when OTR exceeded 455.8 min. Moreover, the adverse effect of OTR on functional outcome became no longer significant when the pre-eGFR was higher than 89.0 mL/min/1.73 mL/min/1.73 m²., Conclusions: Renal function was related to functional outcome at 3 months, and this relationship could be modified by OTR. The results suggested that reducing OTR and improving collateral circulation may mitigate the adverse effect of reduced kidney function on functional outcome., (© 2021 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Impaired cerebrovascular reactivity (CVR) plays an important role in the pathophysiology of white matter hyperintensities (WMHs). The pathogenesis of CVR in the development of WMH-related cognitive impairment (CI) remains poorly understood., Purpose: To detect the CVR status in WMH subjects with/without CI by using a resting-state blood oxygenation level-dependent (BOLD) approach and to explore the mediating relationships among CVR, WMH, and cognitive level., Study Type: Prospective., Subjects: Subjects with moderate to severe WMH (with CI [WMH-CI], n = 68; without CI [WMH-no-CI, n = 63) as well as normal controls (NCs, n = 87)., Field Strength/sequence: 3.0T with gradient-recalled echoplanar imaging and 3D fluid-attenuated inversion recovery., Assessment: The CVR, WMH volume, and cognitive level were assessed. The CVR map was derived using BOLD signal obtained from resting-state functional MRI data., Statistical Tests: CVR maps were compared among the three groups. Partial correlation analyses were performed to correlate impaired CVR with WMH volume and cognitive test scores. Mediation analysis was conducted to determine whether WMH acted as a mediating factor between CVR and cognitive function., Results: Compared with the NC group, both WMH groups showed reduced CVR in the left hemisphere (P < 0.05). The WMH-CI group showed further decreased CVR in the left frontal area, when compared with the WMH-no-CI group (P < 0.05). In the WMH-CI group, the lower CVR in left frontal area was a strong indicator of poor performance on general cognition (r = 0.311), executive function (r = 0.362), and information processing speed (r = 0.399) (all P < 0.05). Periventricular WMH (PWMH) volume mediated these correlations, the β and 95% bootstrap confidence intervals were (0.5097, [0.1498,1.1385]), (-0.4081, [-1.0256,-0.1363]), and (-0.5576, [-1.4666,-0.1538]), respectively., Data Conclusion: WMH-CI subjects showed a greater reduction of CVR derived from a resting-state BOLD approach in the left frontal area than WMH-no-CI subjects. Cognition was highly dependent on the integrity of cerebrovascular reactivity and mediated by PWMH burden., Level of Evidence: 4 TECHNICAL EFFICACY: Stage 2., (© 2020 International Society for Magnetic Resonance in Medicine.)

Objective: To characterize earlier damage pattern of white matter (WM) microstructure in cerebral small vessel disease (CSVD) and its relationship with cognitive domain dysfunction. Methods: A total of 144 CSVD patients and 100 healthy controls who underwent neuropsychological measurements and diffusion tensor imaging (DTI) examination were recruited. Cognitive function, emotion, and gait were assessed in each participant. The automated fiber quantification (AFQ) technique was used to extract different fiber properties between groups, and partial correlation and general linear regression analyses were performed to assess the relationship between position-specific WM microstructure and cognitive function. Results: Specific segments in the association fibers, commissural WM regions of interest (ROIs), and projection fibers were damaged in the CSVD group [ P < 0.05, family-wise error (FWE) correction], and these damaged segments showed interhemispheric symmetry. In addition, the damage to specific tract profiles [including the posteromedial component of the right cingulum cingulate (CC), the occipital lobe portion of the callosum forceps major, the posterior portion of the left superior longitudinal fasciculus (SLF), and the bilateral anterior thalamic radiation (ATR)] was related to the dysfunction in specific cognitive domains. Among these tracts, we found the ATR to be the key set of tracts whose profiles were most associated with cognitive dysfunction. The left ATR was a specific fiber bundle associated with episode memory and language function, whereas the fractional anisotropy (FA) values of the intermediate component of the right ATR were negatively correlated with executive function and gait evaluation. It should be noted that the abovementioned relationships could not survive the Bonferroni correction ( p < 0.05/27), so we chose more liberal uncorrected statistical thresholds. Conclusions: Damage to the WM fiber bundles showed extensive interhemispheric symmetry and was limited to particular segments in CSVD patients. Disruption of strategically located fibers was associated with different cognitive deficits, especially the bilateral ATR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Chen, Sun, Chen, Ye, Yang, Li, Luo, Ma, Shao, Xu, Zhang, Zhu and Xu.)

Purpose: There is a high correlation between white matter hyperintensity (WMH) and cognitive impairment (CI) in elderly people. However, not all WMH will develop into CI, and the potential mechanism of WMH-related CI is still unclear. This study aimed to investigate the topological properties of white matter structural network in WMH-related CI. Methods: Forty-one WMH subjects with CI (WMH-CI), 42 WMH subjects without CI (WMH-no-CI), and 52 elderly healthy controls (HC) were recruited. Diffusion tensor imaging (DTI) fiber tractography and graph theoretical analysis were applied to construct the structural network. We compared network properties and clinical features among the three groups. Multiple linear regression analysis was performed to investigate the relationships among WMH volumes, impaired network properties, and cognitive functions in the WMH-CI group. Results: Compared with the controls, both WMH groups showed decreased network strength, global efficiency, and increased characteristic path length (Lp) at the level of the whole brain. The WMH-CI group displayed more profound impairments of nodal efficiency and nodal path length (NLp) within multiple regions including precentral, cingulate, and medial temporal gyrus. The disrupted network properties were associated with CI and WMH burdens in the WMH-CI group. Furthermore, a mediation effect of NLp in the left inferior frontal gyrus was observed for the association between periventricular WMH (PWMH) and memory deficit. Conclusions: Brain structural network in WMH-CI is significantly disturbed, and this disturbance is related to the severity of WMH and CI. Increased NLp in the left opercular part of inferior frontal gyrus (IFGoperc.L) was shown to be a mediation framework between PWMH and WMH-related memory, which shed light on investigating the underlying mechanisms of CI caused by WMH., (Copyright © 2020 Yang, Huang, Luo, Li, Qin, Ma, Shao, Xu, Zhang, Xu and Zhang.)