Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium.

Using machine learning, we recently decomposed the neuroanatomical heterogeneity of established schizophrenia to discover two volumetric subgroups-a 'lower brain volume' subgroup (SG1) and an 'higher striatal volume' subgroup (SG2) with otherwise normal brain structure. In this study, we investigated whether the MRI signatures of these subgroups were also already present at the time of the first-episode of psychosis (FEP) and whether they were related to clinical presentation and clinical remission over 1-, 3-, and 5-years. We included 572 FEP and 424 healthy controls (HC) from 4 sites (Sao Paulo, Santander, London, Melbourne) of the PHENOM consortium. Our prior MRI subgrouping models (671 participants; USA, Germany, and China) were applied to both FEP and HC. Participants were assigned into 1 of 4 categories: subgroup 1 (SG1), subgroup 2 (SG2), no subgroup membership ('None'), and mixed SG1 + SG2 subgroups ('Mixed'). Voxel-wise analyses characterized SG1 and SG2 subgroups. Supervised machine learning analyses characterized baseline and remission signatures related to SG1 and SG2 membership. The two dominant patterns of 'lower brain volume' in SG1 and 'higher striatal volume' (with otherwise normal neuromorphology) in SG2 were identified already at the first episode of psychosis. SG1 had a significantly higher proportion of FEP (32%) vs. HC (19%) than SG2 (FEP, 21%; HC, 23%). Clinical multivariate signatures separated the SG1 and SG2 subgroups (balanced accuracy = 64%; p < 0.0001), with SG2 showing higher education but also greater positive psychosis symptoms at first presentation, and an association with symptom remission at 1-year, 5-year, and when timepoints were combined. Neuromorphological subtypes of schizophrenia are already evident at illness onset, separated by distinct clinical presentations, and differentially associated with subsequent remission. These results suggest that the subgroups may be underlying risk phenotypes that could be targeted in future treatment trials and are critical to consider when interpreting neuroimaging literature.

Design of quetiapine fumarate loaded polyethylene glycol decorated graphene oxide nanosheets: Invitro-exvivo characterization.

Quetiapine Fumarate (QF) is an atypical antipsychotic with poor oral bioavailability (9%) due to its low permeability and pH-dependent solubility. Therefore, this study aims to design QF-loaded polyethylene glycol (PEG) functionalized graphene oxide nanosheets (GON) for nasal delivery of QF. In brief, GO was synthesized using a modified Hummers process, followed by ultra-sonication to produce GON. Subsequently, PEG-functionalized GON was prepared using carbodiimide chemistry (PEG-GON). QF was then decorated onto the cage of PEG-GON using the π-π stacking phenomenon (QF@PEG-GON). The QF@PEG-GON nanocomposite underwent several spectral characterizations, in vitro drug release, mucoadhesion study, ex vivo diffusion study, etc. The surface morphology of QF@PEG-GON nanocomposite validates the cracked nature of the nanocomposite, whereas the diffractograms and thermogram of nanocomposite confirm the conversion of QF into an amorphous form with uniform distribution in PEG-GON. Moreover, an ex vivo study of PEG-GON demonstrates superior mucoadhesion capacity due to its surface functional groups and hydrophilicity. The percent drug loading content and percent entrapment efficiency of the nanocomposite were found to be 9.2±0.62% and 92.3±1.02%, respectively. The developed nanocomposite exhibited 43.82±1.65% drug release within 24h, with the Korsemeyer-Peppas model providing the best-fit release kinetics (R2: 0.8614). Here, the interlayer spacing of PEG-GON prevented prompt diffusion of the buffer, leading to a delayed release pattern. In conclusion, the anticipated QF@PEG-GON nanocomposite shows promise as a nanocarrier platform for nasal delivery of QF.

Design and Development of Gastro-retentive Drug Delivery System for Trazodone Hydrochloride: a Promising Alternative to Innovator's Controlled-Release Tablet.

