SORL1 rs1699102 Moderates the Effect of Sex on Language Network.

BACKGROUND: Language ability differs between the sexes. However, it is unclear how this sex difference is moderated by genetic factors and how the brain interacts with genetics to support this specific language capacity. Previous studies have demonstrated that the sorting protein-related receptor (SORL1) polymorphism influences cognitive function and brain structure differently in males and females and is associated with Alzheimer's disease risk. OBJECTIVE: The aim of this study was to investigate the effects of sex and the SORL1 rs1699102 (CC versus T carriers) genotype on language. METHODS: 103 non-demented Chinese older adults from Beijing Aging Brain Rejuvenation Initiative (BABRI) database were included in this study. Participants completed language tests, T1-weighted structural magnetic resonance imaging (MRI) and resting-state functional MRI. Language test performance, gray matter volume, and network connections were compared between genotype and sex groups. RESULTS: The rs1699102 polymorphism moderated the effects of sex on language performance, with the female having reversed language advantages in T carriers. The T allele carriers had lower gray matter volume in the left precentral gyrus. The effect of sex on language network connections was moderated by rs1699102; male CC homozygotes and female T carriers had higher internetwork connections, which were negatively correlated with language performance. CONCLUSION: These results suggest that SORL1 moderates the effects of sex on language, with T being a risk allele, especially in females. Our findings underscore the importance of considering the influence of genetic factors when examining sex effects.

Association between exposure to phenols and parabens and cognitive function in older adults in the United States: A cross-sectional study.

BACKGROUND: People are commonly exposed to mixtures of parabens and phenols. Most studies investigating such exposure and cognitive performance tend to assess only single chemicals, and the tools used to assess cognitive function are not uniform. OBJECTIVE: This study aimed to examine the association between multiple parabens and phenols and cognitive function in older Americans. METHODS: The study included data of older Americans from two cycles of the NHANES survey. Participants were divided into normal cognitive performance and low cognitive performance groups based on the scores of four cognitive tests: the Immediate Recall test (IRT), the Delayed Recall test (DRT), the Animal Fluency test (AFT) and the Digit Symbol Substitution test (DSST). Generalized linear regression models (GLMs), restricted cubic spline (RCS), weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) were used to assess relationships between chemical exposure and cognitive performance. RESULTS: In this cross-sectional study, a total of 961 participants, 470 males and 491 females, were included. GLMs revealed positive association between high levels of bisphenol A (BPA) and low cognitive performance on DRT, especially in male (OR (95%CI): 2.25 (1.10-4.61)), and this association was consistent with WQS and BKMR. In female participants, the third quartile of BPA exposure showed a positive association with low cognition on IRT and global cognition. GLMs also showed that high levels of propylparaben were positively associated with cognitive performance on the IRT in male participants (OR (95%CI): 0.37 (0.18-0.76)). In BKMR, an overall positive correlation between the mixture and low cognition as measured with DRT was observed in male subjects when the mixture was at the 65th percentile or higher. CONCLUSION: Exposure to a mixture of parabens and phenols was positively associated with low cognitive performance on DRT in older male subjects, while BPA was the main driver of this outcome.

The treatment efficacy of pharmacotherapies for rapid eye movement sleep behavior disorder with polysomnography evaluation: A systematic review and meta-analysis.

Clonazepam and melatonin are commonly used as first-line medications for the treatment of rapid eye movement (REM) sleep behavior disorder (RBD), with other medications used in the clinic including pramipexole, ramelteon, and rotigotine. We performed a systematic review and meta-analysis of randomized and non-randomized controlled trials to assess the efficacy of these treatment options in RBD patients with polysomnography. We systematically retrieved results of randomized and non-randomized controlled trials using the PubMed, Embase, and Cochrane databases. Of the 454 studies identified, 13 were considered eligible for inclusion in the study. In comparison to baseline, clonazepam was found to significantly decrease the percentage of stage 2 sleep [4.00 (95% CI = 0.90 to 7.10)] in RBD patients. Melatonin was found to significantly improve patients' sleep efficiency [2.51(95% CI = 0.75 to 4.28)], significantly reduce the time spent in bed (TIB) [-11.71(95% CI = -23.05 to -0.37)], phasic activity[-25.79(95% CI = -42.13 to -9.46)] and tonic activity[-10.44(95% CI = -12.24 to -8.64)]. RWA[-5.87 (95% CI = -8.25 to -3.50)] significantly improve with the use of ramelteon. Pramipexole was found to significantly increase the total sleep time (TST) [27.17 (95% CI = 0.06 to 54.29)], and significantly reduce the periodic limb movements of sleep (PLMS) index [-11.42(95% CI = -21.38 to -1.47)]. We also found that pramipexole had different effects on idiopathic RBD (iRBD) and secondary RBD (sRBD). These results will help to guide the clinical use of medication in patients with RBD.

Prediction of Alzheimer's Disease Using Patterns of Methylation Levels in Key Immunologic-Related Genes.

