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• Damage to the white matter and gray matter of the cerebellum has already occurred in prediabetes. • Damage of the cerebellum is more serious in the stage of diabetes. • The damaged brain area with prediabetic lesions was closely related to motor function. • The area affected by diabetes was related to complex cognitive function. To investigate alterations in cerebrum and cerebellum in prediabetes. Cerebellar injury in diabetes is traceable, but it has not been systematically studied, and whether cerebellar injury occurs and the degree of damage in prediabetes are not known. The current study investigated cerebral and cerebellar gray matter volume, white matter volume, white matter microstructure and white matter hyperintensity on T1-weighted, T2-weighted fluid-attenuated inversion recovery and diffusion tensor imaging scans in 78 individuals with normal glucose metabolism, 92 with prediabetes, and 108 with type 2 diabetes. Participants with prediabetes showed significant gray matter and white matter atrophy, microstructural damage in the cerebellar and cerebral regions. Additionally, widespread structural alterations were observed in the diabetic stage. The function of the damaged brain area was further decoded in Neurosynth, and the damaged cerebellar area with prediabetic lesions was closely related to motor function, while the area affected by diabetes was related to complex cognitive function in addition to motor function. Cerebellar injury had already appeared in the prediabetic stage, and cerebellar injury was aggravated in the diabetic stage; therefore, the cerebellum is a key area that is damaged early in the development of diabetes. [ABSTRACT FROM AUTHOR]

Background and purpose: The anterior and posterior hippocampal networks represent verbal and spatial memory, respectively, and may play different roles in the pathological mechanism of amnestic mild cognitive impairment (aMCI) and non‐amnestic MCI (naMCI), which has not been explored. Methods: A total of 990 older adults with 791 normal controls (NCs) (65 ± 6 years, 502 women), 140 aMCI (66 ± 7 years, 84 women) and 59 naMCI (66 ± 7 years, 38 women) were included. A multivariate method, partial least squares, was used to assess the structural covariance networks of the anterior hippocampus (aHC) and posterior hippocampus (pHC), and their relationships with verbal memory and spatial memory in the three groups. Results: Three aHC and pHC structural covariance network patterns emerged: (1) the age pattern; (2) the specific aMCI pattern; and (3) the spatial memory pattern. Furthermore, aMCI patients had more extensive and severe damage in the three patterns, and correlated with greater decline in verbal memory, which was mainly characterized by the aHC network. Conclusions: The aMCI and naMCI showed different patterns and damage in the structural covariance networks, and functional segregation of the aHC and pHC networks still exists in the process of pathological aging. A potential neural explanation is provided for the conversion of aMCI and naMCI into different types of dementia in the future. [ABSTRACT FROM AUTHOR]

Neuropsychiatric symptoms (NPSs) are common in patients with Alzheimer's disease (AD) and are associated with accelerated cognitive impairment and earlier deaths. This review aims to explore the neural pathogenesis of NPSs in AD and its association with the progression of AD. We first provide a literature overview on the onset times of NPSs. Different NPSs occur in different disease stages of AD, but most symptoms appear in the preclinical AD or mild cognitive impairment stage and develop progressively. Next, we describe symptom-general and -specific patterns of brain lesions. Generally, the anterior cingulate cortex is a commonly damaged region across all symptoms, and the prefrontal cortex, especially the orbitofrontal cortex, is also a critical region associated with most NPSs. In contrast, the anterior cingulate-subcortical circuit is specifically related to apathy in AD, the frontal-limbic circuit is related to depression, and the amygdala circuit is related to anxiety. Finally, we elucidate the associations between the NPSs and AD by combining the onset time with the neural basis of NPSs. [ABSTRACT FROM AUTHOR]

White matter hyperintensity (WMH) is a common finding in aging population and considered to be a contributor to cognitive decline. Our study aimed to characterize the spatial patterns of WMH in different severities and explore its impact on cognition and brain microstructure in non-demented elderly. Lesions were both qualitatively (Fazekas scale) and quantitatively assessed among 321 community-dwelled individuals with MRI scanning. Voxel- and atlas-based analyses of the whole-brain white matter microstructure were performed. The WMH of the same severities was found to occur uniformly with a specific pattern of lesions. The severity of WMH had a significant negative association with the performance of working and episodic memory, beginning to appear in Fazekas 3 and 4. The white matter tracts presented significant impairments in Fazekas 3, which showed brain-wide changes above Fazekas 4. Lower FA in the superior cerebellar peduncle and left posterior thalamic radiation was mainly associated with episodic memory, and the middle cerebellar peduncle was significantly associated with working memory. These results support that memory is the primary domain to be affected by WMH, and the effect may potentially be influenced by tract-specific WM abnormalities. Fazekas scale 3 might be the critical stage predicting a future decline in cognition. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases such as Alzheimer's disease (AD) have been recognized to exhibit disease-specific brain vulnerability patterns. Apolipoprotein E ( APOE) ɛ4 allele imparts a high genetic risk of developing AD. Whether the APOE ɛ4 allele damages the brain when cognitive functions are still intact is important to understand, especially for possible early detection and intervention. This study aimed to examine the selective degeneration pattern associated with the APOE ɛ4 allele in the brains of cognitively normal elderly subjects. We enrolled 35 cognitively healthy ɛ4 carriers and 40 non-carriers (53 to 81 years old) to evaluate group differences in cortical thickness and brain activation during a memory-encoding task. We also assessed the functional connectivity of the brain regions with both structural and functional damages. The results from the neuropsychological tests showed that the performances of ɛ4 carriers and non-carriers were comparable. Primarily, we found that the precuneus exhibited thinner cortical thickness and decreased deactivation during memory encoding. Furthermore, the connectivity analyses show that carriers exhibited damaged connectivity of the precuneus to several regions in the default mode network and the attention/executive control network. Our study reveals the degeneration pattern of the ɛ4 allele, which could be used as a potential biomarker for early detection for possible interventions and treatments. Hum Brain Mapp 38:271-282, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aims Episodic memory depends on the maintenance of an intact default mode network (DMN), and is one of the earliest cognitive domains to become impaired in type 2 diabetes mellitus (T2DM). Therefore, exploring the alterations in task-related DMN deactivation and functional connectivity that affect episodic memory in T2DM will help to enhance our understanding of the allocation patterns underlying memory function in T2DM. Methods The current study assessed changes in DMN activation and architecture during the encoding of a functional magnetic resonance imaging task in 39 patients with T2DM and 41 healthy controls which were recruited from local communities in Beijing, China. Results We found that patients with T2DM and intact episodic memory performance exhibited reduced deactivation in the right precuneus and the middle temporal gyrus during the episodic memory task. Furthermore, an anterior-posterior disconnection phenotype and altered topological configuration of the DMN were observed in patients with T2DM using graph-theoretical approaches. Correlation analysis showed that altered deactivation during the episodic memory task was closely related to connectivity dysfunction and topological properties in the DMN. Conclusions Our findings demonstrate that the maintenance of memory in patients with T2DM involves reduced deactivation and impaired anterior-posterior connections in the DMN during encoding. [ABSTRACT FROM AUTHOR]

