Predicting Outcomes Following Lower Extremity Endovascular Revascularization Using Machine Learning.

BACKGROUND: Lower extremity endovascular revascularization for peripheral artery disease carries nonnegligible perioperative risks; however, outcome prediction tools remain limited. Using machine learning, we developed automated algorithms that predict 30-day outcomes following lower extremity endovascular revascularization. METHODS AND RESULTS: The National Surgical Quality Improvement Program targeted vascular database was used to identify patients who underwent lower extremity endovascular revascularization (angioplasty, stent, or atherectomy) for peripheral artery disease between 2011 and 2021. Input features included 38 preoperative demographic/clinical variables. The primary outcome was 30-day postprocedural major adverse limb event (composite of major reintervention, untreated loss of patency, or major amputation) or death. Data were split into training (70%) and test (30%) sets. Using 10-fold cross-validation, 6 machine learning models were trained using preoperative features. The primary model evaluation metric was area under the receiver operating characteristic curve. Overall, 21 886 patients were included, and 30-day major adverse limb event/death occurred in 1964 (9.0%) individuals. The best performing model for predicting 30-day major adverse limb event/death was extreme gradient boosting, achieving an area under the receiver operating characteristic curve of 0.93 (95% CI, 0.92-0.94). In comparison, logistic regression had an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.70-0.74). The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.09. The top 3 predictive features in our algorithm were (1) chronic limb-threatening ischemia, (2) tibial intervention, and (3) congestive heart failure. CONCLUSIONS: Our machine learning models accurately predict 30-day outcomes following lower extremity endovascular revascularization using preoperative data with good discrimination and calibration. Prospective validation is warranted to assess for generalizability and external validity.

Machine Learning to Predict Outcomes of Endovascular Intervention for Patients With PAD.

Importance: Endovascular intervention for peripheral artery disease (PAD) carries nonnegligible perioperative risks; however, outcome prediction tools are limited. Objective: To develop machine learning (ML) algorithms that can predict outcomes following endovascular intervention for PAD. Design, Setting, and Participants: This prognostic study included patients who underwent endovascular intervention for PAD between January 1, 2004, and July 5, 2023, with 1 year of follow-up. Data were obtained from the Vascular Quality Initiative (VQI), a multicenter registry containing data from vascular surgeons and interventionalists at more than 1000 academic and community hospitals. From an initial cohort of 262 242 patients, 26 565 were excluded due to treatment for acute limb ischemia (n = 14 642) or aneurysmal disease (n = 3456), unreported symptom status (n = 4401) or procedure type (n = 2319), or concurrent bypass (n = 1747). Data were split into training (70%) and test (30%) sets. Exposures: A total of 112 predictive features (75 preoperative [demographic and clinical], 24 intraoperative [procedural], and 13 postoperative [in-hospital course and complications]) from the index hospitalization were identified. Main Outcomes and Measures: Using 10-fold cross-validation, 6 ML models were trained using preoperative features to predict 1-year major adverse limb event (MALE; composite of thrombectomy or thrombolysis, surgical reintervention, or major amputation) or death. The primary model evaluation metric was area under the receiver operating characteristic curve (AUROC). After selecting the best performing algorithm, additional models were built using intraoperative and postoperative data. Results: Overall, 235 677 patients who underwent endovascular intervention for PAD were included (mean [SD] age, 68.4 [11.1] years; 94 979 [40.3%] female) and 71 683 (30.4%) developed 1-year MALE or death. The best preoperative prediction model was extreme gradient boosting (XGBoost), achieving the following performance metrics: AUROC, 0.94 (95% CI, 0.93-0.95); accuracy, 0.86 (95% CI, 0.85-0.87); sensitivity, 0.87; specificity, 0.85; positive predictive value, 0.85; and negative predictive value, 0.87. In comparison, logistic regression had an AUROC of 0.67 (95% CI, 0.65-0.69). The XGBoost model maintained excellent performance at the intraoperative and postoperative stages, with AUROCs of 0.94 (95% CI, 0.93-0.95) and 0.98 (95% CI, 0.97-0.99), respectively. Conclusions and Relevance: In this prognostic study, ML models were developed that accurately predicted outcomes following endovascular intervention for PAD, which performed better than logistic regression. These algorithms have potential for important utility in guiding perioperative risk-mitigation strategies to prevent adverse outcomes following endovascular intervention for PAD.

Link among apolipoprotein E E4, gait, and cognition in neurodegenerative diseases: ONDRI study.

