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Objective: Type 2 diabetes mellitus (T2DM) is a risk factor for cognitive impairment, and reduced heart rate variability (HRV) has been correlated with cognitive impairment in elderly individuals. This study investigated risk factors and validated a predictive model for mild cognitive impairment (MCI) in patients with T2DM using an autonomic function test.Patients with T2DM, 50–85 years of age, who attended the diabetes clinic at Gyeongsang National University Hospital between March 2018 and December 2019, were included. A total of 201 patients had been screened; we enrolled 124 patients according to the inclusion and exclusion criteria in this study. Cognitive function was assessed using the Montreal Cognitive Assessment-Korean version (MOCA-K); MCI was defined as a total MOCA-K score ≤ 23. Risk factors for MCI in patients with T2DM, including demographic- and diabetes-related factors, and autonomic function test results, were analyzed. Based on multivariate logistic regression, a nomogram was developed as a prediction model for MCI.Thirty-nine of 124 patients were diagnosed with MCI. Age, education, and decreased cardiovagal function were associated with a high risk for MCI, with cardiovagal function exerting the greatest influence. However, diabetes-related factors, such as glycemic control, duration of diabetes, or medications, were not associated with the risk for MCI. The nomogram demonstrated excellent discrimination (area under the curve, 0.832) and was well calibrated.Approximately one-third of patients had MCI; as such, carefully evaluating cognitive function in elderly T2DM patients with reduced HRV is important to prevent progression to dementia.Methods: Type 2 diabetes mellitus (T2DM) is a risk factor for cognitive impairment, and reduced heart rate variability (HRV) has been correlated with cognitive impairment in elderly individuals. This study investigated risk factors and validated a predictive model for mild cognitive impairment (MCI) in patients with T2DM using an autonomic function test.Patients with T2DM, 50–85 years of age, who attended the diabetes clinic at Gyeongsang National University Hospital between March 2018 and December 2019, were included. A total of 201 patients had been screened; we enrolled 124 patients according to the inclusion and exclusion criteria in this study. Cognitive function was assessed using the Montreal Cognitive Assessment-Korean version (MOCA-K); MCI was defined as a total MOCA-K score ≤ 23. Risk factors for MCI in patients with T2DM, including demographic- and diabetes-related factors, and autonomic function test results, were analyzed. Based on multivariate logistic regression, a nomogram was developed as a prediction model for MCI.Thirty-nine of 124 patients were diagnosed with MCI. Age, education, and decreased cardiovagal function were associated with a high risk for MCI, with cardiovagal function exerting the greatest influence. However, diabetes-related factors, such as glycemic control, duration of diabetes, or medications, were not associated with the risk for MCI. The nomogram demonstrated excellent discrimination (area under the curve, 0.832) and was well calibrated.Approximately one-third of patients had MCI; as such, carefully evaluating cognitive function in elderly T2DM patients with reduced HRV is important to prevent progression to dementia.Results: Type 2 diabetes mellitus (T2DM) is a risk factor for cognitive impairment, and reduced heart rate variability (HRV) has been correlated with cognitive impairment in elderly individuals. This study investigated risk factors and validated a predictive model for mild cognitive impairment (MCI) in patients with T2DM using an autonomic function test.Patients with T2DM, 50–85 years of age, who attended the diabetes clinic at Gyeongsang National University Hospital between March 2018 and December 2019, were included. A total of 201 patients had been screened; we enrolled 124 patients according to the inclusion and exclusion criteria in this study. Cognitive function was assessed using the Montreal Cognitive Assessment-Korean version (MOCA-K); MCI was defined as a total MOCA-K score ≤ 23. Risk factors for MCI in patients with T2DM, including demographic- and diabetes-related factors, and autonomic function test results, were