As the Apolipoprotein E (APOE) ɛ4 allele is a major genetic risk factor for sporadic Alzheimer's disease (AD), which has been suggested as a disconnection syndrome manifested by the disruption of white matter (WM) integrity and functional connectivity (FC), elucidating the subtle brain structural and functional network changes in cognitively normal ɛ4 carriers is essential for identifying sensitive neuroimaging based biomarkers and understanding the preclinical AD-related abnormality development. We first constructed functional network on the basis of resting-state functional magnetic resonance imaging and a structural network on the basis of diffusion tensor image. Using global, local and nodal efficiencies of these two networks, we then examined (i) the differences of functional and WM structural network between cognitively normal ɛ4 carriers and non-carriers simultaneously, (ii) the sensitivity of these indices as biomarkers, and (iii) their relationship to behavior measurements, as well as to cholesterol level. For ɛ4 carriers, we found reduced global efficiency significantly in WM and marginally in FC, regional FC dysfunctions mainly in medial temporal areas, and more widespread for WM network. Importantly, the right parahippocampal gyrus (PHG.R) was the only region with simultaneous functional and structural damage, and the nodal efficiency of PHG.R in WM network mediates the APOE ɛ4 effect on memory function. Finally, the cholesterol level correlated with WM network differently than with the functional network in ɛ4 carriers. Our results demonstrated ɛ4-specific abnormal structural and functional patterns, which may potentially serve as biomarkers for early detection before the onset of the disease. [ABSTRACT FROM AUTHOR]

Silent or asymptomatic lacunar infarcts (LACI) are common in elderly individuals, but it remains largely unclear how these often neglected silent brain infarcts lead to multiple domain cognitive deficits and even Alzheimer's disease (AD). In this study, we investigated the difference between patients with silent LACI in basal ganglia region and healthy controls for the structural and functional changes in the aspects of alterations of gray matter (GM) volume and intra-/inter-default mode network (DMN) and salience network (SN) connectivity. Thirty patients with silent LACI in the basal ganglia region and thirty healthy controls participated in the study. Voxel-based morphometry analysis was employed to measure the GM volume. We further investigated the intra/inter-network connectivity of DMN and SN using resting-state functional magnetic resonance imaging. Compared with healthy controls, patients performed worse in cognitive function in the aspects of general mental status, attention, and memory. The LACIs showed more severe GM atrophy in insula, anterior cingulate cortex, caudate, and superior temporal pole than controls. The connectivity within and between two networks was also reduced in patients. Importantly, the disrupted connectivity correlated with the patients' cognitive performance. Our findings support the hypothesis that silent lacunar infarcts result in cognitive decline, GM, and functional connectivity loss. [ABSTRACT FROM AUTHOR]

Background: Language ability differs between the sexes. However, it is unclear how this sex difference is moderated by genetic factors and how the brain interacts with genetics to support this specific language capacity. Previous studies have demonstrated that the sorting protein-related receptor (SORL1) polymorphism influences cognitive function and brain structure differently in males and females and is associated with Alzheimer's disease risk. Objective: The aim of this study was to investigate the effects of sex and the SORL1 rs1699102 (CC versus T carriers) genotype on language. Methods: 103 non-demented Chinese older adults from Beijing Aging Brain Rejuvenation Initiative (BABRI) database were included in this study. Participants completed language tests, T1-weighted structural magnetic resonance imaging (MRI) and resting-state functional MRI. Language test performance, gray matter volume, and network connections were compared between genotype and sex groups. Results: The rs1699102 polymorphism moderated the effects of sex on language performance, with the female having reversed language advantages in T carriers. The T allele carriers had lower gray matter volume in the left precentral gyrus. The effect of sex on language network connections was moderated by rs1699102; male CC homozygotes and female T carriers had higher internetwork connections, which were negatively correlated with language performance. Conclusion: These results suggest that SORL1 moderates the effects of sex on language, with T being a risk allele, especially in females. Our findings underscore the importance of considering the influence of genetic factors when examining sex effects. [ABSTRACT FROM AUTHOR]

