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1.
Front Neurosci ; 16: 876568, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35557608

RESUMO

Background: Mild cognitive impairment (MCI) is known as the prodromal stage of the Alzheimer's disease (AD) spectrum. The recent studies have advised that functional alterations in the dorsal attention network (DAN) could be used as a sensitive marker to forecast the progression from MCI to AD. Therefore, our aim was to investigate specific functional alterations in the DAN in MCI. Methods: We systematically searched PubMed, EMBASE, and Web of Science and chose relevant articles based on the three functional indicators, the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) in the DAN in MCI. Based on the activation likelihood estimation, we accomplished the aggregation of specific coordinates and the analysis of functional alterations. Results: A total of 38 studies were involved in our meta-analysis. By summing up included articles, we acquired specific brain region alterations in the DAN mainly in the superior temporal gyrus (STG), middle temporal gyrus (MTG), superior frontal gyrus (SFG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG), precentral gyrus (preCG), inferior parietal lobule (IPL), superior parietal lobule (SPL). At the same time, the key area that shows anti-interaction with default mode network included the IPL in the DAN. The one showing interactions with executive control network was mainly in the MFG. Finally, the frontoparietal network showed a close connection with DAN especially in the IPL and IFG. Conclusion: This study demonstrated abnormal functional markers in the DAN and its interactions with other networks in MCI group, respectively. It provided the foundation for future targeted interventions in preventing the progression of AD. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021287958].

2.
Front Immunol ; 13: 705379, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386719

RESUMO

Objectives: Recent studies suggest that asthma may have a protective effect on COVID-19.We aimed to investigate the causality between asthma and two COVID-19 outcomes and explore the mechanisms underlining this connection. Methods: Summary results of GWAS were used for the analyses, including asthma (88,486 cases and 447,859 controls), COVID-19 hospitalization (6,406 hospitalized COVID-19 cases and 902,088 controls), and COVID-19 infection (14,134 COVID-19 cases and 1,284,876 controls). The Mendelian randomization (MR) analysis was performed to evaluate the causal effects of asthma on the two COVID-19 outcomes. A cross-trait meta-analysis was conducted to analyze genetic variants within two loci shared by COVID-19 hospitalization and asthma. Results: Asthma is associated with decreased risk both for COVID-19 hospitalization (odds ratio (OR): 0.70, 95% confidence interval (CI): 0.70-0.99) and for COVID-19 infection (OR: 0.83, 95%CI: 0.51-0.95). Asthma and COVID-19 share two genome-wide significant genes, including ABO at the 9q34.2 region and OAS2 at the 12q24.13 region. The meta-analysis revealed that ABO and ATXN2 contain variants with pleiotropic effects on both COVID-19 and asthma. Conclusion: In conclusion, our results suggest that genetic liability to asthma is associated with decreased susceptibility to SARS-CoV-2 and to severe COVID-19 disease, which may be due to the protective effects of ongoing inflammation and, possibly, related compensatory responses against COVID-19 in its early stage.


Assuntos
Asma , COVID-19 , Asma/epidemiologia , Asma/genética , COVID-19/genética , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , SARS-CoV-2
3.
Neuroscience ; 490: 79-88, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35278629

RESUMO

Contralateral regions play critical role in functional compensation in glioma patients. Voxel-mirrored homotopic connectivity (VMHC) characterizes the intrinsic functional connectivity (FC) of the brain, considered to have a regional functional basis. We aimed to investigate the alterations of brain regional function and VMHC in patients with frontal glioma, and further investigated the correlation between these alterations and cognition. We enrolled patients with frontal glioma and matched healthy controls (HC). We chose degree centrality (DC), regional homogeneity (ReHo), and VMHC to investigate the alterations of regional function and intrinsic FC in patients. Furthermore, partial correlation analyses were conducted to explore the relationship between imaging functional indicators and cognitions. Compared with HC, patients showed decreased static VMHC within right and left middle frontal gyrus (MFG.R, MFG.L), left superior frontal gyrus (SFG.L), right precuneus (PCUN.R), and left precuneus (PCUN.L), decreased static DC within left cingulate gyrus (CG.L), right superior frontal gyrus (SFG.R), and right postcentral gyrus (POCG.R), decreased static ReHo within CG.L, decreased dynamic ReHo within right inferior parietal lobule (IPL.R), but increased dynamic VMHC (dVMHC) within PCUN.R and PCUN.L. Furthermore, values of decreased VMHC within MFG.R, decreased DC within CG.L, decreased ReHo within CG.L, and increased dVMHC within PCUN.R were significantly positively correlated with cognitive functions. We preliminarily confirmed glioma causes regional dysfunction and disturbs long-distance FC, and long-distance FC showed strong instability in patients with frontal glioma. Meanwhile, the correlation analyses indicated directions for cognitive protection in patients with frontal glioma.