INTRODUCTION: Apolipoprotein E E4 allele (APOE E4) and slow gait are independently associated with cognitive impairment and dementia. However, it is unknown whether their coexistence is associated with poorer cognitive performance and its underlying mechanism in neurodegenerative diseases. METHODS: Gait speed, APOE E4, cognition, and neuroimaging were assessed in 480 older adults with neurodegeneration. Participants were grouped by APOE E4 presence and slow gait. Mediation analyses were conducted to determine if brain structures could explain the link between these factors and cognitive performance. RESULTS: APOE E4 carriers with slow gait had the lowest global cognitive performance and smaller gray matter volumes compared to non-APOE E4 carriers with normal gait. Coexistence of APOE E4 and slow gait best predicted global and domain-specific poorer cognitive performances, mediated by smaller gray matter volume. DISCUSSION: Gait slowness in APOE E4 carriers with neurodegenerative diseases may indicate extensive gray matter changes associated with poor cognition. HIGHLIGHTS: APOE E4 and slow gait are risk factors for cognitive decline in neurodegenerative diseases. Slow gait and smaller gray matter volumes are associated, independently of APOE E4. Worse cognition in APOE E4 carriers with slow gait is explained by smaller GM volume. Gait slowness in APOE E4 carriers indicates poorer cognition-related brain changes.

Predicting outcomes following lower extremity open revascularization using machine learning.

Lower extremity open revascularization is a treatment option for peripheral artery disease that carries significant peri-operative risks; however, outcome prediction tools remain limited. Using machine learning (ML), we developed automated algorithms that predict 30-day outcomes following lower extremity open revascularization. The National Surgical Quality Improvement Program targeted vascular database was used to identify patients who underwent lower extremity open revascularization for chronic atherosclerotic disease between 2011 and 2021. Input features included 37 pre-operative demographic/clinical variables. The primary outcome was 30-day major adverse limb event (MALE; composite of untreated loss of patency, major reintervention, or major amputation) or death. Our data were split into training (70%) and test (30%) sets. Using tenfold cross-validation, we trained 6 ML models. Overall, 24,309 patients were included. The primary outcome of 30-day MALE or death occurred in 2349 (9.3%) patients. Our best performing prediction model was XGBoost, achieving an area under the receiver operating characteristic curve (95% CI) of 0.93 (0.92-0.94). The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.08. Our ML algorithm has potential for important utility in guiding risk mitigation strategies for patients being considered for lower extremity open revascularization to improve outcomes.

Vision Transformer-based Decision Support for Neurosurgical Intervention in Acute Traumatic Brain Injury: Automated Surgical Intervention Support Tool.

Purpose To develop an automated triage tool to predict neurosurgical intervention for patients with traumatic brain injury (TBI). Materials and Methods A provincial trauma registry was reviewed to retrospectively identify patients with TBI from 2005 to 2022 treated at a specialized Canadian trauma center. Model training, validation, and testing were performed using head CT scans with binary reference standard patient-level labels corresponding to whether the patient received neurosurgical intervention. Performance and accuracy of the model, the Automated Surgical Intervention Support Tool for TBI (ASIST-TBI), were also assessed using a held-out consecutive test set of all patients with TBI presenting to the center between March 2021 and September 2022. Results Head CT scans from 2806 patients with TBI (mean age, 57 years ± 22 [SD]; 1955 [70%] men) were acquired between 2005 and 2021 and used for training, validation, and testing. Consecutive scans from an additional 612 patients (mean age, 61 years ± 22; 443 [72%] men) were used to assess the performance of ASIST-TBI. There was accurate prediction of neurosurgical intervention with an area under the receiver operating characteristic curve (AUC) of 0.92 (95% CI: 0.88, 0.94), accuracy of 87% (491 of 562), sensitivity of 87% (196 of 225), and specificity of 88% (295 of 337) on the test dataset. Performance on the held-out test dataset remained robust with an AUC of 0.89 (95% CI: 0.85, 0.91), accuracy of 84% (517 of 612), sensitivity of 85% (199 of 235), and specificity of 84% (318 of 377). Conclusion A novel deep learning model was developed that could accurately predict the requirement for neurosurgical intervention using acute TBI CT scans. Keywords: CT, Brain/Brain Stem, Surgery, Trauma, Prognosis, Classification, Application Domain, Traumatic Brain Injury, Triage, Machine Learning, Decision Support Supplemental material is available for this article. © RSNA, 2024 See also commentary by Haller in this issue.

Using machine learning to predict outcomes following suprainguinal bypass.

