Visualized Lead Selection for Arrhythmia Classification Based on a Lead Activation Heatmap Using Multi-Lead ECGs.

Visualizing the decision-making process is a key aspect of research regarding explainable arrhythmia recognition. This study proposed a visualized lead selection method to classify arrhythmia for multi-lead ECG signals. The proposed method has several advantages, as it uses a visualized approach to select effective leads, avoiding redundant leads and invalid information. It also captures the temporal dependencies of ECG signals and the complementary information between leads. The method deployed a lead activation heatmap (LA heatmap) based on a lead-wise network to select the proper 5 leads from 12-lead ECG heartbeats extracted from the public 2018 Chinese Physiological Signal Challenge database (CPSC 2018 DB), which were then fed into a ResBiTime network combining bidirectional long short-term memory (Bi-LSTM) networks and residual connections for a classification task of nine heartbeat categories (i.e., N, AF, I-AVB, RBBB, PAC, PVC, STD, LBBB, and STE). The results indicate an average precision of 93.25%, an average recall of 93.03%, an average F1-score of 0.9313, and that the proposed method can effectively extract additional information from ECG heartbeat data.

Mitochondrial dysfunction is associated with cognitive impairment in adults with OSA without dementia.

STUDY OBJECTIVES: Increased reactive oxygen species associated with loss of mitochondrial function affect synaptic activity, which is an important mechanism underlying cognitive decline. This study assesses the role of mitochondrial proteins in neuron-derived exosomes (NDEs) on cognitive impairment in patients with obstructive sleep apnea (OSA) without dementia. METHODS: Analyses were conducted in 268 study participants with complete polysomnography data, cognitive tests, and important clinical data available. NDEs were isolated immunochemically for enzyme-linked immunosorbent assay quantification of mitochondrial proteins, i.e., humanin and mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), and synaptic protein, i.e., neurogranin (NRGN). A mediation analysis of the relationship between sleep parameters and cognition was performed using humanin, MOTS-c, and NRGN values as a mediating factor. Twenty-two patients with moderate to severe OSA who received CPAP therapy were followed up, and humanin, MOTS-c and NRGN levels were reassessed after 1 year of treatment. RESULTS: All participants were divided into the OSA + MCI group (n = 91), OSA-MCI group (n = 89), MCI group (MCI without OSA) (n = 38) and control group (normal cognitive state without OSA) (n = 50). The mean CD63-normalized NDE levels of humanin, MOTS-c, and NRGN in the OSA + MCI group were higher than those in the OSA-MCI and control groups. The NDE levels of humanin, MOTS-c, and NRGN in the MCI group were lower than those in controls. The odds of cognitive impairment in patients with OSA were higher with higher NDE levels of humanin, MOTS-c, and NRGN (odds ratio (OR): 2.100, 95 % confidence interval (CI): 1.646-2.679, P < 0.001; OR: 5.453, 95 % CI: 3.112-9.556, P < 0.001; OR: 3.115, 95 % CI: 2.163-4.484, P < 0.001). The impaired cognitive performance was associated with higher NDE levels of humanin (ß: 0.505, SE: 0.048, P < 0.001), MOTS-c (ß: 0.580, SE: 0.001, P < 0.001), and NRGN (ß: 0.585, SE: 0.553, P < 0.001). The relationship between sleep parameters (mean SaO2 and T90) and MoCA scores was mediated by the NDE levels of humanin, MOTS-c, and NRGN with the proportion of mediation varying from 35.33 % to 149.07 %. Receiver operating characteristic curve revealed an area under the curve of 0.905 for humanin, 0.873 for MOTS-c, and 0.934 for NRGN to predict MCI in OSA patients without dementia. Increased humanin, MOTS-c, and NRGN levels significantly decreased after CPAP treatment. CONCLUSIONS: Mitochondrial dysfunction is implicated in cognitive impairment in OSA patients without dementia, and mainly mediates the association between intermittent hypoxia and cognitive impairment in adults with OSA without dementia. Mitochondrial dysfunction can be partially reversible by CPAP treatment. Mitochondrial proteins can be used as markers of cognitive impairment in patients with OSA.