Assuntos
Mapeamento Encefálico , Glioma , Encéfalo , Mapeamento Encefálico/métodos , Glioma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Lobo Parietal
4.
Artigo em Inglês | MEDLINE | ID: mdl-35235646

RESUMO

BACKGROUND: The association of cognitive function with symptoms of psychological distress during the coronavirus 2019 (COVID-19) pandemic or adherence to COVID-19 protective health behaviors is not well understood. METHODS: We examined 2,890 older women from the Women's Health Initiative cohort. Pre-pandemic (i.e., within 12 months prior to pandemic onset) and peri-pandemic global cognitive function scores were assessed with the modified Telephone Interview for Cognitive Status (TICS-m). Anxiety, stress, and depressive symptom severity during the pandemic were assessed using validated questionnaires. We examined adherence to protective behaviors that included safe hygiene, social distancing, mask wearing, and staying home. Multivariable models were adjusted for age, race, ethnicity, education, region of residence, alcohol intake, and comorbidities. RESULTS: Every five-point lower pre-pandemic TICS-m score was associated with 0.33-point mean higher (95% CI, 0.20,0.45) perceived stress, and 0.20-point mean higher (95% CI, 0.07,0.32) depressive symptom severity during the pandemic. Higher depressive symptom severity, but not anxiety or perceived stress, was associated with a 0.69-point (95% CI, -1.13, -0.25) mean decline in TICS-m from the pre- to peri-pandemic period. Every five-point lower peri-pandemic TICS-m score was associated with 12% lower odds (OR, 0.88; 95% CI, 0.80,0.97) of practicing safe hygiene. CONCLUSIONS: Among older women, we observed that: 1) lower pre-pandemic global cognitive function was associated with higher stress and depressive symptom severity during the pandemic; 2) higher depressive symptom severity during the pandemic was associated with cognitive decline; and 3) lower global cognitive function during the pandemic was associated with lower odds of practicing safe hygiene.

7.
Front Genet ; 13: 823075, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281822

RESUMO

The tumor microenvironment (TME) plays an important regulatory role in the progression of non-small cell lung cancer (NSCLC). Mesenchymal stem cells (MSCs) in the TME might contribute to the occurrence and development of cancer. This study evaluates the role of differentially expressed genes (DEGs) of MSCs and the development of NSCLC and develops a prognostic risk model to assess the therapeutic responses. The DEGs in MSCs from lung tissues and from normal tissues were analyzed using GEO2R. The functions and mechanisms of the DEGs were analyzed using the Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Additionally, the Cancer Genome Atlas (TCGA) database was used to determine the expression levels of the DEGs of MSCs in the NSCLC tissues. The prognostic factors of NSCLC related to MSCs were screened by survival analysis, meta-analysis, Cox regression analysis, and a prognostic risk model and nomogram was developed. The signaling mechanisms and immune roles that risk model participate in NSCLC development were determined via Gene Set Enrichment Analysis and CIBERSORT analysis. Compared to the normal tissues, 161 DEGs were identified in the MSCs of the lung tissues. These DEGs were associated with mechanisms, such as DNA replication, nuclear division, and homologous recombination. The overexpression of DDIT4, IL6, ITGA11, MME, MSX2, POSTN, and TRPA1 were associated with dismal prognosis of NSCLC patients. A high-risk score based on the prognostic risk model indicated the dismal prognosis of NSCLC patients. The nomogram showed that the age, clinical stage, and risk score affected the prognosis of NSCLC patients. Further, the high-risk model was associated with signaling mechanisms, such as the ECM-receptor interaction pathways, cytokine-cytokine receptor interaction, and MAPK pathways, involved in the progression of NSCLC and was also related to the components of the immune system, such as macrophages M0, T follicular helper cells, regulatory T cells. Therefore, the risk model and nomogram that was constructed on the basis of MSC-related factors such as POSTN, TRPA1, and DDIT4 could facilitate the discovery of target molecules that participate in the progression of NSCLC, which might also serve as new candidate markers for evaluating the prognosis of NSCLC patients.

8.
Alzheimers Dement ; 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35103387

RESUMO

INTRODUCTION: Particulate air pollutants may induce neurotoxicity by increasing homocysteine levels, which can be lowered by high B vitamin intakes. Therefore, we examined whether intakes of three B vitamins (folate, B12 , and B6 ) modified the association between PM2.5 exposure and incidence of all-cause dementia. METHODS: This study included 7183 women aged 65 to 80 years at baseline. B vitamin intakes from diet and supplements were estimated by food frequency questionnaires at baseline. The 3-year average PM2.5 exposure was estimated using a spatiotemporal model. RESULTS: During a mean follow-up of 9 years, 342 participants developed all-cause dementia. We found that residing in locations with PM2.5 exposure above the regulatory standard (12 µg/m3 ) was associated with a higher risk of dementia only among participants with lower intakes of these B vitamins. DISCUSSION: This is the first study suggesting that the putative neurotoxicity of PM2.5 exposure may be attenuated by high B vitamin intakes.