OBJECTIVE: Suprainguinal bypass for peripheral artery disease (PAD) carries important surgical risks; however, outcome prediction tools remain limited. We developed machine learning (ML) algorithms that predict outcomes following suprainguinal bypass. METHODS: The Vascular Quality Initiative database was used to identify patients who underwent suprainguinal bypass for PAD between 2003 and 2023. We identified 100 potential predictor variables from the index hospitalization (68 preoperative [demographic/clinical], 13 intraoperative [procedural], and 19 postoperative [in-hospital course/complications]). The primary outcomes were major adverse limb events (MALE; composite of untreated loss of patency, thrombectomy/thrombolysis, surgical revision, or major amputation) or death at 1 year following suprainguinal bypass. Our data were split into training (70%) and test (30%) sets. Using 10-fold cross-validation, we trained six ML models using preoperative features (Extreme Gradient Boosting [XGBoost], random forest, Naïve Bayes classifier, support vector machine, artificial neural network, and logistic regression). The primary model evaluation metric was area under the receiver operating characteristic curve (AUROC). The best performing algorithm was further trained using intra- and postoperative data. Model robustness was evaluated using calibration plots and Brier scores. Performance was assessed on subgroups based on age, sex, race, ethnicity, rurality, median Area Deprivation Index, symptom status, procedure type, prior intervention for PAD, concurrent interventions, and urgency. RESULTS: Overall, 16,832 patients underwent suprainguinal bypass, and 3136 (18.6%) developed 1-year MALE or death. Patients with 1-year MALE or death were older (mean age, 64.9 vs 63.5 years; P < .001) with more comorbidities, had poorer functional status (65.7% vs 80.9% independent at baseline; P < .001), and were more likely to have chronic limb-threatening ischemia (67.4% vs 47.6%; P < .001) than those without an outcome. Despite being at higher cardiovascular risk, they were less likely to receive acetylsalicylic acid or statins preoperatively and at discharge. Our best performing prediction model at the preoperative stage was XGBoost, achieving an AUROC of 0.92 (95% confidence interval [CI], 0.91-0.93). In comparison, logistic regression had an AUROC of 0.67 (95% CI, 0.65-0.69). Our XGBoost model maintained excellent performance at the intra- and postoperative stages, with AUROCs of 0.93 (95% CI, 0.92-0.94) and 0.98 (95% CI, 0.97-0.99), respectively. Calibration plots showed good agreement between predicted and observed event probabilities with Brier scores of 0.12 (preoperative), 0.11 (intraoperative), and 0.10 (postoperative). Of the top 10 predictors, nine were preoperative features including chronic limb-threatening ischemia, previous procedures, comorbidities, and functional status. Model performance remained robust on all subgroup analyses. CONCLUSIONS: We developed ML models that accurately predict outcomes following suprainguinal bypass, performing better than logistic regression. Our algorithms have potential for important utility in guiding perioperative risk mitigation strategies to prevent adverse outcomes following suprainguinal bypass.

Predicting Outcomes Following Endovascular Abdominal Aortic Aneurysm Repair Using Machine Learning.

OBJECTIVE: To develop machine learning (ML) models that predict outcomes following endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). BACKGROUND: EVAR carries non-negligible perioperative risks; however, there are no widely used outcome prediction tools. METHODS: The National Surgical Quality Improvement Program targeted database was used to identify patients who underwent EVAR for infrarenal AAA between 2011 and 2021. Input features included 36 preoperative variables. The primary outcome was 30-day major adverse cardiovascular event (composite of myocardial infarction, stroke, or death). Data were split into training (70%) and test (30%) sets. Using 10-fold cross-validation, 6 ML models were trained using preoperative features. The primary model evaluation metric was area under the receiver operating characteristic curve. Model robustness was evaluated with calibration plot and Brier score. Subgroup analysis was performed to assess model performance based on age, sex, race, ethnicity, and prior AAA repair. RESULTS: Overall, 16,282 patients were included. The primary outcome of 30-day major adverse cardiovascular event occurred in 390 (2.4%) patients. Our best-performing prediction model was XGBoost, achieving an area under the receiver operating characteristic curve (95% CI) of 0.95 (0.94-0.96) compared with logistic regression [0.72 [0.70-0.74)]. The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.06. Model performance remained robust on all subgroup analyses. CONCLUSIONS: Our newer ML models accurately predict 30-day outcomes following EVAR using preoperative data and perform better than logistic regression. Our automated algorithms can guide risk mitigation strategies for patients being considered for EVAR.

Using Machine Learning (XGBoost) to Predict Outcomes After Infrainguinal Bypass for Peripheral Artery Disease.

OBJECTIVE: To develop machine learning (ML) algorithms that predict outcomes after infrainguinal bypass. BACKGROUND: Infrainguinal bypass for peripheral artery disease carries significant surgical risks; however, outcome prediction tools remain limited. METHODS: The Vascular Quality Initiative database was used to identify patients who underwent infrainguinal bypass for peripheral artery disease between 2003 and 2023. We identified 97 potential predictor variables from the index hospitalization [68 preoperative (demographic/clinical), 13 intraoperative (procedural), and 16 postoperative (in-hospital course/complications)]. The primary outcome was 1-year major adverse limb event (composite of surgical revision, thrombectomy/thrombolysis, or major amputation) or death. Our data were split into training (70%) and test (30%) sets. Using 10-fold cross-validation, we trained 6 ML models using preoperative features. The primary model evaluation metric was the area under the receiver operating characteristic curve (AUROC). The top-performing algorithm was further trained using intraoperative and postoperative features. Model robustness was evaluated using calibration plots and Brier scores. RESULTS: Overall, 59,784 patients underwent infrainguinal bypass, and 15,942 (26.7%) developed 1-year major adverse limb event/death. The best preoperative prediction model was XGBoost, achieving an AUROC (95% CI) of 0.94 (0.93-0.95). In comparison, logistic regression had an AUROC (95% CI) of 0.61 (0.59-0.63). Our XGBoost model maintained excellent performance at the intraoperative and postoperative stages, with AUROCs (95% CI's) of 0.94 (0.93-0.95) and 0.96 (0.95-0.97), respectively. Calibration plots showed good agreement between predicted and observed event probabilities with Brier scores of 0.08 (preoperative), 0.07 (intraoperative), and 0.05 (postoperative). CONCLUSIONS: ML models can accurately predict outcomes after infrainguinal bypass, outperforming logistic regression.

