Prodromal Research Articles

Multi-Modal Diagnosis of Alzheimer's Disease using Interpretable Graph Convolutional Networks.

The interconnection between brain regions in neurological disease encodes vital information for the advancement of biomarkers and diagnostics. Although graph convolutional networks are widely applied for discovering brain connection patterns that point to disease conditions, the potential of connection patterns that arise from multiple imaging modalities has yet to be fully realized. In this paper, we propose a multi-modal sparse interpretable GCN framework (SGCN) for the detection of Alzheimer's disease (AD) and its prodromal stage, known as mild cognitive impairment (MCI). In our experimentation, SGCN learned the sparse regional importance probability to find signature regions of interest (ROIs), and the connective importance probability to reveal disease-specific brain network connections. We evaluated SGCN on the Alzheimer's Disease Neuroimaging Initiative database with multi-modal brain images and demonstrated that the ROI features learned by SGCN were effective for enhancing AD status identification. The identified abnormalities were significantly correlated with AD-related clinical symptoms. We further interpreted the identified brain dysfunctions at the level of large-scale neural systems and sex-related connectivity abnormalities in AD/MCI. The salient ROIs and the prominent brain connectivity abnormalities interpreted by SGCN are considerably important for developing novel biomarkers. These findings contribute to a better understanding of the network-based disorder via multi-modal diagnosis and offer the potential for precision diagnostics. The source code is available at https://github.com/Houliang-Zhou/SGCN.

Prodromal Alzheimer's disease can affect activities of daily living for adults with Down syndrome.

Alzheimer's disease (AD) affecting adults with Down syndrome (DS-AD), like late-onset AD (LOAD) in the neurotypical population, has preclinical, prodromal, and more advanced stages. Only tasks placing high demands on cognition are expected to be affected during the prodromal stage, with activities of daily living (ADLs) typically being spared. However, cognitive demands of ADLs could be high for adults with DS and may be affected during prodromal DS-AD. Cognitively stable cases that subsequently developed prodromal DS-AD were identified within a set of archived data from a previous longitudinal study. Measures of ADLs and multiple cognitive domains were examined over time. Clear declines in ADLs accompanied cognitive declines with prodromal DS-AD while stability in all measures was verified during preclinical DS-AD. Operationally defining prodromal DS-AD is essential to disease staging in this high-risk population and for informing treatment options and timing as new disease-modifying drugs become available. Cognitive and functional stability were demonstrated prior to the onset of prodromal DS-AD.ADL declines accompanied cognitive declines as adults with DS transitioned to prodromal AD.Declines in ADLs should be a defining feature of prodromal AD for adults with DS.Better characterization of prodromal DS-AD can improve AD diagnosis and disease staging.Improvements in DS-AD diagnosis and staging could also inform the timing of interventions.

Assessment of the significance of dilated perivascular spaces and nocture arterial hypertension in the development of Alzheimer's disease

To study the severity and localization of dilated perivascular spaces (DPVS), the levels of protein markers of amyloidosis and neurodegeneration in the cerebrospinal fluid (CSF) at different daily blood pressure (BP) profiles in patients with Alzheimer's disease (AD) and other types of cognitive impairment. A total of 119 people, aged 53 to 92 years, including 55 patients with AD, 27 patients with vascular cognitive disorders (VCD), 19 patients with frontotemporal degeneration (FTD). All patients underwent BP monitoring for 24 hours using a standard oscillometric measurement method, lumbar puncture to assess Aβ-42 and Aβ-40 amyloid protein, total and phosphorylated tau protein in the CSF, magnetic resonance imaging tomography of the brain with subsequent assessment of the severity of expansion and localization of DPVS according to the G.M. Potter scale. In 58.3% of patients with AD, there is no adequate reduction in BP at night in comparison with patients with VCD (p<0.05). A significant degree of expansion of the DPVS turned out to be most typical for patients with AD: grade 3 was detected in 45.7% of patients, and the maximum, grade 4, was detected in 13.4%. At the same time, DPVSs were significantly more often detected in the group of subjects with insufficient reduction in diastolic BP (DBP) at night. A strong inverse correlation was established between the level of Aβ-42 in the CSF and the variability of DBP at night (r= -0.92; p<0.05). The decrease in the level of Aβ-42 in AD, especially at the prodromal stage, is directly related to the low variability of DBP at night, which is more characteristic of an insufficient decrease or increase in BP during night sleep. Patients with AD were characterized by an insufficient decrease in BP at night, which is associated with the severity and degree of maximum expansion of the DPVS. A decrease in the level of Aβ-42 amyloid protein in the CSF strongly correlates with the variability of DBP at night.