9.
Lancet Healthy Longev ; 3(1): e42-e53, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35112096

RESUMO

BACKGROUND: Whether blood pressure (BP), and at what level of controlled BP, reduces risk of cognitive impairment remains uncertain. We investigated the association of BP and hypertension treatment status with mild cognitive impairment and dementia in older women. METHODS: We prospectively analysed a sample of 7207 community-dwelling women aged 65-79 years participating in the Women's Health Initiative Memory Study (WHIMS). Participants were recruited between May 28, 1996, and Dec 13, 1999, at 39 US clinical centres, and they were followed up until Dec 31, 2019. Cognitive function was assessed annually. Mild cognitive impairment and probable dementia were defined through a centralised adjudication process. BP was measured by trained and certified staff at baseline. Pulse pressure (PP) was calculated as systolic BP (SBP) minus diastolic BP. Hypertension was defined using the American Heart Association 2017 Guideline for High BP in Adults. Outcomes were (1) mild cognitive impairment, (2) probable dementia, and (3) cognitive loss (the combined endpoint of either mild cognitive impairment or probable dementia, or both). We estimated hazard ratios (HRs) to assess the association between hypertension, SBP, and PP with the risk of study outcomes using Cox proportional hazards regression models, with adjustment for key covariates. FINDINGS: During a median follow-up of 9 years (IQR 6-15), 1132 (15·7%) participants were classified as mild cognitive impairment, 739 (10·3%) as probable dementia, and 1533 (21·3%) as cognitive loss. The incidence rates per 1000 person-years were 15·3 cases (95% CI 14·4-16·2) for mild cognitive impairment, 9·7 cases (9·0-10·4) for probable dementia, and 20·3 (19·3-21·3) for cognitive loss. Elevated SBP and PP were significantly associated with increased risk of mild cognitive impairment and cognitive loss (test for trends across SBP and PP strata, p<0·01). Individuals with hypertension, but with controlled SBP of less than 120 mm Hg did not have a significantly increased risk of mild cognitive impairment (HR 1·33, 95% CI 0·98-1·82, p=0·071), and of cognitive loss (1·09, 0·82-1·44, p=0·57) compared with normotension. Individuals on anti-hypertensive treatment with PP of less than 50 mm Hg did not have a significantly higher risk of mild cognitive impairment (1·26, 0·98-1·62, p=0·07) and of cognitive loss (1·17, 0·94-1·46, p=0·16). There were no significant associations between hypertension, SBP, or PP and probable dementia. INTERPRETATION: Results of our study show significant associations of hypertension and elevated SBP and PP levels with risk of mild cognitive impairment and the combined endpoint of either mild cognitive impairment or probable dementia, suggesting that intensive control of hypertension, SBP, and PP can preserve cognitive health in older women. FUNDING: National Heart, Lung, and Blood Institute, National Institutes of Health, and US Department of Health and Human Services.

10.
Sci Total Environ ; 823: 153642, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35122843

RESUMO

Exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) have been associated with the emergence of depressive symptoms in older adulthood, although most studies used cross-sectional outcome measures. Elucidating the brain structures mediating the adverse effects can strengthen the causal role between air pollution and increasing depressive symptoms. We evaluated whether smaller volumes of brain structures implicated in late-life depression mediate associations between ambient air pollution exposure and changes in depressive symptoms. This prospective study included 764 community-dwelling older women (aged 81.6 ± 3.6 in 2008-2010) from the Women's Health Initiative Memory Study (WHIMS) Magnetic Resonance Imaging study (WHIMS-MRI; 2005-06) and WHIMS-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO; 2008-16). Three-year average annual mean concentrations (scaled by interquartile range [IQR]) of ambient PM2.5 (in µg/m3; IQR = 3.14 µg/m3) and NO2 (in ppb; IQR = 7.80 ppb) before WHIMS-MRI were estimated at participants' addresses via spatiotemporal models. Mediators included structural brain MRI-derived grey matter volumes of the prefrontal cortex and structures of the limbic-cortical-striatal-pallidal-thalamic circuit. Depressive symptoms were assessed annually by the 15-item Geriatric Depression Scale. Structural equation models were constructed to estimate associations between exposure, structural brain volumes, and depressive symptoms. Increased exposures (by each IQR) were associated with greater annual increases in depressive symptoms (ßPM2.5 = 0.022; 95% Confidence Interval (CI) = 0.003, 0.042; ßNO2 = 0.019; 95% CI = 0.001, 0.037). The smaller volume of prefrontal cortex associated with exposures partially mediated the associations of increased depressive symptoms with NO2 (8%) and PM2.5 (13%), and smaller insula volume associated with NO2 contributed modestly (13%) to the subsequent increase in depressive symptoms. We demonstrate the first evidence that the smaller volumes of the prefrontal cortex and insula may mediate the subsequent increases in depressive symptoms associated with late-life exposures to NO2 and PM2.5.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Idoso , Idoso de 80 Anos ou mais , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Estudos Transversais , Depressão/epidemiologia , Exposição Ambiental/análise , Feminino , Humanos , Dióxido de Nitrogênio/análise , Material Particulado/análise , Córtex Pré-Frontal/diagnóstico por imagem , Estudos Prospectivos
11.
PLoS Med ; 19(2): e1003893, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35113870

