Matrix metalloproteinase 9 (MMP-9) activity, hippocampal extracellular free water, and cognitive deficits are associated with each other in early phase psychosis.

Increasing evidence points toward the role of the extracellular matrix, specifically matrix metalloproteinase 9 (MMP-9), in the pathophysiology of psychosis. MMP-9 is a critical regulator of the crosstalk between peripheral and central inflammation, extracellular matrix remodeling, hippocampal development, synaptic pruning, and neuroplasticity. Here, we aim to characterize the relationship between plasma MMP-9 activity, hippocampal microstructure, and cognition in healthy individuals and individuals with early phase psychosis. We collected clinical, blood, and structural and diffusion-weighted magnetic resonance imaging data from 39 individuals with early phase psychosis and 44 age and sex-matched healthy individuals. We measured MMP-9 plasma activity, hippocampal extracellular free water (FW) levels, and hippocampal volumes. We used regression analyses to compare MMP-9 activity, hippocampal FW, and volumes between groups. We then examined associations between MMP-9 activity, FW levels, hippocampal volumes, and cognitive performance assessed with the MATRICS battery. All analyses were controlled for age, sex, body mass index, cigarette smoking, and years of education. Individuals with early phase psychosis demonstrated higher MMP-9 activity (p < 0.0002), higher left (p < 0.05) and right (p < 0.05) hippocampal FW levels, and lower left (p < 0.05) and right (p < 0.05) hippocampal volume than healthy individuals. MMP-9 activity correlated positively with hippocampal FW levels (all participants and individuals with early phase psychosis) and negatively with hippocampal volumes (all participants and healthy individuals). Higher MMP-9 activity and higher hippocampal FW levels were associated with slower processing speed and worse working memory performance in all participants. Our findings show an association between MMP-9 activity and hippocampal microstructural alterations in psychosis and an association between MMP-9 activity and cognitive performance. Further, more extensive longitudinal studies should examine the therapeutic potential of MMP-9 modulators in psychosis.

Diagnostic approach with Z-score mapping to reduce artifacts caused by cerebral atrophy in regional CBF assessment of mild cognitive impairment (MCI) and Alzheimer's disease by [99mTc]-ECD and SPECT.

PURPOSE: The aim of this study was to develop a novel approach that enhanced diagnostic accuracy in the diagnosis of mild cognitive impairment (MCI) and early Alzheimer's disease (AD) using cerebral perfusion SPECT by minimizing artifacts caused by cerebral atrophy. MATERIALS AND METHODS: [99mTc]-ECD and SPECT studies were performed on 15 cognitively normal patients, 40 patients with MCI, and 16 patients with AD. SPECT images were compared using SPM. The atrophy correction method was incorporated to reduce artifacts through the MRI masking procedure. Regional Z-score, percent extent, and atrophy correction rate were obtained and compared. The Z-score mapping program was structured as a single package that ran semi-automatically. RESULTS: The method significantly reduced regional Z-score in most regions, leading to improved estimates. The mean atrophy correction rate ranged from 10.4 to 12.0%. In MCI and AD, the convexities of the frontal and parietal lobes and the posterior medial cerebrum were particularly sensitive to cerebral atrophy, and the Z-scores were overestimated, whereas the posterior cingulate cortex and the cerebellum were less sensitive. The diagnostic accuracy for MCI increased from 67 to 69% and for AD from 78 to 82%. CONCLUSION: The proposed approach provided more precise Z-scores with less over- or underestimation, artifacts, and improved diagnostic accuracy, being recommended for clinical studies.

Cortical Thickness Patterns of Cognitive Impairment Phenotypes in Drug-Resistant Temporal Lobe Epilepsy.