Video surveillance systems have been widely deployed in public places such as shopping malls, hospitals, banks, and streets to improve the safety of public life and assets. In most cases, how to detect video abnormal events in a timely and accurate manner is the main goal of social public safety risk prevention and control. Due to the ambiguity of anomaly definition, the scarcity of anomalous data, as well as the complex environmental background and human behavior, video anomaly detection is a major problem in the field of computer vision. Existing anomaly detection methods based on deep learning often use trained networks to extract features. These methods are based on existing network structures, instead of designing networks for the goal of anomaly detection. This paper proposed a method based on Deep Support Vector Data Description (DSVDD). By learning a deep neural network, the input normal sample space can be mapped to the smallest hypersphere. Through DSVDD, not only can the smallest size data hypersphere be found to establish SVDD but also useful data feature representations and normal models can be learned. In the test, the samples mapped inside the hypersphere are judged as normal, while the samples mapped outside the hypersphere are judged as abnormal. The proposed method achieves 86.84% and 73.2% frame-level AUC on the CUHK Avenue and ShanghaiTech Campus datasets, respectively. By comparison, the detection results achieved by the proposed method are better than those achieved by the existing state-of-the-art methods. [ABSTRACT FROM AUTHOR]

Background: The aging population and high rates of Alzheimer's disease (AD) create significant medical burdens, prompting a need for early prevention. Targeting modifiable risk factors like vascular risk factors (VRFs), closely linked to AD, may provide a promising strategy for intervention. Objective: This study investigates how VRFs influence cognitive performance and brain structures in a community-based cohort. Methods: In this cross-sectional study, 4,667 participants over 50 years old, drawn from the Beijing Ageing Brain Rejuvenation Initiative project, were meticulously examined. Cognitive function and VRFs (diabetes mellitus, hypertension, hyperlipidemia, obesity, and smoking), were comprehensively assessed through one-to-one interviews. Additionally, a subset of participants (n = 719) underwent MRI, encompassing T1-weighted and diffusion-weighted scans, to elucidate gray matter volume and white matter structural network organization. Results: The findings unveil diabetes as a potent detriment to memory, manifesting in atrophy within the right supramarginal gyrus and diminished nodal efficiency and degree centrality in the right inferior parietal lobe. Hypertension solely impaired memory without significant structural changes. Intriguingly, individuals with comorbid diabetes and hypertension exhibited the most pronounced deficits in both brain structure and cognitive performance. Remarkably, hyperlipidemia emerged as a factor associated with enhanced cognition, and preservation of brain structure. Conclusions: This study illuminates the intricate associations between VRFs and the varied patterns of cognitive and brain structural damage. Notably, the synergistic effect of diabetes and hypertension emerges as particularly deleterious. These findings underscore the imperative to tailor interventions for patients with distinct VRF comorbidities, especially when addressing cognitive decline and structural brain changes. [ABSTRACT FROM AUTHOR]

Background: Pathologic processes in Creutzfeldt-Jakob disease (CJD) are not fully understood. Familial CJD (fCJD) gives opportunities to discover pathologic changes in the preclinical stage.Objective: To investigate cerebral glucose metabolism in the preclinical stage via 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in fCJD.Methods: Seven asymptomatic carriers of G114V mutation and six family members without PRNP mutation from the same fCJD kindred were included, and were followed for 2 years. Ten symptomatic CJD patients were also recruited. All subjects underwent standardized clinical examinations and 18F-FDG PET scans. Results were compared in three groups: baseline carriers against non-carriers (baseline analysis), changes after 2 years in carriers (follow-up analysis), and differences between symptomatic CJD patients and healthy controls (CJD patients analysis).Results: No carriers developed any neurological symptoms during 2-year follow-up. Baseline analysis: carriers demonstrates decreased metabolism (p < 0.001) in left and right postcentral, left fusiform, left superior temporal, left lingual, left superior parietal, and left Heschl gyrus. Follow-up analysis shows metabolic decline (p < 0.001) in right inferior temporal, left supra-marginal and left postcentral lobe, and increased metabolism (p < 0.001) in left fusiform, left angular, left thalamus, left Heschl's, right Rolandic operculum, and left superior parietal gyrus. CJD patients demonstrates decreased metabolism in right inferior triangularis frontal gyrus, right middle occipital gyrus, right putamen, right thalamus, and right middle temporal gyrus.Conclusion: Hypo-metabolism of parietal and temporal lobe can be detected by 18F-FDG PET in the preclinical stage of CJD. Subcortical area might compensate in the preclinical stage and decompensate in the symptomatic stage. [ABSTRACT FROM AUTHOR]

Background: Understanding the pathological characteristics of various mild cognitive impairment (MCI) subtypes is crucial for the differential diagnosis of dementia. The purpose of this study was to feature divergent symptom-deficit profiles in amnestic MCI (aMCI) and non-amnestic MCI (naMCI). Methods: T1 and DTI MRI data from a total of 158 older adults with 50 normal controls, 56 aMCI, and 52 naMCI were included. The voxel-wise gray matter volumes and the number of seed-based white matter fiber bundles were compared among these three groups. Furthermore, correlation and mediation analyses between the neuroimaging indices and cognitive measures were performed. Results: The aMCI with specific memory abnormalities was characterized by volumetric atrophy of the left hippocampus but not by damage in the linked white matter fiber bundles. Conversely, naMCI was characterized by both the altered volume of the right inferior frontal gyrus and the significant damage to fiber bundles traversing the region in all three directions, not only affecting fibers around the atrophied area but also distant fibers. Mediation analyses of gray matter-white matter-cognition showed that gray matter atrophy affects the number of fiber bundles and further affects attention and executive function. Meanwhile, fiber bundle damage also affects gray matter volume, which further affects visual processing and language. Conclusions: The divergent structural damage patterns of the MCI subtypes and cognitive dysfunctions highlight the importance of detailed differential diagnoses in the early stages of pathological neurodegenerative diseases to deepen the understanding of dementia subtypes and inform targeted early clinical interventions. [ABSTRACT FROM AUTHOR]

