Diana Younan1, Xinhui Wang2, Ramon Casanova2, Ryan Barnard2, Sarah A Gaussoin2, Santiago Saldana2, Andrew J Petkus2, Daniel P Beavers2, Susan M Resnick2, JoAnn E Manson2, Marc L Serre2, William Vizuete2, Victor W Henderson2, Bonnie C Sachs2, Joel A Salinas2, Margaret Gatz2, Mark A Espeland2, Helena C Chui2, Sally A Shumaker2, Stephen R Rapp2, Jiu-Chiuan Chen2. 1. From the Departments of Preventive Medicine (D.Y., J.C.C) and Neurology (X.W., A.J.P., H.C.C., J.C.C.), and the Center for Economic and Social Research (M.G.), University of Southern California, Los Angeles, CA; Departments of Biostatistics and Data Science (R.C., R.B., S.A.G., S.S., D.P.B., M.A.E.), Psychiatry and Behavioral Medicine (S.R.R.), Social Sciences & Health Policy (S.A.S., S.R.R., B.C.S.), and Neurology (B.C.S.), Wake Forest School of Medicine, Winston-Salem, NC; Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD (S.M.R.); Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC (M.L.S., W.V.); Departments of Health Research and Policy (Epidemiology) and Neurology and Neurological Sciences, Stanford University, Stanford, CA (V.W.H.); Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (J. E.M.); and Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (J.A.S.) dyounan@usc.edu. 2. From the Departments of Preventive Medicine (D.Y., J.C.C) and Neurology (X.W., A.J.P., H.C.C., J.C.C.), and the Center for Economic and Social Research (M.G.), University of Southern California, Los Angeles, CA; Departments of Biostatistics and Data Science (R.C., R.B., S.A.G., S.S., D.P.B., M.A.E.), Psychiatry and Behavioral Medicine (S.R.R.), Social Sciences & Health Policy (S.A.S., S.R.R., B.C.S.), and Neurology (B.C.S.), Wake Forest School of Medicine, Winston-Salem, NC; Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD (S.M.R.); Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC (M.L.S., W.V.); Departments of Health Research and Policy (Epidemiology) and Neurology and Neurological Sciences, Stanford University, Stanford, CA (V.W.H.); Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (J. E.M.); and Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (J.A.S.).
Abstract
OBJECTIVE: To examine whether late-life exposure to PM2.5 (particulate matter with aerodynamic diameters <2.5-µm) contributes to progressive brain atrophy predictive of Alzheimer's disease (AD) using a community-dwelling cohort of women (aged 70-89) with up to two brain MRI scans (MRI-1: 2005-6; MRI-2: 2010-11). METHODS: AD pattern similarity (AD-PS) scores, developed by supervised machine learning and validated with MRI data from the AD Neuroimaging Initiative, was used to capture high-dimensional gray matter atrophy in brain areas vulnerable to AD (e.g., amygdala, hippocampus, parahippocampal gyrus, thalamus, inferior temporal lobe areas and midbrain). Based on participants' addresses and air monitoring data, we implemented a spatiotemporal model to estimate 3-year average exposure to PM2.5 preceding MRI-1. General linear models were used to examine the association between PM2.5 and AD-PS scores (baseline and 5-year standardized change), accounting for potential confounders and white matter lesion volumes. RESULTS: For 1365 women aged 77.9±3.7 years in 2005-6, there was no association between PM2.5 and baseline AD-PS score in cross-sectional analyses (β=-0.004; 95% CI: -0.019, 0.011). Longitudinally, each interquartile range increase of PM2.5 (2.82-µg/m3) was associated with increased AD-PS scores during the follow-up, equivalent to a 24% (hazard ratio=1.24; 95% CI: 1.14, 1.34) increase in AD risk over 5-years (n=712; aged 77.4±3.5 years). This association remained after adjustment for socio-demographics, intracranial volume, lifestyle, clinical characteristics, and white matter lesions, and was present with levels below US regulatory standards (<12-µg/m3). CONCLUSIONS: Late-life exposure to PM2.5 is associated with increased neuroanatomical risk of AD, which may not be explained by available indicators of cerebrovascular damage.
OBJECTIVE: To examine whether late-life exposure to PM2.5 (particulate matter with aerodynamic diameters <2.5-µm) contributes to progressive brain atrophy predictive of Alzheimer's disease (AD) using a community-dwelling cohort of women (aged 70-89) with up to two brain MRI scans (MRI-1: 2005-6; MRI-2: 2010-11). METHODS: AD pattern similarity (AD-PS) scores, developed by supervised machine learning and validated with MRI data from the AD Neuroimaging Initiative, was used to capture high-dimensional gray matter atrophy in brain areas vulnerable to AD (e.g., amygdala, hippocampus, parahippocampal gyrus, thalamus, inferior temporal lobe areas and midbrain). Based on participants' addresses and air monitoring data, we implemented a spatiotemporal model to estimate 3-year average exposure to PM2.5 preceding MRI-1. General linear models were used to examine the association between PM2.5 and AD-PS scores (baseline and 5-year standardized change), accounting for potential confounders and white matter lesion volumes. RESULTS: For 1365 women aged 77.9±3.7 years in 2005-6, there was no association between PM2.5 and baseline AD-PS score in cross-sectional analyses (β=-0.004; 95% CI: -0.019, 0.011). Longitudinally, each interquartile range increase of PM2.5 (2.82-µg/m3) was associated with increased AD-PS scores during the follow-up, equivalent to a 24% (hazard ratio=1.24; 95% CI: 1.14, 1.34) increase in AD risk over 5-years (n=712; aged 77.4±3.5 years). This association remained after adjustment for socio-demographics, intracranial volume, lifestyle, clinical characteristics, and white matter lesions, and was present with levels below US regulatory standards (<12-µg/m3). CONCLUSIONS: Late-life exposure to PM2.5 is associated with increased neuroanatomical risk of AD, which may not be explained by available indicators of cerebrovascular damage.