RESUMO

BACKGROUND: Late-life exposure to ambient air pollution is a modifiable risk factor for dementia, but epidemiological studies have shown inconsistent evidence for cognitive decline. Air quality (AQ) improvement has been associated with improved cardiopulmonary health and decreased mortality, but to the best of our knowledge, no studies have examined the association with cognitive function. We examined whether AQ improvement was associated with slower rate of cognitive decline in older women aged 74 to 92 years. METHODS AND FINDINGS: We studied a cohort of 2,232 women residing in the 48 contiguous US states that were recruited from more than 40 study sites located in 24 states and Washington, DC from the Women's Health Initiative (WHI) Memory Study (WHIMS)-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO) study. They were predominantly non-Hispanic White women and were dementia free at baseline in 2008 to 2012. Measures of annual (2008 to 2018) cognitive function included the modified Telephone Interview for Cognitive Status (TICSm) and the telephone-based California Verbal Learning Test (CVLT). We used regionalized universal kriging models to estimate annual concentrations (1996 to 2012) of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) at residential locations. Estimates were aggregated to the 3-year average immediately preceding (recent exposure) and 10 years prior to (remote exposure) WHIMS-ECHO enrollment. Individual-level improved AQ was calculated as the reduction from remote to recent exposures. Linear mixed effect models were used to examine the associations between improved AQ and the rates of cognitive declines in TICSm and CVLT trajectories, adjusting for sociodemographic (age; geographic region; race/ethnicity; education; income; and employment), lifestyle (physical activity; smoking; and alcohol), and clinical characteristics (prior hormone use; hormone therapy assignment; depression; cardiovascular disease (CVD); hypercholesterolemia; hypertension; diabetes; and body mass index [BMI]). For both PM2.5 and NO2, AQ improved significantly over the 10 years before WHIMS-ECHO enrollment. During a median of 6.2 (interquartile range [IQR] = 5.0) years of follow-up, declines in both general cognitive status (ß = -0.42/year, 95% CI: -0.44, -0.40) and episodic memory (ß = -0.59/year, 95% CI: -0.64, -0.54) were observed. Greater AQ improvement was associated with slower decline in TICSm (ßPM2.5improvement = 0.026 per year for improved PM2.5 by each IQR = 1.79 µg/m3 reduction, 95% CI: 0.001, 0.05; ßNO2improvement = 0.034 per year for improved NO2 by each IQR = 3.92 parts per billion [ppb] reduction, 95% CI: 0.01, 0.06) and CVLT (ßPM2.5 improvement = 0.070 per year for improved PM2.5 by each IQR = 1.79 µg/m3 reduction, 95% CI: 0.02, 0.12; ßNO2improvement = 0.060 per year for improved NO2 by each IQR = 3.97 ppb reduction, 95% CI: 0.005, 0.12) after adjusting for covariates. The respective associations with TICSm and CVLT were equivalent to the slower decline rate found with 0.9 to 1.2 and1.4 to 1.6 years of younger age and did not significantly differ by age, region, education, Apolipoprotein E (ApoE) e4 genotypes, or cardiovascular risk factors. The main limitations of this study include measurement error in exposure estimates, potential unmeasured confounding, and limited generalizability. CONCLUSIONS: In this study, we found that greater improvement in long-term AQ in late life was associated with slower cognitive declines in older women. This novel observation strengthens the epidemiologic evidence of an association between air pollution and cognitive aging.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Disfunção Cognitiva/epidemiologia , Exposição Ambiental/efeitos adversos , Vida Independente/tendências , Entrevistas como Assunto/métodos , Idoso , Idoso de 80 Anos ou mais , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/psicologia , Estudos de Coortes , Exposição Ambiental/prevenção & controle , Feminino , Seguimentos , Humanos , Vida Independente/psicologia , Estudos Longitudinais , Material Particulado/efeitos adversos , Material Particulado/análise , Melhoria de Qualidade , Estados Unidos/epidemiologia , Aprendizagem Verbal/fisiologia
12.
Menopause ; 29(3): 255-263, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013056