Objective: To create a comprehensive map of strategic lesion network localizations for neurological deficits, and identify prognostic neuroimaging biomarkers to facilitate the early detection of patients with a high risk of poor functional outcomes in acute ischemic stroke (AIS). Methods: In a large‐scale multicenter study of 7,807 patients with AIS, we performed voxel‐based lesion‐symptom mapping, functional disconnection mapping (FDC), and structural disconnection mapping (SDC) to identify distinct lesion and network localizations for National Institutes of Health Stroke Scale (NIHSS) score. Impact scores were calculated based on the odds ratios or t‐values of voxels from voxel‐based lesion‐symptom mapping, FDC, and SDC results. Ordinal regression models were used to investigate the predictive value of the impact scores on functional outcome (defined as the modified Rankin score at 3 months). Results: We constructed lesion, FDC, and SDC maps for each item of the NIHSS score, which provided insights into the neuroanatomical substrate and network localization of neurological function deficits after AIS. The lesion impact score of limb ataxia, the SDC impact score of limb deficit, and FDC impact score of sensation and dysarthria were significantly associated with modified Rankin Scale at 3 months. Adding the SDC impact score, FDC impact score, and lesion impact score to the NIHSS total score improved the performance in predicting functional outcomes, as compared with using the NIHSS score alone. Interpretation: We constructed comprehensive maps of strategic lesion network localizations for neurological deficits that were predictive of functional outcomes in AIS. These results may provide specifically localized targets for future neuromodulation therapies. ANN NEUROL 2023;94:572–584 [ABSTRACT FROM AUTHOR]

External prestressing technology has been widely applied to mitigate the cracking and deflection of variable cross-section continuous box-girder bridges. However, it remains a challenging task to establish a reliable safety monitoring and evaluation method in engineering applications. This paper takes a practical project as the research background and installs a sensing monitoring system on a bridge before strengthening. The evolutions of the strain at the characteristic sections, crack width, and deflection of bridges before and after strengthening were compared and analyzed. The construction process's safety and strengthening measures' effectiveness were monitored and evaluated. According to the construction process monitoring, the prestress tensioning process did not bring torsion to the bridge, and the strain at each monitoring point was within safe boundaries. After strengthening, the bridge appeared to camber with a value of 3–6 mm. The typical cracks were mitigated to different extents, and the closure degree of the crack width was (2.5–4)×10−2 mm. The strain distribution of the bridge was more stable after strengthening, and the frequency of large strain was significantly reduced, which reflected the improvement of section stiffness. The study can provide meaningful references for the optimization design and strengthening strategies of similar projects. [ABSTRACT FROM AUTHOR]

The A/T/N research framework has been proposed for the diagnosis and prognosis of Alzheimer's disease (AD). However, the spatial distribution of ATN biomarkers and their relationship with cognitive impairment and neuropsychiatric symptoms (NPS) need further clarification in patients with AD. We scanned 83 AD patients and 38 cognitively normal controls who independently completed the mini‐mental state examination and Neuropsychiatric Inventory scales. Tau, Aβ, and hypometabolism spatial patterns were characterized using Statistical Parametric Mapping together with [18F]flortaucipir, [18F]florbetapir, and [18F]FDG positron emission tomography. Piecewise linear regression, two‐sample t‐tests, and support vector machine algorithms were used to explore the relationship between tau, Aβ, and hypometabolism and cognition, NPS, and AD diagnosis. The results showed that regions with tau deposition are region‐specific and mainly occurred in inferior temporal lobes in AD, which extensively overlaps with the hypometabolic regions. While the deposition regions of Aβ were unique and the regions affected by hypometabolism were widely distributed. Unlike Aβ, tau and hypometabolism build up monotonically with increasing cognitive impairment in the late stages of AD. In addition, NPS in AD were associated with tau deposition closely, followed by hypometabolism, but not with Aβ. Finally, hypometabolism and tau had higher accuracy in differentiating the AD patients from controls (accuracy = 0.88, accuracy = 0.85) than Aβ (accuracy = 0.81), and the combined three were the highest (accuracy = 0.95). These findings suggest tau pathology is superior over Aβ and glucose metabolism to identify cognitive impairment and NPS. Its results support tau accumulation can be used as a biomarker of clinical impairment in AD. [ABSTRACT FROM AUTHOR]

To solve the problem of insufficient transverse connection of T-girder bridges, this paper investigated the strengthening method of two composite trusses symmetrically installed in mid-span. The composite truss included two top plates, four diagonal braces, and one horizontal brace. An experimental investigation was carried out to study the mechanical properties of reinforced concrete T-girder using single-point loading method under four load cases. The experimental results showed that the maximum transverse stiffness of T-girder specimens strengthened with composite trusses improved by 12.4% compared with control beams. Simultaneously, it had an excellent restraining effect on the cracks development. The maximum percentage decrease in the deflection corresponding to the maximum load when the reinforced concrete T-girder strengthened with composite trusses over the control beam of up to 39.7 was observed. In addition, the load transverse distribution coefficient was investigated according to rigid-jointed slab (girder) method. The composite trusses were chosen as intermediate diaphragm to calculate moment of inertia. The analytical model was in an accurate with the experimental result under the same loading condition. The optimize spacing of composite trusses was given from 600 mm (L /10) to 1200 mm (L /5), and thickness of top plate was 30 mm when the load transverse distribution coefficient was homogeneously distributed. Finally, a three-dimensional finite element model was used to evaluate the effectiveness of composite trusses. [ABSTRACT FROM AUTHOR]

