{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:19:13Z","timestamp":1768565953336,"version":"3.49.0"},"posted":{"date-parts":[[2023,11,29]]},"group-title":"Epidemiology","reference-count":69,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,11,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Ambient air pollution exposures increase risk for Alzheimer\u2019s disease (AD) and related dementias, possibly due to structural changes in the medial temporal lobe (MTL). However, existing MRI studies examining exposure effects on the MTL were cross-sectional and focused on the hippocampus, yielding mixed results.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Method<\/jats:title>\n                  <jats:p>\n                    To determine whether air pollution exposures were associated with MTL atrophy over time, we conducted a longitudinal study including 653 cognitively unimpaired community-dwelling older women from the Women\u2019s Health Initiative Memory Study with two MRI brain scans (MRI-1: 2005-6; MRI-2: 2009-10; M\n                    <jats:sub>age<\/jats:sub>\n                    at MRI-1=77.3\u00b13.5years). Using regionalized universal kriging models, exposures at residential locations were estimated as 3-year annual averages of fine particulate matter (PM\n                    <jats:sub>2.5<\/jats:sub>\n                    ) and nitrogen dioxide (NO\n                    <jats:sub>2<\/jats:sub>\n                    ) prior to MRI-1. Bilateral gray matter volumes of the hippocampus, amygdala, parahippocampal gyrus (PHG), and entorhinal cortex (ERC) were summed to operationalize the MTL. We used linear regressions to estimate exposure effects on 5-year volume changes in the MTL and its subregions, adjusting for intracranial volume, sociodemographic, lifestyle, and clinical characteristics.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    On average, MTL volume decreased by 0.53\u00b11.00cm\n                    <jats:sup>3<\/jats:sup>\n                    over 5 years. For each interquartile increase of PM\n                    <jats:sub>2.5<\/jats:sub>\n                    (3.26\u00b5g\/m\n                    <jats:sup>3<\/jats:sup>\n                    ) and NO\n                    <jats:sub>2<\/jats:sub>\n                    (6.77ppb), adjusted MTL volume had greater shrinkage by 0.32cm\n                    <jats:sup>3<\/jats:sup>\n                    (95%CI=[-0.43,-0.21]) and 0.12cm\n                    <jats:sup>3<\/jats:sup>\n                    (95%CI=[-0.22,-0.01]), respectively. The exposure effects did not differ by\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54 genotype, sociodemographic, and cardiovascular risk factors, and remained among women with low-level PM\n                    <jats:sub>2.5<\/jats:sub>\n                    exposure. Greater PHG atrophy was associated with higher PM\n                    <jats:sub>2.5<\/jats:sub>\n                    (b=-0.24, 95%CI=[-0.29,-0.19]) and NO\n                    <jats:sub>2<\/jats:sub>\n                    exposures (b=-0.09, 95%CI=[-0.14,-0.04]). Higher exposure to PM\n                    <jats:sub>2.5<\/jats:sub>\n                    but not NO\n                    <jats:sub>2<\/jats:sub>\n                    was also associated with greater ERC atrophy. Exposures were not associated with amygdala or hippocampal atrophy.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>\n                    In summary, higher late-life PM\n                    <jats:sub>2.5<\/jats:sub>\n                    and NO\n                    <jats:sub>2<\/jats:sub>\n                    exposures were associated with greater MTL atrophy over time in cognitively unimpaired older women. The PHG and ERC - the MTL cortical subregions where AD neuropathologies likely begin, may be preferentially vulnerable to air pollution neurotoxicity.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>First longitudinal study on air pollution and medial temporal lobe (MTL) volume.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Late-life PM\n                        <jats:sub>2.5<\/jats:sub>\n                        and NO\n                        <jats:sub>2<\/jats:sub>\n                        associated with MTL atrophy over time in older women.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Heterogeneous adverse effects were observed across different subregions of the MTL.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Results not differ by\n                        <jats:italic>APOE<\/jats:italic>\n                        genotype, age, education, or cardiovascular risk factors.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Adverse effects remained at low-level exposure compliant with regulatory standards.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2023.11.28.23298708","type":"posted-content","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T13:40:43Z","timestamp":1701265243000},"source":"Crossref","is-referenced-by-count":1,"title":["Association between late-life air pollution exposure and medial temporal lobe atrophy in older women"],"prefix":"10.64898","author":[{"given":"Xinhui","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0684-9991","authenticated-orcid":false,"given":"Lauren E.","family":"Salminen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Petkus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ira","family":"Driscoll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua","family":"Millstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel P.","family":"Beavers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Espeland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guray","family":"Erus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meredith N.","family":"Braskie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul M.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Gatz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena C.","family":"Chui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan M","family":"Resnick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4174-9037","authenticated-orcid":false,"given":"Joel D.","family":"Kaufman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen R.","family":"Rapp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally","family":"Shumaker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Younan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiu-Chiuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023120100452032000_2023.11.28.23298708v1.1","unstructured":"Bacigalupo, Mayer, Lacorte. 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