RESUMO

OBJECTIVE: To examine the association of sleep disturbance with Parkinson disease (PD) during 10+ years of follow-up among postmenopausal women, 50 to 79 years of age at baseline. METHODS: Longitudinal data on 130,502 study-eligible women (mean ± standard deviation baseline age = 63.16 ±â€Š7.20 y) from the Women's Health Initiative Clinical Trials and Women's Health Initiative Observational Study were analyzed. The cohort was followed for 15.88 ±â€Š6.50 years, yielding 2,829 (2.17%) PD cases. Sleep disturbance (habitual sleep duration, insomnia symptoms, obstructive sleep apnea risk factors, sleep aids among those with WHI Insomnia Rating Scale scores (WHIIRS) > 9) was measured at baseline and one follow-up time by September 12, 2005. Cox proportional hazards models evaluated relationships controlling for sociodemographic, lifestyle, and health characteristics. RESULTS: PD was significantly associated with long sleep duration (≥9 h) versus a benchmark of 7 to 8 hours (hazard ratio [HR] = 1.296, 95% confidence interval [CI]: 1.153-1.456), WHIIRS (>9 vs ≤9) (HR = 1.114, 95% CI:1.023-1.214), and use of sleep aids (yes vs no) (HR = 1.332, 95% CI:1.153-1.539) among those with WHIIRS > 9. Compared with 7 to 8 hours, short (<7 h) sleep duration was unrelated to PD. Finally, the presence of obstructive sleep apnea risk factors was not associated with PD. CONCLUSIONS: Among postmenopausal women, sleep disturbance was associated with approximately 10% to 30% increased PD risk after ∼16 years follow-up. Prospective cohort studies with objective exposures and adjudicated outcomes that include men and women of diverse backgrounds are required to confirm and extend these findings.


Assuntos
Doença de Parkinson , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Pós-Menopausa , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Sono , Saúde da Mulher
13.
Proc Natl Acad Sci U S A ; 119(2)2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-34983871

RESUMO

Late-life ambient air pollution is a risk factor for brain aging, but it remains unknown if improved air quality (AQ) lowers dementia risk. We studied a geographically diverse cohort of older women dementia free at baseline in 2008 to 2012 (n = 2,239, aged 74 to 92). Incident dementia was centrally adjudicated annually. Yearly mean concentrations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were estimated using regionalized national universal kriging models and averaged over the 3-y period before baseline (recent exposure) and 10 y earlier (remote exposure). Reduction from remote to recent exposures was used as the indicator of improved AQ. Cox proportional hazard ratios (HRs) for dementia risk associated with AQ measures were estimated, adjusting for sociodemographic, lifestyle, and clinical characteristics. We identified 398 dementia cases during follow up (median = 6.1 y). PM2.5 and NO2 reduced significantly over the 10 y before baseline. Larger AQ improvement was associated with reduced dementia risks (HRPM2.5 0.80 per 1.78 µg/m3, 95% CI 0.71-0.91; HRNO2 0.80 per 3.91 parts per billion, 95% CI 0.71-0.90), equivalent to the lower risk observed in women 2.4 y younger at baseline. Higher PM2.5 at baseline was associated with higher dementia risk (HRPM2.5 1.16 per 2.90 µg/m3, 95% CI 0.98-1.38), but the lower dementia risk associated with improved AQ remained after further adjusting for recent exposure. The observed associations did not substantially differ by age, education, geographic region, Apolipoprotein E e4 genotypes, or cardiovascular risk factors. Long-term AQ improvement in late life was associated with lower dementia risk in older women.


Assuntos
Poluição do Ar/análise , Demência/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Poluentes Atmosféricos/análise , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Incidência , Dióxido de Nitrogênio , Material Particulado/análise , Modelos de Riscos Proporcionais , Fatores de Risco
14.
Environ Health Perspect ; 130(1): 17008, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35040691