OBJECTIVE: In temporal lobe epilepsy (TLE), a taxonomy classifying patients into 3 cognitive phenotypes has been adopted: minimally, focally, or multidomain cognitively impaired (CI). We examined gray matter (GM) thickness patterns of cognitive phenotypes in drug-resistant TLE and assessed potential use for predicting postsurgical cognitive outcomes. METHODS: TLE patients undergoing presurgical evaluation were categorized into cognitive phenotypes. Network edge weights and distances were calculated using type III analysis of variance F-statistics from comparisons of GM regions within each TLE cognitive phenotype and age- and sex-matched healthy participants. In resected patients, logistic regression models (LRMs) based on network analysis results were used for prediction of postsurgical cognitive outcome. RESULTS: A total of 124 patients (63 females, mean age ± standard deviation [SD] = 36.0 ± 12.0 years) and 117 healthy controls (63 females, mean age ± SD = 36.1 ± 12.0 years) were analyzed. In the multidomain CI group (n = 66, 53.2%), 28 GM regions were significantly thinner compared to healthy controls. Focally impaired patients (n = 37, 29.8%) showed 13 regions, whereas minimally impaired patients (n = 21, 16.9%) had 2 significantly thinner GM regions. Regions affected in both multidomain and focally impaired patients included the anterior cingulate cortex, medial prefrontal cortex, medial temporal, and lateral temporal regions. In 69 (35 females, mean age ± SD = 33.6 ± 18.0 years) patients who underwent surgery, LRMs based on network-identified GM regions predicted postsurgical verbal memory worsening with a receiver operating curve area under the curve of 0.70 ± 0.15. INTERPRETATION: A differential pattern of GM thickness can be found across different cognitive phenotypes in TLE. Including magnetic resonance imaging with clinical measures associated with cognitive profiles has potential in predicting postsurgical cognitive outcomes in drug-resistant TLE. ANN NEUROL 2024;95:984-997.

Intra-Atlas Node Size Effects on Graph Metrics in fMRI Data: Implications for Alzheimer's Disease and Cognitive Impairment.

Network neuroscience, a multidisciplinary field merging insights from neuroscience and network theory, offers a profound understanding of neural network intricacies. However, the impact of varying node sizes on computed graph metrics in neuroimaging data remains underexplored. This study addresses this gap by adopting a data-driven methodology to delineate functional nodes and assess their influence on graph metrics. Using the Neuromark framework, automated independent component analysis is applied to resting state fMRI data, capturing functional network connectivity (FNC) matrices. Global and local graph metrics reveal intricate connectivity patterns, emphasizing the need for nuanced analysis. Notably, node sizes, computed based on voxel counts, contribute to a novel metric termed 'node-metric coupling' (NMC). Correlations between graph metrics and node dimensions are consistently observed. The study extends its analysis to a dataset comprising Alzheimer's disease, mild cognitive impairment, and control subjects, showcasing the potential of NMC as a biomarker for brain disorders. The two key outcomes underscore the interplay between node sizes and resultant graph metrics within a given atlas, shedding light on an often-overlooked source of variability. Additionally, the study highlights the utility of NMC as a valuable biomarker, emphasizing the necessity of accounting for node sizes in future neuroimaging investigations. This work contributes to refining comparative studies employing diverse atlases and advocates for thoughtful consideration of intra-atlas node size in shaping graph metrics, paving the way for more robust neuroimaging research.

Neurometabolic and Brain Functional Alterations Associated with Cognitive Impairment in Patients with Myasthenia Gravis: A Combined 1H-MRS and fMRI Study.

Whether patients with myasthenia gravis (MG) exhibit cognitive impairment is controversial. Also the underlying mechanisms are unknown. We aimed to investigate alterations in cognitive function, neurometabolite levels, and brain function in patients with MG and to explore the associations between abnormal regional brain functional activity, neurometabolite concentrations in the MPFC and left thalamus, and cognitive activity in patients with MG. Neuropsychological tests, proton magnetic resonance spectroscopy, and resting-state functional magnetic resonance imaging were performed on 41 patients with MG and 45 race-, sex-, age-, and education-matched healthy controls (HCs). The results suggest that MG is accompanied by cognitive decline, as indicated by global cognitive function, visual-spatial function, language, memory, abnormalities in regional brain functional activity, and neurometabolite alterations (including GABA, NAA, and Cho) in the medial prefrontal cortex (MPFC) and left thalamus. Cognitive impairment in patients with MG may be related to abnormal regional brain functional activity and changes in neurometabolites, and regional brain functional activity may be modulated by specific neurometabolites.

Association between plasma CTRPs with cognitive impairment and neurodegeneration of Alzheimer's disease.

