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Background: APOE ɛ4 genotype was correlated with exacerbation of pathology and higher risk of dementia in Parkinson’s disease (PD). Meanwhile, the differential influence of APOE ɛ4 on cognition in young and old individuals interpreted as antagonistic pleiotropy. Objective: To examine whether the effect of APOE ɛ4 on cognitive progression in de novo PD is age dependent. Methods: In this study, 613 de novo PD patients were recruited from Parkinson’s Progression Markers Initiative (PPMI). To examine the age-dependent relationship between APOE ɛ4 and cognitive changes, we added 3-way interaction of APOE ɛ4*baseline age*time to the linear mixed-effect (LME) models and evaluated the specific roles of APOE ɛ4 in the middle age group and elderly group separately. Cox regression was utilized to examine the progression of cognition in age-stratified PD participants. Results: Age significantly modified relationship between APOE ɛ4 and cognitive changes in most cognitive domains (pinteraction

Visual impairment and interventions to preserve vision may impact dementia risk. Thus, we aimed to explore the associations of cataract and cataract surgery with the risk of dementia.Prospective data from 300,823 individuals in the UK Biobank were used. We used multivariate Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals for associations, with healthy control subjects as a reference. The same method was used to explore the effects of surgery on dementia outcomes of patients with cataract. One-way analysis of variance was performed to examine the associations between cataract and brain morphometric measures.After a mean follow-up of 8.4 years, 3226 individuals were diagnosed with dementia. The nonsurgical cataract group had increased risk of all-cause dementia (HR, 1.214; 95% CI, 1.012-1.456; p = .037) and Alzheimer's disease (HR, 1.479; 95% CI, 1.105-1.981; p = .009). However, there was no difference in dementia risk between the cataract surgery group and the healthy control group. Cataract surgery was associated with decreased risk of all-cause dementia (HR, 0.632; 95% CI, 0.421-0.947; p = .026) and Alzheimer's disease (HR, 0.399; 95% CI, 0.196-0.812; p = .011) compared with the nonsurgical group. Additionally, cataract was negatively associated with cortical volumes, aging-related subcortical volumes, and fractional anisotropy of white matter fibers.Cataract patients who did not receive surgical treatment had an increased risk of dementia. However, cataract surgery could reverse the risk of dementia. Our findings on brain structures and pathways in patients with cataract also provided evidence for the mechanism. Reversible visual impairment, such as cataract, is a promising modifiable risk factor for dementia.

A subgroup of overweight/obese individuals, who had favorable metabolic profiles, was termed as metabolically healthy overweight/obese (MHO). Several studies suggested that MHO individuals were not at increased risk of cardiovascular disease and all-course mortality. However, whether MHO is associated with excess risk of Alzheimer’s disease (AD) in elders remains unclear. To explore the risk of AD among MHO phenotype and investigate whether MHO associates with neurodegenerative biomarkers of AD, we assessed body mass index-metabolic status phenotypes of 1199 longitudinal elders from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort using the Adult Treatment Panel-III (ATP- III) criteria. MHO subjects were at a significantly decreased risk for AD (adjusted HR=0.73, 95% CI: 0.54-0.97) compared with metabolically healthy normal weight (MHNW) subjects. In multivariable linear regression models, the cross-sectional associations of MHO with cerebrospinal fluid (CSF) biomarkers, brain Aβ load, and cortical structure were explored. MHO was positively correlated with CSF-Aβ (β=0.746, P=0.015), hippocampal volume (β=0.181, P=0.011), and whole brain volume (β=0.133, P=0.004). The MHO phenotype of the elder conferred a decreased risk of AD and its role may be driven by Aβ.