Silent lacunar infarcts, which are present in over 20% of healthy elderly individuals, are associated with subtle deficits in cognitive functions. However, it remains largely unclear how these silent brain infarcts lead to cognitive deficits and even dementia. Here, we used diffusion tensor imaging tractography and graph theory to examine the topological organization of white matter networks in 27 patients with silent lacunar infarcts in the basal ganglia territory and 30 healthy controls. A whole-brain white matter network was constructed for each subject, where the graph nodes represented brain regions and the edges represented interregional white matter tracts. Compared with the controls, the patients exhibited a significant reduction in local efficiency and global efficiency. In addition, a total of eighteen brain regions showed significantly reduced nodal efficiency in patients. Intriguingly, nodal efficiency-behavior associations were significantly different between the two groups. The present findings provide new aspects into our understanding of silent infarcts that even small lesions in subcortical brain regions may affect large-scale cortical white matter network, as such may be the link between subcortical silent infarcts and the associated cognitive impairments. Our findings highlight the need for network-level neuroimaging assessment and more medical care for individuals with silent subcortical infarcts. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is a metabolic disorder and a risk factor for dementia and mild cognitive impairment (MCI), which could also increase the risk of progression from MCI to dementia. The present study evaluated the spontaneous neuronal activity of 31 patients with MCI using resting-state functional MRI. The patients were divided into two groups (17 MCI patients without diabetes, and 14 patients with type 2 diabetes who were considered as the MCI-DM group) and 17 well-matched healthy controls were also recruited. The amplitude of low-frequency fluctuations (ALFF) of spontaneous blood oxygen level dependent signals was then applied to assess neuroimaging changes. To further investigate the impact of type 2 diabetes on cognition, the correlation of ALFF and the neuropsychological tests for the MCI-DM and MCI group were calculated. MCI-DM patients showed diffused ALFF changes in a variety of brain regions that were significantly related to cognitive performance, including the frontal lobe, the temporal lobe, the hippocampus, the amygdala, and the precuneus during a resting state; whereas, the alterations were much less pronounced in the MCI patients without diabetes. These findings provide new insights into understanding essential of diabetes mellitus and may help to clarify the relationship between diabetes mellitus and dementia. [ABSTRACT FROM AUTHOR]

Background: Lobar cerebral microbleeds (CMBs), which can impair white matter (WM), are often concomitant with definite Alzheimer's disease (AD).Objective: To explore the features of cognitive impairments and WM disruptions due to lobar CMBs in patients with AD.Methods: There were 310 participants who underwent Florbetapir F18 (AV45) amyloid PET and susceptibility-weighted imaging. Participants with cognitive impairment and amyloid-β positive (ADCI) were included into three groups: ADCI without CMBs, with strictly lobar CMBs (SL-CMBs), and with mixed CMBs (M-CMBs). Tract-based spatial statistics were performed to detect the group differences in WM integrity.Results: There were 82 patients and 29 healthy controls finally included. A decreasing tendency in memory and executive performance can be found among HCs > no CMBs (n = 16) >SL-CMBs (n = 41) >M-CMBs (n = 25) group. Compared to no CMBs, M-CMBs group had significantly decreased fractional anisotropy in left anterior thalamic radiation (ATR), forceps major, forceps minor and inferior longitudinal fasciculus, bilateral inferior fronto-occipital fasciculus (IFOF), and superior longitudinal fasciculus. M-CMBs group also had lower fractional anisotropy in left ATR, IFOF, uncinate fasciculus, and forceps minor compared with SL-CMBs. Furthermore, analysis of Pearson correlation indicated damages in discrepant WMs were positively associated with impairment of memory, executive function, and attention.Conclusion: This study showed lobar CMBs had intensively aggravated cognitive impairments associated with extensive WM damages in definite AD. These findings highlight that lobar CMBs play an important role in AD progression and need to be taken into consideration for the early detection of AD. [ABSTRACT FROM AUTHOR]

Patients with type 2 diabetes mellitus (T2DM) have a considerably high risk of developing dementia, especially for those with mild cognitive impairment (MCI). The investigation of the microstructural change of white matter (WM) between T2DM with amnesic MCI (T2DM-aMCI) and T2DM with normal cognition (T2DM-NC) and their relationships to cognitive performances can help to understand the brain variations in T2DM-related amnesic cognitive impairment. In the current study, 36 T2DM-aMCI patients, 40 T2DM-NC patients, and 40 healthy control (HC) individuals underwent diffusion tensor image and T1-weighted MRI scans and comprehensive cognition assessments. All of these cognitive functions exhibited intergroup ranking differences in patients. The T2DM-NC patients and HC individuals did not reveal any significant differences in WM integrity. The T2DM-aMCI patients showed disrupted integrity in multiple WM tracts compared with HC and T2DM-NC. Specifically, the damaged WM integrity of the right inferior fronto-occipital fasciculus and the right inferior longitudinal fasciculus exhibited significant correlations with episodic memory and attention function impairment in T2DM patients. Furthermore, cognitive impairment-related WM microstructural damage was associated with the degeneration of cortex connected to the affected WM tract. These findings indicate that degeneration exists extensively in WM tracts in T2DM-aMCI, whereas no brain WM damage is evident in T2DM-NC. [ABSTRACT FROM AUTHOR]