AIMS: Recent evidence indicated the biological basis of complement 1q (C1q)/tumor necrosis factor (TNF)-related protein (CTRP) 3, 4, and 14 for affecting brain structure and cognitive function. Thus, we aimed to investigate the association between plasma CTRPs with Alzheimer's disease (AD). METHODS: A multicenter, cross-sectional study recruited patients with AD (n = 137) and cognitively normal (CN) controls (n = 140). After the data collection of demographic characteristics, lifestyle risk factors, and medical history, plasma levels of tau phosphorylated at threonine 217 (pT217), pT181, neurofilament light (NfL), CTRP3, 4, and 14 were examined and compared. Multivariate logistic regression analysis was applied to determine associations of plasma CTPRs with the presence of AD. The correlation analysis was used to explore correlations between plasma CTPRs with scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL) scale, and Clinical Dementia Rating Sum of Boxes (CDR-SB), and levels of plasma pT217, pT181, and NfL. Receiver-operating characteristic (ROC) analysis and Delong's test were used to determine the diagnostic power of plasma CTPRs. RESULTS: Plasma levels of CTRP3, 4, and 14 were higher in AD group than those in CN group. After adjusting for conventional risk factors, CTRP3, CTRP4, and CTRP14 were associated with the presence of AD. In AD patients, CTRP3 was negatively correlated with scores of MMSE and MoCA, while positively correlated with ADL score, CDR-SB score, pT217, and pT181; CTRP4 was positively correlated with CDR-SB score, pT181, and NfL; CTRP14 was negatively correlated with MMSE score, while positively correlated with CDR-SB score, pT217, and NfL. An independent addition of CTRP3 and 4 to the basic model combining age, sex, years of education, APOE4 status, BMI, TG, and HDL-C led to a significant improvement in diagnostic power for AD, respectively. CONCLUSIONS: All the findings preliminarily uncovered associations between plasma CTRPs and AD and suggested the potential of CTRPs as a blood-derived biomarker for AD.

The Early Postoperative Course of Cognitive Function and Preoperative Cerebrovascular Reserve.

BACKGROUND: Patients with severe steno-occlusive disease of a main cerebral artery without causative lesions on magnetic resonance imaging (MRI) often develop cognitive impairment. However, the effects of revascularization surgery and the source of the cognitive impairment remain unclear. Therefore, we investigated the early postoperative course of cognitive function and its association with cerebral blood flow (CBF), cerebrovascular reserve (CVR), white matter disease (WMD), lacunar infarction, and cerebrovascular risk factors. METHODS: Cognitive function was examined using neurobehavioral cognitive status examination (COGNISTAT) in 52 patients with steno-occlusive disease of a main cerebral artery before and at 6 months after superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. We examined how cognition changed before and at 1, 3, and 6 months after STA-MCA anastomosis in 27 of 52 patients. CVR and CBF were calculated from 123I-N-isopropyl-p-iodoamphetamine single photon emission computed tomography, in addition to other cerebrovascular risk factors in 34 of 52 patients. Cerebral infarction and WMD (periventricular hyperintensity [PVH] and deep subcortical white matter hyperintensity) were also evaluated preoperatively by MRI. RESULTS: COGNISTAT scores improved at 1 month after STA-MCA anastomosis in patients with severe steno-occlusive disease of a main cerebral artery. Multiple stepwise regression analysis revealed that CVR (regression coefficient = -2.237, p = 0.0020) and PVH (regression coefficient = 2.364, p = 0.0029) were the best predictors of postoperative improvement in COGNISTAT scores (R 2 = 0.415; p = 0.0017). CONCLUSION: Cognitive function improves in relation to preoperative CVR and PVH early after STA-MCA anastomosis in patients with steno-occlusive disease of a main cerebral artery.

Abnormal brain activities of cognitive processes in cerebral small vessel disease: A systematic review of task fMRI studies.

