Correlations between plasma markers and brain Aß deposition across the AD continuum: Evidence from SILCODE.

BACKGROUND: Previous studies have found that Alzheimer's disease (AD)-related plasma markers are associated with amyloid beta (Aß) deposition, but the change of this association in different Aß pathological stages remains unclear. METHODS: Data were obtained from the SILCODE. According to the standardized uptake value ratio (SUVR) and Aß stage classification, correlation analysis was performed among plasma biomarkers, and voxel/SUVR values in the regions of interest (ROI) and clinical scale information, respectively. Mediation analysis was used to study the possible pathways. RESULTS: The proportion of cognitively normal (CN) and subjective cognitive decline (SCD) was the highest in stages A0 to 1, while in stages A2 to 4, the proportion of mild cognitive impairment (MCI) and AD increased. Plasma phosphorylated tau (p-tau)181 and glial fibrillary acidic protein (GFAP) levels were significantly lower in stage A0 compared to the later phases. Two pathways demonstrated fully mediated effects: positron emission tomography (PET) SUVR-plasma p-tau181-Mini-Mental State Examination (MMSE) and PET SUVR-plasma GFAP-MMSE. DISCUSSION: This study demonstrated the role of plasma biomarkers in the early stage of AD, especially in SCD, from both the clinical diagnosis and Aß stage dimensions. HIGHLIGHTS: Plasma ptau181 and GFAP level serve as indicators of early Alzheimer's disease and the pathologic Aß staging classification. A possible ceiling effect of GFAP was observed in the mid-to-late stages of the AD course. This study confirms the role of AD plasma markers in promoting Aß deposition at an early stage, particularly in females with subjective cognitive decline(SCD). The overlapping brain regions of plasma p-tau181, GFAP, and neurofilament light for Aß deposition in the brain in early AD were distributed across various regions, including the posterior cingulate gyrus, rectus gyrus, and inferior temporal gyrus.

Whole-brain glucose metabolic pattern differentiates minimally conscious state from unresponsive wakefulness syndrome.

AIMS: The patient being minimally conscious state (MCS) may benefit from wake-up interventions aimed at improving quality of life and have a higher probability of recovering higher level of consciousness compared to patients with the unresponsive wakefulness syndrome (UWS). However, differentiation of the MCS and UWS poses challenge in clinical practice. This study aimed to explore glucose metabolic pattern (GMP) obtained from 18F-labeled-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) in distinguishing between UWS and MCS. METHODS: Fifty-seven patients with disorders of consciousness (21 cases of UWS and 36 cases of MCS) who had undergone repeated standardized Coma Recovery Scale-Revised (CRS-R) evaluations were enrolled in this prospective study. 18F-FDG-PET was carried out in all patients and healthy controls (HCs). Voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was used to generate GMPs. The expression score of whole-brain GMP was obtained, and its diagnostic accuracy was compared with the standardized uptake value ratio (SUVR). The diagnostic efficiency was validated by one-year later clinical outcomes. RESULTS: UWS-MCS GMP exhibited hypometabolism in the frontal-parietal cortex, along with hypermetabolism in the unilateral lentiform nucleus, putamen, and anterior cingulate gyrus. The UWS-MCS-GMP expression score was significantly higher in UWS compared to MCS patients (0.90 ± 0.85 vs. 0 ± 0.93, p < 0.001). UWS-MCS-GMP expression score achieved an area under the curve (AUC) of 0.77 to distinguish MCS from UWS, surpassing that of SUVR based on the frontoparietal cortex (AUC = 0.623). UWS-MCS-GMP expression score was significantly correlated with the CRS-R score (r = -0.45, p = 0.004) and accurately predicted the one-year outcome in 73.7% of patients. CONCLUSION: UWS and MCS exhibit specific glucose metabolism patterns, the UWS-MCS-GMP expression score significantly distinguishes MCS from UWS, making SSM/PCA a potential diagnostic methods in clinical practice for individual patients.

Tau Protein Accumulation Trajectory-Based Brain Age Prediction in the Alzheimer's Disease Continuum.