Multi-view multi-input CNN-based architecture for diagnosis of Alzheimer's disease in its prodromal stages

Multi-view multi-input CNN-based architecture for diagnosis of Alzheimer's disease in its prodromal stages

Dual-3DM3AD: Mixed Transformer Based Semantic Segmentation and Triplet Pre-Processing for Early Multi-Class Alzheimer's Diagnosis.

Alzheimer's Disease (AD) is a widespread, chronic, irreversible, and degenerative condition, and its early detection during the prodromal stage is of utmost importance. Typically, AD studies rely on single data modalities, such as MRI or PET, for making predictions. Nevertheless, combining metabolic and structural data can offer a comprehensive perspective on AD staging analysis. To address this goal, this paper introduces an innovative multi-modal fusion-based approach named as Dual-3DM3-AD. This model is proposed for an accurate and early Alzheimer's diagnosis by considering both MRI and PET image scans. Initially, we pre-process both images in terms of noise reduction, skull stripping and 3D image conversion using Quaternion Non-local Means Denoising Algorithm (QNLM), Morphology function and Block Divider Model (BDM), respectively, which enhances the image quality. Furthermore, we have adapted Mixed-transformer with Furthered U-Net for performing semantic segmentation and minimizing complexity. Dual-3DM3-AD model is consisted of multi-scale feature extraction module for extracting appropriate features from both segmented images. The extracted features are then aggregated using Densely Connected Feature Aggregator Module (DCFAM) to utilize both features. Finally, a multi-head attention mechanism is adapted for feature dimensionality reduction, and then the softmax layer is applied for multi-class Alzheimer's diagnosis. The proposed Dual-3DM3-AD model is compared with several baseline approaches with the help of several performance metrics. The final results unveil that the proposed work achieves 98% of accuracy, 97.8% of sensitivity, 97.5% of specificity, 98.2% of f-measure, and better ROC curves, which outperforms other existing models in multi-class Alzheimer's diagnosis.

Multi-view multi-input CNN-based architecture for diagnosis of Alzheimer's disease in its prodromal stages

Multi-view multi-input CNN-based architecture for diagnosis of Alzheimer's disease in its prodromal stages

Demographics and clinical manifestations of lupus patients: experience from a private hospital in Saudi Arabia

Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a chronic pattern of relapses and remissions, with variable presentations ranging from mild skin manifestations to severe, life-threatening illness. The disease is multisystematic, with the most severe complications related to the kidneys and nervous system. Among the SLE manifestations, lupus nephritis is common, observable in approximately 40% of SLE patients. This study, conducted at a private hospital in Saudi Arabia, aimed to evaluate the demographic characteristics, clinical presentations, and laboratory results of patients with SLE. Methods: This retrospective study involved 105 SLE patients who were seen in the rheumatology clinic at the Specialized Medical Center in Riyadh from 2007 to 2022. The medical records of the patients were reviewed for patient demographics, clinical and serological characteristics, and therapeutic data. Results: The largest proportion (34.3%) was aged between 31 and 40 years. Female dominancy was found, as females represented 91 patients (86.7%). Joint involvement was found to be the most affected organ in the majority of the patients, accounting for 80 patients (76.2%), while the least affected organ was the heart, with cardiac manifestations present in 7 patients (6.7%). Conclusion: The majority of patients (95.2%) displayed a positive antinuclear antibody test, and more than one-half of the patients (68.6%) displayed positive anti-double stranded DNA. The most reported medication was hydroxychloroquine in 104 patients (99%), followed by steroids in 89 patients (84.8%).

Visual Event-Related Potentials under External Emotional Stimuli as Early Signs for Mild Cognitive Impairment.