Predicting Major Adverse Cardiovascular Events Following Carotid Endarterectomy Using Machine Learning.

Background Carotid endarterectomy (CEA) is a major vascular operation for stroke prevention that carries significant perioperative risks; however, outcome prediction tools remain limited. The authors developed machine learning algorithms to predict outcomes following CEA. Methods and Results The National Surgical Quality Improvement Program targeted vascular database was used to identify patients who underwent CEA between 2011 and 2021. Input features included 36 preoperative demographic/clinical variables. The primary outcome was 30-day major adverse cardiovascular events (composite of stroke, myocardial infarction, or death). The data were split into training (70%) and test (30%) sets. Using 10-fold cross-validation, 6 machine learning models were trained using preoperative features. The primary metric for evaluating model performance was area under the receiver operating characteristic curve. Model robustness was evaluated with calibration plot and Brier score. Overall, 38 853 patients underwent CEA during the study period. Thirty-day major adverse cardiovascular events occurred in 1683 (4.3%) patients. The best performing prediction model was XGBoost, achieving an area under the receiver operating characteristic curve of 0.91 (95% CI, 0.90-0.92). In comparison, logistic regression had an area under the receiver operating characteristic curve of 0.62 (95% CI, 0.60-0.64), and existing tools in the literature demonstrate area under the receiver operating characteristic curve values ranging from 0.58 to 0.74. The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.02. The strongest predictive feature in our algorithm was carotid symptom status. Conclusions The machine learning models accurately predicted 30-day outcomes following CEA using preoperative data and performed better than existing tools. They have potential for important utility in guiding risk-mitigation strategies to improve outcomes for patients being considered for CEA.

Machine learning to predict outcomes following endovascular abdominal aortic aneurysm repair.

BACKGROUND: Endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) carries important perioperative risks; however, there are no widely used outcome prediction tools. The aim of this study was to apply machine learning (ML) to develop automated algorithms that predict 1-year mortality following EVAR. METHODS: The Vascular Quality Initiative database was used to identify patients who underwent elective EVAR for infrarenal AAA between 2003 and 2023. Input features included 47 preoperative demographic/clinical variables. The primary outcome was 1-year all-cause mortality. Data were split into training (70 per cent) and test (30 per cent) sets. Using 10-fold cross-validation, 6 ML models were trained using preoperative features with logistic regression as the baseline comparator. The primary model evaluation metric was area under the receiver operating characteristic curve (AUROC). Model robustness was evaluated with calibration plot and Brier score. RESULTS: Some 63 655 patients were included. One-year mortality occurred in 3122 (4.9 per cent) patients. The best performing prediction model for 1-year mortality was XGBoost, achieving an AUROC (95 per cent c.i.) of 0.96 (0.95-0.97). Comparatively, logistic regression had an AUROC (95 per cent c.i.) of 0.69 (0.68-0.71). The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.04. The top 3 predictive features in the algorithm were 1) unfit for open AAA repair, 2) functional status, and 3) preoperative dialysis. CONCLUSIONS: In this data set, machine learning was able to predict 1-year mortality following EVAR using preoperative data and outperformed standard logistic regression models.

Perivascular spaces mediate a relationship between diabetes and other cerebral small vessel disease markers in cerebrovascular and neurodegenerative diseases.

Type 2 diabetes mellitus (T2DM) and hypertension are risk factors for cerebral small vessel disease (SVD); however, few studies have characterised their relationships with MRI-visible perivascular spaces (PVS). MRI was used to quantify deep (d) and periventricular (p) white matter hyperintensities (WMH), lacunes, PVS in the white matter (wmPVS) or basal ganglia (bgPVS), and diffusion metrics in white matter. Patients with T2DM had greater wmPVS volume and there were greater wmPVS volumes in patients with T2DM and hypertension together. Counterfactual moderated mediation models found indirect effects of T2DM on volumes of other SVD and diffusion markers that were mediated by wmPVS: pWMH, dWMH, periventricular lacunes, and deep lacunes, and progression of deep lacunes over 1 year, in patients with hypertension, but not in patients without hypertension. Studying the regulation of cortical perivascular fluid dynamics may reveal mechanisms that mediate the impact of T2DM on cerebral small vessels.