Clinical cognitive advancement within the Alzheimer's disease (AD) continuum is intimately connected with sustained accumulation of tau protein pathology. The biological brain age and its gap show great potential for pathological risk and disease severity. In the present study, we applied multivariable linear support vector regression to train a normative brain age prediction model using tau brain images. We further assessed the predicted biological brain age and its gap for patients within the AD continuum. In the AD continuum, evaluated pathologic tau binding was found in the inferior temporal, parietal-temporal junction, precuneus/posterior cingulate, dorsal frontal, occipital, and inferior-medial temporal cortices. The biological brain age gaps of patients within the AD continuum were notably higher than those of the normal controls (p < 0.0001). Significant positive correlations were observed between the brain age gap and global tau protein accumulation levels for mild cognitive impairment (r = 0.726, p < 0.001), AD (r = 0.845, p < 0.001), and AD continuum (r = 0.797, p < 0.001). The pathologic tau-based age gap was significantly linked to neuropsychological scores. The proposed pathologic tau-based biological brain age model could track the tau protein accumulation trajectory of cognitive impairment and further provide a comprehensive quantification index for the tau accumulation risk.

Innovative Multivariable Model Combining MRI Radiomics and Plasma Indexes Predicts Alzheimer's Disease Conversion: Evidence from a 2-Cohort Longitudinal Study.

To explore the complementary relationship between magnetic resonance imaging (MRI) radiomic and plasma biomarkers in the early diagnosis and conversion prediction of Alzheimer's disease (AD), our study aims to develop an innovative multivariable prediction model that integrates those two for predicting conversion results in AD. This longitudinal multicentric cohort study included 2 independent cohorts: the Sino Longitudinal Study on Cognitive Decline (SILCODE) project and the Alzheimer Disease Neuroimaging Initiative (ADNI). We collected comprehensive assessments, MRI, plasma samples, and amyloid positron emission tomography data. A multivariable logistic regression analysis was applied to combine plasma and MRI radiomics biomarkers and generate a new composite indicator. The optimal model's performance and generalizability were assessed across populations in 2 cross-racial cohorts. A total of 897 subjects were included, including 635 from the SILCODE cohort (mean [SD] age, 64.93 [6.78] years; 343 [63%] female) and 262 from the ADNI cohort (mean [SD] age, 73.96 [7.06] years; 140 [53%] female). The area under the receiver operating characteristic curve of the optimal model was 0.9414 and 0.8979 in the training and validation dataset, respectively. A calibration analysis displayed excellent consistency between the prognosis and actual observation. The findings of the present study provide a valuable diagnostic tool for identifying at-risk individuals for AD and highlight the pivotal role of the radiomic biomarker. Importantly, built upon data-driven analyses commonly seen in previous radiomics studies, our research delves into AD pathology to further elucidate the underlying reasons behind the robust predictive performance of the MRI radiomic predictor.

Characterization of tau propagation pattern and cascading hypometabolism from functional connectivity in Alzheimer's disease.

Tau pathology and its spatial propagation in Alzheimer's disease (AD) play crucial roles in the neurodegenerative cascade leading to dementia. However, the underlying mechanisms linking tau spreading to glucose metabolism remain elusive. To address this, we aimed to examine the association between pathologic tau aggregation, functional connectivity, and cascading glucose metabolism and further explore the underlying interplay mechanisms. In this prospective cohort study, we enrolled 79 participants with 18F-Florzolotau positron emission tomography (PET), 18F-fluorodeoxyglucose PET, resting-state functional, and anatomical magnetic resonance imaging (MRI) images in the hospital-based Shanghai Memory Study. We employed generalized linear regression and correlation analyses to assess the associations between Florzolotau accumulation, functional connectivity, and glucose metabolism in whole-brain and network-specific manners. Causal mediation analysis was used to evaluate whether functional connectivity mediates the association between pathologic tau and cascading glucose metabolism. We examined 22 normal controls and 57 patients with AD. In the AD group, functional connectivity was associated with Florzolotau covariance (ß = .837, r = 0.472, p < .001) and glucose covariance (ß = 1.01, r = 0.499, p < .001). Brain regions with higher tau accumulation tend to be connected to other regions with high tau accumulation through functional connectivity or metabolic connectivity. Mediation analyses further suggest that functional connectivity partially modulates the influence of tau accumulation on downstream glucose metabolism (mediation proportion: 49.9%). Pathologic tau may affect functionally connected neurons directly, triggering downstream glucose metabolism changes. This study sheds light on the intricate relationship between tau pathology, functional connectivity, and downstream glucose metabolism, providing critical insights into AD pathophysiology and potential therapeutic targets.