Neuronal glutamate transporters are associated with cognitive impairment in obstructive sleep apnea patients without dementia.

Increasing evidence supports a link between obstructive sleep apnea (OSA) and cognition, and the mechanism is complex and still not well understood. We analyzed the relationship between the glutamate transporters and cognitive impairment in OSA. For this study 317 subjects without dementia, including 64 healthy controls (HCs), 140 OSA patients with mild cognitive impairment (MCI) and 113 OSA patients without cognitive impairment were assessed. All participants who completed polysomnography, cognition and white matter hyperintensity (WMH) volume were used. Plasma neuron-derived exosomes (NDEs) excitatory amino acid transporter 2 (EAAT2) and vesicular glutamate transporter 1 (VGLUT1) proteins were measured by ELISA kits. After 1 year of continuous positive airway pressure (CPAP) treatment, we analyzed plasma NDEs EAAT2 level and cognition changes. Plasma NDEs EAAT2 level was significantly higher in OSA patients than in HCs. Higher plasma NDEs EAAT2 level were significantly associated with cognitive impairment than normal cognition in OSA patients. Plasma NDEs EAAT2 level was inversely associated with the total Montreal Cognitive Assessment (MoCA) scores, visuo-executive function, naming, attention, language, abstraction, delayed recall and orientation. One year after CPAP treatment, plasma NDEs EAAT2 level (P = 0.019) was significantly lower, while MoCA scores (P = 0.013) were significantly increased compared with baseline. Upregulation of neuronal glutamate transporters at baseline may reflect a self-compensatory mechanism to prevent further neuronal damage, while plasma NDEs EAAT2 level was decreased after one year of CPAP therapy, which may be due to the loss of astrocytes and neurons.

Complement protein levels in serum astrocyte-derived exosomes are associated with cognitive impairment in obstructive sleep apnea.

STUDY OBJECTIVES: An association between neuroinflammation and cognitive decline has been established. The complement system regulates neuroinflammation. Dysregulation, impairment, or inadvertent activation of complement components contribute to preclinical Alzheimer's disease. The astrocyte-derived exosome (ADE) complement proteins, including C3b and C5b-9, may be predictive biomarkers of mild cognitive impairment conversion to Alzheimer's disease dementia. We hypothesized that complement proteins might be involved in cognitive impairment during obstructive sleep apnea (OSA). The aim of our study was to explore the correlation between the complement system and mild cognitive impairment (MCI) in patients with OSA. METHODS: All participants with subjective snoring complaints from the Sleep Medicine Center underwent polysomnography. OSA was defined as apnea-hypopnea index ≥ 5 events/h. MCI was defined as the Montreal Cognitive Assessment < 26 and met the criteria: (1) a subjective cognitive impairment; (2) an objective impairment in 1 or more cognitive domains; (3) complex instrumental daily abilities can be slightly impaired but independent daily living abilities are maintained; and (4) no dementia. The ADEs were isolated immunochemically for enzyme-linked immunosorbent assay quantification of complement proteins, including C3b, C5b-9, and CD55. The participants who received continuous positive airway pressure were followed up and their complement protein levels were reassessed after 1 year of treatment. RESULTS: A total of 212 participants (66.98% males; mean age of 56.71 ± 10.10 years) were divided into the OSA+MCI group (n = 90), OSA-MCI group (n = 79), and controls (normal cognitive state without OSA) (n = 43). The ADE levels of C3b and C5b-9 in the OSA+MCI group were higher than those in the OSA-MCI and control groups. The C3b and C5b-9 were independently associated with cognitive impairment in patients with OSA. The relationship between apnea-hypopnea index and Montreal Cognitive Assessment scores was mediated by C3b and C5b-9. We found no linear correlation between the complement proteins and the severity of OSA. The complement proteins were negatively correlated with global cognitive performance and cognitive subdomains. The complement protein levels significantly decreased after continuous positive airway pressure treatment. CONCLUSIONS: Complement proteins were implicated in cognitive impairment in patients with OSA and may be promising biomarkers for predicting cognitive impairment in patients with OSA. CLINICAL TRIAL REGISTRATION: Registry: Chinese Clinical Trial Registry; Name: Study on early diagnostic markers in patients with dementia and mild cognitive impairment; URL: https://www.chictr.org.cn/; Identifier: ChiCTR1900021544. CITATION: Li M, Sun C, Xue S, et al. Complement proteins levels in serum astrocyte-derived exosomes are associated with cognitive impairment in obstructive sleep apnea. J Clin Sleep Med. 2023;19(4):727-739.