RESUMO

BACKGROUND: Studies have shown that air pollution exposures during pregnancy are associated with an increased risk of autism spectrum disorder (ASD) in children, and the risk appears to be greater for boys. However, studies assessing gestational windows of susceptibility have been mostly limited by trimesters. OBJECTIVE: We identified sensitive windows of exposure to regional air pollution and risk of ASD and examined sex differences in a large birth cohort. METHODS: This population-based retrospective cohort study included 294,937 mother-child pairs with singleton deliveries in Kaiser Permanente Southern California (KPSC) hospitals from 2001 to 2014. Children were followed using electronic medical records until clinical ASD diagnosis, non-KPSC membership, death, or 31 December 2019, whichever came first. Weekly mean fine particulate matter [PM with an aerodynamic diameter of ≤2.5µm (PM2.5)], nitrogen dioxide (NO2), and ozone (O3) pregnancy exposures were estimated using spatiotemporal prediction models. Cox proportional hazard models with distributed lags were used to estimate weekly pollutant exposure associations with ASD risk for the entire cohort, and separately for boys and for girls. Models were adjusted for child sex (for full cohort), maternal race/ethnicity, maternal age at delivery, parity, maternal education, maternal comorbidities, medical center, census tract median household income, birth year, and season. RESULTS: There were 5,694 ASD diagnoses (4,636 boys, 1,058 girls). Sensitive PM2.5 exposure windows associated with ASD were found early in pregnancy, statistically significant throughout the first two trimesters [1-27 wk of gestation, cumulative hazard ratio (HR)=1.14 [95% confidence interval (CI): 1.06, 1.23] per interquartile range (IQR) (7.4-µg/m3) increase]. O3 exposure during 34-37 wk of gestation was associated with increased risk [HR=1.06 (95% CI: 1.01, 1.11) per IQR (17.4 ppb) increase] but with reduced risk during 20-28 wk of gestation [HR=0.93 (95% CI: 0.89, 0.98)]. No associations were observed with NO2. Sex-stratified early gestational PM2.5 associations were stronger among boys [boys HR=1.16 (95% CI: 1.08, 1.26); girls HR=1.06 (95% CI: 0.89, 1.26)]. O3 associations in later gestation were observed only in boys [boys HR=1.10 (95% CI: 1.04, 1.16); girls HR=0.94 (95% CI: 0.84, 1.05)]. CONCLUSIONS: Exposures to PM2.5 in the first two gestational trimesters were associated with increased ASD risk in children, with stronger associations observed for boys. The role of O3 exposure on ASD risk merits further investigation. https://doi.org/10.1289/EHP9509.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Transtorno do Espectro Autista , Efeitos Tardios da Exposição Pré-Natal , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Transtorno do Espectro Autista/induzido quimicamente , Feminino , Humanos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos Retrospectivos , Caracteres Sexuais
15.
Environ Int ; 158: 106888, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34563749

RESUMO

BACKGROUND: Epidemiological findings are inconsistent regarding the associations between air pollution exposure during pregnancy and gestational diabetes mellitus (GDM). Several limitations exist in previous studies, including potential outcome and exposure misclassification, unassessed confounding, and lack of simultaneous consideration of air pollution mixtures and particulate matter (PM) constituents. OBJECTIVES: To assess the association between GDM and maternal residential exposure to air pollution, and the joint effect of the mixture of air pollutants and PM constituents. METHODS: Detailed clinical data were obtained for 395,927 pregnancies in southern California (2008-2018) from Kaiser Permanente Southern California (KPSC) electronic health records. GDM diagnosis was based on KPSC laboratory tests. Monthly average concentrations of fine particulate matter < 2.5 µm (PM2.5), <10 µm (PM10), nitrogen dioxide (NO2), and ozone (O3) were estimated using kriging interpolation of Environmental Protection Agency's routine monitoring station data, while PM2.5 constituents (i.e., sulfate, nitrate, ammonium, organic matter and black carbon) were estimated using a fine-resolution geoscience-derived model. A multilevel logistic regression was used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of air pollution and PM component mixtures. Main analyses adjusted for maternal age, race/ethnicity, education, median family household income, pre-pregnancy BMI, smoking during pregnancy, insurance type, season of conception and year of delivery. RESULTS: The incidence of GDM was 10.9% in the study population. In single-pollutant models, we observed an increased odds for GDM associated with exposures to PM2.5, PM10, NO2 and PM2.5 constituents. The association was strongest for NO2 [adjusted odds ratio (OR) per interquartile range: 1.176, 95% confidence interval (CI): 1.147-1.205)]. In multi-pollutant models, increased ORs for GDM in association with one quartile increase in air pollution mixtures were found for both kriging-based regional air pollutants (NO2, PM2.5, and PM10, OR = 1.095, 95% CI: 1.082-1.108) and PM2.5 constituents (i.e., sulfate, nitrate, ammonium, organic matter and black carbon, OR = 1.258, 95% CI: 1.206-1.314); NO2 (78%) and black carbon (48%) contributed the most to the overall mixture effects among all krigged air pollutants and all PM2.5 constituents, respectively. The risk of GDM associated with air pollution exposure were significantly higher among Hispanic mothers, and overweight/obese mothers. CONCLUSION: This study found that exposure to a mixture of ambient PM2.5, PM10, NO2, and PM2.5 chemical constituents was associated with an increased risk of GDM. NO2 and black carbon PM2.5 contributed most to GDM risk.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Diabetes Gestacional , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , California/epidemiologia , Diabetes Gestacional/induzido quimicamente , Diabetes Gestacional/epidemiologia , Registros Eletrônicos de Saúde , Exposição Ambiental , Feminino , Humanos , Dióxido de Nitrogênio/análise , Material Particulado/análise , Gravidez
16.
CNS Neurosci Ther ; 28(2): 259-268, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34821045