Prediction of Cognitive Progression Due to Alzheimer's Disease in Normal Participants Based on Individual Default Mode Network Metabolic Connectivity Strength.

BACKGROUND: Predicting cognitive decline among individuals in the aging population who are already amyloid-ß (Aß) positive or tau positive poses clinical challenges. In Alzheimer's disease research, intra-default mode network (DMN) connections play a pivotal role in diagnosis. In this article, we propose metabolic connectivity within the DMN as a supplementary biomarker to the Aß, pathological tau, and neurodegeneration framework. METHODS: Extracting data from 1292 participants in the Alzheimer's Disease Neuroimaging Initiative, we collected paired T1-weighted structural magnetic resonance imaging and 18F-labeled-fluorodeoxyglucose positron emission computed tomography scans. Individual metabolic DMN networks were constructed, and metabolic connectivity (MC) strength in the DMN was assessed. In the cognitively unimpaired group, the Cox model identified cognitively unimpaired (MC+), high-risk participants, with Kaplan-Meier survival analyses and hazard ratios revealing the strength of MC's predictive performance. Spearman correlation analyses explored relationships between MC strength, and Aß, pathological tau, neurodegeneration biomarkers, and clinical scales. DMN standard uptake value ratio (SUVR) provided comparative insights in the analyses. RESULTS: Both MC strength and SUVR exhibited gradual declines with cognitive deterioration, displaying significant intergroup differences. Survival analyses indicated enhanced Aß and tau prediction with both metrics, with MC strength outperforming SUVR. Combined MC strength and Aß yielded optimal predictive performance (hazard ratio = 9.29), followed by MC strength and tau (hazard ratio = 8.92). Generally, the strength of MC's correlations with Aß, pathological tau, and neurodegeneration biomarkers exceeded SUVR. CONCLUSIONS: Individuals with normal cognition and disrupted DMN metabolic connectivity face an elevated risk of cognitive decline linked to Aß that precedes metabolic issues.

The Effects of Traditional Chinese Herbal Dietary Formula on the Ability of Daily Life and Physical Function in Elderly Patients with Mild Cognitive Impairment.

We aimed to examine the association of traditional Chinese herbal dietary formulas with ability of daily life and physical function in elderly patients with mild cognitive impairment. The current study included 60 cases of elderly patients with mild cognitive impairment from Yueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine, Shanghai University of Traditional Chinese Medicine and Hongkou District, Shanghai. The participants were randomly divided into two groups: group A (herbal dietary formula group, consisting of Alpiniae Oxyphyllae Fructus, Nelumbinis plumula, Chinese Yam, Poria cocos, and Jineijin), 30 cases, and group B (vitamin E), 30 cases, treatment for 3 months. Cognitive function was measured using the Montreal Cognitive Assessment (MOCA) and Mini-Mental State Examination (MMSE); body function was measured using the Chinese Simplified Physical Performance Test (CMPPT), including stand static balance, sitting-up timing, squat timing, and six-meter walk timing. Daily life based on ability was measured by grip strength and the Activity of Daily Living Scale (ADL). The lower the scores of the above items, the poorer the disease degree, except for ADL: the lower the score, the higher the self-care ability. After 3 months of treatment, the two-handed grip strength of both the herbal dietary formula group and vitamin E group increased; the ADL, sitting-up timing, squatting timing, and six-meter walking timing decreased after medication, being statistically significantly different (p < 0.05). The two-handed grip strength of group A increased significantly, and the ADL, sitting-up timing, squatting timing, and six-meter walking timing decreased distinctly compared with the vitamin E group. There was a statistically significant difference (p < 0.05). The scores of MMSE, MOCA, total CMPPT, and standing static balance of the herbal dietary formula group increased after medication. The difference was statistically significant (p < 0.05). The vitamin E group's MMSE and MOCA scores, CMPPT total scores, and standing resting balance scores did not change significantly after medication (p > 0.05). In summary, a traditional Chinese herbal dietary formula can improve body and cognitive function in patients with MCI, and the curative effect is better than that of vitamin E. Traditional Chinese herbal dietary formulas can improve the daily life quality of MCI patients, which has clinical application value.

