Obesity paradox and stroke outcomes according to stroke subtype: a propensity score-matched analysis.

OBJECTIVE: Obesity has traditionally been considered a risk factor for ischemic stroke. However, some clinical observations have reported a complex relationship between patients who are overweight or obese with paradoxically better stroke outcomes. Stroke subtypes have differing distributions of risk factors, so this study aimed to explain the relationship between body mass index (BMI) and functional prognosis according to stroke subtype. METHODS: A prospective institutional database on stroke was accessed between March 2014 and December 2021, and consecutive patients with ischemic stroke were retrospectively selected. BMI was categorized into five groups (underweight, normal weight, overweight, obese, and morbid obesity). The outcome of interest in this study was the modified Rankin Scale (mRS) at 90 d, which was divided into favorable (mRS = 0-2) and unfavorable (mRS ≥ 3) groups. The relationship between functional outcome and BMI was analyzed according to stroke subtype. RESULTS: Among 2779 patients with stroke, 913 (32.9%) had unfavorable outcomes. After a propensity score-matched analysis, obesity was inversely associated with unfavorable outcomes (adjusted odds ratio [aOR] = 0.61, 95% confidence interval [95% CI]: 0.46-0.80) in all patients with stroke. Among the stroke subtypes, overweight (aOR = 0.38, 95% CI: 0.20-0.74) and obese (aOR = 0.40, 95% CI: 0.21-0.76) groups were inversely associated with unfavorable outcomes in the cardioembolism subtype. Obesity (aOR = 0.55, 95% CI: 0.32-0.95) was inversely associated with unfavorable outcomes in the small vessel disease subtype. There was no significant relationship between stroke outcome and BMI classification in the large artery disease subtype. CONCLUSIONS: These findings suggest that the obesity paradox in ischemic stroke outcomes might differ according to the stroke subtype.

Plasminogen Activator Inhibitor-1: Potential Inflammatory Marker in Late-life Depression.

Objective: Although several previous studies have examined the association between late-life depression and blood adipokine levels, a marker of chronic inflammation, no studies have comprehensively considered the effects of metabolic syndrome, which is known to affect blood adipokine levels. This study examined blood adipokine levels in geriatric depression after adjusting for the effects of metabolic syndrome. Methods: Participants were selected from the Ansan Geriatric Study (depression group [n = 76] and control group [n = 76]). Blood concentrations of four adipokines (adiponectin, resistin, neutrophil-gelatinase-associated lipocalin [NGAL], and plasminogen activator inhibitor-1 [PAI-1]) were measured using immunoassays. The effects of blood adipokine concentration on the diagnosis of depression were analyzed using multivariate logistic regression to adjust for the effects of metabolic syndrome and potential confounding factors. Results: When the effects of metabolic syndrome and potential confounding factors were adjusted, only PAI-1 could explain the diagnosis of depression among all the adipokines. The depression group showed a lower blood PAI-1 level than the control group. Adiponectin, resistin, and NGAL could not explain the diagnosis of depression when the effects of metabolic syndrome and potential confounding factors were adjusted. Conclusion: This study suggests the possibility that the blood PAI-1 levels in clinically pathological late-life depression may show contrasting results to those with subclinical depressive symptoms. Additionally, considering that most previous studies have been conducted with pre-geriatric populations, the study suggests the possibility that geriatric depression may show inflammatory changes with patterns that are different from those of depression in the pre-geriatric population.

Altered TIMP-3 Levels in the Cerebrospinal Fluid and Plasma of Patients with Alzheimer's Disease.

Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a component of the extracellular environment and is suggested to play an indirect role in regulating Aß production and the pathophysiology of Aß deposition in brains. However, studies on the amount of TIMP-3 in bodily fluids of Alzheimer's disease (AD) patients have not been conducted. Here, we investigated the relationship between fluid TIMP-3 levels and AD pathology. We first showed that the fluid levels of TIMP-3 were lower in AD dementia patients compared with in non-AD patients. ELISA results revealed that plasma levels of TIMP-3 in 65 patients with AD were significantly lower than those in 115 healthy control subjects and 71 mild cognitive impairment (MCI) subjects. Furthermore, we found that cerebrospinal fluid (CSF) level of TIMP-3 was decreased in AD compared with that in healthy control. These data suggest that fluid TIMP-3 levels negatively correlated with progress of cognitive decline. Collectively, our study suggests that alterations of fluid TIMP-3 levels might be associated with AD pathology.