Alzheimer's disease (AD) is a neurodegenerative disorder featured by progressive cognitive decline, which manifests in severe impairment of memory, attention, emotional processing and daily activities, leading to significant disability and social burden. Investigation on Mild Cognitive Impairment (MCI), the prodromal and transitional stage between normal aging and AD, serves as a key in diagnosing and slowing down the progression of AD. Numerous effects have been made up to date, however, the attentional mechanisms under different external emotion stimuli in MCI and AD are still unexplored in deep. To further explore the attentional mechanisms under different external emotion stimuli in both MCI and AD patients. In 51 healthy volunteers (Controls, 24 males and 27 females), 52 MCI (19 males and 33 females), and 47 AD (15 males and 32 females) patients, we administered the visual oddball event-related potentials (ERPs) under three types of external emotional stimuli: Neutral, Happiness and Sadness, in which the components N1, P2, N2 and P3 as well as the abnormal cortical activations corresponding to the significant ERP differences in the three groups were observed. Under all three external emotions, in AD patients, N2 and P3 latencies were significantly prolonged compared to both Controls and MCI. In addition, under Happiness, in MCI, P3 latencies were significantly delayed compared to Controls. Meanwhile, under both Happiness and Sadness, in AD patients, P3 amplitudes were significantly decreased compared to Controls and MCI, respectively. During N2 time window, under Neutral emotion, significant hypoactivation in the right superior temporal gyrus was found in AD patients compared to Controls, and under Happiness, the activation of the right inferior frontal gyrus was significantly attenuated in MCI compared to Controls. Under Sadness, in AD patients, the activation of the right superior frontal gyrus was significantly decreased compared to MCI. During P3 time window, under both Happiness and Sadness, when AD patients compared to MCI, the significantly attenuated activations were located in the right fusiform gyrus and the right middle occipital gyrus, respectively. Our results demonstrated visual attentional deficits under external emotional stimuli in both MCI and AD patients, highlighting the function of Happiness for early detecting MCI, in which the P3 latency and the hypoactivation of right inferior frontal gyrus during N2 time window can be early signs. The current study sheds further light of attentional mechanisms in MCI and AD patients, and indicates the value of emotional processing in the early detection of cognitive dysfunction.

Do beta-amyloid-targeted interventions improve cognition, physical functioning, and overt behaviour of Alzheimer's Disease (AD) patients: Protocol for meta-analysis of Phase 3 clinical trials both completed and terminated.

Accumulation of amyloid-beta (Aβ) in the brain has been explored as a primary cause of Alzheimer's Disease (AD). Better known as the amyloid hypothesis, it has been the main target of researchers vying to bring their therapeutic interventions to market despite several failed attempts by predecessors. In June 2021, Aduhelm (Aducanumab) became the first U.S. Food and Drug Administration (FDA) approved treatment for AD based on the amyloid hypothesis in which sparked controversy. This meta-analysis aims to investigate the efficacy of amyloid-beta targeting interventions at all stages of the disease including the prodromal or mild cognitive impairment (MCI) stage compared to placebo. All completed and terminated Phase III trials are assessed to provide a comprehensive overview of interventions targeting amyloid-beta to inform the legitimacy of the amyloid hypothesis.

Ultra-high risk for psychosis stigma: an updated Systematic Review.

To clarify if stigma associated with schizophrenia has also been directed towards the ultra-high risk for psychosis (UHR) population, the present review aimed at synthetizing the existing literature to update and extend our understanding on the topic. A systematic PRISMA-compliant review was performed in PubMed, Embase, Cochrane and Web of Science for articles published until 30/04/2023, using a combination of search terms describing the at-risk mental states for psychosis and stigma and correlated terms. Thirty-eight studies were included. Twenty-nine addressed UHR individuals directly, and 9 conducted interviews with non-patients regarding UHR. A total of 2560 UHR individuals were assessed; mean sample size was of 88.3 participants. Most of the studies were quantitative non-randomized/observational with young adults, 71.4% used SIPS (Structured Interview for Psychosis-risk Syndromes) and 25.0% used CAARMS (Comprehensive Assessment of At-Risk Mental States). Overall, the summarized studies have mainly involved individuals already attending UHR clinics from Western and high income countries. Studies can be grouped into five forms of stigma, among which the most frequently explored was perceived public stigma, followed by public stigma, self-stigma/internalized stigma, stigma stress and associative stigma. The main study design was quantitative nonrandomized, with only one interventional study. Most of the results confirmed the presence of stigma toward UHR individuals and findings provide additional support to the fact that stigma seems to be present since the very early stages of the disease. There is still a paucity of research and knowledge gaps about UHR-related stigma. Nevertheless, results suggest the presence of stigma toward UHR individuals, supporting the fact that stigma is present since the early stages of psychosis.