A novel spatiotemporal graph convolutional network framework for functional connectivity biomarkers identification of Alzheimer's disease.

BACKGROUND: Functional connectivity (FC) biomarkers play a crucial role in the early diagnosis and mechanistic study of Alzheimer's disease (AD). However, the identification of effective FC biomarkers remains challenging. In this study, we introduce a novel approach, the spatiotemporal graph convolutional network (ST-GCN) combined with the gradient-based class activation mapping (Grad-CAM) model (STGC-GCAM), to effectively identify FC biomarkers for AD. METHODS: This multi-center cross-racial retrospective study involved 2,272 participants, including 1,105 cognitively normal (CN) subjects, 790 mild cognitive impairment (MCI) individuals, and 377 AD patients. All participants underwent functional magnetic resonance imaging (fMRI) and T1-weighted MRI scans. In this study, firstly, we optimized the STGC-GCAM model to enhance classification accuracy. Secondly, we identified novel AD-associated biomarkers using the optimized model. Thirdly, we validated the imaging biomarkers using Kaplan-Meier analysis. Lastly, we performed correlation analysis and causal mediation analysis to confirm the physiological significance of the identified biomarkers. RESULTS: The STGC-GCAM model demonstrated great classification performance (The average area under the curve (AUC) values for different categories were: CN vs MCI = 0.98, CN vs AD = 0.95, MCI vs AD = 0.96, stable MCI vs progressive MCI = 0.79). Notably, the model identified specific brain regions, including the sensorimotor network (SMN), visual network (VN), and default mode network (DMN), as key differentiators between patients and CN individuals. These brain regions exhibited significant associations with the severity of cognitive impairment (p < 0.05). Moreover, the topological features of important brain regions demonstrated excellent predictive capability for the conversion from MCI to AD (Hazard ratio = 3.885, p < 0.001). Additionally, our findings revealed that the topological features of these brain regions mediated the impact of amyloid beta (Aß) deposition (bootstrapped average causal mediation effect: ß = -0.01 [-0.025, 0.00], p < 0.001) and brain glucose metabolism (bootstrapped average causal mediation effect: ß = -0.02 [-0.04, -0.001], p < 0.001) on cognitive status. CONCLUSIONS: This study presents the STGC-GCAM framework, which identifies FC biomarkers using a large multi-site fMRI dataset.

Detection of individual brain tau deposition in Alzheimer's disease based on latent feature-enhanced generative adversarial network.

OBJECTIVE: The conventional methods for interpreting tau PET imaging in Alzheimer's disease (AD), including visual assessment and semi-quantitative analysis of fixed hallmark regions, are insensitive to detect individual small lesions because of the spatiotemporal neuropathology's heterogeneity. In this study, we proposed a latent feature-enhanced generative adversarial network model for the automatic extraction of individual brain tau deposition regions. METHODS: The latent feature-enhanced generative adversarial network we propose can learn the distribution characteristics of tau PET images of cognitively normal individuals and output the abnormal distribution regions of patients. This model was trained and validated using 1131 tau PET images from multiple centres (with distinct races, i.e., Caucasian and Mongoloid) with different tau PET ligands. The overall quality of synthetic imaging was evaluated using structural similarity (SSIM), peak signal to noise ratio (PSNR), and mean square error (MSE). The model was compared to the fixed templates method for diagnosing and predicting AD. RESULTS: The reconstructed images archived good quality, with SSIM = 0.967 ± 0.008, PSNR = 31.377 ± 3.633, and MSE = 0.0011 ± 0.0007 in the independent test set. The model showed higher classification accuracy (AUC = 0.843, 95 % CI = 0.796-0.890) and stronger correlation with clinical scales (r = 0.508, P < 0.0001). The model also achieved superior predictive performance in the survival analysis of cognitive decline, with a higher hazard ratio: 3.662, P < 0.001. INTERPRETATION: The LFGAN4Tau model presents a promising new approach for more accurate detection of individualized tau deposition. Its robustness across tracers and races makes it a potentially reliable diagnostic tool for AD in practice.

An effective and robust lattice Boltzmann model guided by atlas for hippocampal subregions segmentation.