Cerebral small vessel disease (CSVD) is characterized by widespread functional changes in the brain, as evident from abnormal brain activations during cognitive tasks. However, the existing findings in this area are not yet conclusive. We systematically reviewed 25 studies reporting task-related fMRI in five cognitive domains in CSVD, namely executive function, working memory, processing speed, motor, and affective processing. The findings highlighted: (1) CSVD affects cognitive processes in a domain-specific manner; (2) Compensatory and regulatory effects were observed simultaneously in CSVD, which may reflect the interplay between the negative impact of brain lesion and the positive impact of cognitive reserve. Combined with behavioral and functional findings in CSVD, we proposed an integrated model to illustrate the relationship between altered activations and behavioral performance in different stages of CSVD: functional brain changes may precede and be more sensitive than behavioral impairments in the early pre-symptomatic stage; Meanwhile, compensatory and regulatory mechanisms often occur in the early stages of the disease, while dysfunction/decompensation and dysregulation often occur in the late stages. Overall, abnormal hyper-/hypo-activations are crucial for understanding the mechanisms of small vessel lesion-induced behavioral dysfunction, identifying potential neuromarker and developing interventions to mitigate the impact of CSVD on cognitive function.

Relationship Between Microstructural Alterations and Cognitive Decline After Whole-Brain Radiation Therapy for Brain Metastases: An Exploratory Whole-Brain MR Analysis Based on Neurite Orientation Dispersion and Density Imaging.

BACKGROUND: Cognitive impairment frequently occurs in patients with brain metastases (BM) after whole-brain radiotherapy (WBRT). It is crucial to explore the underlying mechanisms of cognitive impairment in BM patients receiving WBRT. PURPOSE: To detect brain microstructural alterations in patients after WBRT by neurite orientation dispersion and density imaging (NODDI), and evaluate the performance of microstructural alterations in predicting cognitive impairment. STUDY TYPE: Prospective. POPULATION: Twenty-six patients (seven female; mean age, 60.9 years). FIELD STRENGTH/SEQUENCE: 3-T, multi-shell diffusion-weighted single-shot echo-planar sequence. Three-dimensional magnetization-prepared rapid acquisition with gradient echo sequence. ASSESSMENT: Mini-mental state examination (MMSE) evaluations were conducted prior to, following, 1 and 3 months after WBRT. The diffusion data were collected twice, 1 week before and 1 week after WBRT. NODDI analysis was conducted to assess microstructural alterations in whole brain (orientation dispersion index, neurite density index, volume fraction of isotropic water molecules). Reliable change indices (RCI) of MMSE were used to measure cognitive decline. The performance of support vector machine models based on NODDI parameters and clinical features (prednisone usage, tumor volume, etc.) in predicting MMSE-RCI was evaluated. STATISTICAL TESTS: Paired t-test to assess alterations of NODDI measures and MMSE during follow-up. Statistical significance level of P-value <0.05. RESULTS: Significantly decreased MMSE score was found at 3 months after WBRT. After WBRT, corpus callosum, medial prefrontal cortex, limbic lobe, occipital lobe, parietal lobe, putamen, globus pallidus lentiform, and thalamus demonstrated damage in NODDI parameters. The predicted MMSE-RCI based on NODDI features was significantly associated with the measured MMSE-RCI at 1 month (R = 0.573; P = 0.003) and 3 months (R = 0.687; P < 0.0001) after WBRT. DATA CONCLUSION: Microstructural alterations in several brain regions including the middle prefrontal and limbic cortexes were observed in patients with BM following WBRT, which may contribute to subsequent cognitive decline. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Long period changes of hippocampal diffusion kurtosis imaging and its correlation with cognitive dysfunction after incomplete cerebral ischemia-reperfusion in rats.

This study aims to summarize the changes of functional diffusion kurtosis imaging (DKI) parameters in the bilateral hippocampal CA1 region of the hemorrhagic shock reperfusion (HSR) model of rats and their correlation with cognitive dysfunction. Adult male Sprague-Dawley rats (9-10 weeks of age, weighing 350-400 g) were randomized into the HSR group (n = 30) and the sham-operated group (Sham) (n = 30). Rats in the HSR group and the Sham group were subdivided into five time points (1, 2, 4, 8, and 12 weeks) for examination. Diffusion kurtosis imaging (DKI) was performed. Cognitive dysfunction was analyzed by the Morris Water Maze. The correlation between the DKI parameters and cognitive dysfunction was analyzed by the Spearman correlation. In the HSR group, the values of axial kurtosis (Ka), radial kurtosis (Kr), and mean kurtosis (MK) in the bilateral hippocampal CA1 of rats at 1, 2, 4, 8 and 12 weeks after the surgery were significantly higher. The rats in the HSR group had significantly longer escape latency than in the Sham group. The rats in the HSR group had significantly shorter time and shorter distance in target quadrant than those in the Sham group. The escape latency had positive correlation with MK, Ka, and Kr. The distance and the time in target quadrant had negative correlation with MK, Ka, and Kr. The parameters get from the DKI could accurately evaluate the abnormal blood perfusion and microstructure changes in hippocampal CA1 area of the incomplete cerebral ischemia reperfusion rats induced by HSR. MK, Ka, and Kr values could reflect the decreased learning and memory ability in HSR rat model.