analyzed. Based on multivariate logistic regression, a nomogram was developed as a prediction model for MCI.Thirty-nine of 124 patients were diagnosed with MCI. Age, education, and decreased cardiovagal function were associated with a high risk for MCI, with cardiovagal function exerting the greatest influence. However, diabetes-related factors, such as glycemic control, duration of diabetes, or medications, were not associated with the risk for MCI. The nomogram demonstrated excellent discrimination (area under the curve, 0.832) and was well calibrated.Approximately one-third of patients had MCI; as such, carefully evaluating cognitive function in elderly T2DM patients with reduced HRV is important to prevent progression to dementia.Conclusion: Type 2 diabetes mellitus (T2DM) is a risk factor for cognitive impairment, and reduced heart rate variability (HRV) has been correlated with cognitive impairment in elderly individuals. This study investigated risk factors and validated a predictive model for mild cognitive impairment (MCI) in patients with T2DM using an autonomic function test.Patients with T2DM, 50–85 years of age, who attended the diabetes clinic at Gyeongsang National University Hospital between March 2018 and December 2019, were included. A total of 201 patients had been screened; we enrolled 124 patients according to the inclusion and exclusion criteria in this study. Cognitive function was assessed using the Montreal Cognitive Assessment-Korean version (MOCA-K); MCI was defined as a total MOCA-K score ≤ 23. Risk factors for MCI in patients with T2DM, including demographic- and diabetes-related factors, and autonomic function test results, were analyzed. Based on multivariate logistic regression, a nomogram was developed as a prediction model for MCI.Thirty-nine of 124 patients were diagnosed with MCI. Age, education, and decreased cardiovagal function were associated with a high risk for MCI, with cardiovagal function exerting the greatest influence. However, diabetes-related factors, such as glycemic control, duration of diabetes, or medications, were not associated with the risk for MCI. The nomogram demonstrated excellent discrimination (area under the curve, 0.832) and was well calibrated.Approximately one-third of patients had MCI; as such, carefully evaluating cognitive function in elderly T2DM patients with reduced HRV is important to prevent progression to dementia. [ABSTRACT FROM AUTHOR]

Background: Meningitis is an inflammatory process involving meninges. It is difficult to diagnose because of the absence of a diagnostic biomarker. We first report here the possibility of cerebrospinal fluid (CSF) vitamin D-binding protein (VDBP) as a new biomarker for the diagnosis of meningitis.Methods: This prospective study enrolled a total of 102 subjects (58 patients with non-neurologic disease, 17 patients with meningitis, and 27 patients with other neurologic diseases) from 2017 to 2018. CSF and blood samples were collected in pairs. Total 25(OH)D in CSF and serum and VDBP levels in serum were measured. GC genotyping was also performed to determine polymorphisms of rs4588 and rs7041. CSF total 25(OH)D and VDBP levels were compared with serum total 25(OH)D and VDBP levels according to disease (meningitis vs. non-meningitis). Receiver operating characteristic (ROC) analysis for the diagnosis of meningitis using CSF VDBP level was performed.Results: Mean CSF VDBP and serum VDBP levels of all patients were 1.48 ± 1.32 and 181.28 ± 56.90 μg/mL, respectively. CSF VDBP level in the meningitis disease group (3.20 ± 1.49 μg/mL) was significantly (P < 0.001) higher than that in other disease groups. According to ROC curve analysis, the appropriate cut-off value for CSF VDBP was 1.96 μg/mL, showing sensitivity of 82.4% and specificity of 85.9%. AUC of CSF VDBP was 0.879 (95% CI: 0.789-0.962).Conclusions: CSF VDBP level showed very good diagnostic performance. It could be used as a potential biomarker for the diagnosis of meningitis. [ABSTRACT FROM AUTHOR]