BACKGROUND: Given the varying vulnerability of the rostral and caudal regions of the hippocampus to neuropathology in the Alzheimer's disease (AD) continuum, accurately assessing structural changes in these subregions is crucial for early AD detection. The development of reliable and robust automatic segmentation methods for hippocampal subregions (HS) is of utmost importance. OBJECTIVE: Our aim is to propose and validate a HS segmentation model that is both training-free and highly generalizable. This method should exhibit comparable accuracy and efficiency to state-of-the-art techniques. The segmented HS can serve as a biomarker for studying the progression of AD. METHODS: We utilized the functional magnetic resonance imaging of the Brain's Integrated Registration and Segmentation Tool (FIRST) to segment the entire hippocampus. By intersecting the segmentation results with the Brainnetome (BN) atlas, we obtained coarse segmentation of the four HS regions. This coarse segmentation was then employed as a shape prior term in the lattice Boltzmann (LB) model, as well as for initializing contours. Additionally, image gradients and local gray levels were integrated into the external force terms of the LB model to refine the coarse segmentation results. We assessed the segmentation accuracy of the model using the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset and evaluated the potential of the segmentation results as AD biomarkers on both the ADNI and Xuanwu datasets. RESULTS: The median Dice similarity coefficients (DSC) for the left caudal, right caudal, left rostral, and right rostral hippocampus were 0.87, 0.88, 0.88, and 0.89, respectively. The proportion of segmentation results with a DSC exceeding 0.8 was 77%, 78%, 77%, and 94% for the respective regions. In terms of volume, the correlation coefficients between the segmentation results of the four HS regions and the gold standard were 0.95, 0.93, 0.96, and 0.96, respectively. Regarding asymmetry, the correlation coefficient between the segmentation result's right caudal minus left caudal and the corresponding gold standard was 0.91, while for right rostral minus left rostral, it was 0.93. Over time, we observed a decline in the volumes of the four HS regions and the total hippocampal volume of mild cognitive impairment (MCI) converters. Analysis of inter-group differences revealed that, except for the right rostral region in the ADNI dataset, the p-values for the four HS regions in the normal controls (NC), MCI, and AD groups from both datasets were all below 0.05. The right caudal hippocampal volume demonstrated correlation coefficients of 0.47 and 0.43 with the mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA), respectively. Similarly, the left rostral hippocampal volume showed correlation coefficients of 0.50 and 0.58 with MMSE and MoCA, respectively. CONCLUSIONS: Our framework allows for direct application to different brain magnetic resonance (MR) datasets without the need for training. It eliminates the requirement for complex image preprocessing steps while achieving segmentation accuracy comparable to deep learning (DL) methods even with small sample sizes. Compared to traditional active contour models (ACM) and atlas-based methods, our approach exhibits significant speed advantages. The segmented HS regions hold promise as potential biomarkers for studying the progression of AD.

Diagnostic performance of artificial intelligence-assisted PET imaging for Parkinson's disease: a systematic review and meta-analysis.

Artificial intelligence (AI)-assisted PET imaging is emerging as a promising tool for the diagnosis of Parkinson's disease (PD). We aim to systematically review the diagnostic accuracy of AI-assisted PET in detecting PD. The Ovid MEDLINE, Ovid Embase, Web of Science, and IEEE Xplore databases were systematically searched for related studies that developed an AI algorithm in PET imaging for diagnostic performance from PD and were published by August 17, 2023. Binary diagnostic accuracy data were extracted for meta-analysis to derive outcomes of interest: area under the curve (AUC). 23 eligible studies provided sufficient data to construct contingency tables that allowed the calculation of diagnostic accuracy. Specifically, 11 studies were identified that distinguished PD from normal control, with a pooled AUC of 0.96 (95% CI: 0.94-0.97) for presynaptic dopamine (DA) and 0.90 (95% CI: 0.87-0.93) for glucose metabolism (18F-FDG). 13 studies were identified that distinguished PD from the atypical parkinsonism (AP), with a pooled AUC of 0.93 (95% CI: 0.91 - 0.95) for presynaptic DA, 0.79 (95% CI: 0.75-0.82) for postsynaptic DA, and 0.97 (95% CI: 0.96-0.99) for 18F-FDG. Acceptable diagnostic performance of PD with AI algorithms-assisted PET imaging was highlighted across the subgroups. More rigorous reporting standards that take into account the unique challenges of AI research could improve future studies.