Cortical Iron Accumulation as an Imaging Marker for Neurodegeneration in Clinical Cognitive Impairment Spectrum: A Quantitative Susceptibility Mapping Study.

OBJECTIVE: Cortical iron deposition has recently been shown to occur in Alzheimer's disease (AD). In this study, we aimed to evaluate how cortical gray matter iron, measured using quantitative susceptibility mapping (QSM), differs in the clinical cognitive impairment spectrum. MATERIALS AND METHODS: This retrospective study evaluated 73 participants (mean age ± standard deviation, 66.7 ± 7.6 years; 52 females and 21 males) with normal cognition (NC), 158 patients with mild cognitive impairment (MCI), and 48 patients with AD dementia. The participants underwent brain magnetic resonance imaging using a three-dimensional multi-dynamic multi-echo sequence on a 3-T scanner. We employed a deep neural network (QSMnet+) and used automatic segmentation software based on FreeSurfer v6.0 to extract anatomical labels and volumes of interest in the cortex. We used analysis of covariance to investigate the differences in susceptibility among the clinical diagnostic groups in each brain region. Multivariable linear regression analysis was performed to study the association between susceptibility values and cognitive scores including the Mini-Mental State Examination (MMSE). RESULTS: Among the three groups, the frontal (P < 0.001), temporal (P = 0.004), parietal (P = 0.001), occipital (P < 0.001), and cingulate cortices (P < 0.001) showed a higher mean susceptibility in patients with MCI and AD than in NC subjects. In the combined MCI and AD group, the mean susceptibility in the cingulate cortex (ß = -216.21, P = 0.019) and insular cortex (ß = -276.65, P = 0.001) were significant independent predictors of MMSE scores after correcting for age, sex, education, regional volume, and APOE4 carrier status. CONCLUSION: Iron deposition in the cortex, as measured by QSMnet+, was higher in patients with AD and MCI than in NC participants. Iron deposition in the cingulate and insular cortices may be an early imaging marker of cognitive impairment related neurodegeneration.

Segmental disturbance of white matter microstructure in predicting mild cognitive impairment in idiopathic Parkinson's disease: An individualized study based on automated fiber quantification tractography.

PURPOSE: The neurobiological mechanisms and an early identification of MCI in idiopathic Parkinson's disease (IPD) remain unclear. To investigate the abnormalities of types of white matter (WM) fiber tracts segmentally and establish reliable indicator in IPD-MCI. METHODS: Forty IPD with normal cognition (IPD-NCI), thirty IPD-MCI, and thirty healthy controls were included. Automated fiber quantification was applied to extract the fractional anisotropy (FA) and mean diffusivity (MD) values at 100 locations along the major fibers. Partial correlation was performed between diffusion values and cognitive performance. Furthermore, machine learning analyses were conducted to determine the imaging biomarker of MCI. Permutation tests were performed to evaluate the pointwise differences under the FWE correction. RESULTS: IPD-MCI had similar but more severe and widespread WM degeneration in the association, projection, and commissural fibers compared with IPD-NCI. Meanwhile, IPD-MCI showed distinct degeneration pattern in the association fibers. The FA of the anterior segment of right inferior fronto-occipital fasciculus (IFOF) was positively correlated with MoCA (P < 0.05) and executive function (P < 0.05). The MD of the middle and posterior segment of left superior longitudinal fasciculus (SLF) was negatively correlated with MoCA P < 0.05), executive (P < 0.05), visuospatial function (P < 0.05). Furthermore, the AUC of support vector machine model was 0.80 in the validation dataset. The FA of anterior segment of right IFOF contribute the most. CONCLUSION: This study demonstrated that regional tract-specific microstructural degeneration, especially the association fibers, can be used to predict MCI in IPD. Especially, the right IFOF may be a significant imaging biomarker in predicting IPD with MCI.