The effects of microglial activation on the associations between depression and Alzheimer’s disease (AD) are still unclear. TREM2 gene plays a pivotal role in microglial activation, has been identified as a risk factor for AD. In this work, we aimed to assess the interrelationships of soluble TREM2 (sTREM2) level in cerebrospinal fluid (CSF), minimal depressive symptoms (MDSs), and CSF amyloid markers. The linear regression analyses were conducted on 796 cognitively unimpaired participants from the CABLE (Chinese Alzheimer’s Biomarker and LifestylE) study. Causal mediation analyses with 10,000 bootstrapped iterations were used to test the mediation effects. In addition, similar statistical analyses were performed in subgroups stratified by sex, age, and APOE ε4 carrier status. In total subjects, MDSs were associated with lower CSF sTREM2 levels (p p p = 0.0014). The influence of MDSs on CSF amyloid markers was partially mediated by CSF sTREM2 (proportion from 2.91 to 32.58%, p APOE ε4 (−) group. These results suggest that early depression is associated with amyloid pathology, which might be partly mediated by microglial activation, especially in the absence of APOE ε4.

Background: Existed evidence suggests that midlife obesity increases the risk of Alzheimer’s disease (AD), while there is an inverse association between AD and obesity in late life. However, the underlying metabolic changes of AD pathological proteins attributed to obesity in two life stages were not clear. Objective: To investigate the associations of obesity types and obesity indices with AD biomarkers in cerebrospinal fluid (CSF) in different life stages. Methods: We recruited 1,051 cognitively normal individuals (61.94±10.29 years, 59.66%male) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study with CSF detections for amyloid-β 42 (Aβ42), total-tau (T-tau), and phosphorylated tau (P-tau). We utilized body mass index, waist circumference, waist-to-height ratio, and metabolic risk factors to determine human obesity types. Multiple linear models and interaction analyses were run to assess the impacts of obesity on AD biomarkers. Results: The metabolically unhealthy obesity or healthy obesity might exert a reduced tau pathology burden (p

Background Data on the association between free-living daytime sunlight exposure and incident dementia are scarce. The objective is to evaluate whether the time spent in outdoor light is related to the dementia risk and to investigate whether the optimal duration varies with clinical parameters. Methods Data were from a prospective cohort of 362,094 UK Biobank participants. A questionnaire survey was conducted to investigate how many hours the participants spent outdoors on typical summer and winter days. A restricted cubic spline (RCS) was performed to explore the potential nonlinear relationship between sunlight exposure and the risk of dementia. We used multivariate Cox proportional hazard regression models to estimate the hazard ratios (HRs) for the associations between sunlight exposure and dementia outcomes, with the change points as a reference. Results After a median follow-up of 9.0 years, 4149 (1.15%) individuals were diagnosed with dementia. RCS showed a J-shaped relationship between time spent in outdoor light and the dementia risk, with the lowest risk at three change points (1.5 h/day on average, 2 h/day in summer, and 1 h/day in winter). Cox hazard regression models showed a marked increase in risk at low exposure (HR=1.287, 95%CI 1.094–1.515) but a relatively slow increase at higher exposure (HR=1.070, 95%CI 1.031–1.10). Results are more pronounced among participants over 60 years old, females, and those with exactly 7 h of sleep every night. Conclusions Sunlight exposure had a J-shaped association with dementia risk. Giving detailed guidance on sunlight exposure can effectively prevent dementia.

Background: Neurofilament light (NfL) can reflect the extent of neuron/axon damage, thus providing an opportunity to examine the severity and progression of the diseases with such damage. Objective: Whether serum NfL can be used as an indicator to monitor the cognitive progress of de novo Parkinson’s disease (PD) remains unclear. Methods: In this research, 144 healthy controls and 301 de novo PD patients from Parkinson’s Progression Markers Initiative (PPMI) were recruited. Linear mixed effects models were used to examine the associations of baseline/longitudinal serum NfL with cognitive decline. Cox regression was used to detect cognitive progression in PD participants. Results: We found PD patients had higher serum NfL than controls at baseline (p = 0.031), and NfL increase was faster in PD group (p