Authors: Elissa H Wilker; Sarah R Preis; Alexa S Beiser; Philip A Wolf; Rhoda Au; Itai Kloog; Wenyuan Li; Joel Schwartz; Petros Koutrakis; Charles DeCarli; Sudha Seshadri; Murray A Mittleman Journal: Stroke Date: 2015-05 Impact factor: 7.914
Authors: Shawn D Gale; Lance D Erickson; Jacqueline E Anderson; Bruce L Brown; Dawson W Hedges Journal: Environ Res Date: 2020-03-11 Impact factor: 6.498
Authors: Mark A Espeland; Jiu-Chiuan Chen; Julie Weitlauf; Kathleen M Hayden; Stephen R Rapp; Susan M Resnick; Lorena Garcia; Brad Cannell; Laura D Baker; Bonnie C Sachs; Hilary A Tindle; Robert Wallace; Ramon Casanova Journal: J Am Geriatr Soc Date: 2018-07-04 Impact factor: 5.562
Authors: Sally A Shumaker; Claudine Legault; Stephen R Rapp; Leon Thal; Robert B Wallace; Judith K Ockene; Susan L Hendrix; Beverly N Jones; Annlouise R Assaf; Rebecca D Jackson; Jane Morley Kotchen; Sylvia Wassertheil-Smoller; Jean Wactawski-Wende Journal: JAMA Date: 2003-05-28 Impact factor: 56.272
Authors: Sally A Shumaker; Claudine Legault; Lewis Kuller; Stephen R Rapp; Leon Thal; Dorothy S Lane; Howard Fillit; Marcia L Stefanick; Susan L Hendrix; Cora E Lewis; Kamal Masaki; Laura H Coker Journal: JAMA Date: 2004-06-23 Impact factor: 56.272
Authors: Melinda C Power; Archana P Lamichhane; Duanping Liao; Xiaohui Xu; Clifford R Jack; Rebecca F Gottesman; Thomas Mosley; James D Stewart; Jeff D Yanosky; Eric A Whitsel Journal: Environ Health Perspect Date: 2018-02-16 Impact factor: 9.031
Authors: Diana Younan; Xinhui Wang; Tara Gruenewald; Margaret Gatz; Marc L Serre; William Vizuete; Meredith N Braskie; Nancy F Woods; Ka Kahe; Lorena Garcia; Fred Lurmann; JoAnn E Manson; Helena C Chui; Robert B Wallace; Mark A Espeland; Jiu-Chiuan Chen Journal: J Gerontol A Biol Sci Med Sci Date: 2022-05-05 Impact factor: 6.591
Authors: Andrew J Petkus; Diana Younan; Xinhui Wang; Daniel P Beavers; Mark A Espeland; Margaret Gatz; Tara Gruenewald; Joel D Kaufman; Helena C Chui; Joshua Millstein; Stephen R Rapp; JoAnn E Manson; Susan M Resnick; Gregory A Wellenius; Eric A Whitsel; Keith Widaman; Jiu-Chiuan Chen Journal: J Alzheimers Dis Date: 2021 Impact factor: 4.160
Authors: Stephanie E Cleland; Lauren H Wyatt; Linda Wei; Naman Paul; Marc L Serre; J Jason West; Sarah B Henderson; Ana G Rappold Journal: Environ Health Perspect Date: 2022-06-14 Impact factor: 11.035
Authors: Xinhui Wang; Diana Younan; Joshua Millstein; Andrew J Petkus; Erika Garcia; Daniel P Beavers; Mark A Espeland; Helena C Chui; Susan M Resnick; Margaret Gatz; Joel D Kaufman; Gregory A Wellenius; Eric A Whitsel; JoAnn E Manson; Stephen R Rapp; Jiu-Chiuan Chen Journal: Proc Natl Acad Sci U S A Date: 2022-01-11 Impact factor: 12.779
Authors: Jennifer Weuve; Erin E Bennett; Lynsie Ranker; Kan Z Gianattasio; Meredith Pedde; Sara D Adar; Jeff D Yanosky; Melinda C Power Journal: Environ Health Perspect Date: 2021-09-24 Impact factor: 9.031
Authors: Kristen M C Malecki; Julie K Andersen; Andrew M Geller; G Jean Harry; Chandra L Jackson; Katherine A James; Gary W Miller; Mary Ann Ottinger Journal: Front Aging Neurosci Date: 2022-02-21 Impact factor: 5.750
Authors: Ramon Casanova; Fang-Chi Hsu; Ryan T Barnard; Andrea M Anderson; Rajesh Talluri; Christopher T Whitlow; Timothy M Hughes; Michael Griswold; Kathleen M Hayden; Rebecca F Gottesman; Lynne E Wagenknecht Journal: Alzheimers Dement Date: 2021-07-26 Impact factor: 16.655
Authors: Diana Younan; Xinhui Wang; Joshua Millstein; Andrew J Petkus; Daniel P Beavers; Mark A Espeland; Helena C Chui; Susan M Resnick; Margaret Gatz; Joel D Kaufman; Gregory A Wellenius; Eric A Whitsel; JoAnn E Manson; Stephen R Rapp; Jiu-Chiuan Chen Journal: PLoS Med Date: 2022-02-03 Impact factor: 11.069