Aortic valve Replacement compared to Transcatheter Implant and its relationship with COgnitive Impairment (ARTICO) evaluated with neuropsychological and advanced neuroimaging: a longitudinal cohort study.

BACKGROUND: Aortic stenosis is the most common valvulopathy in Western countries. The treatment of choice had been surgery aortic valve replacement (SAVR), but the improvement in endovascular approaches as transcatheter aortic valve implantation (TAVI), initially reserved for patients with very high surgical risk, has been extended to high and intermediate, and recently also to low-risk patients. Stroke and vascular cognitive impairment are the most important complications. It is not entirely clear which technique is best to avoid these complications as well as their impact. Our goal is to evaluate changes in cognitive performance in the early (1-month) and late (1-year) postoperative period in patients undergoing SAVR or TAVI, by extensive neuropsychological study (NRP) and advanced Magnetic Resonance Imaging (MRI). Specifically, to compare early and late cognitive changes after the intervention between both groups, the occurrence of stroke during follow-up and to compare the appearance of silent vascular lesions and changes in brain activity and functional connectivity with functional MRI during follow-up between both groups. METHODS/DESIGN: Prospective longitudinal cohort study. A non-selected representative sample of 80 subjects, 40 SAVR and 40 TAVI to obtain a final sample of 36 eligible subjects in each group, ranging from 70 to 85 years old, with indication for aortic replacement and intermediate or high surgical risk will be studied. At baseline, within one month before the treatment, all individuals will undergo an extensive NRP and advanced MRI study. These studies will also be performed 1-month and 1-year after treatment, to assess the appearance of new vascular lesions, as well as changes in cognitive performance with respect to baseline. DISCUSSION: This study aims to evaluate changes in cognitive performance as well as both clinical and silent vascular events occurring in the early (1-month) and late (1-year) periods after SAVR and TAVI. We will also analyze the correlation between neuropsychological and neuroimaging approaches in order to evaluate cognition. Therefore, it may provide high-quality data of cognitive changes and vascular events for both techniques, and be useful to tailor interventions to individual characteristics and ultimately aiding in decision-making. TRIAL REGISTRATION: This study is register in Clinicaltrials.gov (NCT05235529) on 11th February 2022.

Cortical Amyloid Burden Relates to Basal Forebrain Volume in Subjective Cognitive Decline.

BACKGROUND: Atrophy of cholinergic basal forebrain (BF) nuclei is a frequent finding in magnetic resonance imaging (MRI) volumetry studies that examined patients with prodromal or clinical Alzheimer's disease (AD), but less clear for individuals in earlier stages of the clinical AD continuum. OBJECTIVE: To examine BF volume reductions in subjective cognitive decline (SCD) participants with AD pathologic changes. METHODS: The present study compared MRI-based BF volume measurements in age- and sex-matched samples of N = 24 amyloid-positive and N = 24 amyloid-negative SCD individuals, based on binary visual ratings of Florbetaben positron emission tomography (PET) measurements. Additionally, we assessed associations of BF volume with cortical amyloid burden, based on semiquantitative Centiloid (CL) analyses. RESULTS: Group differences approached significance for BF total volume (p = 0.061) and the Ch4 subregion (p = 0.059) only, showing the expected relative volume reductions for the amyloid-positive subgroup. There were also significant inverse correlations between BF volumes and CL values, which again were most robust for BF total volume and the Ch4 subregion. CONCLUSIONS: The results are consistent with the hypothesis that amyloid-positive SCD individuals, which are considered to represent a transitional stage on the clinical AD continuum, already show incipient alterations of BF integrity. The negative association with a continuous measure of cortical amyloid burden also suggests that this may reflect an incremental process. Yet, further research is needed to evaluate whether BF changes already emerge at "grey zone" levels of amyloid accumulation, before amyloidosis is reliably detected by PET visual readings.

White Matter Microstructural Alterations over the Year after Acute Ischemic Stroke in Patients with Baseline Impaired Cognitive Functions.