Glucose metabolism in posterior cingulate cortex has supplementary value to predict the progression of cognitively unimpaired to dementia due to Alzheimer's disease: an exploratory study of 18F-FDG-PET.

Amyloid-ß (Aß) and tau are important biomarkers to predict the progression of cognitively unimpaired (CU) to dementia due to Alzheimer's disease (AD), according to the diagnosis framework from the US National Institute on Aging and the Alzheimer's Association (NIA-AA). However, it is clinically difficult to predict those subjects who were already with Aß positive (A +) or tau positive (T +). As a typical characteristic of neurodegeneration in the diagnosis framework, the hypometabolism of the posterior cingulate cortex (PCC) has significant clinical value in the early prediction and prevention of AD. In this paper, we proposed the glucose metabolism in the PCC as a biomarker supplement to Aß and tau biomarkers. First, we calculated the standard uptake value ratio (SUVR) of PCC based on fluorodeoxyglucose positron emission computed tomography (FDG PET) imaging. Secondly, we performed Kaplan-Meier (KM) survival analyses to explore the predictive performance of PCC SUVR, and the hazard ratio (HR) was calculated. Finally, we performed Pearson correlation analyses to explore the physiological significance of PCC SUVR. As a result, the PCC SUVR showed a consistent downward trend along the AD continuum. KM analyses showed better predictive performance when we combined PCC SUVR with cerebro-spinal fluid (CSF) Aß42 (from HR = 2.56 to 3.00 within 5 years; from HR = 2.76 to 4.20 within 10 years) and ptau-181 (from 2.83 to 3.91 within 5 years; from HR = 2.32 to 4.17 within 10 years). There was a slight correlation between Aß42/Aß40 and PCC SUVR (r = 0.14, p = 0.02). In addition, several cognition scales were also correlated to PCC SUVR (from r = -0.407 to 0.383, p < 0.05). Our results showed that glucose metabolism in PCC may be a potential biomarker supplement to the Aß and tau biomarkers to predict the progression of CU to AD.

rTMS concurrent with cognitive training rewires AD brain by enhancing GM-WM functional connectivity: a preliminary study.

Repetitive transcranial magnetic stimulation (rTMS) and cognitive training for patients with Alzheimer's disease (AD) can change functional connectivity (FC) within gray matter (GM). However, the role of white matter (WM) and changes of GM-WM FC under these therapies are still unclear. To clarify this problem, we applied 40 Hz rTMS over angular gyrus (AG) concurrent with cognitive training to 15 mild-moderate AD patients and analyzed the resting-state functional magnetic resonance imaging before and after treatment. Through AG-based FC analysis, corona radiata and superior longitudinal fasciculus (SLF) were identified as activated WM tracts. Compared with the GM results with AG as seed, more GM regions were found with activated WM tracts as seeds. The averaged FC, fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) of the above GM regions had stronger clinical correlations (r/P = 0.363/0.048 vs 0.299/0.108, 0.351/0.057 vs 0.267/0.153, 0.420/0.021 vs 0.408/0.025, for FC/fALFF/ReHo, respectively) and better classification performance to distinguish pre-/post-treatment groups (AUC = 0.91 vs 0.88, 0.65 vs 0.63, 0.87 vs 0.82, for FC/fALFF/ReHo, respectively). Our results indicated that rTMS concurrent with cognitive training could rewire brain network by enhancing GM-WM FC in AD, and corona radiata and SLF played an important role in this process.

Bidirectional Mapping Perception-enhanced Cycle-consistent Generative Adversarial Network for Super-resolution of Brain MRI images.