Constipation preceding depression: a population-based cohort study

Constipation is generally considered a common physical symptom of depression or a side effect of antidepressant treatments. However, according to the gut-brain axis hypothesis, the association between depression and constipation might be bi-directional. This study investigated the association between premorbid constipation and depression. We conducted a retrospective cohort study using data from UK Biobank. Individuals free of depression between 2006 and 2010 were included. Constipation status was determined using diagnostic codes from electronic health records or a baseline questionnaire. Data on covariates, including socio-demographic characteristics, lifestyle factors, health conditions, and regular medication use, were also collected through a baseline questionnaire. The primary outcome is incident depression, which was extracted from hospital inpatient admissions, primary care, self-report, and death data from baseline to 2022. The secondary outcome is depressive symptoms, which was assessed by Patient Health Questionnaire-9 (PHQ-9) from an online survey in 2016. Cox proportional hazard regression models were employed to assess the prospective association between constipation and incident depression. Logistic regression models were used to assess its association with depressive symptoms. Among the 449,459 participants included in the study, 18,596 (4.1%) experienced constipation at baseline, and 18,576 (4.1%) developed depression over a median follow-up period of 12.3 years. Premorbid constipation is associated with a 2.28-fold higher risk of depression. After adjusting the covariates, we found those with constipation still had a 48% higher risk of developing depression (adjusted hazard ratio [aHR] 1.48; 95% CI, 1.41-1.56) than those without constipation. Self-reported and diagnosed constipation were both associated with a higher risk of depression, with the aHR being 1.42 (95% CI: 1.34-1.51) and 1.66 (95% CI: 1.51-1.82), respectively. Participants with constipation were more likely to report depressive symptoms than people without (adjusted odds ratio 2.18; 95% CI, 1.97-2.43). These findings remained consistent in sensitivity analyses. Diagnosed and self-reported constipation are both prospectively associated with an elevated risk of depression. These explorative findings suggest that constipation may be an independent risk factor or a prodromal symptom of depression. Gastroenterologists and primary care physicians should pay more attention to the depressive symptoms of their constipation patients. The Shenzhen Science and Technology Program and the Strategic Priority Research Program of Chinese Academy of Sciences.

Clinical characteristics and genetic analysis of children with Omicron BF.7.14 type novel coronavirus-related acute necrotizing encephalopathy.

To explore the clinical characteristics, etiological factors, and clinical-related genetic variant of children with acute necrotizing encephalopathy (ANE) related to the Omicron BF.7.14 novel coronavirus. Genomic variations were detected through whole exome sequencing. Additionally, we summarized the clinical data to explore the inheritance patterns associated with novel coronavirus-related ANE. This study included four patients (2 males and 2 females) with an average age of 2.78 ± 1.93 years. All the patients had prodromal symptoms of Omicron BF.7.14 virus infection, and exhibited symptoms such as altered consciousness, seizures and cognitive/language disturbances. Cranial MRI scans revealed damage to the thalamus, basal ganglia and brainstem. The cerebrospinal fluid (CSF) cell counts were nearly normal, but protein level in CSF increased significantly. Genetic analysis revealed a novel truncated variant of CRMP2 gene in one patient who suffered more severe coma score and prognosis and dead in the later stages. All children exhibited a decrease in the absolute count of T lymphocytes, helper T cells, suppressor T cells, and NK cells to varying degrees. Furthermore, levels of cytokines, including IL-1 β, IL-5, IL-6 and IL-8 were significantly elevated in the CSF, especially in patient with truncated variant of CRMP2 gene. The Omicron BF.7.14 type novel coronavirus can lead to ANE, characterized by T cell immunosuppression and a significant increase in cytokine levels in the CSF. The truncated variation of CRMP2 gene may affect the prognosis of ANE by affecting the migration of cerebral T cells.

Prodromal period of psychosis: diagnostic criteria.