Background: The disruption of white matter (WM) integrity is related to poststroke cognitive impairment (PSCI). The exploration of WM integrity alterations in the chronic stage of acute ischemic stroke (AIS) may help to improve the long-term outcomes of PSCI. Methods: Sixty patients showing impaired cognitive functions within 3 days after AIS (baseline) and 25 healthy controls underwent diffusion kurtosis imaging scan and cognitive assessment at baseline and 1 year. Based on the tract-based spatial statistics (TBSS), kurtosis fractional anisotropy (KFA) and mean kurtosis (MK) were compared in WM tracts between the groups. Results: One year after AIS, 25 patients were diagnosed with PSCI and 35 patients with non-cognitive impairment (NCI). Compared with baseline, cognitive performance improved in 54 patients and remained unchanged in 6 patients at 1 year. TBSS analysis showed that there were no significant differences in WM tract integrity between the AIS and control groups at baseline (P > 0.05). Compared with the control group, the KFA and MK in multiple WM tracts in the AIS group decreased significantly at 1 year (P < 0.05). Longitudinal analysis showed that the KFA and MK of multiple WM tracts recorded at 1 year were significantly lower than those recorded at baseline in the AIS, PSCI, and NCI groups (P < 0.05), and PSCI group had a faster degeneration than NCI group (P < 0.05). Conclusion: The finding suggests that the patients with baseline impaired cognitive functions still have WM microstructural damages at 1 year poststroke, even if their cognitive function has improved or returned to normal. Cautions should be taken against the possible negative impact of these changes on long-term cognition.

Evaluation of the default mode network using nonnegative matrix factorization in patients with cognitive impairment induced by occupational aluminum exposure.

Aluminum (Al) is an important environmental pathogenic factor for neurodegenerative diseases, especially mild cognitive impairment (MCI). The aim of this study was to evaluate the gray matter volume of structural covariance network alterations in patients with Al-induced MCI. Male subjects who had been exposed to Al for >10 years were included in the present study. The plasma Al concentration, Montreal cognitive assessment (MoCA) score, and verbal memory assessed by the Rey auditory verbal learning test (AVLT) score were collected from each participant. Nonnegative matrix factorization was used to identify the structural covariance network. The neural structural basis for patients with Al-induced MCI was investigated using correlation analysis and group comparison. Plasma Al concentration was inversely related to MoCA scores, particularly AVLT scores. In patients with Al-induced MCI, the gray matter volume of the default mode network (DMN) was considerably lower than that in controls. Positive correlations were discovered between the DMN and MoCA scores as well as between the DMN and AVLT scores. In sum, long-term occupational Al exposure has a negative impact on cognition, primarily by affecting delayed recognition. The reduced gray matter volume of the DMN may be the neural mechanism of Al-induced MCI.

The Presence and Severity of NAFLD are Associated With Cognitive Impairment and Hippocampal Damage.

CONTEXT: Although cognitive impairment in nonalcoholic fatty liver disease (NAFLD) has received attention in recent years, little is known about detailed cognitive functions in histologically diagnosed individuals. OBJECTIVE: This study aimed to investigate the association of liver pathological changes with cognitive features and further explore the underlying brain manifestations. METHODS AND PATIENTS: We performed a cross-sectional study in 320 subjects who underwent liver biopsy. Among the enrolled participants, 225 underwent assessments of global cognition and cognitive subdomains. Furthermore, 70 individuals received functional magnetic resonance imaging scans for neuroimaging evaluations. The associations among liver histological features, brain alterations, and cognitive functions were evaluated using structural equation model. RESULTS: Compared with controls, patients with NAFLD had poorer immediate memory and delayed memory. Severe liver steatosis (odds ratio, 2.189; 95% CI, 1.020-4.699) and ballooning (OR, 3.655; 95% CI, 1.419-9.414) were related to a higher proportion of memory impairment. Structural magnetic resonance imaging showed that patients with nonalcoholic steatohepatitis exhibited volume loss in left hippocampus and its subregions of subiculum and presubiculum. Task-based magnetic resonance imaging showed that patients with nonalcoholic steatohepatitis had decreased left hippocampal activation. Path analysis demonstrated that higher NAFLD activity scores were associated with lower subiculum volume and reduced hippocampal activation, and such hippocampal damage contributed to lower delayed memory scores. CONCLUSIONS: We are the first to report the presence and severity of NAFLD to be associated with an increased risk of memory impairment and hippocampal structural and functional abnormalities. These findings stress the significance of early cognitive evaluation in patients with NAFLD.