As an effective tool for visualizing neurodegeneration, high-resolution structural magnetism facilitates quantitative image analysis and clinical applications. Super-resolution reconstruction technology allows to improve the resolution of images without upgrading the scanning hardware. However, existing super-resolution techniques relied on paired image data sets and lacked further quantitative analysis of the generated images. In this study, we proposed a semi-supervised generative adversarial network (GAN) model for super-resolution of brain MRI, and the synthetic images were evaluated using various quantitative measures. This model adopted the cycle-consistency structure to allow for a mixture of unpaired data for training. Perceptual loss was further introduced into the model to preserve detailed texture features at high frequencies. 363 subjects with both high-resolution (HR) and low-resolution (LR) scans and 217 subjects with HR scans only were used for model derivation, training, and validation. We extracted multiple voxel-based and surface-based morphological features of the synthetic and real 3D HR images for comparison. We further evaluated the synthetic images in the differential diagnosis of diseases. Our model achieved superior mean absolute error (0.049±0.021), mean squared error (0.0059±0.0043), peak signal-to-noise ratio (29.41±3.71), structural similarity index measure (0.914±0.048). Eight morphological metrics, both voxel-based and surface-based, showed significant agreement (P<0.0001). The gap of accuracy in disease diagnosis between synthetic and real HR images was within 5% and significantly outperformed the LR images. Our proposed model enables the reconstruction of HR MRI and could be used accurately for image quantification.Clinical relevance- Quantitative evaluation of the synthetic high-resolution images was used to determine whether the synthetic images have sufficient realism and diversity.

Different Cortical Activation of Facial Synkinesis Patients with Different Course of Disease: A Task fMRI Study.

Facial synkinesis is a disease characterized by unintentional activation of facial muscles, which causes that the patients cannot control their facial expressions independently. Previous studies have shown that its pathogenesis is related to the reorganization of cerebral cortex, but it remains unclear what brain changes the patients have at different stage of the disease. For this study, we recruited 30 patients with facial synkinesis and 19 healthy control subjects from Shanghai Huashan Hospital. All participants completed bilateral blinking and grinning tasks while functional magnetic resonance imaging (fMRI) data was collected. We measured the brain activation strength of each task and observed the activation similarity of the ipsilateral tasks. Then we explored the correlation between activation pattern and clinical scale. Results showed different activation pattern along the courses of disease for blinking and grinning task, which may be due to the inconsistent process of cortical reorganization. The late stage group activated more in blinking task, but the least in grinning tasks, especially on the affected side (p<0.001 at voxel level, p<0.05 at cluster level, FWE corrected). Compared with healthy controls, the activation of patients between tasks on the affected side is more similar(p<0.05). There was a negative correlation in right postcentral gyrus between activation similarity and scale scores (symmetry of voluntary movement scores: R = -0.469, p = 0.009). This could be attributed to the rearrangement of the nervous system following facial nerve injury, leading to incorrect connections between nerves and muscles. Our study may be helpful for understanding mechanism of facial synkinesis and provide basis for the stage-dependent diagnosis and treatment.

Early Diagnosis and Biomarkers of Alzheimer's Disease Based on Spatio-temporal Graph Convolution Network.

Functional magnetic resonance imaging (fMRI) could detect the dynamic activity of brain function and communication. Previous studies have found reduced brain functional connectivity in Alzheimer's disease (AD) patients. In this study, we proposed to process fMRI data by spatio-temporal graph convolution network (ST-GCN) to achieve an early differential diagnosis of AD and to extract image markers using gradient-weighted class activation mapping (Grad-CAM). The data used in this study were from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, Xuanwu Hospital, and Tongji Hospital. The study included 1105 normal controls and 790 patients with mild cognitive impairment (MCI). The grid search method of K-fold cross-validation was used to train the model. In addition, we used Grad-CAM to extract image markers and carried out visualization analysis. This model obtains better AD diagnosis power: accuracy = 0.92, sensitivity = 0.97, specificity = 0.89, and area under the curve=0.96. Salient brain regions extracted by Grad-CAM include the paracentral lobule, inferior occipital gyrus, middle frontal gyrus, superior temporal gyrus, cuneus, posterior cingulate gyrus, and superior parietal gyrus. Our proposed ST-GAN model will help to explore objective markers that can be used for the early diagnosis of AD.Clinical relevance- Our proposed model shows great potential for enhancing the understanding of the pathology of AD by detecting functional connectivity interruptions.

A Novel Diffusion Tensor Image Analysis Along the Perivascular Space Method to Evaluate Glymphatic Alterations in Alzheimer's Disease.