Aim: To study the psychopathological mechanisms of the development of the prodromal stage of psychosis in order to identify risk factors for the formation of psychosis. Materials and Methods: In this research 137 patients with newly diagnosed psychosis were examined: 65 patients with a diagnosis of paranoid schizophrenia; 72 patients - with a diagnosis of acute polymorphic psychotic disorder. Results: According to the analysis of symptoms using the PANSS, the absence of signs of an anxious state, conceptual disorganization of thinking, emotional withdrowal are reliable signs of PPP in PS, and unusual thought content, absence of signs of stereotyped thinking, tension, anxiety, and hallucinations are reliable signs of PPP in APPD. According to the analysis of symptoms using the SOPS, unusual thought content/delusional ideas, bizarre thinking, social anhedonia, suspiciousness/persecutory ideas, decrease in expressiveness of emotions are reliable signs of PPP in PS, and bizarre thinking, impaired tolerance to normal stress, sleep disturbance, perceptual abnormalities/hallucinations, trouble with focus and attention are reliable signs of PPP in APPD. Conclusions: In the process of studying the clinical-psychopathological and pathopsychological aspects of the development of the PPP, a number of risk factors for the formation of psychosis were identified. We found that he most important diagnostic signs of PPP in PS patients are: stereotyped thinking, social isolation, disorganizational thinking disorders, passive-apathetic social detachment, suspiciousness. The most informative prodromal symptoms of HP in PS patients are: conceptual disorganization of thinking, bizzare thinking, social isolation, suspiciousness/persecutory ideas, reduced expression of emotions.

Screening and Targeting Risk Factors for Prodromal Synucleinopathy: Taking Steps toward a Prescriptive Multi-modal Framework.

As the prevalence of Parkinson's disease (PD) grows, so too does the population at-risk of developing PD, those in the so-called prodromal period. This period can span from those experiencing subtle motor deficits yet not meeting full diagnostic criteria or those with physiologic markers of disease alone. Several disease-modifying therapies have failed to show a neuroprotective effect. A common criticism is that neurodegeneration, even in the early motor stages, has advanced too far for neuro-restoration-based interventions to be effective. Therefore, identifying this early population is essential. Once identified, these patients could then potentially benefit from sweeping lifestyle modifications to alter their disease trajectory. Herein, we review the literature on risk factors for, and prodromal symptoms of, PD with an emphasis on ones which may be modifiable in the earliest possible stages. We propose a process for identifying this population and speculate on some strategies which may modulate disease trajectory. Ultimately, this proposal warrants prospective studies.

Investigating characteristics of patients and healthcare Visits Prior to Out-of-Hospital Cardiac Arrest in Two Tertiary Hospitals in Oman

Introduction The high incidence of out of hospital cardiac arrest (OHCA) as well as its low survival rates are contributing to the burden on public health. Emerging evidence have recognized prodromal symptoms and patterns of healthcare use suggesting the possibility of predicting these cardiac events despite the general belief that they are merely sudden. Our study aimed to identify the characteristics of patients who present in OHCA and the utilization pattern of healthcare facilities by these patients in the period preceding the cardiac arrest. Methods This is a retrospective study which included adult OHCA patients who presented at two emergency departments (ED) in Muscat, Oman between 2016 and 2020. The ED visits that occurred within the six months preceding the arrest were investigated. Descriptive statistics and frequency tables were used to report the baseline characteristics of all patients. Associations were tested using chi-square test. Results The final cohort consisted of 822 patients with mean age of 60.2 years. The male and female percentages were 65.7% and 34.3% respectively. Less than 10% survived to hospital discharge. About two thirds of all recorded ED visits occurred in the three months immediately before the arrest. A significant association was observed between the frequency of pre-OHCA visits and cardiopulmonary resuscitation (CPR) outcome among patients (P-value = 0.000004). Conclusion Over a quarter of the cohort subjects have approached ED prior to the arrest. Patients are more likely to seek medical attention before the arrest complaining mainly of cardiac and respiratory symptoms. The chances of survival after receiving CPR were higher for those with higher number of visits prior to the arrest. Having a unified system to document and monitor frequent emergency presentations as well as demographics of the patients concerned will aid in the pattern recognition and prevention of OHCA in many subjects.

ALZHEIMER DISEASE: WHAT’S NEW, WHAT’S TRUE?