Trazodone hydrochloride (TZN) is a serotonin reuptake inhibitor that treats a major depressive disorder. It exhibits a short plasma half-life of 4.1 h and shows pH-dependent solubility. Above its pKa (6.74), solubility of TZN is very low, affecting its dissolution in the lower part of GIT. Hence, the present work aimed to develop gastro-retentive floating tablet of TZN. Central composite design was employed to optimize the formulation. Formulation variables like the concentration of HPMC-K100M, Polyox WSR 303 Leo, and sodium bicarbonate were evaluated for the responses like floating lag time and drug release. X-ray imaging study was performed on rabbits to determine the in vivo gastric retention of the optimized formulation. The accelerated stability study was conducted on optimized tablets as per ICH guidelines. Floating lag time and f2 value of the optimized formulation were found to be 2.51±0.02 min and 62.79, respectively. X-ray imaging studies in rabbits determined the in vivo gastro retention time. After 12 h of administration, tablet remained in the gastric region, indicating better retentive power. Accelerated stability studies showed sufficient formulation stability even after 3 months of storage. All these studies depict that the floating gastro-retentive system could be used as an alternative to the innovator formulation.

Two distinct neuroanatomical subtypes of schizophrenia revealed using machine learning.

Neurobiological heterogeneity in schizophrenia is poorly understood and confounds current analyses. We investigated neuroanatomical subtypes in a multi-institutional multi-ethnic cohort, using novel semi-supervised machine learning methods designed to discover patterns associated with disease rather than normal anatomical variation. Structural MRI and clinical measures in established schizophrenia (n = 307) and healthy controls (n = 364) were analysed across three sites of PHENOM (Psychosis Heterogeneity Evaluated via Dimensional Neuroimaging) consortium. Regional volumetric measures of grey matter, white matter, and CSF were used to identify distinct and reproducible neuroanatomical subtypes of schizophrenia. Two distinct neuroanatomical subtypes were found. Subtype 1 showed widespread lower grey matter volumes, most prominent in thalamus, nucleus accumbens, medial temporal, medial prefrontal/frontal and insular cortices. Subtype 2 showed increased volume in the basal ganglia and internal capsule, and otherwise normal brain volumes. Grey matter volume correlated negatively with illness duration in Subtype 1 (r = -0.201, P = 0.016) but not in Subtype 2 (r = -0.045, P = 0.652), potentially indicating different underlying neuropathological processes. The subtypes did not differ in age (t = -1.603, df = 305, P = 0.109), sex (chi-square = 0.013, df = 1, P = 0.910), illness duration (t = -0.167, df = 277, P = 0.868), antipsychotic dose (t = -0.439, df = 210, P = 0.521), age of illness onset (t = -1.355, df = 277, P = 0.177), positive symptoms (t = 0.249, df = 289, P = 0.803), negative symptoms (t = 0.151, df = 289, P = 0.879), or antipsychotic type (chi-square = 6.670, df = 3, P = 0.083). Subtype 1 had lower educational attainment than Subtype 2 (chi-square = 6.389, df = 2, P = 0.041). In conclusion, we discovered two distinct and highly reproducible neuroanatomical subtypes. Subtype 1 displayed widespread volume reduction correlating with illness duration, and worse premorbid functioning. Subtype 2 had normal and stable anatomy, except for larger basal ganglia and internal capsule, not explained by antipsychotic dose. These subtypes challenge the notion that brain volume loss is a general feature of schizophrenia and suggest differential aetiologies. They can facilitate strategies for clinical trial enrichment and stratification, and precision diagnostics.

Newer variants of retroaortic left renal vein.

The left renal vein (LRV) passing behind the abdominal aorta is termed as a retroaortic LRV (RLRV) and it is a relatively uncommon condition. Since the left kidney is preferred in the setting of live donor kidney transplantation, urologists must be familiar with the anomalies of the LRV. There are four variants of RLRV mentioned in the literature. However, we came across two newer variants of RLRV in two donors for renal transplantation. Both donors underwent successful left donor nephrectomy.