Using machine learning to predict outcomes following open abdominal aortic aneurysm repair.

OBJECTIVE: Prediction of outcomes following open abdominal aortic aneurysm (AAA) repair remains challenging with a lack of widely used tools to guide perioperative management. We developed machine learning (ML) algorithms that predict outcomes following open AAA repair. METHODS: The Vascular Quality Initiative (VQI) database was used to identify patients who underwent elective open AAA repair between 2003 and 2023. Input features included 52 preoperative demographic/clinical variables. All available preoperative variables from VQI were used to maximize predictive performance. The primary outcome was in-hospital major adverse cardiovascular event (MACE; composite of myocardial infarction, stroke, or death). Secondary outcomes were individual components of the primary outcome, other in-hospital complications, and 1-year mortality and any reintervention. We split our data into training (70%) and test (30%) sets. Using 10-fold cross-validation, six ML models were trained using preoperative features (Extreme Gradient Boosting [XGBoost], random forest, Naïve Bayes classifier, support vector machine, artificial neural network, and logistic regression). The primary model evaluation metric was area under the receiver operating characteristic curve (AUROC). Model robustness was evaluated with calibration plot and Brier score. The top 10 predictive features in our final model were determined based on variable importance scores. Performance was assessed on subgroups based on age, sex, race, ethnicity, rurality, median area deprivation index, proximal clamp site, prior aortic surgery, and concomitant procedures. RESULTS: Overall, 12,027 patients were included. The primary outcome of in-hospital MACE occurred in 630 patients (5.2%). Compared with patients without a primary outcome, those who developed in-hospital MACE were older with more comorbidities, demonstrated poorer functional status, had more complex aneurysms, and were more likely to require concomitant procedures. Our best performing prediction model for in-hospital MACE was XGBoost, achieving an AUROC of 0.93 (95% confidence interval, 0.92-0.94). Comparatively, logistic regression had an AUROC of 0.71 (95% confidence interval, 0.70-0.73). For secondary outcomes, XGBoost achieved AUROCs between 0.84 and 0.94. The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.05. These findings highlight the excellent predictive performance of the XGBoost model. The top three predictive features in our algorithm for in-hospital MACE following open AAA repair were: (1) coronary artery disease; (2) American Society of Anesthesiologists classification; and (3) proximal clamp site. Model performance remained robust on all subgroup analyses. CONCLUSIONS: Open AAA repair outcomes can be accurately predicted using preoperative data with our ML models, which perform better than logistic regression. Our automated algorithms can help guide risk-mitigation strategies for patients being considered for open AAA repair to improve outcomes.

Predicting outcomes following open revascularization for aortoiliac occlusive disease using machine learning.

OBJECTIVE: Open surgical treatment options for aortoiliac occlusive disease carry significant perioperative risks; however, outcome prediction tools remain limited. Using machine learning (ML), we developed automated algorithms that predict 30-day outcomes following open aortoiliac revascularization. METHODS: The National Surgical Quality Improvement Program (NSQIP) targeted vascular database was used to identify patients who underwent open aortoiliac revascularization for atherosclerotic disease between 2011 and 2021. Input features included 38 preoperative demographic/clinical variables. The primary outcome was 30-day major adverse limb event (MALE; composite of untreated loss of patency, major reintervention, or major amputation) or death. The 30-day secondary outcomes were individual components of the primary outcome, major adverse cardiovascular event (MACE; composite of myocardial infarction, stroke, or death), individual components of MACE, wound complication, bleeding, other morbidity, non-home discharge, and unplanned readmission. Our data were split into training (70%) and test (30%) sets. Using 10-fold cross-validation, we trained six ML models using preoperative features. The primary model evaluation metric was area under the receiver operating characteristic curve (AUROC). Model robustness was evaluated with calibration plot and Brier score. Variable importance scores were calculated to determine the top 10 predictive features. Performance was assessed on subgroups based on age, sex, race, ethnicity, symptom status, procedure type, and urgency. RESULTS: Overall, 9649 patients were included. The primary outcome of 30-day MALE or death occurred in 1021 patients (10.6%). Our best performing prediction model for 30-day MALE or death was XGBoost, achieving an AUROC of 0.95 (95% confidence interval [CI], 0.94-0.96). In comparison, logistic regression had an AUROC of 0.79 (95% CI, 0.77-0.81). For 30-day secondary outcomes, XGBoost achieved AUROCs between 0.87 and 0.97 (untreated loss of patency [0.95], major reintervention [0.88], major amputation [0.96], death [0.97], MACE [0.95], myocardial infarction [0.88], stroke [0.93], wound complication [0.94], bleeding [0.87], other morbidity [0.96], non-home discharge [0.90], and unplanned readmission [0.91]). The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.05. The strongest predictive feature in our algorithm was chronic limb-threatening ischemia. Model performance remained robust on all subgroup analyses of specific demographic/clinical populations. CONCLUSIONS: Our ML models accurately predict 30-day outcomes following open aortoiliac revascularization using preoperative data, performing better than logistic regression. They have potential for important utility in guiding risk-mitigation strategies for patients being considered for open aortoiliac revascularization to improve outcomes.