BACKGROUND: DNA methylation is expected to become a kind of new diagnosis and treatment method of Alzheimer's disease (AD). Neuroinflammation- and immune-related pathways represent one of the major genetic risk factors for AD. OBJECTIVE: We aimed to investigate DNA methylation levels of 7 key immunologic-related genes in peripheral blood and appraise their applicability in the diagnosis of AD. METHODS: Methylation levels were obtained from 222 participants (101 AD, 72 MCI, 49 non-cognitively impaired controls). Logistic regression models for diagnosing AD were established after least absolute shrinkage and selection operator (LASSO) and best subset selection (BSS), evaluated by respondent working curve and decision curve analysis for sensitivity. RESULTS: Six differentially methylated positions (DMPs) in the MCI group and 64 in the AD group were found, respectively. Among them, there were 2 DMPs in the MCI group and 30 DMPs in the AD group independent of age, gender, and APOE4 carriers (p <  0.05). AD diagnostic prediction models differentiated AD from normal controls both in a training dataset (LASSO: 8 markers, including methylation levels at ABCA7 1040077, CNR1 88166293, CX3CR1 39322324, LRRK2 40618505, LRRK2 40618493, NGFR 49496745, TARDBP 11070956, TARDBP 11070840 area under the curve [AUC] = 0.81; BSS: 2 markers, including methylation levels at ABCA7 1040077 and CX3CR1 39322324, AUC = 0.80) and a testing dataset (AUC = 0.84, AUC = 0.82, respectively). CONCLUSION: Our work indicated that methylation levels of 7 key immunologic-related genes (ABCA7, CNR1, CX3CR1, CSF1R, LRRK2, NGFR, and TARDBP) in peripheral blood was altered in AD and the models including methylation of immunologic-related genes biomarkers improved prediction of AD.

Bone marrow hematopoiesis drives multiple sclerosis progression.

Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system (CNS). Bone marrow hematopoietic stem and progenitor cells (HSPCs) rapidly sense immune activation, yet their potential interplay with autoreactive T cells in MS is unknown. Here, we report that bone marrow HSPCs are skewed toward myeloid lineage concomitant with the clonal expansion of T cells in MS patients. Lineage tracing in experimental autoimmune encephalomyelitis, a mouse model of MS, reveals remarkable bone marrow myelopoiesis with an augmented output of neutrophils and Ly6Chigh monocytes that invade the CNS. We found that myelin-reactive T cells preferentially migrate into the bone marrow compartment in a CXCR4-dependent manner. This aberrant bone marrow myelopoiesis involves the CCL5-CCR5 axis and augments CNS inflammation and demyelination. Our study suggests that targeting the bone marrow niche presents an avenue to treat MS and other autoimmune disorders.

APOE ε4 allele accelerates age-related multi-cognitive decline and white matter damage in non-demented elderly.

Advanced age and apolipoprotein E (APOE) ε4 allele are both associated with increased risk of the Alzheimer's disease (AD). However, the extent of the joint contribution of APOE ε4 allele and age on the brain white matter integrity, cognition and their relationship are unclear. We assessed the age-related variation differences of major cognitions in 846 non-demented elderly, and brain major white matter tracts in an MRI sub-cohort of 111 individuals between ε4 carriers and noncarriers. We found that: (i) carriers showed a steeper age-related decline after age 50 in general mental status, attention, language, and executive function and performed worse than noncarriers at almost all ages; (ii) main effect of age on anterior fibers, but main effect of APOE ε4 on posterior fibers, and the interactive effect of them existed on anterior and posterior fibers; (iii) carriers showed an accelerated age-related integrity reduction of these fibers compared to noncarriers who had a slight decrease but not significant; and (iv) significant associations of the higher white matter integrity with better multi-cognitive performance in old ε4 carriers. Overall, combining APOE status with age may be useful in assessing possible mechanisms of disease development in AD.

Severity of white matter hyperintensities: Lesion patterns, cognition, and microstructural changes.

White matter hyperintensity (WMH) is a common finding in aging population and considered to be a contributor to cognitive decline. Our study aimed to characterize the spatial patterns of WMH in different severities and explore its impact on cognition and brain microstructure in non-demented elderly. Lesions were both qualitatively (Fazekas scale) and quantitatively assessed among 321 community-dwelled individuals with MRI scanning. Voxel- and atlas-based analyses of the whole-brain white matter microstructure were performed. The WMH of the same severities was found to occur uniformly with a specific pattern of lesions. The severity of WMH had a significant negative association with the performance of working and episodic memory, beginning to appear in Fazekas 3 and 4. The white matter tracts presented significant impairments in Fazekas 3, which showed brain-wide changes above Fazekas 4. Lower FA in the superior cerebellar peduncle and left posterior thalamic radiation was mainly associated with episodic memory, and the middle cerebellar peduncle was significantly associated with working memory. These results support that memory is the primary domain to be affected by WMH, and the effect may potentially be influenced by tract-specific WM abnormalities. Fazekas scale 3 might be the critical stage predicting a future decline in cognition.

Lead sorption performance on active silica derived from fly ash.

The object of this study was to estimate the sorption property of active silica derived from fly ash after separation of silica and aluminum. The specific surface area of active silica enlarged to 115 m(2)/g was compared with the original fly ash (4 m(2)/g). Field emission scanning electron microscopy displayed the active silica, which looked like a honeycomb or curly layer with many lamellae that formed many mesopores. The uptake kinetics indicated that the residual concentration of Pb(2+) in the aqueous solution decreased rapidly from the initial 1.25 mg/L to less than 10 µg/L within 45 min. The removal efficiency of Pb(2+) on active silica was pH dependent. The increase in pH value promoted Pb(2+) removal because the negative surface provided more electrostatic attraction sites. A stepwise non-linear isotherm was obtained because the lamellae of active silica provided a heterogeneous surface with various kinds of active sites. The maximum sorption amount of Pb on active silica was more than 90 mg/g, which was better than some pristine-activated carbon.