Annual Incidence of Dementia from 2003 to 2018 in Metropolitan Seoul, Korea: A Population-Based Study.

National dementia plans were applied in dementia support centers established in Seoul, Korea between 2007 and 2009. However, the annual incidence rates of dementia in Seoul have not been reported. We investigated this annual incidence and the characteristics of incident cases from 2003 to 2018. The customized research database of the Korean National Health Insurance Services was used. The annual crude and age-standardized incidence of dementia patients and their characteristics were analyzed. This study analyzed 108,596 incident dementia cases aged ≥60 years. The incidence rate increased from 2003 to 2011, including a rapid increment from 2007 to 2011. From 2011 to 2018, the crude (age-standardized) incidence per 105 person-years decreased from 641.51 (577.12) to 448.26 (361.23). The proportion of incident dementia cases was highest in the highest income group every year. However, the proportion of incident dementia cases in the lowest income group increased from 10.4% in 2003 to 25.8% in 2011. The annual incidence rate of dementia showed a sharp increase immediately after 2007, the year dementia support centers began to be introduced, and then stabilized after 2011. The characteristics of incident dementia cases have changed, including the proportion in the low-income group.

No sonographer, no radiologist: Assessing accuracy of artificial intelligence on breast ultrasound volume sweep imaging scans.

Breast ultrasound provides a first-line evaluation for breast masses, but the majority of the world lacks access to any form of diagnostic imaging. In this pilot study, we assessed the combination of artificial intelligence (Samsung S-Detect for Breast) with volume sweep imaging (VSI) ultrasound scans to evaluate the possibility of inexpensive, fully automated breast ultrasound acquisition and preliminary interpretation without an experienced sonographer or radiologist. This study was conducted using examinations from a curated data set from a previously published clinical study of breast VSI. Examinations in this data set were obtained by medical students without prior ultrasound experience who performed VSI using a portable Butterfly iQ ultrasound probe. Standard of care ultrasound exams were performed concurrently by an experienced sonographer using a high-end ultrasound machine. Expert-selected VSI images and standard of care images were input into S-Detect which output mass features and classification as "possibly benign" and "possibly malignant." Subsequent comparison of the S-Detect VSI report was made between 1) the standard of care ultrasound report by an expert radiologist, 2) the standard of care ultrasound S-Detect report, 3) the VSI report by an expert radiologist, and 4) the pathological diagnosis. There were 115 masses analyzed by S-Detect from the curated data set. There was substantial agreement of the S-Detect interpretation of VSI among cancers, cysts, fibroadenomas, and lipomas to the expert standard of care ultrasound report (Cohen's κ = 0.73 (0.57-0.9 95% CI), p<0.0001), the standard of care ultrasound S-Detect interpretation (Cohen's κ = 0.79 (0.65-0.94 95% CI), p<0.0001), the expert VSI ultrasound report (Cohen's κ = 0.73 (0.57-0.9 95% CI), p<0.0001), and the pathological diagnosis (Cohen's κ = 0.80 (0.64-0.95 95% CI), p<0.0001). All pathologically proven cancers (n = 20) were designated as "possibly malignant" by S-Detect with a sensitivity of 100% and specificity of 86%. Integration of artificial intelligence and VSI could allow both acquisition and interpretation of ultrasound images without a sonographer and radiologist. This approach holds potential for increasing access to ultrasound imaging and therefore improving outcomes related to breast cancer in low- and middle- income countries.

Validation of Four Methods for Converting Scores on the Montreal Cognitive Assessment to Scores on the Mini-Mental State Examination-2.

BACKGROUND AND PURPOSE: There are many methods for converting scores from the Montreal Cognitive Assessment (MoCA) to those on the Mini-Mental State Examination (MMSE). In this study we aimed to validate 4 methods that convert the full score range (0-30 points) of the MoCA to an equivalent range for the MMSE. METHODS: We examined the medical records of 506 subjects who completed the MoCA and MMSE-second edition (MMSE-2) on the same day. For the validation index, we calculated mean, median, and root-mean-squared error (RMSE) of the difference between true and equivalent MMSE-2 scores. We also calculated intraclass correlation coefficients (ICCs), the Bland-Altman plot, and the generalizability coefficient between true and equivalent MMSE-2 scores for reliability. We compared the ICCs according to age, sex, education, MMSE, and cognitive-status subgroups. For accuracy, we evaluated a ±2 point difference between the true and equivalent MMSE-2 scores. RESULTS: The 4 conversion methods had a mean of -0.79 to -0.05, a median of -1 to 0, and an RMSE of 2.61-2.94 between true and equivalent MMSE-2 scores. All conversion methods had excellent reliability, with an ICC greater than 0.75 between true and equivalent MMSE-2 scores. These results were almost maintained in the subgroup analyses. These conversion methods provided more than 65% accuracy within ±2 points of the true MMSE-2 scores. CONCLUSIONS: We suggest that these 4 conversion methods are applicable for converting MoCA scores to MMSE-2 scores. They will greatly enhance the usefulness of existing cognitive data in clinical and research settings.