Disrupted interactions among the hippocampal, dorsal attention, and central-executive networks in amnestic mild cognitive impairment.

Neuroimaging investigations consistently demonstrate that the neural processes involve complex interactions between the large-scale networks. Among those networks, the dorsal attention network (DAN) and the central-executive network (CEN) have been previously shown to exhibit anti-correlated activity with the default-mode network (DMN) in cognitively normal people. In amnestic mild cognitive impairment (MCI) and Alzheimer's disease, the hippocampal network (HCN)-a key memory processing system-and its interactions with other networks have gathered central interest. The current study aims to evaluate the patterns of functional architectures of the HCN with the three networks-DAN, CEN, and DMN-in amnestic MCI and normal controls (NC) to test the hypothesis that the interactions of HCN with other networks alter in MCI. We recorded the resting state functional MRI, assessed patterns of functional architectures between the four networks using dynamical causal modeling, and compared between NC and MCI. Our analysis showed that the DAN modulates the activity between the HCN and the DMN in both MCI and NC. We further uncovered that the DAN modulates the activity between the HCN and the CEN in NC, but such modulation is impaired in MCI. We found an association between impaired modulation and Montreal cognitive assessment (R = 0.349). Overall, our findings provide important insight in understanding the neuroimaging signature of amnestic MCI and/or Alzheimer's disease.

Terahertz Spectroscopic Probe of Hot Electron and Hole Transfer from Colloidal CsPbBr3 Perovskite Nanocrystals.

Colloidal all inorganic CsPbX3 (X = Cl, Br, I) nanocrystals (NCs) have emerged to be an excellent material for applications in light emission, photovoltaics, and photocatalysis. Efficient interfacial transfer of photogenerated electrons and holes are essential for a good photovoltaic and photocatalytic material. Using time-resolved terahertz spectroscopy, we have measured the kinetics of photogenerated electron and hole transfer processes in CsPbBr3 NCs in the presence of benzoquinone and phenothiazine molecules as electron and hole acceptors, respectively. Efficient hot electron/hole transfer with a sub-300 fs time scale is the major channel of carrier transfer thus overcomes the problem related to Auger recombination. A secondary transfer of thermalized carriers also takes place with time scales of 20-50 ps for electrons and 137-166 ps for holes. This work suggests that suitable interfaces of CsPbX3 NCs with electron and hole transport layers would harvest hot carriers, increasing the photovoltaic and photocatalytic efficiencies.

Interactions between the anterior cingulate-insula network and the fronto-parietal network during perceptual decision-making.

Information processing in the human brain during cognitively demanding goal-directed tasks is thought to involve several large-scale brain networks, including the anterior cingulate-insula network (aCIN) and the fronto-parietal network (FPN). Recent functional MRI (fMRI) studies have provided clues that the aCIN initiates activity changes in the FPN. However, when and how often these networks interact remains largely unknown to date. Here, we systematically examined the oscillatory interactions between the aCIN and the FPN by using the spectral Granger causality analysis of reconstructed brain source signals from the scalp electroencephalography (EEG) recorded from human participants performing a face-house perceptual categorization task. We investigated how the aCIN and the FPN interact, what the temporal sequence of events in these nodes is, and what frequency bands of information flow bind these nodes in networks. We found that beta band (13-30Hz) and gamma (30-100Hz) bands of interactions are involved between the aCIN and the FPN during decision-making tasks. In gamma band, the aCIN initiated the Granger causal control over the FPN in 25-225 ms timeframe. In beta band, the FPN achieved a control over the aCIN in 225-425 ms timeframe. These band-specific time-dependent Granger causal controls of the aCIN and the FPN were retained for behaviorally harder decision-making tasks. These findings of times and frequencies of oscillatory interactions in the aCIN and FPN provide us new insights into the general neural mechanisms for sensory information-guided, goal-directed behaviors, including perceptual decision-making processes.