RESUMO

OBJECTIVE: The International Parkinson and Movement Disorder Society (MDS) has published research criteria for prodromal Parkinson's disease (pPD), which includes cognitive impairment as a prodromal marker. However, the clinical features of mild cognitive impairment (MCI) in pPD remain unknown. Our study aimed to evaluate the frequency and clinical features of mild cognitive impairment of pPD in the elderly in China. METHODS: The cross-sectional community-based study recruited 2688 participants aged ≥50 years. Subjects were diagnosed with pPD according to the MDS criteria. Overall, 39 pPD and 22 healthy controls underwent comprehensive clinical and neuropsychological assessment. MCI was also diagnosed by the MDS criteria. Next, we investigated the relationship between clinical factors and cognition. RESULTS: Among the 2,663 dementia-free and Parkinson disease (PD)-free participants, 55 met the criteria for pPD (2.1%) and 23 pPD met the criteria for MCI. Memory, attention/working memory, and executive function were the most frequent impaired domains, and amnestic MCI multidomain phenotype was the most frequent MCI subtype (69.57%) in pPD. Additionally, correlation analysis revealed that the global cognitive performance was negatively related to UPDRS-III score (r = -0.456, p = 0.004). CONCLUSION: MCI, specifically impairment in memory, attention/working memory, and executive domain, is present at the prodromal stage of PD. In addition, cognitive performance is correlated with motor symptoms in pPD. Our results reflect that cognitive profile, combined with motor symptoms, can help clinicians to identify individuals with pPD early, as those would be the optimal candidates for neuroprotective therapy.


Assuntos
Disfunção Cognitiva/fisiopatologia , Doença de Parkinson/fisiopatologia , Sintomas Prodrômicos , Idoso , China/epidemiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia
17.
J Stroke Cerebrovasc Dis ; 31(2): 106222, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34839235

RESUMO

OBJECTIVE: A self-rating post stroke depression scale (PSDS) showed a good reliability and validity to assess severity of depressive symptoms among stroke patients. This study aimed to retest the psychometric properties of PSDS in different types of post-stroke depression (PSD). MATERIALS AND METHODS: A total of 170 stroke patients were recruited in the study. 82 and 25 patients were respectively diagnosed as PSD symptoms disorder (PSDSD) and PSD disorder (PSDD) patients according to their respective diagnostic criteria. The PSDS and the 9-item Patient Health Questionnaire (PHQ-9) were used to assess the severity of depression. Cronbach α, Spearman rank coefficient and independent sample t-test were conducted to examine reliability, internal consistency and discriminate validity. Then the receiver operating characteristic curve and Youden index were used to performance evaluation and cut-off value respectively in different subtypes of PSD patients. RESULTS: The Cronbach α of PSDS was 0.857, indicting a good reliability. The Spearman correlation coefficient between PSDS and PHQ-9 was 0.942 (P<0.001). The discriminate validity displayed significant difference between PSDSD as well as PSDD and no depression patients (all P<0.001). 5/24 and 10/24 were the cut-off value for PSDSD and PSDD patients. CONCLUSIONS: PSDS is a useful screen tool with an acceptable psychometric properties for estimation of different subtypes of PSD patients.


Assuntos
Depressão , Questionário de Saúde do Paciente , Acidente Vascular Cerebral , Depressão/diagnóstico , Depressão/etiologia , Humanos , Psicometria , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/complicações
18.
CNS Neurosci Ther ; 28(2): 183-205, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34873859

RESUMO

AIMS: The aim of this study was to identify brain regions with local, structural, and functional abnormalities in dementia with Lewy bodies (DLB) and uncover the differences between DLB and Alzheimer's disease (AD). The neural networks involved in the identified abnormal brain regions were further described. METHODS: PubMed, Web of Science, OVID, Science Direct, and Cochrane Library databases were used to identify neuroimaging studies that included DLB versus healthy controls (HCs) or DLB versus AD. The coordinate-based meta-analysis and functional meta-analytic connectivity modeling were performed using the activation likelihood estimation algorithm. RESULTS: Eleven structural studies and fourteen functional studies were included in this quantitative meta-analysis. DLB patients showed a dysfunction in the bilateral inferior parietal lobule and right lingual gyrus compared with HC patients. DLB patients showed a relative preservation of the medial temporal lobe and a tendency of lower metabolism in the right lingual gyrus compared with AD. The frontal-parietal, salience, and visual networks were all abnormally co-activated in DLB, but the default mode network remained normally co-activated compared with AD. CONCLUSIONS: The convergence of local brain regions and co-activation neural networks might be potential specific imaging markers in the diagnosis of DLB. This might provide a pathway for the neural regulation in DLB patients, and it might contribute to the development of specific interventions for DLB and AD.