Alzheimer’s Disease (AD) is a devastating disorder estimated to affect 55 million individuals worldwide with 6.2 million cases in the US. AD is a significant clinical problem and numbers are only expected to increase. Alzheimer’s disease is characterized by structural changes in the brain including abnormal amyloid beta (Aβ) and neurofibrillary tau aggregation, neuroinflammation, and neuronal death. There is no effective treatment for AD and AD-related dementia (ADRD). For decades, the hypothesis that brain deposition of the amyloid-beta (Aβ) peptide initiates AD has dominated research and clinical trials. However, the FDA- approved antibody treatments targeting Aβ have yet to show convincing evidence for slowing the progression of disease symptomatology3, including no benefit to women and ApoE4 carriers over a period of 1.5 years4. Treatment failures can be attributed, at least in part, to an incomplete understanding of the pathogenic mechanisms of AD, which underscores the urgent need to examine alternative pathogenic mechanisms and therapeutic targets for AD. AD has been increasingly recognized as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, where neuroinflammation is considered one of the cardinal features of AD. Traditionally, the pathways of Aβ production and neuroinflammation have been considered independently; however, recent studies suggest that these processes may converge to promote the pathology associated with AD. Surmounting evidence supports chronic dysregulation in inflammatory and immune pathways as drivers of AD neurodegeneration and provides insights into possible microbial mechanisms involved in the onset and progression of AD. Mounting evidence implicates gut microbiome dysbiosis in AD, even at the preclinical/asymptomatic and prodromal stages of the disease. Links have been made between the gut microbiome and established biomarkers of AD, including Aß, ApoE status, and tau. Further, links between the gut microbiota and brain connectivity, as measured by functional magnetic resonance imaging (fMRI), have recently emerged but are poorly understood in AD. Our research group previously demonstrated cerebrovascular dysfunction in prodromal AD, correlated with cognitive dysfunction. Specifically, reduced cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) are associated with lower cognitive functioning in prodromal AD. Findings from our recent cross-sectional study indicate that pro-inflammatory gut bacteria more abundant in prodromal AD are associated with reduced CBF and CVR and elevated arterial transit time (ATT). Conversely, beneficial gut bacteria, more abundant in normal controls, are associated with better CBF and CVR and shorter ATT. Further, we identified the bile acid and lipid metabolism modifying organism and the oral pathogen (causes gingivitis and periodontal disease), to be differentially abundant in prodromal AD and CU cohorts, respectively. These results are undeniably promising for the future of AD in many ways including novel mechanistic discovery, non-invasive diagnostic testing, and novel treatment targets.

Abnormal dynamics of functional brain network in Apolipoprotein E ε4 carriers with mild cognitive impairment

&lt;abstract&gt; &lt;p&gt;As is well known, the Apolipoprotein E (APOE) ε4 allele is the most pertinent genetic hazardous element for Alzheimer's disease (AD). Mild cognitive impairment (MCI) is considered a prodromal stage of AD. How the APOE ε4 allele modulates functional connectivity of brain network in MCI group is a question worth exploring. At present, some studies have evaluated the relationship between APOE ε4 allele and static functional network connectivity (sFNC) for MCI individuals, while the relationship of dynamic FNC (dFNC) with APOE ε4 allele still remained puzzled. Thus, we aim to detect aberrant dFNC for APOE ε4 carriers in the MCI group. On the basis of the resting-state functional magnetic resonance imaging (rs-fMRI) data, seven intrinsic brain functional networks were first recognized by the group independent component analysis. Then, the technique of sliding window was employed to determine the dFNC, and two dFNC states were detected by the k-means clustering algorithm. Finally, three temporal properties of fraction time, mean dwell time as well as transition numbers in the dFNC states were investigated. The results found that the dFNC and temporal properties in APOE ε4 carriers were abnormal compared with those in APOE ε4 noncarriers. In detail, in the MCI group, compared with APOE ε4 noncarriers, carriers had 9 pairs of abnormal dFNC and had significant differences in all the three temporal properties of the two dFNC states. In addition, two pairs of dFNC were found significantly correlated with clinical measure. This detected abnormal dynamics of temporal properties and dFNC in APOE ε4 carriers were similar with that reported for AD patients in previous studies. These results may suggest that in the MCI group, APOE carriers are more at risk for AD compared to noncarriers. Our findings may offer novel insights into the mechanisms of abnormal brain reconfiguration for individuals at genetic risk for AD, which could also be regarded as biomarkers for the early identification of AD.&lt;/p&gt; &lt;/abstract&gt;

Hierarchical Graph Convolutional Network Built by Multiscale Atlases for Brain Disorder Diagnosis Using Functional Connectivity.