Advances of neuroimaging in chemotherapy related cognitive impairment (CRCI) of patients with breast cancer.

BACKGROUND: Chemotherapy related cognitive impairment (CRCI) has seriously affected the quality of life (QOL) of patients with breast cancer (BCs), thus the neurobiological mechanism of CRCI attracted widespread attention. Previous studies have found that chemotherapy causes CRCI through affecting brain structure, function, metabolism, and blood perfusion. FINDINGS: A variety of neuroimaging techniques such as functional magnetic resonance imaging (fMRI), event-related potential (ERP), near-infrared spectroscopy (NIRS) have been widely applied to explore the neurobiological mechanism of CRCI. CONCLUSION: This review summarized the progress of neuroimaging research in BCs with CRCI, which provides a theoretical basis for further exploration of CRCI mechanism, disease diagnosis and symptom intervention in the future. Multiple neuroimaging techniques for CRCI research.

Improvement in the Prediction of Cerebrovascular Events With White Matter Hyperintensity.

Background It remains unclear if white matter hyperintensity (WMH) on magnetic resonance imaging adds relevant cerebrovascular prognostic information beyond vascular risk factors and demographics alone. Methods and Results We performed a post hoc analysis of hypertensive individuals in SPRINT-MIND (Systolic Blood Pressure Intervention Trial-Memory and Cognition in Decreased Hypertension). The primary outcome was incident stroke or cognitive impairment (mild cognitive impairment or dementia). We fit logistic regression models with the predictors of Atherosclerotic Cardiovascular Disease Risk Score, age, sex, race, education, current cigarette smoking, and the SPRINT-MIND randomization arm. WMH was subsequently included in the model to determine if it improved area under the receiver operating curve using the DeLong test. We used a structural equation model to determine the indirect effect on the primary outcome mediated through WMH. We included 727 individuals (mean age at baseline 67.7±8.4 years, 61.1% were men, 62.6% were non-Hispanic White, and mean years of follow-up was 3.6±0.9). Of the 727 individuals, 67 (9.2%) developed incident stroke or cognitive decline. The area under the receiver operating curve of the baseline model (without WMH) was 0.75 (95% CI, 0.70-0.81), and after the addition of WMH it increased to 0.81 (95% CI, 0.76-0.86) (P=0.004 for difference). The mediation analysis showed that 26.3% of the vascular risk's effect on the primary outcome is indirectly mediated through WMH. Conclusions In adult hypertensive individuals, we found that the addition of WMH to models predicting incident stroke or cognitive impairment improved the prognostic ability above vascular risk and demographics alone to a level consistent with excellent prediction. Registration Information REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

Distinct resting-state functional connectivity patterns of Anterior Insula affected by smoking in mild cognitive impairment.

Smoking is a modifiable risk factor for Alzheimer's disease (AD). The insula plays a vital role in both smoking and cognition. However, the smoking effects on insula-related networks in cognitively normal controls (CN) and mild cognitive impairment (MCI) patients remain unknown. We identified 129 CN (85 non-smokers and 44 smokers) and 83 MCI (54 non-smokers and 29 smokers). Each underwent neuropsychological assessment and MRI (structural and resting-state functional). Seed-based functional analyses in the anterior and posterior insula were performed to calculate the functional connectivity (FC) with voxels in the whole brain. Mixed-effect analyses were performed to explore the interactive effects on smoking and cognitive status. Associations between FC and neuropsychological scales were assessed. Mixed-effect analyses revealed the FC differences between the right anterior insula (RAI) with the left middle temporal gyrus (LMTG) and that with the right inferior parietal lobule (RIPL) (p < 0.01, cluster level < 0.05, two-tailed, gaussian random field correction). The FC of RAI in both LMTG and RIPL sees a significant decrease in MCI smokers (p < 0.01). Smoking affects insula FC differently between MCI and CN, and could decrease the insula FC in MCI patients. Our study provides evidence of neural mechanisms between smoking and AD.