Elevated complement component 8 gamma levels in astrocyte-derived exosomes are associated with cognitive impairment in obstructive sleep apnea patients without dementia.

The complement system plays a crucial role in cognitive impairment in obstructive sleep apnea (OSA). The present study aimed to investigate the connections between complement component 8 gamma (C8G) levels in astrocyte-derived exosomes (ADEs) and cognitive impairment in OSA patients without dementia. This cross-sectional cohort study recruited 274 participants without dementia, including 124 OSA patients with mild cognitive impairment (MCI), 100 OSA patients without MCI, and 50 healthy control subjects. Enrolled participants underwent polysomnography (PSG) evaluation, neuropsychological scale assessment, magnetic resonance imaging scanning, and collection of peripheral blood samples for quantification of complement proteins in ADEs. The findings showed higher C8G concentrations in ADEs from OSA patients with MCI than in the controls and OSA without MCI group. Logistic regression analysis suggested that C8G levels in ADEs were independently associated with MCI in OSA patients. Multivariable linear regression analysis demonstrated that C8G levels in ADEs were significantly correlated with global cognitive scores and all cognitive subdomain scores after adjusting for demographic factors (age, sex, education), vascular risk factors (Body mass index, history of hypertension, diabetes, dyslipidemia), depressive symptoms measures, and apnea-hypopnea index (AHI) values. The levels of C8G were linearly positively related to the white matter hyperintensity (WMH) volumes in Pearson's correlation analysis. Our research confirmed that C8G levels are significantly associated with cognitive impairment in OSA patients, which paves the way for novel therapeutic targets for neurocognitive dysfunction progression in OSA patients in the future.

Paroxysmal slow wave events are associated with cognitive impairment in patients with obstructive sleep apnea.

BACKGROUND: Increasing evidence has supported a link between obstructive sleep apnea (OSA) and cognition, and blood-brain barrier (BBB) dysfunction which can be reflected by paroxysmal slow wave events (PSWEs) may be a potential mechanism. The purpose of our study was to investigate the correlation between the PSWEs and cognitive impairment in patients with OSA, with a focus on the possible mechanism. METHODS: In total, 339 subjects with subjective snoring complaints from the Sleep Medicine Center underwent magnetic resonance imaging and whole-night polysomnography. OSA was defined as apnea-hypopnea index (AHI) ≥ 5 events/h. MCI was defined as the MoCA < 26 and met the criteria: (1) subjective cognitive impairment; (2) objective impairment in one or more cognitive domains; (3) slightly impaired complex instrumental daily abilities, but independent daily living abilities; and (4) no dementia. The PSWEs calculated by self-developed Python scripts were defined for EEG recordings as a median power frequency of < 6 Hz for more than five consecutive seconds. Serum cyclophilin A (CyPA) and matrix metalloproteinase-9 (MMP-9) levels and amyloid-ß 42 levels in neuron-derived exosomes were determined. The participants who received continuous positive airway pressure (CPAP) were followed up and their PSWEs were recalculated after 1 year of treatment. RESULTS: A total of 339 participants were divided into the OSA+MCI group (n = 157), OSA-MCI group (n = 118), and controls (normal cognitive state without OSA) (n = 64). The total PSWEs and the occurrence per minute of PSWEs at stage REM in the OSA+MCI group were higher than those in the OSA-MCI and control groups. The duration ratio of PSWEs at stage REM in the OSA+MCI group significantly increased. The total PSWEs and PSWEs at the F4-M1, O1-M2, and O2-M1 channels in stage REM were independently associated with cognitive impairment in OSA patients. There were positive correlations between the PSWEs and serum CyPA and MMP-9 levels in patients with OSA. The mediation analysis showed that the relationship between mean SaO2 and percentage of sleep time spent with oxygen saturation <90% with MoCA scores was mediated by the total PSWEs (proportion of mediation 77.89% and 82.89%). The PSWEs were negatively correlated with global cognitive performance and cognitive subdomains. After 1 year of CPAP treatment, the total PSWEs, PSWEs in stage REM, and serum CyPA and MMP-9 levels decreased significantly, and MoCA scores were improved compared with baseline. CONCLUSIONS: The PSWEs were implicated in cognitive impairment in patients with OSA, and the mechanisms of cognitive impairment due to hypoxia in OSA patients could be BBB dysfunction. The PSWEs can be used as a marker of cognitive impairment in patients with OSA. TRIAL REGISTRATION: This trial is registered on the Chinese Clinical Trial Registry, number ChiCTR1900021544. The trial was registered on February 27, 2019.

