Menstrual pain mediated the association between daytime sleepiness and suicidal risk: A prospective study.

BACKGROUND: Adolescents with daytime sleepiness have been demonstrated to have a higher level of suicidal risk than those without. Currently, few studies had examined the pathway from daytime sleepiness to suicidal risk among female adolescents. This study aimed to explore the association among menstrual pain, daytime sleepiness, and suicidal risk among female adolescents in China. METHODS: Of 7072 adolescents who participated in the follow-up survey of Shandong Adolescents Behavior & Health Cohort (SABHC), 3001 were female adolescents who had begun to menstruate and included for the analysis. A structured self-administrated questionnaire was used to measure menstrual pain, daytime sleepiness, suicidal risk and demographic characteristics. Participants were first surveyed in November-December 2015 and resurveyed 1 year later. RESULTS: Of 3001 participants, 11.43 % had suicidal risk, 79.8 % experienced menstrual pain. Cross-lagged analysis showed that there was cause-and-effect relationship between menstrual pain and daytime sleepiness. Moderate (OR = 1.79, 95%CI: 1.22-2.63) and severe (OR = 2.73, 95%CI: 1.80-4.12) menstrual pain (follow-up) were associated with suicidal risk (follow-up). Daytime sleepiness (baseline: OR = 1.04, 95%CI: 1.02-1.06, follow-up: OR = 1.07, 95%CI: 1.05-1.09) had effects on suicidal risk (follow-up). Mediation analysis showed that menstrual pain played a partially mediating role between daytime sleepiness and suicidal risk, with the indirect effect being 0.002 (95%CI: 0.001-0.004). LIMITATIONS: All data were self-reported. CONCLUSIONS: Menstrual pain and daytime sleepiness had effects on each other, and they both were the risk factors of suicidal risk. Among female adolescents, the association between daytime sleepiness and suicidal risk could be partially mediated by menstrual pain. Releasing the menstrual pain of female adolescents with daytime sleepiness could reduce their suicidal risk.

ß-Amyloid in blood neuronal-derived extracellular vesicles is elevated in cognitively normal adults at risk of Alzheimer's disease and predicts cerebral amyloidosis.

BACKGROUND: Blood biomarkers that can be used for preclinical Alzheimer's disease (AD) diagnosis would enable trial enrollment at a time when the disease is potentially reversible. Here, we investigated plasma neuronal-derived extracellular vesicle (nEV) cargo in patients along the Alzheimer's continuum, focusing on cognitively normal controls (NCs) with high brain ß-amyloid (Aß) loads (Aß+). METHODS: The study was based on the Sino Longitudinal Study on Cognitive Decline project. We enrolled 246 participants, including 156 NCs, 45 amnestic mild cognitive impairment (aMCI) patients, and 45 AD dementia (ADD) patients. Brain Aß loads were determined using positron emission tomography. NCs were classified into 84 Aß- NCs and 72 Aß+ NCs. Baseline plasma nEVs were isolated by immunoprecipitation with an anti-CD171 antibody. After verification, their cargos, including Aß, tau phosphorylated at threonine 181, and neurofilament light, were quantified using a single-molecule array. Concentrations of these cargos were compared among the groups, and their receiver operating characteristic (ROC) curves were constructed. A subset of participants underwent follow-up cognitive assessment and magnetic resonance imaging. The relationships of nEV cargo levels with amyloid deposition, longitudinal changes in cognition, and brain regional volume were explored using correlation analysis. Additionally, 458 subjects in the project had previously undergone plasma Aß quantification. RESULTS: Only nEV Aß was included in the subsequent analysis. We focused on Aß42 in the current study. After normalization of nEVs, the levels of Aß42 were found to increase gradually across the cognitive continuum, with the lowest in the Aß- NC group, an increase in the Aß+ NC group, a further increase in the aMCI group, and the highest in the ADD group, contributing to their diagnoses (Aß- NCs vs. Aß+ NCs, area under the ROC curve values of 0.663; vs. aMCI, 0.857; vs. ADD, 0.957). Furthermore, nEV Aß42 was significantly correlated with amyloid deposition, as well as longitudinal changes in cognition and entorhinal volume. There were no differences in plasma Aß levels among NCs, aMCI, and ADD individuals. CONCLUSIONS: Our findings suggest the potential use of plasma nEV Aß42 levels in diagnosing AD-induced cognitive impairment and Aß+ NCs. This biomarker reflects cortical amyloid deposition and predicts cognitive decline and entorhinal atrophy.

Exploring brain glucose metabolic patterns in cognitively normal adults at risk of Alzheimer's disease: A cross-validation study with Chinese and ADNI cohorts.