Converting from the Montreal Cognitive Assessment to the Mini-Mental State Examination-2.

OBJECTIVE: The Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination-2 (MMSE-2) are useful psychometric tests for cognitive screening. Many clinicians want to predict the MMSE-2 score based on the MoCA score. To facilitate the transition from the MoCA to the MMSE-2, this study developed a conversion method. METHODS: This study retrospectively examined the relationship between the MoCA and MMSE-2. Overall, 303 participants were evaluated. We produced a conversion table using the equipercentile equating method with log-linear smoothing. Then, we evaluated the reliability and accuracy of this algorithm to convert the MoCA to the MMSE-2. RESULTS: MoCA scores were converted to MMSE-2 scores according to a conversion table that achieved a reliability of 0.961 (intraclass correlation). The accuracy of this algorithm was 84.5% within 3 points difference from the raw score. CONCLUSIONS: This study reports a reliable and easy conversion algorithm for transforming MoCA scores into converted MMSE-2 scores. This method will greatly enhance the utility of existing cognitive data in clinical and research settings.

Technology trends and applications of deep learning in ultrasonography: image quality enhancement, diagnostic support, and improving workflow efficiency.

In this review of the most recent applications of deep learning to ultrasound imaging, the architectures of deep learning networks are briefly explained for the medical imaging applications of classification, detection, segmentation, and generation. Ultrasonography applications for image processing and diagnosis are then reviewed and summarized, along with some representative imaging studies of the breast, thyroid, heart, kidney, liver, and fetal head. Efforts towards workflow enhancement are also reviewed, with an emphasis on view recognition, scanning guide, image quality assessment, and quantification and measurement. Finally some future prospects are presented regarding image quality enhancement, diagnostic support, and improvements in workflow efficiency, along with remarks on hurdles, benefits, and necessary collaborations.

Effects of Multicomponent Exercise on Cognitive Function in Elderly Korean Individuals.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the effects of multicomponent exercise on cognitive function, depression, and quality of life in elderly individuals. METHODS: This study prospectively recruited 605 participants, and constructed an exercise pyramid comprising even distributions of daily physical activities, aerobic exercise, muscle-strengthening exercise, flexibility exercise, balance exercise, and activities that subjects could perform while sitting down. The exercise program was divided into six stages according to the participant's level of frailty. The 12-week exercise program intervention was conducted once yearly. RESULTS: The exercise regimen was followed by 402 of the 605 enrolled participants, giving a dropout rate of 33.6%. The 27-month exercise program was completed by 60 participants. The scores for the Mini Mental State Examination for dementia screening (MMSE-DS), short form of the Geriatric Depression Scale, World Health Organization Quality of Life Assessment (WHOQOL-BREF), International Physical Activity Questionnaire (IPAQ), fear of falling, handgrip strength, and walking speed were improved after the exercise intervention. The analysis of frailty revealed that participants in the frail group showed greater improvements for the MMSE-DS, WHOQOL-BREF, IPAQ, fear of falling, handgrip strength, and walking speed. CONCLUSIONS: Individually customized, multicomponent exercise programs lead to improved levels of cognitive function, depression, and quality of life, especially among those who are more frail.

Predictive value of free fatty acid levels in embolic stroke of undetermined source: A retrospective observational study.