Association of Dual-Task Gait Cost and White Matter Hyperintensity Burden Poststroke: Results From the ONDRI.

BACKGROUND: Acute change in gait speed while performing a mental task [dual-task gait cost (DTC)], and hyperintensity magnetic resonance imaging signals in white matter are both important disability predictors in older individuals with history of stroke (poststroke). It is still unclear, however, whether DTC is associated with overall hyperintensity volume from specific major brain regions in poststroke. METHODS: This is a cohort study with a total of 123 older (69 ± 7 years of age) participants with history of stroke were included from the Ontario Neurodegenerative Disease Research Initiative. Participants were clinically assessed and had gait performance assessed under single- and dual-task conditions. Structural neuroimaging data were analyzed to measure both, white matter hyperintensity (WMH) and normal appearing volumes. Percentage of WMH volume in frontal, parietal, occipital, and temporal lobes as well as subcortical hyperintensities in basal ganglia + thalamus were the main outcomes. Multivariate models investigated associations between DTC and hyperintensity volumes, adjusted for age, sex, years of education, global cognition, vascular risk factors, APOE4 genotype, residual sensorimotor symptoms from previous stroke and brain volume. RESULTS: There was a significant positive global linear association between DTC and hyperintensity burden (adjusted Wilks' λ = .87, P = .01). Amongst all WMH volumes, hyperintensity burden from basal ganglia + thalamus provided the most significant contribution to the global association (adjusted ß = .008, η2 = .03; P = .04), independently of brain atrophy. CONCLUSIONS: In poststroke, increased DTC may be an indicator of larger white matter damages, specifically in subcortical regions, which can potentially affect the overall cognitive processing and decrease gait automaticity by increasing the cortical control over patients' locomotion.

White matter hyperintensities and smaller cortical thickness are associated with neuropsychiatric symptoms in neurodegenerative and cerebrovascular diseases.

BACKGROUND: Neuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical thickness to NPS in participants across neurodegenerative and cerebrovascular diseases. METHODS: Five hundred thirteen participants with one of these conditions, i.e. Alzheimer's Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson's Disease, or Cerebrovascular Disease, were included in the study. NPS were assessed using the Neuropsychiatric Inventory - Questionnaire and grouped into hyperactivity, psychotic, affective, and apathy subsyndromes. White matter hyperintensities were quantified using a semi-automatic segmentation technique and FreeSurfer cortical thickness was used to measure regional grey matter loss. RESULTS: Although NPS were frequent across the five disease groups, participants with frontotemporal dementia had the highest frequency of hyperactivity, apathy, and affective subsyndromes compared to other groups, whilst psychotic subsyndrome was high in both frontotemporal dementia and Parkinson's disease. Results from univariate and multivariate results showed that various predictors were associated with neuropsychiatric subsyndromes, especially cortical thickness in the inferior frontal, cingulate, and insula regions, sex(female), global cognition, and basal ganglia-thalamus white matter hyperintensities. CONCLUSIONS: In participants with neurodegenerative and cerebrovascular diseases, our results suggest that smaller cortical thickness and white matter hyperintensity burden in several cortical-subcortical structures may contribute to the development of NPS. Further studies investigating the mechanisms that determine the progression of NPS in various neurodegenerative and cerebrovascular diseases are needed.

Using machine learning to predict outcomes following carotid endarterectomy.