Objective: Patients with Parkinson's disease (PD) have an increased risk of sarcopenia which is expected to negatively affect gait, leading to poor clinical outcomes including falls. In this study, we investigated the gait patterns of patients with PD with and without sarcopenia (sarcopenia and non-sarcopenia groups, respectively) using an app-derived program and explored if gait parameters could be utilized to predict sarcopenia based on machine learning. Methods: Clinical and sarcopenia profiles were collected from patients with PD at Hoehn and Yahr (HY) stage ≤ 2. Sarcopenia was defined based on the updated criteria of the Asian Working Group for Sarcopenia. The gait patterns of the patients with and without sarcopenia were recorded and analyzed using a smartphone application. The random forest model was applied to predict sarcopenia in patients with PD. Results: Data from 38 patients with PD were obtained, among which 9 (23.7%) were with sarcopenia. Clinical parameters were comparable between the sarcopenia and non-sarcopenia groups. Among various clinical and gait parameters, the average range of motion of the hip joint showed the highest association with sarcopenia. Based on the random forest algorithm, the combined difference in knee and ankle angles from standing still before walking to the maximum angle during walking (Kneeankle_diff), the difference between the angle when standing still before walking and the maximum angle during walking for the ankle (Ankle_dif), and the min angle of the hip joint (Hip_min) were the top three features that best predict sarcopenia. The accuracy of this model was 0.949. Conclusions: Using smartphone app and machine learning technique, our study revealed gait parameters that are associated with sarcopenia and that help predict sarcopenia in PD. Our study showed potential application of advanced technology in clinical research. [ABSTRACT FROM AUTHOR]

However, these explanations cannot explain PPI-induced vitiligo fully because the key pathogenesis in vitiligo is the loss of melanocytes rather than decreased melanin production. Proton pump inhibitor-induced vitiligo following airborne occupational sensitization Keywords: airborne dermatitis; case report; occupational; pantoprazole; proton pump inhibitors; rabeprazole; vitiligo EN airborne dermatitis case report occupational pantoprazole proton pump inhibitors rabeprazole vitiligo 595 596 2 10/22/21 20211101 NES 211101 The literature reports that proton-pump-inhibitor (PPI)-induced adverse skin reactions are mostly instances of immunological and PPI-related occupational contact dermatitis after direct contact or airborne exposure.1 Although there are few cases of vitiligo after the ingestion of oral PPIs,2 vitiligo after airborne PPI exposure has yet to be reported. [Extracted from the article]

Visual symptoms are frequently observed in posterior cortical atrophy compared to typical amnestic Alzheimer's disease (AD). We report the case of a patient with amnestic AD with long-lasting homonymous hemianopia. A 62-year-old woman, who was diagnosed in amnestic AD, complained of visual disturbance. She had left homonymous hemianopia in the perimetry test and left tactile extinction. Regardless of posture, retinotopically leftward error was observed on 21 cm line bisection test. Brain single photon emission computerized tomography (SPECT) showed bilateral temporoparietal hypoperfusion, which was more severe to the right than left side. This case suggested that long-lasting hemianopia could occur in the patient with amnestic AD and that hemianopic line bisection error might be compensatory mechanism. [ABSTRACT FROM AUTHOR]

Age-related microglial activation is associated with cognitive impairment. Tonicity-responsive enhancer-binding protein (TonEBP) is a critical mediator of microglial activation in response to neuroinflammation. However, the precise role of TonEBP in the middle-aged brain is not yet known. We used TonEBP haploinsufficient mice to investigate the role of TonEBP in middle-aged or amyloid β oligomer (AβO)–injected brains and examined the effect of TonEBP knockdown on AβO-treated BV2 microglial cells. Consistent with an increase in microglial activation with aging, hippocampal TonEBP expression levels were increased in middle-aged (12-month-old) and old (24-month-old) mice compared with young (6-month-old) mice. Middle-aged TonEBP haploinsufficient mice showed reduced microglial activation and fewer memory deficits than wild-type mice. Electron microscopy revealed that synaptic pruning by microglial processes was reduced by TonEBP haploinsufficiency. TonEBP haploinsufficiency also reduced dendritic spine loss and improved memory deficits in AβO-treated mice. Furthermore, TonEBP knockdown attenuated migration and phagocytosis in AβO-treated BV2 cells. These findings suggest that TonEBP plays important roles in age-related microglial activation and memory deficits. [ABSTRACT FROM AUTHOR]