Blood neuroexosomal excitatory amino acid transporter-2 is associated with cognitive decline in Parkinson's disease with RBD.

Background: Rapid eye movement (REM) sleep behavior disorder (RBD) predicts cognitive decline in Parkinson's disease (PD) patients without dementia. However, underlying mechanisms remain unknown. Accumulating studies suggest glutamatergic system dysregulation is associated. Objective: To examine the effect of RBD on the rate of cognitive decline in PD patients and investigate whether plasma levels of the neuroexosomal vesicular glutamate transporter-1 (VGLUT-1) and excitatory amino acid transporter-2 (EAAT-2) are altered in PD patients with RBD. Methods: This study included 157 newly diagnosed cognitive normal PD patients and 70 healthy controls (HCs). Based on one-night polysomnography recordings, the PD subjects were divided into PD with and without RBD (PD-RBD and PD-nRBD) groups. All participants received a complete clinical and neuropsychological evaluation at baseline. Plasma levels of neuroexosomal VGLUT-1 and EAAT-2 were measured by ELISA kits. After a 3-year follow-up, we evaluated baseline plasma levels of neuroexosomal glutamate transporters in each group as a predictor of cognitive decline using MoCA score changes over 3 years in regression models. Results: Plasma levels of neuron-derived exosomal EAAT-2 and VGLUT-1 were significantly lower in PD patients than in HCs. Plasma levels of neuroexosomal EAAT-2 were significantly lower in PD-RBD than PD-nRBD group at baseline. At the 3-year follow-up, PD-RBD patients presented greater cognitive decline. Lower baseline blood neuroexosomal EAAT-2 predicted cognitive decline over 3 years in PD-RBD patients (ß = 0.064, P = 0.003). Conclusion: These findings indicate that blood neuroexosomal EAAT-2 is associated with cognitive decline in PD with RBD.

Altered amyloid-ß and tau proteins in neural-derived plasma exosomes in obstructive sleep apnea.