Alzheimer 's disease (AD) is the most prevalent neurodegenerative disorder worldwide. The glymphatic system is considered to be associated with the pathogenesis of AD. However, the alterations of glymphatic system along the AD continuum are still unknown. In this study, we used a novel DTI analysis method, diffusion tensor image analysis along the perivascular space (DTI-ALPS), to evaluate the difference in the activity of the glymphatic system among normal control (NC) subjects, mild cognitive impairment (MCI) and AD patients. The data utilized in the study was obtained from Tongji Hospital in Shanghai, China, including 65 NCs, 58 MCIs and 36 ADs. First, we calculated the ALPS-index to evaluate the activity of the glymphatic system. Then, analysis of variance (ANOVA) was used to find the differences of ALPS-index among different groups, and to explore the correlation between ALPS-index and the three clinical scales: Minimum Mental State Examination (MMSE), Montreal Cognitive Assessment-Basic (MoCA-B) and Instrumental Activity of Daily Living (IADL). Receiver operating characteristic curve (ROC) analysis was used to evaluate the role of the ALPS-index in disease classification. The findings indicated a significant difference in the ALPS-index between the groups of participants with normal cognition, MCI, and AD. In addition, we found that ALPS-index was significantly correlated with the scores of the three clinical scales (with MoCA-B: r=0.233, p=0.001). Furthermore, with ALPS-index, Fractional Anisotropy (FA) values achieved best classification results (AUC=0.8899). Cognitive dysfunction is closely associated with the activity of the glymphatic system, and ALPS-index can be used as a biomarker for alterations along the AD continuum.

Brain Connectome Imaging Markers Research of Glucose Metabolism in the Early Stage of Alzheimer's Disease.

In recent years, increasing evidence had suggested that subjective cognitive decline (SCD) in unimpaired individuals may be the first symptom of Alzheimer's disease (AD). This study investigated the differences in the glucose metabolism network and the influence of the Apolipoprotein E (ApoE) gene between the SCD and normal control (NC) group by using graph theory. In this study, we included 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scans from Xuanwu Hospital in Beijing, China. 85 SCD subjects and 74 NC subjects were included. First, we calculated and compared network parameters between the two groups. We then identified the bilateral insula and bilateral parahippocampal gyrus as seed sites and studied the connections to the whole brain. The results showed that both the SCD and the NC showed small-world nature, but the metabolic network of SCD tended to be more regular. The clustering coefficient and local efficiency of SCD were significantly higher than those of NC (P<0.05). In addition, we found that carrying APOE resulted in enhanced metabolic connectivity, but with weaker aggregation and local information exchangeability. Our results suggested that there are differences in the glucose metabolic brain network between SCD and NC, suggesting that the graph-theoretic analysis method may provide evidence for the early pathological mechanism of AD.Clinical relevance- This study suggests that the graph-theoretic analysis method may provide evidence for the early pathological mechanism of AD.

Application of Entity-BERT model based on neuroscience and brain-like cognition in electronic medical record entity recognition.

Introduction: In the medical field, electronic medical records contain a large amount of textual information, and the unstructured nature of this information makes data extraction and analysis challenging. Therefore, automatic extraction of entity information from electronic medical records has become a significant issue in the healthcare domain. Methods: To address this problem, this paper proposes a deep learning-based entity information extraction model called Entity-BERT. The model aims to leverage the powerful feature extraction capabilities of deep learning and the pre-training language representation learning of BERT(Bidirectional Encoder Representations from Transformers), enabling it to automatically learn and recognize various entity types in medical electronic records, including medical terminologies, disease names, drug information, and more, providing more effective support for medical research and clinical practices. The Entity-BERT model utilizes a multi-layer neural network and cross-attention mechanism to process and fuse information at different levels and types, resembling the hierarchical and distributed processing of the human brain. Additionally, the model employs pre-trained language and sequence models to process and learn textual data, sharing similarities with the language processing and semantic understanding of the human brain. Furthermore, the Entity-BERT model can capture contextual information and long-term dependencies, combining the cross-attention mechanism to handle the complex and diverse language expressions in electronic medical records, resembling the information processing method of the human brain in many aspects. Additionally, exploring how to utilize competitive learning, adaptive regulation, and synaptic plasticity to optimize the model's prediction results, automatically adjust its parameters, and achieve adaptive learning and dynamic adjustments from the perspective of neuroscience and brain-like cognition is of interest. Results and discussion: Experimental results demonstrate that the Entity-BERT model achieves outstanding performance in entity recognition tasks within electronic medical records, surpassing other existing entity recognition models. This research not only provides more efficient and accurate natural language processing technology for the medical and health field but also introduces new ideas and directions for the design and optimization of deep learning models.