As brain insults, sleep disorders could enhance microglial activation and aggravate neuroinflammation. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) serves as a readout for TREM2-associated microglial responses. We aimed to study the association of sleep characteristics with CSF sTREM2 in cognitively normal (CN) older adults. Linear and non-linear regression analyses were conducted in 830 participants with measurements of sleep characteristics and CSF sTREM2, after adjusting for age, sex, education, the Chinese-Modified Mini-Mental State Examination (CM-MMSE) scores, and APOE4 status. These analyses were also performed in amyloid-negative (A −) and amyloid-positive (A +) individuals. Linear relationships between sleep characteristics and CSF sTREM2 were found. In all the participants, sleep efficiency score in Pittsburgh Sleep Quality Index (PSQI) (p = 0.037) showed a positive linear association with CSF sTREM2. In A + individuals, the grade of PSQI total score (p = 0.011) as well as subjective sleep quality score (p = 0.048) and sleep efficiency score (p

Relationship between serum calcium and Alzheimer's disease (AD) remains unclear. The aim of this study is to test whether serum calcium is associated with other AD-associated biomarkers and could predict clinical progression in nondemented elders. This was a longitudinal population-based study. The sample was derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, which included 1224 nondemented elders: 413 cognitively normal (CN) and 811 mild cognition impairment (MCI). Associations were investigated between serum calcium and longitudinal changes in Aβ/tau pathologic features, brain structure, cognitive function, and disease progression. Serum calcium concentrations increased with disease severity. Serum calcium predicted longitudinal cognitive decline and conversion from nondemented status to AD dementia (adjusted HR = 1.41, 95% CI 1.13-1.76). Furthermore, serum calcium levels were negatively correlated with CSF-Aβ

Background Ultrafast ultrasound imaging has been demonstrated to be an effective method to evaluate carotid stiffness through carotid pulse wave velocity (PWV) with high reproducibility, but lack of reference values has precluded its widespread use in clinical practice. This study aimed to establish reference values of PWV for ultrafast ultrasound imaging in a prospective, multicenter, population-based cohort study and to investigate the main determinants of carotid PWV. Methods A total of 1,544 healthy Han Chinese volunteers (581 [38%] men; age, 18–95 years) were enrolled from 32 collaborating laboratories in China. The participants were categorized by age, blood pressure (BP), and body mass index (BMI). The basic clinical parameters and the carotid PWV at the beginning of systole (BS) and end of systole (ES) were measured via ultrafast ultrasound imaging techniques. Results The PWV at both BS and ES was significantly higher in the left carotid artery than in the right carotid artery. The PWV at BS was significantly higher in men than in women; however, no significant difference was noted in the PWV at ES between men and women. Multiple linear regression analyses revealed that age, BP, and BMI were independently correlated with the PWV at both BS and ES. The PWV at BS and ES progressively increased with increase in age, BP, and BMI. Further, the age- and sex-specific reference values of carotid PWV for ultrafast ultrasound imaging were established. Conclusions Reference values of carotid PWV for ultrafast ultrasound imaging, stratified by sex and age, were determined for the first time. Age, BP, and BMI were the dominant determinants of carotid PWV for ultrafast ultrasound imaging, which should be considered in clinical practice for assessing arterial stiffness.

Objective: To determine the discrepancy of crown-root morphology of anterior teeth, using cone-beam computed tomography (CBCT), and to provide a guidance for proper torque expression. Methods: A total of eligible 200 CBCT were imported into Invivo v. 5.4 software, to obtain the middle labio-lingual sections of anterior teeth. AutoCAD 2007 software was applied to measure the crown-root angulation (Collum angle) and the angle formed by a tangent to the center of the labial surface and the long axis of the crown (labial surface angle). SPSS 18.0 was used for statistical comparisons of the two measurements, at the level of p< 0.05, and the Pearson correlation analysis was applied to investigate the association between the two measurements. Results: The value of Collum angle in maxillary central incisor was close to 0°. Significantly negative Collum angle in lateral incisors and maxillary canine, and positive value in mandibular canine were detected (p < 0.001). The labial surface angle in canine was significantly greater than the intra-arch incisors (p< 0.001), and no significant difference was detected between the central and lateral incisors (p > 0.05). Notably, there was also a significant positive correlation between the two measurements. Conclusions: The crown-root angulations were greatly different among anterior teeth. Accompanying the obvious crown-root angulations, the canines both in maxillary and mandibular arches presented considerable labial surface curvatures. Hence, equivalent deviation during bracket bonding might cause greater torque expression error and increase the risk of alveolar fenestration and dehiscence.