OBJECTIVE: Prediction of outcomes following carotid endarterectomy (CEA) remains challenging, with a lack of standardized tools to guide perioperative management. We used machine learning (ML) to develop automated algorithms that predict outcomes following CEA. METHODS: The Vascular Quality Initiative (VQI) database was used to identify patients who underwent CEA between 2003 and 2022. We identified 71 potential predictor variables (features) from the index hospitalization (43 preoperative [demographic/clinical], 21 intraoperative [procedural], and 7 postoperative [in-hospital complications]). The primary outcome was stroke or death at 1 year following CEA. Our data were split into training (70%) and test (30%) sets. Using 10-fold cross-validation, we trained six ML models using preoperative features (Extreme Gradient Boosting [XGBoost], random forest, Naïve Bayes classifier, support vector machine, artificial neural network, and logistic regression). The primary model evaluation metric was area under the receiver operating characteristic curve (AUROC). After selecting the best performing algorithm, additional models were built using intra- and postoperative data. Model robustness was evaluated using calibration plots and Brier scores. Performance was assessed on subgroups based on age, sex, race, ethnicity, insurance status, symptom status, and urgency of surgery. RESULTS: Overall, 166,369 patients underwent CEA during the study period. In total, 7749 patients (4.7%) had the primary outcome of stroke or death at 1 year. Patients with an outcome were older with more comorbidities, had poorer functional status, and demonstrated higher risk anatomic features. They were also more likely to undergo intraoperative surgical re-exploration and have in-hospital complications. Our best performing prediction model at the preoperative stage was XGBoost, achieving an AUROC of 0.90 (95% confidence interval [CI], 0.89-0.91). In comparison, logistic regression had an AUROC of 0.65 (95% CI, 0.63-0.67), and existing tools in the literature demonstrate AUROCs ranging from 0.58 to 0.74. Our XGBoost models maintained excellent performance at the intra- and postoperative stages, with AUROCs of 0.90 (95% CI, 0.89-0.91) and 0.94 (95% CI, 0.93-0.95), respectively. Calibration plots showed good agreement between predicted and observed event probabilities with Brier scores of 0.15 (preoperative), 0.14 (intraoperative), and 0.11 (postoperative). Of the top 10 predictors, eight were preoperative features, including comorbidities, functional status, and previous procedures. Model performance remained robust on all subgroup analyses. CONCLUSIONS: We developed ML models that accurately predict outcomes following CEA. Our algorithms perform better than logistic regression and existing tools, and therefore, have potential for important utility in guiding perioperative risk mitigation strategies to prevent adverse outcomes.

Cognitive correlates of antisaccade behaviour across multiple neurodegenerative diseases.

Oculomotor tasks generate a potential wealth of behavioural biomarkers for neurodegenerative diseases. Overlap between oculomotor and disease-impaired circuitry reveals the location and severity of disease processes via saccade parameters measured from eye movement tasks such as prosaccade and antisaccade. Existing studies typically examine few saccade parameters in single diseases, using multiple separate neuropsychological test scores to relate oculomotor behaviour to cognition; however, this approach produces inconsistent, ungeneralizable results and fails to consider the cognitive heterogeneity of these diseases. Comprehensive cognitive assessment and direct inter-disease comparison are crucial to accurately reveal potential saccade biomarkers. We remediate these issues by characterizing 12 behavioural parameters, selected to robustly describe saccade behaviour, derived from an interleaved prosaccade and antisaccade task in a large cross-sectional data set comprising five disease cohorts (Alzheimer's disease/mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson's disease, and cerebrovascular disease; n = 391, age 40-87) and healthy controls (n = 149, age 42-87). These participants additionally completed an extensive neuropsychological test battery. We further subdivided each cohort by diagnostic subgroup (for Alzheimer's disease/mild cognitive impairment and frontotemporal dementia) or degree of cognitive impairment based on neuropsychological testing (all other cohorts). We sought to understand links between oculomotor parameters, their relationships to robust cognitive measures, and their alterations in disease. We performed a factor analysis evaluating interrelationships among the 12 oculomotor parameters and examined correlations of the four resultant factors to five neuropsychology-based cognitive domain scores. We then compared behaviour between the abovementioned disease subgroups and controls at the individual parameter level. We theorized that each underlying factor measured the integrity of a distinct task-relevant brain process. Notably, Factor 3 (voluntary saccade generation) and Factor 1 (task disengagements) significantly correlated with attention/working memory and executive function scores. Factor 3 also correlated with memory and visuospatial function scores. Factor 2 (pre-emptive global inhibition) correlated only with attention/working memory scores, and Factor 4 (saccade metrics) correlated with no cognitive domain scores. Impairment on several mostly antisaccade-related individual parameters scaled with cognitive impairment across disease cohorts, while few subgroups differed from controls on prosaccade parameters. The interleaved prosaccade and antisaccade task detects cognitive impairment, and subsets of parameters likely index disparate underlying processes related to different cognitive domains. This suggests that the task represents a sensitive paradigm that can simultaneously evaluate a variety of clinically relevant cognitive constructs in neurodegenerative and cerebrovascular diseases and could be developed into a screening tool applicable to multiple diagnoses.

Classification and staging of Parkinson's disease using video-based eye tracking.