Effect of Lipid Composition in Propofol Formulations: Decisive Component in Reducing the Free Propofol Content and Improving Pharmacodynamic Profiles.

Current endeavor was aimed towards studying significance of lipid composition on free propofol concentration in aqueous phase and associated pain on injection. Three different nanoformulations, namely long-chain triglyceride (LCT)/medium-chain glyceride (MCG)-based nanoemulsion (ProNano), MCG-based self-nanoemulsifying formulation (PSNE), and lipid-free nanoformulation (PNS) were accessed for the same. In vitro and in vivo performances of developed formulations were compared with Diprivan®. ProNano showed minimum free propofol concentration (0.13%) and hence lower pain on injection (rat paw-lick test, 6 ± 2 s) compared to Diprivan®, PSNE, and PNS (0.21%, 0.23%, and 0.51% free propofol, respectively, and rat paw-lick test; 12 ± 3, 14 ± 2, and 22 ± 3 s, respectively). These results conjecture the role of MCG in effective encapsulation of propofol. Anesthetic action assessed by measuring duration of loss of righting reflex (LORR), which was found similar in case of ProNano and PSNE (14 ± 3 and 15 ± 3 min, respectively) compared to Diprivan® (13 ± 3 min). In case of lipid-free formulation, PNS, extended anesthetic action (21 ± 2 min) was observed which may be due to sustained release of propofol from nanosponges. Studies on effect of lipoproteins on propofol release highlighted significance of HDL (100% release with maximum concentration of about 1.2 µg/ml of HDL) from all three formulations.

The salience network dynamics in perceptual decision-making.

Recent neuroimaging studies have demonstrated that the network consisting of the right anterior insula (rAI), left anterior insula (lAI) and dorsal anterior cingulate cortex (dACC) is activated in sensory stimulus-guided goal-directed behaviors. This network is often known as the salience network (SN). When and how a sensory signal enters and organizes within SN before reaching the central executive network including the prefrontal cortices is still a mystery. Previous electrophysiological studies focused on individual nodes of SN, either on dACC or rAI, have reports of conflicting findings of the earliest cortical activity within the network. Functional magnetic resonance imaging (fMRI) studies are not able to answer these questions in the time-scales of human sensory perception and decision-making. Here, using clear and noisy face-house image categorization tasks and human scalp electroencephalography (EEG) recordings combined with source reconstruction techniques, we study when and how oscillatory activity organizes SN during a perceptual decision. We uncovered that the beta-band (13-30Hz) oscillations bound SN, became most active around 100ms after the stimulus onset and the rAI acted as a main outflow hub within SN for easier decision making task. The SN activities (Granger causality measures) were negatively correlated with the decision response time (decision difficulty). These findings suggest that the SN activity precedes the executive control in mediating sensory and cognitive processing to arrive at visual perceptual decisions.

Therapeutic Potential for Targeting the Suppressor of Cytokine Signalling-1 Pathway for the Treatment of SLE.