• MicroRNA-485-3p concentrations in salivary EE-EVs were increased in the patients with AD vs. those in healthy controls. • MicroRNA-485-3p concentrations from salivary EE-EVs were increased in Aβ-PET-positive AD participants vs. those in Aβ-PET-negative AD participants. • MicroRNA-485-3p concentrations from salivary EE-EVs showed high diagnostic accuracy for predicting Aβ-PET positivity. Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by progressive long-term memory loss and cognitive dysfunction. Neuroimaging tests for abnormal amyloid-β (Aβ) deposition are considered the most reliable methods for the diagnosis of AD; however, the cost for such testing is very high and generally not covered by national insurance systems. Accordingly, it is only recommended for individuals exhibiting clinical symptoms of AD supported by clinical cognitive assessments. Recently, it was suggested that dysregulated microRNA-485-3p (miRNA-485-3p) in the brain and cerebrospinal fluid is closely related to pathogenesis of AD. However, a relationship between circulating miRNA-485-3p in salivary exosome-enriched extracellular vesicles (EE-EV) and Aβ deposition in the brain has not been observed. Using quantitative real-time polymerase chain reaction, we analyzed miRNA-485-3p concentration in salivary EE-EV. We used receiver operating characteristic (ROC) curve analysis to evaluate its predictive value for Aβ positron emission tomography (Aβ-PET) positivity in patients with AD. Our results showed that the miRNA-485-3p concentration in salivary EE-EV isolated from patients with AD was significantly increased compared with that in the healthy controls (p < 0.0001). In the analysis of all participants, the miRNA-485-3p concentration was significantly increased in Aβ-PET-positive participants compared to Aβ-PET-negative participants (p < 0.0001). Further analysis using only AD patients also showed that the miRNA-485-3p concentration was significantly increased in Aβ-PET-positive AD patients vs. Aβ-PET-negative AD patients (p = 0.0063). The ROC curve analysis for differentiating Aβ-PET-positive and negative participants showed that the area under the curve for miRNA-485-3p was 0.9217. These findings suggested that the miRNA-485-3p concentration in salivary EE-EV was closely related to Aβ deposition in the brain and had high diagnostic accuracy for predicting Aβ-PET positivity. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) is a useful tool to predict the diagnosis and progression of Alzheimer's disease (AD), especially for primary physicians. However, the correlation between baseline MRI findings and AD progression has not been fully established.Objective: To investigate the correlation between hippocampal atrophy (HA) and white matter hyperintensities (WMH) on initial brain MRI images and the degree of cognitive decline and functional changes over 1 year.Methods: In this prospective, 12-month observational study, dementia outpatients were recruited from 29 centers across South Korea. Baseline assessments of HA and WMH on baseline brain MRI were derived as well as cognitive function, dementia severity, activities of daily living, and acetylcholinesterase inhibitor (AChEI) use. Follow-up assessments were conducted at 6 and 12 months.Results: Among 899 enrolled dementia patients, 748 were diagnosed with AD of whom 654 (87%) were taking AChEIs. Baseline WMH showed significant correlations with age, current alcohol consumption, and Clinical Dementia Rating score; baseline HA was correlated with age, family history, physical exercise, and the results of cognitive assessments. Among the AChEI group, changes in the Korean version of the Instrumental Activities of Daily Living (K-IADL) were correlated with the severity of HA on baseline brain MRI, but not with the baseline severity of WMH. In the no AChEI group, changes in K-IADL were correlated with the severity of WMH and HA at baseline.Conclusion: Baseline MRI findings could be a useful tool for predicting future clinical outcomes by primary physicians, especially in relation to patients' functional status. [ABSTRACT FROM AUTHOR]