INTRODUCTION: 83% of those diagnosed with Parkinson's Disease (PD) eventually progress to PD with mild cognitive impairment (PD-MCI) followed by dementia (PDD) - suggesting a complex spectrum of pathology concomitant with aging. Biomarkers sensitive and specific to this spectrum are required if useful diagnostics are to be developed that may supplement current clinical testing procedures. We used video-based eye tracking and machine learning to develop a simple, non-invasive test sensitive to PD and the stages of cognitive dysfunction. METHODS: From 121 PD (45 Cognitively Normal/45 MCI/20 Dementia/11 Other) and 106 healthy controls, we collected video-based eye tracking data on an interleaved pro/anti-saccade task. Features of saccade, pupil, and blink behavior were used to train a classifier to predict confidence scores for PD/PD-MCI/PDD diagnosis. RESULTS: The Receiver Operator Characteristic Area Under the Curve (ROC-AUC) of the classifier was 0.88, with the cognitive-dysfunction subgroups showing progressively increased AUC, and the AUC of PDD being 0.95. The classifier reached a sensitivity of 83% and a specificity of 78%. The confidence scores predicted PD motor and cognitive performance scores. CONCLUSION: Biomarkers of saccade, pupil, and blink were extracted from video-based eye tracking to create a classifier with high sensitivity to the landscape of PD cognitive and motor dysfunction. A complex landscape of PD is revealed through a quick, non-invasive eye tracking task and our model provides a framework for such a task to be used as a supplementary screening tool in the clinic.

White matter hyperintensity burden predicts cognitive but not motor decline in Parkinson's disease: results from the Ontario Neurodegenerative Diseases Research Initiative.

BACKGROUND AND PURPOSE: The pathophysiology of Parkinson's disease (PD) negatively affects brain network connectivity, and in the presence of brain white matter hyperintensities (WMHs) cognitive and motor impairments seem to be aggravated. However, the role of WMHs in predicting accelerating symptom worsening remains controversial. The objective was to investigate whether location and segmental brain WMH burden at baseline predict cognitive and motor declines in PD after 2 years. METHODS: Ninety-eight older adults followed longitudinally from Ontario Neurodegenerative Diseases Research Initiative with PD of 3-8 years in duration were included. Percentages of WMH volumes at baseline were calculated by location (deep and periventricular) and by brain region (frontal, temporal, parietal, occipital lobes and basal ganglia + thalamus). Cognitive and motor changes were assessed from baseline to 2-year follow-up. Specifically, global cognition, attention, executive function, memory, visuospatial abilities and language were assessed as were motor symptoms evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III, spatial-temporal gait variables, Freezing of Gait Questionnaire and Activities Specific Balance Confidence Scale. RESULTS: Regression analysis adjusted for potential confounders showed that total and periventricular WMHs at baseline predicted decline in global cognition (p < 0.05). Also, total WMH burden predicted the decline of executive function (p < 0.05). Occipital WMH volumes also predicted decline in global cognition, visuomotor attention and visuospatial memory declines (p < 0.05). WMH volumes at baseline did not predict motor decline. CONCLUSION: White matter hyperintensity burden at baseline predicted cognitive but not motor decline in early to mid-stage PD. The motor decline observed after 2 years in these older adults with PD is probably related to the primary neurodegenerative process than comorbid white matter pathology.

Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke.

Background Cerebral small vessel disease is associated with higher ratios of soluble-epoxide hydrolase derived linoleic acid diols (12,13-dihydroxyoctadecenoic acid [DiHOME] and 9,10-DiHOME) to their parent epoxides (12(13)-epoxyoctadecenoic acid [EpOME] and 9(10)-EpOME); however, the relationship has not yet been examined in stroke. Methods and Results Participants with mild to moderate small vessel stroke or large vessel stroke were selected based on clinical and imaging criteria. Metabolites were quantified by ultra-high-performance liquid chromatography-mass spectrometry. Volumes of stroke, lacunes, white matter hyperintensities, magnetic resonance imaging visible perivascular spaces, and free water diffusion were quantified from structural and diffusion magnetic resonance imaging (3 Tesla). Adjusted linear regression models were used for analysis. Compared with participants with large vessel stroke (n=30), participants with small vessel stroke (n=50) had a higher 12,13-DiHOME/12(13)-EpOME ratio (ß=0.251, P=0.023). The 12,13-DiHOME/12(13)-EpOME ratio was associated with more lacunes (ß=0.266, P=0.028) but not with large vessel stroke volumes. Ratios of 12,13-DiHOME/12(13)-EpOME and 9,10-DiHOME/9(10)-EpOME were associated with greater volumes of white matter hyperintensities (ß=0.364, P<0.001; ß=0.362, P<0.001) and white matter MRI-visible perivascular spaces (ß=0.302, P=0.011; ß=0.314, P=0.006). In small vessel stroke, the 12,13-DiHOME/12(13)-EpOME ratio was associated with higher white matter free water diffusion (ß=0.439, P=0.016), which was specific to the temporal lobe in exploratory regional analyses. The 9,10-DiHOME/9(10)-EpOME ratio was associated with temporal lobe atrophy (ß=-0.277, P=0.031). Conclusions Linoleic acid markers of cytochrome P450/soluble-epoxide hydrolase activity were associated with small versus large vessel stroke, with small vessel disease markers consistent with blood brain barrier and neurovascular-glial disruption, and temporal lobe atrophy. The findings may indicate a novel modifiable risk factor for small vessel disease and related neurodegeneration.