Although the specific events dictating systemic lupus erythematosus (SLE) pathology remain unclear, abundant evidence indicates a critical role for dysregulated cytokine signalling in disease progression. Notably, the suppressor of cytokine signalling (SOCS) family of intracellular proteins, in particular the kinase inhibitory region (KIR) bearing SOCS1 and SOCS3, plays a critical role in regulating cytokine signalling. To assess a relationship between SOCS1/SOCS3 expression and SLE, the goals of this study were to (1) evaluate the time kinetics of SOCS1/SOCS3 message and protein expression based on SLE-associated stimulations, (2) compare levels of SOCS1 and SOCS3 present in SLE patients and healthy controls by message and protein, (3) relate SOCS1/SOCS3 expression to inflammatory markers in SLE patients and (4) correlate SOCS1/SOCS3 levels to current treatments. We found that SOCS1 and SOCS3 were most abundant in murine splenic samples at 48 h subsequent to stimulation by anti-CD3, LPS or interferon-gamma. In addition, significant reductions in SOCS1 and SOCS3 were present within PMBCs of SLE patients compared to controls by both mRNA and protein expression. We also found that decreased levels of SOCS1 in SLE patients were correlated with enhanced levels of inflammatory markers and upregulated expression of MHC class II. Finally, we show that patients receiving steroid treatment possessed higher levels SOCS1 compared to SLE patient counterparts and that steroid administration to human PBMCs upregulated SOCS1 message in a dose- and time-dependent manner. Together, these results suggest that therapeutic strategies focused on SOCS1 signalling may have efficacy in the treatment of SLE.

An audit of histopathology reports of carcinoma endometrium: experience from a tertiary referral center.

BACKGROUND: The aim was to assess compliance to reporting minimum data sets in carcinoma endometrium reports, in a team of 13 pathologists, and also to analyze parameters such as. tumor size, type, grade, depth of myometrial invasion, lymph node yield, pTNM stage etc. MATERIALS AND METHODS: Reports of 114 cases of carcinoma endometrium, that were operated in-house during the years 2008 to 2010 were analyzed from the files of the Pathology department of our hospital. RESULTS: The median age was 58.04 years and median tumor size was 4 cm. Endometrioid adenocarcinoma was the most common type (82.5%), followed by malignant mixed Mullerian tumor (MMMT) (6.1%) and Serous carcinoma (3.5%). Grade 2 was the commonest tumor grade (42.1%). Less than half of myometrial invasion was seen in 50% of the cases and more than half of the myometrial invasion was seen in 46.5% of cases. (Information was not available in four cases). Parametrial involvement was seen in 5.3% cases. The pTNM stage was not mentioned in 71.9% reports. The median lymph node yield was 15. CONCLUSION: The compliance to adhere to and to provide minimum data information in carcinoma endometrium reports is generally good. Lymph node yield is reasonable. Mentioning of pTNM staging is to be done more meticulously. Use of proformas/checklists is recommended.

Cutaneous Collagenous Vasculopathy: A Rare Entity Treated With Pulsed Dye Laser.

Cutaneous collagenous vasculopathy (CCV) is a rare idiopathic dermal microangiopathy. Clinically, it presents as diffuse cutaneous telangiectasias that are indistinguishable from other benign vascular entities, thereby posing a diagnostic challenge. We present a case of CCV successfully treated with pulsed dye laser (PDL). A 27-year-old male presented with generalized erythematous macules, diagnosed as CCV via histopathology. After a successful test spot, PDL treatment resulted in significant improvement. The pathogenesis of CCV involves altered dermal microvasculature and veil cell activation. Epidemiologically, it primarily affects Caucasians, most often in the middle-aged adult population. A negative family history of similar lesions can help narrow down the differential diagnosis. Diagnosis requires biopsy, with histopathological examination demonstrating vessel ectasia and collagenous vessel wall thickening. Given its rarity, CCV presents diagnostic and management challenges though PDL emerges as a promising treatment modality for this condition.

Dysregulated Salience Network Control over Default-Mode and Central-Executive Networks in Schizophrenia Revealed Using Stochastic Dynamical Causal Modeling.