A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the coronavirus disease 2019 (COVID-19) global pandemic. Structural studies have led to the development of mutations that stabilize Betacoronavirus spike proteins in the prefusion state, improving their expression and increasing immunogenicity1. This principle has been applied to design mRNA-1273, an mRNA vaccine that encodes a SARS-CoV-2 spike protein that is stabilized in the prefusion conformation. Here we show that mRNA-1273 induces potent neutralizing antibody responses to both wild-type (D614) and D614G mutant2 SARS-CoV-2 as well as CD8+ T cell responses, and protects against SARS-CoV-2 infection in the lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a phase III trial to evaluate its efficacy.

Background To determine the discrepancy of crown-root morphology of central incisors among different types of skeletal malocclusion using cone-beam computed tomography (CBCT) and to provide guidance for proper torque expression of anterior teeth and prevention of alveolar fenestration and dehiscence. Methods In this retrospective study, a total of 108 CBCT images were obtained (ranging from 18.0 to 30.0 years, mean age 25.8 years). Patients were grouped according to routine sagittal and vertical skeletal malocclusion classification criteria. The patients in sagittal groups were all average vertical patterns, with Class I comprised 24 patients—14 females and 10 males; Class II comprised 20 patients—13 females and 7 males; and Class III comprised 22 subjects—13 females and 9 males. The patients in vertical groups were all skeletal Class I malocclusions, with low angle comprised 21 patients—12 females and 9 males; average angle comprised 24 patients; and high angle comprised 21 patients—11 females and 10 males. All the CBCT data were imported into Invivo 5.4 software to obtain a middle labio-lingual section of right central incisors. Auto CAD 2007 software was applied to measure the crown-root angulation (Collum angle), and the angle formed by a tangent to the central of the labial surface of the crown and the long axis of the crown (labial surface angle). One-way analysis of variance (ANOVA) and Scheffe’s test were used for statistical comparisons at the P

Background Metabolic healthy obesity (MHO) is a unique subgroup of overweight and obese individuals with normal metabolic characteristics. Its association with the risk of stroke remains unclear. We aimed to examine the risk of stroke in MHO individuals and the further associations between stroke and metabolic abnormalities under different bodyweight conditions. Methods We systematically searched PubMed, Embase and Cochrane Library from December 1946 to January 2019, and only included prospective cohort studies. Random effects models were used to evaluate the pooled risk ratios (RR) and 95% confidence intervals (95% CI) of incident stroke. Results A total of eight studies comprising 4,256,888 participants were included in the meta-analysis. MHO individuals had an increased risk of stroke compared with metabolically healthy normal weight (MH-NW) individuals (RR =1.17, 95% CI: 1.11-1.23). However, the stroke risk of metabolically healthy overweight individuals was the same (RR =1.02, 95% CI: 0.84-1.23). All groups with unhealthy metabolism had a similarly elevated risk: normal weight (RR =1.83, 95% CI: 1.57-2.14), overweight (RR =1.93, 95% CI: 1.44-2.58), and obesity (RR =2.00, 95% CI: 1.40-2.87). Conclusions The meta-analysis confirms a positive association between MHO phenotype and the risk of stroke. Individuals with metabolic abnormalities under different bodyweight conditions are at elevated risk.

Quasi-classical trajectory (QCT) calculations have been carried out to study the generalized polarization dependent differential cross sections (PDDCSs) for the reactions H + LiH + ( v = 0, j = 0) → H 2 + Li + and H + + LiH( v = 0, j = 0) → H 2 + + Li occurring on the two lowest-lying electronic states of the LiH 2 + system, using the ab initio potential energy surfaces (PESs) of Martinazzo et al. [3] . Four PDDCSs, i.e., (2π/σ)(dσ 00 /dω t ) , (2π/σ)(dσ 20 /dω t ) , (2π/σ)(dσ 22+ /dω t ) , (2π/σ)(dσ 21− /dω t ) have been discussed in detail.