Adults without diabetes are not completely healthy; they are probably heterogeneous with several potential health problems. The management of hemoglobin A1c (HbA1c) is crucial among patients with diabetes; but whether similar management strategy is needed for adults without diabetes is unclear. Thus, this study aimed to investigate the associations of visit-to-visit HbA1c variability with incident dementia and hippocampal volume among middle-aged and older adults without diabetes, providing potential insights into this question. We conducted a prospective analysis for incident dementia in 10,792 participants (mean age 58.9 years, 47.8 % men) from the UK Biobank. A subgroup of 3793 participants (mean age 57.8 years, 48.6 % men) was included in the analysis for hippocampal volume. We defined HbA1c variability as the difference in HbA1c divided by the mean HbA1c over the 2 sequential visits ([latter − former]/mean). Dementia was identified using hospital inpatient records with ICD-9 codes. T1-structural brain magnetic resonance imaging was conducted to derive hippocampal volume (normalized for head size). The nonlinear and linear associations were examined using restricted cubic spline (RCS) models, Cox regression models, and multiple linear regression models. During a mean follow-up (since the second round) of 8.4 years, 90 (0.8 %) participants developed dementia. The RCS models suggested no significant nonlinear associations of HbA1c variability with incident dementia and hippocampal volume, respectively (All P > 0.05). Above an optimal cutoff of HbA1c variability at 0.08, high HbA1c variability (increment in HbA1c) was associated with an increased risk of dementia (Hazard Ratio, 1.88; 95 % Confidence Interval, 1.13 to 3.14, P = 0.015), and lower hippocampal volume (coefficient, −96.84 mm3, P = 0.037), respectively, in models with adjustment of covariates including age, sex, etc. Similar results were found for a different cut-off of 0. A series of sensitivity analyses verified the robustness of the findings. Among middle-aged and older adults without diabetes, increasing visit-to-visit HbA1c variability was associated with an increased dementia risk and lower hippocampal volume. The findings highlight the importance of monitoring and controlling HbA1c fluctuation in apparently healthy adults without diabetes. • High visit-to-visit HbA1c variability was associated with an increased dementia risk. • High visit-to-visit HbA1c variability was associated with low hippocampal volume. • Monitoring HbA1c fluctuation is of great importance in adults without diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Exploring how risk genes cumulatively impair brain function in preclinical phase (i.e., in cognitively normal elderly) could provide critical insights into the pathophysiology of Alzheimer's disease (AD). Working memory impairment has always been a considerable cognitive deficit in AD, which is likely under complex genetic control. Though, the APOE ɛ4 allele could damage the working memory performance in normal elderly, dissociable results have been reported. This allele may exert specific effects in contexts with other genetic variants. The rs2618516 in the spondin 1 gene (SPON1) has been associated with AD risk and brain structure in the elderly. SPON1 may interact with APOE through processing the amyloid precursor protein and suppressing amyloid‐β levels. Using neuropsychological tasks from 710 individuals, we found significant SPON1 × APOE genotype interactions in working memory and executive function performances. Moreover, such interaction was also found in regional brain activations based on functional magnetic resonance imaging data with the n‐back working memory task performed in a sub‐cohort of 64 subjects. The effects of ɛ4 allele on activation of right inferior frontal gyrus, triangular part (IFGtriang.R) were modulated by rs2618516 in a working memory task. Furthermore, lower IFGtriang.R activation was associated with better cognitive functions. Moreover, the IFGtriang.R activation could mediate the impacts of SPON1 × APOE interactions on working memory performance. These findings suggested the importance of weighing APOE effects on brain activation under the working memory task within the context of the SPON1 genotype. [ABSTRACT FROM AUTHOR]

The alteration of the default mode network (DMN) functional connectivity (FC) has been reported in patients with amnestic mild cognitive impairment (aMCI) as a predictor of Alzheimer's disease (AD). However, no studies exist that examined stage-dependent DMN FC changes throughout the course of aMCI. The present study aims to characterize patterns of DMN FC over three aMCI stages as first defined. Utilizing the extreme groups approach on the performance of memory tasks, aMCI subjects were divided into mild, moderate, and severe stages. Independent component analysis was used to assess DMN for individual patients in each of the three cross-sectionally defined stages. Instead of finding that continued monotonic decline was the case for the hippocampus volume, which we also investigated in this study, we observed an increase in DMN functional connectivity from mild aMCI to moderate aMCI and a decrease to severe aMCI, mainly in the left precuneus and superior parietal lobe. Moreover, the FC was significantly associated with cognitive performance. Though a longitudinal study is needed to confirm these results, our cross-sectional finding is that non-linear FC changes in DMN could be a characteristic of prodromal early disease development. [ABSTRACT FROM AUTHOR]

• A new hybrid strengthening method with core-filling and external unbonded prestressing steel strands was proposed. • A quadratic relationship was shown between damage and enhancement coefficients. • Analytical and finite element models were developed for evaluating the flexural behaviours of hollow core beams strengthened with hybrid strengthening method. Extensive investigations show that the core-filling method can markedly improve the shear behaviour of hollow core beams (HCBs). However, few investigations were carried out to study the flexural behaviours of the HCBs strengthened with this method. In this study, the flexural behaviours were first studied, where the HCBs were strengthened with a hybrid strengthening method of the core-filling and external unbonded prestressing steel strands. Six types of HCB specimens were fabricated and investigated. The initial damage and prestress levels were selected as the main parameters. Before strengthening, the HCB specimens were loaded to 40.6 %, 66.3 % and 100 % of their ultimate load to pre-set some cracks in the concrete beams, which corresponded to the maximum crack widths of 0.2 mm, 0.4 mm and wider than 1.5 mm, respectively. Compared with the control beam, the strengthening with the core-filling improved the flexural load carrying capacity by 3.93 %, whereas the hybrid strengthening method improved by 33.67 %; the cracking loads for the two strengthening methods increased by 10.34 % and 128.28 %, respectively. Moreover, the experimental results showed that the initial flexural stiffness can be markedly improved with the hybrid strengthening method. However, the initial damage level had little influence on the final crack width. In addition, an analytical model was proposed to evaluate the flexural behaviors of the strengthened HCBs. The simulation results of the preload, ultimate load and failure modes agreed well with the experimental ones. [ABSTRACT FROM AUTHOR]