The present study aimed to investigate the predictive value of free fatty acid (FFA) in embolic stroke of undetermined source (ESUS) according to the presence of potential embolic sources (PES) after extensive etiologic evaluation.This was a retrospective observational study based on a single-center registry from January 2011 to July 2017. Stroke subtypes were determined through laboratory findings, brain, and angiographic imaging, carotid ultrasonography, transthoracic echocardiography, and 24-hour Holter monitoring. If ESUS was suspected, transesophageal echocardiography was additionally performed. Patients were classified into ESUS with PES and ESUS without PES. PES included mitral annular calcification, mitral valve prolapse, patent foramen ovale, atrial septal aneurysm, spontaneous echo contrast, ventricular aneurysm, and high-risk plaques of aortic arch, or carotid bulb. We compared clinical and laboratory findings between the two groups.Of a total of 110 ESUS patients, 61 patients (55.5%) had no PES. Patients with ESUS without PES had higher levels of serum FFA, systolic blood pressure, diastolic blood pressure (DBP), and left atrial (LA) enlargement compared with those of ESUS with PES. Multivariable analysis demonstrated that the FFA level, DBP, and LA volume index were associated with ESUS without PES [odds ratio (OR) 1.038, 95% confidence interval (CI) 1.019-1.058 for FFA/10 µEq/L, OR 1.414, 95% CI 1.037-1.928 for DBP/10 mm Hg, and OR 1.073, 95% CI 1.009-1.141 for LA volume index].Higher levels of FFA, DBP, and LA volume index are associated with ESUS without PES, highlighting the need to identify the role of these markers in ESUS through further large-scale, multi-center and prospective studies.

Mild cognitive impairment, dementia, and cognitive dysfunction screening using machine learning.

OBJECTIVE: To develop a machine learning algorithm to identify cognitive dysfunction based on neuropsychological screening test results. METHODS: This retrospective study included 955 participants: 341 participants with dementia (dementia), 333 participants with mild cognitive impairment (MCI), and 341 participants who were cognitively healthy. All participants underwent evaluations including the Mini-Mental State Examination and the Montreal Cognitive Assessment. Each participant's caregiver or informant was surveyed using the Korean Dementia Screening Questionnaire at the same visit. Different machine learning algorithms were applied, and their overall accuracies, Cohen's kappa, receiver operating characteristic curves, and areas under the curve (AUCs) were calculated. RESULTS: The overall screening accuracies for MCI, dementia, and cognitive dysfunction (MCI or dementia) using a machine learning algorithm were approximately 67.8% to 93.5%, 96.8% to 99.9%, and 75.8% to 99.9%, respectively. Their kappa statistics ranged from 0.351 to 1.000. The AUCs of the machine learning models were statistically superior to those of the competing screening model. CONCLUSION: This study suggests that a machine learning algorithm can be used as a supportive tool in the screening of MCI, dementia, and cognitive dysfunction.

Elevated Cerebrospinal Fluid and Plasma N-Cadherin in Alzheimer Disease.

N-cadherin is a synaptic adhesion molecule stabilizing synaptic cell structure and function. Cleavage of N-cadherin by γ-secretase produces a C-terminal fragment, which is increased in the brains of Alzheimer disease (AD) patients. Here, we investigated the relationship between fluid N-cadherin levels and AD pathology. We first showed that the cleaved levels of N-cadherin were increased in homogenates of postmortem brain from AD patients compared with that in non-AD patients. We found that cleaved N-cadherin levels in the cerebrospinal fluid were increased in AD dementia compared with that in healthy control. ELISA results revealed that plasma levels of N-cadherin in 76 patients with AD were higher than those in 133 healthy control subjects. The N-cadherin levels in the brains of an AD mouse model, APP Swedish/PS1delE9 Tg (APP Tg) were reduced compared with that in control. The N-terminal fragment of N-cadherin produced by cleavage at a plasma membrane was detected extravascularly, accumulated in senile plaques in the cortex of an APP Tg mouse. In addition, N-cadherin plasma levels were increased in APP Tg mice. Collectively, our study suggests that alteration of N-cadherin levels might be associated with AD pathology.

Elevation of plasma soluble amyloid precursor protein beta in Alzheimer's disease.