OBJECTIVE: The purpose of our study was to investigate the correlation between neural-derived plasma exosomal amyloid-ß (Aß)42, total tau (T-tau) and tau phosphorylated at threonine 181 (P-T181-tau) protein levels and cognitive impairment in patients with obstructive sleep apnea (OSA). METHODS: There were 122 subjects without dementia included in the study: 27 patients with OSA and mild cognitive impairment (MCI), 52 OSA patients without MCI, and 43 subjects diagnosed with simple snoring but not MCI as the control group. Neuronal-derived exosomal proteins were measured by ELISA kits for Aß42, T-tau and P-T181-tau. The cognitive function was evaluated by a Chinese version of the Montreal Cognitive Assessment (MoCA) questionnaire, and a normal cognitive score was ≥26. RESULTS: The exosomal Aß42, T-tau and P-T181-tau levels in the OSA with MCI group were higher than those in the OSA group. The Aß42, T-tau, and P-T181-tau levels in the plasma neuronal-derived exosomes were associated with an increased risk of cognitive impairment in OSA patients after additional adjustment for age, gender, education, vascular risk factors, apnea-hypopnea index (AHI) or oxygen reduction index (ODI). Furthermore, there were also significant associations between Aß42, T-tau, and P-T181-tau in neural-derived plasma exosomes and Epworth Sleepiness Scale, AHI, and ODI in OSA patients. After 1 year of continuous positive airway pressure (CPAP) intervention, the neuronal-derived exosome levels of Aß42, T-tau, and P-T181-tau were significantly lower than those at baseline (P = 0.001, P = 0.012, and P = 0.034). CONCLUSIONS: These findings indicate that peripheral blood levels of neuronal-derived exosomal Aß and tau proteins were increased in OSA patients with cognitive impairment. CPAP interventions could possibly improve cognitive function and be associated with decreased levels of exosomal Aß and tau proteins.

Blood Neuroexosomal Mitochondrial Proteins Predict Alzheimer Disease in Diabetes.

There is accumulating evidence that mitochondrial dysfunction is associated with the contribution of diabetes to Alzheimer disease (AD) progression. Neuronal mitochondrial proteins are found in plasma neuronal-derived exosomes (NDEs) at levels that reflect those in brain neurons. Here, we tested the performance of mitochondrial proteins in plasma NDEs to predict cognitive decline and brain injury in participants with diabetes. The study participants with type 2 diabetes mellitus (T2DM) included 41 cognitively normal control subjects, 97 individuals with mild cognitive impairment (MCI) (68 individuals with stable MCI; 29 individuals with progressive MCI), and 36 patients with AD dementia. Plasma neuroexosomal proteins were measured by ELISA kits. Spearman correlation was used to test associations between plasma neuroexosomal mitochondrial proteins and other core biomarkers of AD. Diagnostic accuracy for progressive MCI and AD was obtained for mitochondrial proteins using receiver operating characteristic curve analyses. The associations of mitochondrial proteins with the conversion from MCI to AD were assessed by Cox proportional hazard regression analysis. Plasma levels of neuroexosomal NADH ubiquinone oxidoreductase core subunit S3 (NDUFS3) and succinate dehydrogenase complex subunit B (SDHB) were significantly lower in patients with T2DM with AD dementia and progressive MCI than in cognitively normal subjects (P < 0.001 for both groups). We also found that plasma neuroexosomal NDUFS3 and SDHB levels were lower in progressive MCI subjects than in stable MCI subjects. Both plasma neuroexosomal NDUFS3 and SDHB offer diagnostic utility for AD. Low plasma neuroexosomal SDHB levels significantly predicted conversion from MCI to AD. In addition, low mitochondrial protein levels were associated with the rate of hippocampal and gray matter atrophy and reduced AD signature cortical thickness in progressive MCI over the follow-up period. These data suggest that both plasma neuroexosomal NDUFS3 and SDHB are already increased at the early clinical stage of AD, and indicate the promise of plasma neuroexosomal mitochondrial proteins as diagnostic and prognostic biomarkers for the earliest symptomatic stage of AD in participants with diabetes.

Increased serum levels of cyclophilin a and matrix metalloproteinase-9 are associated with cognitive impairment in patients with obstructive sleep apnea.