Objectives: Hypertension is considered a risk factor of cognitive impairments and could result in white matter changes. Current studies on hypertension-related white matter (WM) changes focus only on regional changes, and the information about global changes in WM structure network is limited.Methods: We assessed the cognitive function in 39 hypertensive patients and 37 healthy controls with a battery of neuropsychological tests. The WM structural networks were constructed by utilizing diffusion tensor tractography and calculated topological properties of the networks using a graph theoretical method. The direct and indirect correlations among cognitive impairments, brain WM network disruptions and hypertension were analyzed with structural equation modelling (SEM).Results: Hypertensive patients showed deficits in executive function, memory and attention compared with controls. An aberrant connectivity of WM networks was found in the hypertensive patients (P Eglob = 0.005, P Lp = 0.005), especially in the frontal and parietal regions. Importantly, SEM analysis showed that the decline of executive function resulted from aberrant WM networks in hypertensive patients (p = 0.3788, CFI = 0.99).Conclusions: These results suggest that the cognitive decline in hypertensive patients was due to frontal and parietal WM disconnections. Our findings highlight the importance of brain protection in hypertension patients.Key Points: • Hypertension has a negative effect on the performance of the cognitive domains • Reduced efficiencies of white matter networks were shown in hypertension • Disrupted white matter networks are responsible for poor cognitive function in hypertension. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is accompanied by cognitive impairment and is associated with an increased risk of dementia. Damage to brain structures such as white matter network disruption may underlie this cognitive disturbance. In the present study, 886 non-diabetic and 163 type 2 diabetic participants completed a battery of neuropsychological tests. Among them, 38 diabetic patients and 34 non-diabetic participants that matched the patients for age/sex/education received a magnetic resonance imaging-based diffusion tensor imaging. Then we calculated the topological properties of the white matter network using a graph theoretical method to investigate network efficiency differences between groups. We found that type 2 diabetic patients had inferior performances compared to the non-diabetic controls, in several cognitive domains involving executive function, spatial processing, memory, and attention. We also found that diabetic patients exhibited a disrupted topological organization of the white matter network (including the global network properties, i.e., network strength, global efficiency, local efficiency and shortest path length, and the nodal efficiency of the right rolandic operculum) in the brain. Moreover, those global network properties and the nodal efficiency of the right rolandic operculum both had positive correlations with executive function in the patient group. The results suggest that type 2 diabetes mellitus leads to an alteration in the topological organization of the cortical white matter network and this alteration may account for the observed cognitive decline. [ABSTRACT FROM AUTHOR]

The apolipoprotein E (APOE) ɛ4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). This study aimed to investigate abnormality of white matter integrity and its relationship to cognitive impairments in Chinese non-demented elderly with and without the ɛ4 allele. We assessed cognitive differences using a series of neuropsychological tests and assessed white matter integrity using tract-based spatial statistics to measure mean diffusivity and fractional anisotropy. We determined that there were no statistically significant group differences in any neuropsychological measures. However, APOEɛ4 carriers without cognitive decline exhibited widespread disruption of the white matter tracts in several areas, including the cingulum, fornix, corpus callosum, and corona radiate. Furthermore, a correlation analysis in ɛ4 carriers indicated that disruption of the right fornix stria terminalis and the genu of the corpus callosum were positively associated with cognitive impairment, including memory, executive function, spatial processing, attention, and language. The present study reveals the deleterious effects of the ɛ4 allele on white matter, and this damage may potentially serve as a biomarker in preclinical investigations. Our promising results encourage further investigation using a multidimensional longitudinal approach with larger samples. [ABSTRACT FROM AUTHOR]

The polymorphism of the Apolipoprotein E (APOE) promoter rs405509 can regulate the transcriptional activity of the APOE gene and is related to Alzheimer's disease (AD). However, its effects on cognitive performance and the underlying brain mechanisms remain unknown. Here, we performed a battery of neuropsychological tests in a large sample (837 subjects) of nondemented elderly Chinese people, and explored the related brain mechanisms via the construction of diffusion MRI-based structural connectome and graph analysis from a subset (84 subjects) of the sample. Cognitively, the rs405509 risk allele (TT) carriers showed decreased attention and execution functions compared with noncarriers (GG/GT). Regarding the topological alterations of the brain connectome, the risk allele group exhibited reduced global and local efficiency of white matter structural networks, mainly in the left anterior and posterior cingulate cortices (PCC). Importantly, the efficiency of the left PCC is correlated with the impaired attention function and mediates the impacts of the rs405509 genotype on attention. These results demonstrated that the rs405509 polymorphism affects attention function in nondemented elderly people, possibly by modulating brain structural connectivity of the PCC. This polymorphism may help us to understand the neural mechanisms of cognitive aging and to serve as a potential marker assessing the risk of AD. [ABSTRACT FROM AUTHOR]