Background and objective: Studies investigating the impact of white matter hyperintensities (WMHs) on the response of acetylcholinesterase inhibitors in patients with Alzheimer’s disease (AD) have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs. Methods: Three hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog) from the baseline to the end of the study. Results: Of the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 136; group 2, n = 46) during the 24-week study period. Demographic factors did not differ between group 1 and group 2. There were no significant differences in change in ADAS-cog between group 1 (-0.62±5.70) and group 2 (-0.23±5.98) after the 24-week rivastigmine patch therapy (p = 0.378). The patients in group 1 had a 0.63-point improvement from baseline on the Frontal Assessment Battery, while group 2 had a 0.16-point decline compared to baseline at the end of the study (p = 0.037). The rates of adverse events (AEs) (42.6 vs. 40.3%) and discontinuation due to AEs (10.3% vs. 4.3%) did not differ between the groups. Conclusions: Although the efficacy and tolerability of rivastigmine patch therapy were not associated with WMH severity in patients with AD, some improvement in frontal function was observed in those with minimal WMHs. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: Rapid and accurate diagnosis of central nervous system (CNS) infections is important, and laboratory tests help diagnose CNS infections. Even when the patient has symptoms, laboratory tests often do not reveal any specific findings. The potential of vitamin D-binding protein (VDBP) to be used as a biomarker for viral and bacterial CNS infections was studied.Methods: A total of 302 subjects with suspected CNS infection who underwent lumbar puncture were included. Clinical and laboratory data were collected retrospectively. VDBP levels were measured in the cerebrospinal fluid (CSF) samples. Genotyping for the GC gene encoding VDBP was also performed. VDBP levels were analyzed and compared by CNS infection, pathogen, CSF opening pressure, and GC genotype.Results: A CNS infection group (n = 90) and a non-CNS infection group (n = 212) were studied. In terms of its receiver operating characteristic, CSF VDBP showed an area under the curve of 0.726 for the diagnosis of CNS infection. CSF VDBP levels were significantly different between the CNS infection and non-infection groups. The CNS infection group with enterovirus showed a statistically lower distribution of CSF VDBP levels than the other virus groups. The group with CSF opening pressure > 25 cmH2O showed higher CSF VDBP levels than the other groups. There was no significant difference in GC gene allele distribution between the CNS infection and non-infection groups.Conclusions: CSF VDBP levels were increased in patients with CNS infection. The CSF VDBP showed potential as a new biomarker for viral and bacterial CNS infections. [ABSTRACT FROM AUTHOR]

There are few studies on the effects of dipeptidyl peptidase-4 inhibitors on steatohepatitis. We explored whether evogliptin (Evo), a dipeptidyl peptidase-4 inhibitor, protects against steatohepatitis in a high-fat diet (HFD)-fed mice and whether these effects involve modulation of mitophagy. Adult male C57BL/J mice were divided into the normal diet (ND), HFD (45% of energy from fat) with Evo (250 mg/kg) (HFD + Evo), and HFD groups at 4 weeks of age and were sacrificed at 20 weeks of age. The HFD group showed hepatic lipid accumulation; this was decreased in the Evo + HFD group. There was an increased 8-hydroxydeoxyguanosine (8-OHDG) expression in the HFD group compared to ND mice. However, 8-OHDG expression levels were significantly decreased in the HFD + Evo group. Expressions of the mitophagy markers PTEN-induced kinase 1 (PINK1), Parkin, and BNIP-3 (BCL2 Interacting Protein 3) were significantly increased in the HFD group. However, the expressions of these markers were lower in the HFD + Evo group than that in the HFD group. Phospho-Akt was upregulated and p53 was downregulated in the HFD + Evo group compared to the HFD group. Evogliptin may alleviate steatohepatitis in HFD-fed mice by ameliorating steatosis and oxidative stress and by modulating mitophagy in the liver. [ABSTRACT FROM AUTHOR]