Introduction: Neuroimaging studies suggest that the human brain consists of intrinsically organized, large-scale neural networks. Among these networks, the interplay among the default-mode network (DMN), salience network (SN), and central-executive network (CEN) has been widely used to understand the functional interaction patterns in health and disease. This triple network model suggests that the SN causally controls over the DMN and CEN in healthy individuals. This interaction is often referred to as SN's dynamic regulating mechanism. However, such interactions are not well understood in individuals with schizophrenia. Methods: In this study, we leveraged resting-state functional magnetic resonance imaging data from schizophrenia (n = 67) and healthy controls (n = 81) and evaluated the directional functional interactions among DMN, SN, and CEN using stochastic dynamical causal modeling methodology. Results: In healthy controls, our analyses replicated previous findings that SN regulates DMN and CEN activities (Mann-Whitney U test; p < 10-8). In schizophrenia, however, our analyses revealed a disrupted SN-based controlling mechanism over the DMN and CEN (Mann-Whitney U test; p < 10-16). Conclusions: These results indicate that the disrupted controlling mechanism of SN over the other two neural networks may be a candidate neuroimaging phenotype in schizophrenia.

Explainable AI-based Deep-SHAP for mapping the multivariate relationships between regional neuroimaging biomarkers and cognition.

BACKGROUND: Mild cognitive impairment (MCI)/Alzheimer's disease (AD) is associated with cognitive decline beyond normal aging and linked to the alterations of brain volume quantified by magnetic resonance imaging (MRI) and amyloid-beta (Aß) quantified by positron emission tomography (PET). Yet, the complex relationships between these regional imaging measures and cognition in MCI/AD remain unclear. Explainable artificial intelligence (AI) may uncover such relationships. METHOD: We integrate the AI-based deep learning neural network and Shapley additive explanations (SHAP) approaches and introduce the Deep-SHAP method to investigate the multivariate relationships between regional imaging measures and cognition. After validating this approach on simulated data, we apply it to real experimental data from MCI/AD patients. RESULTS: Deep-SHAP significantly predicted cognition using simulated regional features and identified the ground-truth simulated regions as the most significant multivariate predictors. When applied to experimental MRI data, Deep-SHAP revealed that the insula, lateral occipital, medial frontal, temporal pole, and occipital fusiform gyrus are the primary contributors to global cognitive decline in MCI/AD. Furthermore, when applied to experimental amyloid Pittsburgh compound B (PiB)-PET data, Deep-SHAP identified the key brain regions for global cognitive decline in MCI/AD as the inferior temporal, parahippocampal, inferior frontal, supratemporal, and lateral frontal gray matter. CONCLUSION: Deep-SHAP method uncovered the multivariate relationships between regional brain features and cognition, offering insights into the most critical modality-specific brain regions involved in MCI/AD mechanisms.

Neutrophilic Panniculitides.

Neutrophilic panniculitides are a heterogeneous group of inflammatory disorders encompassing many different entities. This review article focuses on the epidemiology, pathogenesis, clinicopathological features, diagnosis, and treatment of selected diseases. Patients often seek care due to systemic involvement, but the variable presentation of panniculitides can present a diagnostic challenge. Most therapeutic modalities for neutrophilic disorders are anecdotal at best with a notable lack of standardization of the responses to medications. There is an urgent need for a larger multi-institutional collaboration to address the unmet needs of these challenging, yet rare conditions.

Feasibility of Hepatic Artery Infusion Chemotherapy for Colorectal Liver Metastasis in an Indian Setting.

Hepatic artery infusion chemotherapy (HAIC) is a popular treatment modality for the treatment of colorectal liver metastasis (CRLM). The aim of this study was to determine the feasibility of HAIC for high-risk resected CRLM delivered using repeated femoral puncture and delivering 5-fluorouracil infusional chemotherapy along with systemic adjuvant chemotherapy. The present study is a retrospective review of a prospectively maintained database. All patients who underwent HAIC for colorectal liver metastases between July 2022 and July 2023 were included. A total of 12 patients were included in the study of which 11 completed four sessions as planned. The median age was 47 (29-73) years with nine male (81%) and two female (18%) patients. Rectum (n = 7, 63%) was the most common primary location. All patients received systemic chemotherapy with 5-fluorouracil-based regimens prior to HAIC (median 12 cycles). The median number of metastasis was 2 (1-8). Eight patients had metastasis in unilobar distribution (73%). On completion of HAIC treatment, nine patients (64%) were completely disease free with a median follow-up of 8 months. None of the patients experienced any immediate adverse events during or after completion of the procedure. Conventional HAIC comes with various challenges such as unavailability of the agent floxuridine and the specialized HAIC pump. Percutaneous HAIC has a lower chance of infection. The delivery of HAIC using repeated femoral punctures and 5FU chemotherapy was successful in over 90% of the patients making it a feasible option in the treatment of CRLM.

