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      A national cohort study (2000–2018) of long-term air pollution exposure and incident dementia in older adults in the United States

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          Abstract

          Air pollution may increase risk of Alzheimer’s disease and related dementias (ADRD) in the U.S., but the extent of this relationship is unclear. Here, we constructed two national U.S. population-based cohorts of those aged ≥65 from the Medicare Chronic Conditions Warehouse (2000–2018), combined with high-resolution air pollution datasets, to investigate the association of long-term exposure to ambient fine particulate matter (PM 2.5), nitrogen dioxide (NO 2), and ozone (O 3) with dementia and AD incidence, respectively. We identified ~2.0 million incident dementia cases ( N = 12,233,371; dementia cohort) and ~0.8 million incident AD cases ( N = 12,456,447; AD cohort). Per interquartile range (IQR) increase in the 5-year average PM 2.5 (3.2 µg/m 3), NO 2 (11.6 ppb), and warm-season O 3 (5.3 ppb) over the past 5 years prior to diagnosis, the hazard ratios (HRs) were 1.060 (95% confidence interval [CI]: 1.054, 1.066), 1.019 (95% CI: 1.012, 1.026), and 0.990 (95% CI: 0.987, 0.993) for incident dementias, and 1.078 (95% CI: 1.070, 1.086), 1.031 (95% CI: 1.023, 1.039), and 0.982 (95%CI: 0.977, 0.986) for incident AD, respectively, for the three pollutants. For both outcomes, concentration-response relationships for PM 2.5 and NO 2 were approximately linear. Our study suggests that exposures to PM 2.5 and NO 2 are associated with incidence of dementia and AD.

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          Most cited references47

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          Dementia prevention, intervention, and care

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            The Lancet Commission on pollution and health

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              Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade.

              Currently available evidence strongly supports the position that the initiating event in Alzheimer's disease (AD) is related to abnormal processing of beta-amyloid (Abeta) peptide, ultimately leading to formation of Abeta plaques in the brain. This process occurs while individuals are still cognitively normal. Biomarkers of brain beta-amyloidosis are reductions in CSF Abeta(42) and increased amyloid PET tracer retention. After a lag period, which varies from patient to patient, neuronal dysfunction and neurodegeneration become the dominant pathological processes. Biomarkers of neuronal injury and neurodegeneration are increased CSF tau and structural MRI measures of cerebral atrophy. Neurodegeneration is accompanied by synaptic dysfunction, which is indicated by decreased fluorodeoxyglucose uptake on PET. We propose a model that relates disease stage to AD biomarkers in which Abeta biomarkers become abnormal first, before neurodegenerative biomarkers and cognitive symptoms, and neurodegenerative biomarkers become abnormal later, and correlate with clinical symptom severity. Copyright 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Nature Communications
                Nat Commun
                Springer Science and Business Media LLC
                2041-1723
                December 2021
                November 19 2021
                December 2021
                : 12
                : 1
                Article
                10.1038/s41467-021-27049-2
                9ceff25f-5dad-47da-b1ad-71929bfe06a9
                © 2021

                https://creativecommons.org/licenses/by/4.0

                https://creativecommons.org/licenses/by/4.0

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