OBJECTIVE: Disease-related metabolic brain patterns have been verified for a variety of neurodegenerative diseases including Alzheimer's disease (AD). This study aimed to explore and validate the pattern derived from cognitively normal controls (NCs) in the Alzheimer's continuum. METHODS: This study was based on two cohorts; one from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the other from the Sino Longitudinal Study on Cognitive Decline (SILCODE). Each subject underwent [18F]fluoro-2-deoxyglucose positron emission tomography (PET) and [18F]florbetapir-PET imaging. Participants were binary-grouped based on ß-amyloid (Aß) status, and the positivity was defined as Aß+. Voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was used to generate the "at-risk AD-related metabolic pattern (ARADRP)" for NCs. The pattern expression score was obtained and compared between the groups, and receiver operating characteristic curves were drawn. Notably, we conducted cross-validation to verify the robustness and correlation analyses to explore the relationships between the score and AD-related pathological biomarkers. RESULTS: Forty-eight Aß+ NCs and 48 Aß- NCs were included in the ADNI cohort, and 25 Aß+ NCs and 30 Aß- NCs were included in the SILCODE cohort. The ARADRPs were identified from the combined cohorts and the two separate cohorts, characterized by relatively lower regional loadings in the posterior parts of the precuneus, posterior cingulate, and regions of the temporal gyrus, as well as relatively higher values in the superior/middle frontal gyrus and other areas. Patterns identified from the two separate cohorts showed some regional differences, including the temporal gyrus, basal ganglia regions, anterior parts of the precuneus, and middle cingulate. Cross-validation suggested that the pattern expression score was significantly higher in the Aß+ group of both cohorts (p < 0.01), and contributed to the diagnosis of Aß+ NCs (with area under the curve values of 0.696-0.815). The correlation analysis revealed that the score was related to tau pathology measured in cerebrospinal fluid (p-tau: p < 0.02; t-tau: p < 0.03), but not Aß pathology assessed with [18F]florbetapir-PET (p > 0.23). CONCLUSIONS: ARADRP exists for NCs, and the acquired pattern expression score shows a certain ability to discriminate Aß+ NCs from Aß- NCs. The SSM/PCA method is expected to be helpful in the ultra-early diagnosis of AD in clinical practice.

Glucose metabolism in the right middle temporal gyrus could be a potential biomarker for subjective cognitive decline: a study of a Han population.

INTRODUCTION: Subjective cognitive decline (SCD) represents a cognitively normal state but at an increased risk for developing Alzheimer's disease (AD). Recognizing the glucose metabolic biomarkers of SCD could facilitate the location of areas with metabolic changes at an ultra-early stage. The objective of this study was to explore glucose metabolic biomarkers of SCD at the region of interest (ROI) level. METHODS: This study was based on cohorts from two tertiary medical centers, and it was part of the SILCODE project (NCT03370744). Twenty-six normal control (NC) cases and 32 SCD cases were in cohort 1; 36 NCs, 23 cases of SCD, 32 cases of amnestic mild cognitive impairment (aMCIs), 32 cases of AD dementia (ADDs), and 22 cases of dementia with Lewy bodies (DLBs) were in cohort 2. Each subject underwent [18F]fluoro-2-deoxyglucose positron emission tomography (PET) imaging and magnetic resonance imaging (MRI), and subjects from cohort 1 additionally underwent amyloid-PET scanning. The ROI analysis was based on the Anatomical Automatic Labeling (AAL) template; multiple permutation tests and repeated cross-validations were conducted to determine the metabolic differences between NC and SCD cases. In addition, receiver operating characteristic curves were used to evaluate the capabilities of potential glucose metabolic biomarkers in distinguishing different groups. Pearson correlation analysis was also performed to explore the correlation between glucose metabolic biomarkers and neuropsychological scales or amyloid deposition. RESULTS: Only the right middle temporal gyrus (RMTG) passed the methodological verification, and its metabolic levels were correlated with the degrees of complaints (R = - 0.239, p = 0.009), depression (R = - 0.200, p = 0.030), and abilities of delayed memory (R = 0.207, p = 0.025), and were weakly correlated with cortical amyloid deposition (R = - 0.246, p = 0.066). Furthermore, RMTG metabolism gradually decreased across the cognitive continuum, and its diagnostic efficiency was comparable (NC vs. ADD, aMCI, or DLB) or even superior (NC vs. SCD) to that of the metabolism of the posterior cingulate cortex or precuneus. CONCLUSIONS: These findings suggest that the hypometabolism of RMTG could be a typical feature of SCD, and the large-scale hypometabolism in patients with symptomatic stages of AD may start from the RMTG, which gradually progresses starting in the preclinical stage. The specificity of identifying SCD from the perspective of self-perceived symptoms is likely to be increased by the detection of RMTG metabolism.

Activity of encapsulated Lactobacillus bulgaricus in alginate-whey protein microspheres

In this work, alginate-whey protein was used as wall materials for encapsulating Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus). The characteristics of encapsulated and free L. bulgaricus showed that the free L. bulgaricus lost viability after 1 min exposure to simulated gastric fluid (SGF) at pH 2.0 and 2.5. However, the viability of encapsulated L. bulgaricus did not decrease in SGF at pH 2.5 for 2 h incubation. The viable numbers of encapsulated L. bulgaricus decreased less than 1.0 log unit for 2 h incubation in SGF at pH 2.0. For bile stability, only 1.2 log units and 2.0 log units viability of the encapsulated L. bulgaricus was lost in 1 and 2% bile for 1 h exposure, respectively, compared with no survival of free L. bulgaricus under the same conditions. Encapsulated L. bulgaricus was completely released from the microspheres in simulated intestinal fluid (SIF, pH 6.8) in 3 h. The viability of the encapsulated L. bulgaricus retained more 8.0 log CFU/g after stored at 4°C for four weeks. However, for free L. bulgaricus, only around 3.0 log CFU/mL was found at the same storage conditions. Results showed that the encapsulation could improve the stability of L. bulgaricus.