Design and statistical optimization of osmotically driven capsule based on push-pull technology.

In present investigation attempt was made to develop and statistically optimize osmotically active capsule tailor made from the concept of bilayer (push-pull) osmotic tablet technology. The capsule was comprised of active (drug) and push (osmogen) layer. Active layer was compressed in form of tablet by mixing known amount of drug and formulation excipients. Similarly push layer was made by compressing Mannitol with formulation excipients. Finally, both layers were packed in hard gelatin capsule having small aperture at top and coated with semipermeable membrane to form osmotically active capsule. Formulated and optimized capsules were characterized for Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetric (DSC), scanning electron microscopy, In-vitro drug release study and Release models and kinetics. Statistically optimized formulation showed good correlation between predicted and experimented results, which further confirms the practicability and validity of the model.

A comparative study of the effect of four consecutive firing cycles on the marginal fit of all: ceramic crown system and metal ceramic crown system.

The marginal fit of new all ceramic crown system. To know the marginal adaptability of new all ceramic systems. Finesse all ceramic system and traditional metal ceramic system total 15 samples of all ceramic (test group) and 15 samples of metal ceramic crown system (control group) were fabricated and tested for marginal distortion at four firing cycles using image analyzer and special software (Leco Version La 32) in which instead of measuring at points an area was measured that gives a computed mean measured thickness of marginal distortion. Value obtained were evaluated for significance using two tailed, unpaired, student t test and Tukeys-Kramer multiple comparison test. Finesse all ceramic crown system showed continued clinically acceptable marginal distortion through all firing cycles (12.84 µm). Greatest distortion of metal ceramic system occurred during degassing cycle(16.90 µm). In respect of marginal fit all ceramic (finesse) crowns is better choice when esthetics is more concern.

Predicting cognitive dysfunction and regional hubs using Braak staging amyloid-beta biomarkers and machine learning.

Mild cognitive impairment (MCI) is a transitional stage between normal aging and early Alzheimer's disease (AD). The presence of extracellular amyloid-beta (Aß) in Braak regions suggests a connection with cognitive dysfunction in MCI/AD. Investigating the multivariate predictive relationships between regional Aß biomarkers and cognitive function can aid in the early detection and prevention of AD. We introduced machine learning approaches to estimate cognitive dysfunction from regional Aß biomarkers and identify the Aß-related dominant brain regions involved with cognitive impairment. We employed Aß biomarkers and cognitive measurements from the same individuals to train support vector regression (SVR) and artificial neural network (ANN) models and predict cognitive performance solely based on Aß biomarkers on the test set. To identify Aß-related dominant brain regions involved in cognitive prediction, we built the local interpretable model-agnostic explanations (LIME) model. We found elevated Aß in MCI compared to controls and a stronger correlation between Aß and cognition, particularly in Braak stages III-IV and V-VII (p < 0.05) biomarkers. Both SVR and ANN, especially ANN, showed strong predictive relationships between regional Aß biomarkers and cognitive impairment (p < 0.05). LIME integrated with ANN showed that the parahippocampal gyrus, inferior temporal gyrus, and hippocampus were the most decisive Braak regions for predicting cognitive decline. Consistent with previous findings, this new approach suggests relationships between Aß biomarkers and cognitive impairment. The proposed analytical framework can estimate cognitive impairment from Braak staging Aß biomarkers and delineate the dominant brain regions collectively involved in AD pathophysiology.