OBJECTIVES: To investigate the relationship between serum cyclophilin A (CyPA) and matrix metalloproteinase-9 (MMP-9) levels and mild cognitive impairment (MCI) in patients with obstructive sleep apnea (OSA). METHODS: Study subjects underwent whole-night in-laboratory polysomnography (PSG), and all participants were scored using a neuropsychological scale and peripheral blood samples were collected the next morning. The presence and severity of OSA were assessed with the apnea hypopnea index (AHI), and OSA was defined as AHI ≥5 events/hour. MCI was defined as the MoCA ≤25, and met the revised Mayo Clinic criteria. Serum CyPA and MMP-9 levels were measured with enzyme-linked immunosorbent assays (ELISAs). A univariate analysis and a logistic model were used to assess risk factors for MCI in patients with OSA. A correlation analysis was performed to estimate whether a linear relationship existed between serum CyPA and MMP-9 levels and the severity of cerebral small vessel disease (CSVD) and white matter hyperintensities (WMHs). A linear regression analysis was used to clarify the relationship between serum CyPA and MMP-9 levels and the degree of cognitive impairment in patients with OSA. RESULTS: The 186 patients who met the criteria for inclusion and exclusion comprised 71 patients with OSA presenting with MCI (OSA + MCI), 73 patients with OSA without MCI (OSA-MCI), and 42 controls. Patients with OSA + MCI presented higher serum CyPA and MMP-9 levels than patients in the OSA-MCI (11.56 ± 4.52 ng/ml vs 9.95 ± 3.63 ng/ml, p = 0.020; 597.71 ± 204.41 ng/ml vs 523.05 ± 205.47 ng/ml, p = 0.030) and control groups (11.56 ± 4.52 ng/ml vs 8.80 ± 3.71 ng/m, p = 0.001; 597.71 ± 204.41 ng/ml vs 490.39 ± 155.07 ng/ml, p = 0.002). The logistic regression analysis revealed that both CyPA (OR: 1.111, 95% CIs: 1.012-1.219, p = 0.027) and MMP-9 levels (OR: 1.003, 95% CIs: 1.000-1.004, p = 0.011) contributed significantly to MCI in patients with OSA. In the OSA + MCI group, positive correlations were observed between serum CyPA and MMP-9 levels with Scheltens scores (r = 0.437, p = 0.000; r = 0.613, p = 0.000, respectively) and total CSVD burden scores (r = 0.318, p = 0.003; r = 0.487, p = 0.000, respectively). Serum CyPA and MMP-9 levels were linearly negatively correlated with mean oxygen saturation during sleep (mean SaO2) (r = -0.595, p = 0.000; r = -0.570, p = 0.000). There was linear correlation between mean SaO2 and MoCA scores by Pearson's correlation coefficient (r = 0.403, p = 0.000). The linear regression analysis revealed negative correlations between serum CyPA and MMP-9 levels and the Montreal Cognitive Assessment (MoCA) scores (r = -0.528, p = 0.000; r = -0.459, p = 0.000, respectively), and serum CyPA levels were negatively correlated with score of cognitive subdomainss, including visuo-executive function, attention and delayed recall. However, serum MMP-9 levels were negatively correlated with score of cognitive subdomains, including visuo-executive function and delayed recall. CONCLUSIONS: Increased serum levels of CyPA and MMP-9 are associated with MCI in OSA patients and directly related to the severity of CSVD and WMHs. The results suggest that damage to the blood-brain barrier (BBB) may be involved in the early stages of cognitive impairment in patients with OSA.

Altered Amyloid-ß and Tau Proteins in Neural-Derived Plasma Exosomes of Type 2 Diabetes Patients with Orthostatic Hypotension.

BACKGROUND: Emerging evidence suggests a role for orthostatic hypotension (OH) in contributing to the progression of Alzheimer's disease (AD). The exosomes in the blood can reflect the pathological changes in the brain. OBJECTIVE: To investigate whether neural-derived plasma exosomes pathogenic proteins of AD levels are associated with OH in diabetes mellitus (DM) patients. METHODS: There were 274 subjects without dementia included in the study: 81 control participants (controls), 101 normotensive patients with DM without OH, and 92 patients with DM and neurogenic OH (DMOH). Neural-derived exosomal proteins were measured by ELISA kits for amyloid-ß (Aß) and tau. RESULTS: The neural-derived exosome levels of Aß42, total tau (T-tau), and tau phosphorylated at threonine 181 (P-T181-tau) in the DM with OH group were higher than those in the DM and control groups. Multivariable linear regression analysis showed that the presence of OH in patients with DM was associated with elevated exosomal Aß42 (ß= 0.172, p = 0.018), T-tau (ß= 0.159, p = 0.030), and P-T181-tau (ß= 0.220, p = 0.003) levels after adjustment for age, sex, APOE ɛ4, duration of type 2 diabetes, HbA1c, and cardiovascular risk factors. Furthermore, the levels of Aß42, T-tau, and P-T181-tau in neural-derived exosomes were correlated with HIF-1α levels and the drop in mean cerebral blood flow velocity from the supine to upright position. CONCLUSION: The presence of OH in DM patients was independently associated with elevated the Aß42, T-tau, and P-T181-tau levels in neural-derived plasma exosomes. Cerebral hypoperfusion from DM with OH are likely candidate mechanisms.