Assuntos
Doença de Alzheimer , Doença por Corpos de Lewy , Neuroimagem , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Humanos , Doença por Corpos de Lewy/diagnóstico por imagem , Doença por Corpos de Lewy/patologia , Doença por Corpos de Lewy/fisiopatologia , Funções Verossimilhança
19.
Environ Int ; 158: 106898, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34627014

RESUMO

IMPORTANCE: Previous studies have reported associations between in utero exposure to regional air pollution and autism spectrum disorders (ASD). In utero exposure to components of near-roadway air pollution (NRAP) has been linked to adverse neurodevelopment in animal models, but few studies have investigated NRAP association with ASD risk. OBJECTIVE: To identify ASD risk associated with in utero exposure to NRAP in a large, representative birth cohort. DESIGN, SETTING, AND PARTICIPANTS: This retrospective pregnancy cohort study included 314,391 mother-child pairs of singletons born between 2001 and 2014 at Kaiser Permanente Southern California (KPSC) hospitals. Maternal and child data were extracted from KPSC electronic medical records. Children were followed until: clinical diagnosis of ASD, non-KPSC membership, death, or December 31, 2019, whichever came first. Exposure to the complex NRAP mixture during pregnancy was assessed using line-source dispersion models to estimate fresh vehicle emissions from freeway and non-freeway sources at maternal addresses during pregnancy. Vehicular traffic load exposure was characterized using advanced telematic models combining traditional traffic counts and travel-demand models with cell phone and vehicle GPS data. Cox proportional-hazard models estimated hazard ratios (HR) of ASD associated with near-roadway traffic load and dispersion-modeled NRAP during pregnancy, adjusted for covariates. Non-freeway NRAP was analyzed using quintile distribution due to nonlinear associations with ASD. EXPOSURES: Average NRAP and traffic load exposure during pregnancy at maternal residential addresses. MAIN OUTCOMES: Clinical diagnosis of ASD. RESULTS: A total of 6,291 children (5,114 boys, 1,177 girls) were diagnosed with ASD. The risk of ASD was associated with pregnancy-average exposure to total NRAP [HR(95% CI): 1.03(1.00,1.05) per 5 ppb increase in dispersion-modeled NOx] and to non-freeway NRAP [HR(95% CI) comparing the highest to the lowest quintile: 1.19(1.11, 1.27)]. Total NRAP had a stronger association in boys than in girls, but the association with non-freeway NRAP did not differ by sex. The association of freeway NRAP with ASD risk was not statistically significant. Non-freeway traffic load exposure demonstrated associations with ASD consistent with those of NRAP and ASD. CONCLUSIONS: In utero exposure to near-roadway air pollution, particularly from non-freeway sources, may increase ASD risk in children.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Transtorno do Espectro Autista , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/etiologia , California/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Gravidez , Estudos Retrospectivos
20.
J Clin Invest ; 132(3)2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33905376

RESUMO

BACKGROUNDMajor depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are highly comorbid and exhibit strong correlations with one another. We aimed to investigate mechanisms of underlying relationships between PTSD and 3 kinds of depressive phenotypes, namely, MDD, depressed affect (DAF), and depression (DEP, including both MDD and the broad definition of depression).METHODSGenetic correlations between PTSD and the depressive phenotypes were tested using linkage disequilibrium score regression. Polygenic overlap analysis was used to estimate shared and trait-specific causal variants across a pair of traits. Causal relationships between PTSD and the depressive phenotypes were investigated using Mendelian randomization. Shared genomic loci between PTSD and MDD were identified using cross-trait meta-analysis.RESULTSGenetic correlations of PTSD with the depressive phenotypes were in the range of 0.71-0.80. The estimated numbers of causal variants were 14,565, 12,965, 10,565, and 4,986 for MDD, DEP, DAF, and PTSD, respectively. In each case, causal variants contributing to PTSD were completely or largely covered by causal variants defining each of the depressive phenotypes. Mendelian randomization analysis indicated that the genetically determined depressive phenotypes confer a causal effect on PTSD (b = 0.21-0.31). Notably, genetically determined PTSD confers a causal effect on DEP (b = 0.14) and DAF (b = 0.15), but not MDD. Cross-trait meta-analysis of MDD and PTSD identified 47 genomic loci, including 29 loci shared between PTSD and MDD.CONCLUSIONEvidence from shared genetics suggests that PTSD is a subtype of MDD. This study provides support to the efforts in reducing diagnostic heterogeneity in psychiatric nosology.FUNDINGThe National Key Research and Development Program of China and the National Natural Science Foundation of China.


Assuntos
Transtorno Depressivo Maior/genética , Desequilíbrio de Ligação , Transtornos de Estresse Pós-Traumáticos/genética , Adulto , China/epidemiologia , Transtorno Depressivo Maior/classificação , Transtorno Depressivo Maior/epidemiologia , Feminino , Humanos , Masculino , Transtornos de Estresse Pós-Traumáticos/classificação , Transtornos de Estresse Pós-Traumáticos/etnologia
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