White matter lesions (WMLs) are of considerable research interest because of their high prevalence and serious consequences, such as stroke and dementia. Most existing studies of WMLs have focused on severe WMLs, but mild WMLs, which are clinically and fundamentally significant, have been largely neglected. The present study is a comprehensive investigation on the injury pattern and on the anatomical, functional, and cognitive changes related to mild WMLs. These results may provide better understanding mild WMLs. Fifty-one human subjects with mild WMLs and 49 control participants completed serial neuropsychological tests and underwent a 3-T magnetic resonance imaging (MRI) scan that included diffusion tensor imaging, a resting-state functional MRI, and a structural MRI. We found declines in cognitive functions such as global function, executive function, and episodic memory in mild WMLs subjects. The white matter injuries in the mild WMLs subjects were mainly in the fibers that projected to frontal areas, while gray matter structures were relatively intact. The overall resting state function of the frontal area was significantly increased. The integrity of the neural fibers in the inferior fronto-occipital fasciculus and the inferior longitudinal fasciculus was significantly correlated with the cognitive scores in executive function and episodic memory in both the control and the mild WMLs group. These findings demonstrate that mild WMLs subjects exhibit abnormalities in both white matter structure and functional intrinsic brain activity and that such changes are related to several types of cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Objectives To estimate the prevalence of mild cognitive impairment ( MCI) in Beijing, China, and to explore the potential protective and risk factors for MCI. Design Population-based survey. Setting The Beijing Ageing Brain Rejuvenation Initiative ( BABRI). Participants Participants randomly recruited from BABRI (N = 1,211). Measurements Participants underwent a battery of neuropsychological examinations to determine cognitive function and answered a series of personal questions. The prevalence of MCI and its subtypes were computed using Petersen's criteria. Influencing factors for MCI were estimated based on participant medical history, lifestyle, diet, and leisure activities. Results One thousand twenty (aged >55, mean 63.9 ± 6.6; 36.7% male) subjects completed the neuropsychological tests. The overall prevalence of MCI was 15.7%, with single-domain amnestic, multiple-domain amnestic, and nonamnestic subtype prevalences of 6.4%, 3.7%, and 5.6%, respectively. Eight hundred sixty-four subjects were used for the case-control analysis. Hypertension, diabetes mellitus, and cerebrovascular disease were found to be associated with MCI. Healthy diet and greater involvement in physical, intellectual, and social activities were associated with a lower risk of MCI. Conclusion The prevalence of MCI was compatible with that found in previous published reports, and the information on the epidemiology of MCI, especially risk factors, may help to explore therapeutic strategies and preventive approaches to delay conversion to dementia. [ABSTRACT FROM AUTHOR]

To address the condition that community-based geriatric services for the assessment and promotion of older adults' cognitive ability systemically aimed at delaying or preventing dementia is lacking in China. A community-based model including cognitive assessment and training, geriatric health guidance and long-term support was designed based on a prospective cohort study. Participants (N = 5593) were all from an ongoing cohort study, the Beijing Aging Brain Rejuvenation Initiative (BABRI) study. We conducted receiver operating characteristic, stepwise logistic regression and branch-and-bound algorithm analyses to select the most effective tests from the BABRI neuropsychological test battery. Canonical discriminant analysis was conducted to extract the first canonical variable as a composite index of the tests. In addition, we developed comprehensive surveys and computerized cognitive trainings targeting every cognitive domain. The BABRI brain health system (BABRI-BHS) was designed to include SCREEN, ASSESS, and DIAGNOSE sessions. When distinguishing cognitively impaired older adults from cognitively healthy older adults, the canonical variable extracted from tests in the SCREEN session achieved an area under the curve (AUC) of 0.730 [95% confidence interval (95% CI) 0.671–0.789], with a sensitivity of 0.630 and a specificity of 0.780; in the ASSESS session, the AUC was 0.906 (95% CI 0.894–0.917), the sensitivity was 0.809, and the specificity was 0.854. A stepwise screening pathway is recommended when using the BABRI-BHS in communities to divide older adults into subtypes and to provide targeted interventions and long-term geriatric health guidance. The BABRI-BHS is an effective and efficient geriatric health care solution that is suitable for community-based dementia risk screening, providing stepwise cognitive assessments and helping older adults acquire tailored interventions and guidance conveniently. [ABSTRACT FROM AUTHOR]

Normal aging is accompanied by structural degeneration and glucose hypometabolism in the human brain. However, the relationship between structural network disconnections and hypometabolism in normal aging remains largely unknown. In the present study, by combining MRI and PET techniques, we investigated the metabolic mechanism of the structural brain connectome and its relationship with normal aging in a cross-sectional, community-based cohort of 42 cognitively normal elderly individuals aged 57–84 years. The structural connectome was constructed based on diffusion MRI tractography, and the network efficiency metrics were quantified using graph theory analyses. FDG-PET scanning was performed to evaluate the glucose metabolic level in the cortical regions of the individuals. The results of this study demonstrated that both network efficiency and cortical metabolism decrease with age (both p < 0.05). In the subregions of the bilateral thalamus, significant correlations between nodal efficiency and cortical metabolism could be observed across subjects. Individual-level analyses indicated that brain regions with higher nodal efficiency tend to exhibit higher metabolic levels, implying a tight coupling between nodal efficiency and glucose metabolism (r = 0.56, p = 1.15 × 10−21). Moreover, efficiency-metabolism coupling coefficient significantly increased with age (r = 0.44, p = 0.0046). Finally, the main findings were also reproducible in the ADNI dataset. Together, our results demonstrate a close coupling between structural brain connectivity and cortical metabolism in normal elderly individuals and provide new insight that improve the present understanding of the metabolic mechanisms of structural brain disconnections in normal aging. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Although it has been studied for years, the pathogenesis of AD is still controversial. Genetic factors may play an important role in pathogenesis, with the apolipoprotein E (APOE) gene among the greatest risk factors for AD. In this review, we focus on the influence of genetic factors, including the APOE gene, the interaction between APOE and other genes, and the polygenic risk factors for cognitive function and dementia. The presence of the APOE ε4 allele is associated with increased AD risk and reduced age of AD onset. Accelerated cognitive decline and abnormal internal environment, structure, and function of the brain were also found in ε4 carriers. The effect of the APOE promoter on cognition and the brain was confirmed by some studies, but further investigation is still needed. We also describe the effects of the associations between APOE and other genetic risk factors on cognition and the brain that exhibit a complex gene–gene interaction, and we consider the importance of using a polygenic risk score to investigate the association between genetic variance and phenotype. [ABSTRACT FROM AUTHOR]