INTRODUCTION: Beta-amyloid is considered to be a pathophysiological marker in Alzheimer's disease (AD). Soluble amyloid precursor proteins (sAPPs) -α (sAPPα) and -ß (sAPPß), which are the byproducts of non-amyloidogenic and amyloidogenic process of APP, respectively, have been repeatedly observed in the cerebrospinal fluids (CSF) of AD patients. The present study focused on the determination of sAPP levels in peripheral blood. METHODS: The plasma protein levels of sAPPα and sAPPß were measured with ELISA. Plasma from 52 AD patients, 98 amnestic mild cognitive impairment (MCI) patients, and 114 cognitively normal controls were compared. RESULTS: The plasma level of sAPPß was significantly increased in AD patients than in cognitively healthy controls. However, no significant change in plasma sAPPα was observed among the three groups. Furthermore, the plasma sAPPß levels significantly correlated with cognitive assessment scales, such as clinical dementia rating (CDR), and mini-mental status examination (MMSE). Interestingly, sAPPα and sAPPß had a positive correlation with each other in blood plasma, similar to previous studies on CSF sAPP. This correlation was stronger in the MCI and AD groups than in the cognitively healthy controls. CONCLUSIONS: These results suggest that individuals with elevated plasma sAPPß levels are at an increased risk of AD; elevation in these levels may reflect the progression of disease.

Conversion From The Korean Dementia Screening Questionnaire To The Informant Questionnaire On Cognitive Decline In The Elderly.

PURPOSE: The ability to convert scores between cognitive measurements would facilitate the longitudinal assessment of cognition in clinical practice and the comparison and synthesis of cognitive data from international, multicenter, or longitudinal studies. The primary aim of this study was to apply a simple and reliable method for converting scores from the Korean Dementia Screening Questionnaire (KDSQ) to those of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). PATIENTS AND METHODS: A total of 627 participants, with and without cognitive dysfunction, received both the KDSQ and the IQCODE at the same visit. The scores of both tools were calculated, and equipercentile equating was used to create a method for converting scores from the KDSQ to the IQCODE. RESULTS: KDSQ scores were highly correlated with IQCODE scores (Pearson r = 0.905, P < 0.01). We developed scores for converting the KDSQ to the IQCODE using equipercentile equating and log-linear smoothing. We provide an easy-to-use table that enables the conversion of KDSQ scores to IQCODE scores. CONCLUSION: We delivered a simple and reliable method for converting scores from the KDSQ to the IQCODE. The conversion score table reported here enables direct and easy comparison of these cognitive measurements in older adults.

Diagnosis of Thyroid Nodules: Performance of a Deep Learning Convolutional Neural Network Model vs. Radiologists.

Computer-aided diagnosis (CAD) systems hold potential to improve the diagnostic accuracy of thyroid ultrasound (US). We aimed to develop a deep learning-based US CAD system (dCAD) for the diagnosis of thyroid nodules and compare its performance with those of a support vector machine (SVM)-based US CAD system (sCAD) and radiologists. dCAD was developed by using US images of 4919 thyroid nodules from three institutions. Its diagnostic performance was prospectively evaluated between June 2016 and February 2017 in 286 nodules, and was compared with those of sCAD and radiologists, using logistic regression with the generalized estimating equation. Subgroup analyses were performed according to experience level and separately for small thyroid nodules 1-2 cm. There was no difference in overall sensitivity, specificity, positive predictive value (PPV), negative predictive value and accuracy (all p > 0.05) between radiologists and dCAD. Radiologists and dCAD showed higher specificity, PPV, and accuracy than sCAD (all p < 0.001). In small nodules, experienced radiologists showed higher specificity, PPV and accuracy than sCAD (all p < 0.05). In conclusion, dCAD showed overall comparable diagnostic performance with radiologists and assessed thyroid nodules more effectively than sCAD, without loss of sensitivity.

Altered expression of Notch1 in Alzheimer's disease.

Notch signaling is an evolutionarily conserved pathway that regulates cell-cell interactions through binding of Notch family receptors to their cognate ligands. Notch signaling has an essential role in vascular development and angiogenesis. Recent studies have reported that Notch may be implicated in Alzheimer's disease (AD) pathophysiology. We measured the levels of soluble Notch1 (sNotch1) in the plasma samples from 72 dementia patients (average age 75.1 y), 89 subjects with amnestic mild cognitive impairment (MCI) (average age 73.72 y), and 150 cognitively normal controls (average age 72.34 y). Plasma levels of sNotch1 were 25.27% lower in dementia patients as compared to healthy control subjects. However, the level of Notch1 protein was significantly increased in human brain microvascular endothelial cells (HBMECs) after amyloid-beta treatment. Also, Notch1 mRNA level was significantly increased in HBMECs and iPSC-derived neuronal cells from AD patient compared to normal control. These results indicate that altered expression of Notch1 might be associated with the risk of Alzheimer's disease.