Mediation Effect of Brain Volume on the Relationship Between Peripheral Inflammation and Cognitive Decline.

BACKGROUND: Studies have reported the associations between inflammation, brain volume, and cognition separately. It is reasonable to assume peripheral inflammation may contribute to cognitive decline through brain volume atrophy. OBJECTIVE: To examine the associations between peripheral inflammation, brain volume, and cognition among adults, and to investigate whether brain volume atrophy mediates the inflammation-cognition relationshipMethods:We retrieved 20,381 participants with available data on peripheral inflammation, brain volume, and cognition from the UK Biobank cohort. Cognitive function was assessed by performance on cognitive tasks probing various cognitive domains. Brain volumes were measured by magnetic resonance imaging (MRI). Multivariable linear models were used to investigate the associations between three peripheral inflammatory indexes (C-reactive protein, systemic immune-inflammatory index, neutrophil-to-lymphocyte ratio), brain volume, and cognition. Mediation analyses were conducted to assess the potential mediating effect of brain volume atrophy. All results were corrected for multiple comparisons using the false-discovery rate (FDR). RESULTS: Peripheral inflammation was inversely associated with grey matter volume (GMV), white matter volume (WMV), and cognition after adjusting for potential covariates. For instance, CRP was associated with the GMV of left parahippocampal gyrus (ß= -0.05, 95% confidence interval [CI]: -0.06 to -0.04, pFDR =1.07×10-16) and general cognitive factor (ß= -0.03, 95% CI: -0. -0.04 to -0.01, pFDR = 0.001). Brain volume atrophy mediated the inflammation-cognitive decline relationship, accounting for 15-29% of the overall impact. CONCLUSION: In this cohort study, peripheral inflammation was associated with brain volume atrophy and cognitive decline. Brain atrophy may mediate the inflammation-cognitive decline relationship.

Global burden of chronic obstructive pulmonary disease attributable to ambient particulate matter pollution and household air pollution from solid fuels from 1990 to 2019.

We aimed to estimate the spatiotemporal trends in the global burden of chronic obstructive pulmonary disease (COPD) attributable to both household air pollution from solid fuels (HAP) and ambient particulate matter (APM) from 1990 to 2019 and compared the possible differences between the burdens attributable to APM and HAP. The number of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLLs) of COPD attributable to HAP from solid fuels and APM during 1990-2019 were extracted from the Global Burden of Diseases Study 2019. The proportion of YLLs in DALYs and average YLLs per COPD death were also calculated. Subgroup analyses by sex, age, and socio-demographic index (SDI) were conducted. The estimated annual percentage change (EAPC) was used to assess the temporal trend of age-standardized rate of mortality (ASMR) and DALYs (ASDR). Over the past 30 years, we observed a clear downward trend in COPD deaths attributable to HAP and an upward trend by 97.61% in COPD deaths attributable to APM. The global COPD burden attributable to APM in 2019 was higher than those due to HAP, except in low-SDI regions. For both HAP and APM, YLLs continued to predominate in DALYs of COPD, with an average YLLs per death of more than 10 years in different regions. The ASMR was higher in males and lower in high-SDI regions. The ASMR and ASDR attributable to HAP decreased globally in all age groups during 1990-2019, while those attributable to APM increased among people older than 80 years and in regions with lower SDI. Our study reveals an increasing trend in APM-attributable COPD burden over the past three decades. Comparatively, the global burden due to HAP decreased markedly, but it was still pronounced in low-SDI regions. Continued efforts on PM mitigation are needed for COPD prevention.