Functional connectivity network (FCN) data from functional magnetic resonance imaging (fMRI) is increasingly used for the diagnosis of brain disorders. However, state-of-the-art studies used to build the FCN using a single brain parcellation atlas at a certain spatial scale, which largely neglected functional interactions across different spatial scales in hierarchical manners. In this study, we propose a novel framework to perform multiscale FCN analysis for brain disorder diagnosis. We first use a set of well-defined multiscale atlases to compute multiscale FCNs. Then, we utilize biologically meaningful brain hierarchical relationships among the regions in multiscale atlases to perform nodal pooling across multiple spatial scales, namely "Atlas-guided Pooling (AP)." Accordingly, we propose a multiscale-atlases-based hierarchical graph convolutional network (MAHGCN), built on the stacked layers of graph convolution and the AP, for a comprehensive extraction of diagnostic information from multiscale FCNs. Experiments on neuroimaging data from 1792 subjects demonstrate the effectiveness of our proposed method in the diagnoses of Alzheimer's disease (AD), the prodromal stage of AD i.e., mild cognitive impairment (MCI), as well as autism spectrum disorder (ASD), with the accuracy of 88.9%, 78.6%, and 72.7%, respectively. All results show significant advantages of our proposed method over other competing methods. This study not only demonstrates the feasibility of brain disorder diagnosis using resting-state fMRI empowered by deep learning but also highlights that the functional interactions in the multiscale brain hierarchy are worth being explored and integrated into deep learning network architectures for a better understanding of the neuropathology of brain disorders. The codes for MAHGCN are publicly available at "https://github.com/MianxinLiu/ MAHGCN-code."

Potential dopaminergic deficit in patients with geriatric psychiatric disorders as revealed by DAT-SPECT: a cross-sectional study

BackgroundIt has been reported that patients with geriatric psychiatric disorders include many cases of the prodromal stages of neurodegenerative diseases. Abnormal 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane dopamine transporter single-photon emission computed tomography (DAT-SPECT)...

Optimal dose and type of exercise to improve cognitive function in patients with mild cognitive impairment: a systematic review and network meta-analysis of RCTs.

Mild cognitive impairment (MCI) represents a prodromal stage of dementia, characterized by cognitive decline exceeding that expected with normal aging. Exercise interventions have emerged as a promising approach to counter functional decline and enhance cognitive function in the elderly MCI population. However, the optimal exercise modalities and dosage (dose-response relationship) are understudied. It aims to determine the most effective exercise modality for MCI patients by optimizing the dose-response relationship to ensure sufficient intensity to induce positive neurological adaptations. A systematic search of electronic databases, including PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted from inception to April 15, 2024. Studies evaluating the efficacy of exercise interventions in MCI participants were included. Primary outcomes of interest are global cognition and executive function. Random-effects models will be utilized for both pairwise and network meta-analysis. Following the application of specific inclusion and exclusion criteria, a total of 42 articles, encompassing 2832 participants, were chosen for inclusion in a network meta-analysis. The findings revealed that multi-component exercise demonstrated superior efficacy in mitigating the deterioration of global cognition, as evidenced by standard mean differences (SMDs) of 1.09 (95% CI: 0.68 to 1.51) compared to passive controls. Additionally, multi-component exercise exhibited a significant impact on executive function, with SMDs of 2.50 (95% CI: 0.88 to 4.12) when contrasted with passive controls. Our research has demonstrated that sessions lasting 30 minutes, occurring 3-4 times per week, with interventions lasting 12-24 weeks and an intensity of 60-85% of maximum heart rate, yield higher effect sizes in improving global cognition. However, sessions lasting 30-61 minutes, with interventions lasting 25 weeks or longer, show greater effectiveness in enhancing executive function. A network meta-analysis identified multi-component exercise as the most effective intervention for improving global cognitive and executive function in patients with mild cognitive impairment. Notably, moderate-intensity exercise performed at least three times weekly appears beneficial, with evidence suggesting shorter sessions and higher frequencies may optimize cognitive outcomes. https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024534922.