Plasma exosomal prion protein levels are correlated with cognitive decline in PD patients.

OBJECTIVE: Cognitive decline is a common non-motor symptom of Parkinson disease (PD), and cellular prion protein (PrPC) has been suggested to play a role in this process. This study aimed to investigate the correlation between plasma exosomal prion protein and cognitive decline in PD patients. METHOD: A total of 60 participants, which included 23 PD patients without cognitive impairment (the PD-NCI group), 17 PD patients with cognitive impairment (the PD-CI group) and 20 health controls were included in this study. All participants received a complete evaluation of motor symptoms as well as non-motor symptoms, which include devaluations of cognitive function(assessed with the Montreal Cognitive Assessment (MoCA)) and their psychiatric state(assessed with the Hamilton Anxiety Scale(HAM-A) and Hamilton Depression Scale(HAMD-17)). We used an enzyme-linked immunosorbent assay (ELISA) to measure the plasma exosomal prion protein level. The exosomal marker Heat shock protein 70 (HSP 70) was used to normalize the protein level to the exosome content. RESULT: In PD patients, the plasma exosomal prion protein concentration was negatively correlated with the cognitive level. The plasma exosomal prion protein concentration was significantly higher in the PD-CI group than in the control group (p < 0.05) and the PD-NCI group (p < 0.05).Multivariate regression analysis indicated that plasma exosomal prion protein levels were significantly associated with the cognitive level (t=-3.185, P = 0.001) after adjusting for age, education, disease duration, H&Y stage and MDS-UPDRS-III scores. CONCLUSION: The plasma exosomal prion protein level is correlated with cognitive decline in PD patients and might be a potential biomarker for PD patients at risk for cognitive impairment.

Effects of orthostatic hypotension on cognition in type 2 diabetes mellitus.

OBJECTIVE: To evaluate the effect of a decrease in blood pressure (BP) fulfilling the diagnostic criteria for orthostatic hypotension (OH) on performance in each domain of cognitive function in patients with type 2 diabetes mellitus using a cross-sectional and within-group design. METHODS: Subjects were individuals without dementia and with type 2 diabetes mellitus, including 107 individuals without OH and 94 with OH (DMOH); 95 control participants were also included. BP was assessed in both the supine and standing positions. A detailed neuropsychological assessment was made in each posture for all subjects. RESULTS: There were statistically significant differences between the patients without OH and the DMOH group with regard to some cognitive measures while supine. Standing posture exacerbated and broadened cognitive deficits in the DMOH group for all measures in the different domains of cognition including executive functioning, memory, visuospatial skills, information processing speed, and attention. When group-specific supine scores were used as baseline anchors, both the patients without OH and the DMOH group showed cognitive changes when transitioning from a supine to a standing, upright position, with the DMOH group exhibiting a wider range of neuropsychological deficits in memory, visuospatial skills, executive function, and sustained attention, as well as significant changes in information processing speed. INTERPRETATION: These data demonstrate that type 2 diabetes mellitus patients with OH had transient, posture-mediated cognitive deficits in excess of those found in diabetes mellitus without OH. Understanding the effects of OH on cognition due to autonomic failure is important, particularly as clinical assessments and neuroimaging collect data only in the seated or supine positions. ANN NEUROL 2019;86:754-761.