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1936年洛锡安出生队列研究中一生暴露于空气污染与患痴呆症风险的关系

Life-course exposure to air pollution and the risk of dementia in the Lothian Birth Cohort 1936.

作者信息

Jutila Otto-Emil I, Mullin Donncha, Vieno Massimo, Tomlinson Samuel, Taylor Adele, Corley Janie, Deary Ian J, Cox Simon R, Baranyi Gergő, Pearce Jamie, Luciano Michelle, Karlsson Ida K, Russ Tom C

机构信息

Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, United Kingdom.

Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom.

出版信息

Environ Epidemiol. 2024 Dec 10;9(1):e355. doi: 10.1097/EE9.0000000000000355. eCollection 2025 Feb.

Abstract

BACKGROUND

Air pollution in later life has been associated with dementia; however, limited research has investigated the association between air pollution across the life course, either at specific life periods or cumulatively. The project investigates the association of air pollution with dementia via a life-course epidemiological approach.

METHODS

Participants of the Lothian Birth Cohort, born in 1936, provided lifetime residential history in 2014. Participant's air pollution exposure for time periods 1935, 1950, 1970, 1980, 1990, 2001, and 2007 was modeled using an atmospheric chemistry transport model. Lifetime cumulative exposures were calculated as time-weighted mean exposure. Of 572 participants, 67 developed all-cause dementia [35 with Alzheimer's dementia (AD)] by wave 5 (~82 years). Cox proportional hazards and competing risk models assessed the association between all-cause dementia and AD with particulate matter (diameter of ≤2.5 µm) PM and nitrogen dioxide (NO) exposure at specific life periods and cumulatively. False discovery rate (FDR) correction was applied for multiple testing.

RESULTS

The mean follow-up was 11.26 years. One standard deviation (SD) higher exposure to air pollution in 1935 (PM = 14.03 μg/m, NO = 5.35 μg/m) was positively linked but not statistically significant to all-cause dementia [PM hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 0.90, 1.49; NO HR = 1.13, 95% CI = 0.88, 1.47] and AD (PM HR = 1.38, 95% CI = 1.00, 1.91; NO HR = 1.35, 95% CI = 0.92, 1.99). In the competing risk model, one SD elevated PM exposure (1.12 μg/m) in 1990 was inversely associated with dementia (subdistribution HR = 0.82, 95% CI = 0.67, 0.99) at = 0.034 but not after FDR correction ( = 0.442). Higher cumulative PM per one SD was associated with an increased risk of all-cause dementia and AD for all accumulation models except for the early-life model.

CONCLUSION

The in-utero and early-life exposure to PM and NO was associated with higher AD and all-cause dementia risk, suggesting a sensitive/critical period. Cumulative exposure to PM across the life course was associated with higher dementia risk. Midlife PM exposure's negative association with all-cause dementia risk may stem from unaddressed confounders or bias.

摘要

背景

晚年空气污染与痴呆症有关;然而,有限的研究调查了整个生命过程中空气污染之间的关联,无论是在特定生命时期还是累积暴露情况。该项目通过生命历程流行病学方法研究空气污染与痴呆症之间的关联。

方法

1936年出生的洛锡安出生队列参与者于2014年提供了终生居住史。使用大气化学传输模型对参与者在1935年、1950年、1970年、1980年、1990年、2001年和2007年期间的空气污染暴露情况进行建模。终生累积暴露量计算为时间加权平均暴露量。在572名参与者中,到第5波(约82岁)时,有67人患上全因性痴呆症[35人患阿尔茨海默病(AD)]。Cox比例风险模型和竞争风险模型评估了特定生命时期及累积暴露的全因性痴呆症和AD与细颗粒物(直径≤2.5μm)PM和二氧化氮(NO)暴露之间的关联。对多重检验应用了错误发现率(FDR)校正。

结果

平均随访时间为11.26年。1935年空气污染暴露每增加一个标准差(SD)(PM = 14.03μg/m,NO = 5.35μg/m)与全因性痴呆症呈正相关,但无统计学意义[PM风险比(HR)= 1.16,95%置信区间(CI)= 0.90,1.49;NO HR = 1.13,95% CI = 0.88,1.47]以及与AD(PM HR = 1.38,95% CI = 1.00,1.91;NO HR = 1.35,95% CI = 0.92,1.99)。在竞争风险模型中,1990年PM暴露升高一个SD(1.12μg/m)与痴呆症呈负相关(亚分布HR = 0.82,95% CI = 0.67,0.99),P = 0.034,但在FDR校正后无统计学意义(P = 0.442)。除早期生命模型外,在所有累积模型中,每增加一个SD的较高累积PM与全因性痴呆症和AD风险增加相关。

结论

子宫内和生命早期暴露于PM和NO与较高的AD和全因性痴呆症风险相关,提示存在一个敏感/关键期。整个生命过程中累积暴露于PM与较高的痴呆症风险相关。中年期PM暴露与全因性痴呆症风险的负相关可能源于未解决的混杂因素或偏差。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db08/11634326/1dde8c6302c4/ee9-9-e355-g001.jpg

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