{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:05:32Z","timestamp":1793822732578,"version":"4.6.1"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Poor cerebrovascular reactivity is associated with a higher risk of cerebrovascular disease. The most common method to study cerebrovascular reactivity in aging adults, transcranial Doppler ultrasound, yields measurements in large intracranial arteries, but not in regional brain parenchyma that may be more impaired in some disease processes. Measurements derived from transcranial Doppler ultrasound suggest that there are sex differences in cerebrovascular reactivity for aging adults. We investigated the association between age and sex on cerebrovascular reactivity using blood oxygen level dependent (BOLD) magnetic resonance imaging in a representative group of aging adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      This cross-sectional study investigated BOLD cerebrovascular reactivity to CO\n                      <jats:sub>2<\/jats:sub>\n                      in a representative group of aging adults, 51 to 83 years old. We manipulated end-tidal carbon dioxide with breathing exercises and evaluated changes in 6 brain regions: whole brain, white matter, cortical gray matter, subcortical gray matter, left hippocampus, and right hippocampus. We used 1 linear regression per region to investigate the effects of age, sex, and their interaction on BOLD cerebrovascular reactivity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      We report an age-by-sex interaction for all brain regions (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u22640.050), except cortical gray matter (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.062). For white matter and subcortical gray matter, female participants trended toward an age-related BOLD cerebrovascular reactivity increase (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u22640.058), while male participants did not change with age (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &gt;0.580). In the whole brain and bilateral hippocampi, the age trends for each sex were in opposite directions but not significant (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &gt;0.211). We report a main effect of sex (female greater than male participants) for subcortical gray matter and the right hippocampus (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u22640.048) and no main effect of age in any model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>We present the first report of age-related BOLD cerebrovascular reactivity increases in older female participants and higher BOLD cerebrovascular reactivity in older female compared with male participants. Sex and age-by-sex-based differences seem to be driven by changes in white matter, subcortical gray matter, and bilateral hippocampi.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.125.051026","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T05:00:58Z","timestamp":1747803658000},"page":"2177-2189","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Sex Differences in the Neurovascular Health of Aging Adults"],"prefix":"10.1161","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8162-897X","authenticated-orcid":true,"given":"Bethany L.","family":"Sussman","sequence":"first","affiliation":[{"name":"Fetal and Neonatal Institute, Division of Neonatology, Children\u2019s Hospital Los Angeles, Keck School of Medicine (B.L.S., H.E.W., S.R., M.T.B.), University of Southern California, Los Angeles."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4493-7112","authenticated-orcid":true,"given":"Hannah E.","family":"Wiseman","sequence":"additional","affiliation":[{"name":"Fetal and Neonatal Institute, Division of Neonatology, Children\u2019s Hospital Los Angeles, Keck School of Medicine (B.L.S., H.E.W., S.R., M.T.B.), University of Southern California, Los Angeles."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudarshan","family":"Ranganathan","sequence":"additional","affiliation":[{"name":"Fetal and Neonatal Institute, Division of Neonatology, Children\u2019s Hospital Los Angeles, Keck School of Medicine (B.L.S., H.E.W., S.R., M.T.B.), University of Southern California, Los Angeles."},{"name":"Division of Cardiology, Department of Pediatrics, Children\u2019s Hospital Los Angeles, Keck School of Medicine (S.R., B.X., J.C.W.), University of Southern California, Los Angeles."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1277-6266","authenticated-orcid":true,"given":"K. Austin","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Anatomy, University of North Texas Health Science Center, Fort Worth (K.A.D., R.V., C.A.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5243-4298","authenticated-orcid":true,"given":"Botian","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Pediatrics, Children\u2019s Hospital Los Angeles, Keck School of Medicine (S.R., B.X., J.C.W.), University of Southern California, Los Angeles."},{"name":"Alfred E. Mann Department of Biomedical Engineering, Viterbi School of Engineering (B.X., J.C.W., M.T.B.), University of Southern California, Los Angeles."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4176-0001","authenticated-orcid":true,"given":"Raul","family":"Vintimilla","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Anatomy, University of North Texas Health Science Center, Fort Worth (K.A.D., R.V., C.A.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0996-3439","authenticated-orcid":true,"given":"John C.","family":"Wood","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Pediatrics, Children\u2019s Hospital Los Angeles, Keck School of Medicine (S.R., B.X., J.C.W.), University of Southern California, Los Angeles."},{"name":"Alfred E. Mann Department of Biomedical Engineering, Viterbi School of Engineering (B.X., J.C.W., M.T.B.), University of Southern California, Los Angeles."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5759-6912","authenticated-orcid":true,"given":"Caroline A.","family":"Rickards","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Anatomy, University of North Texas Health Science Center, Fort Worth (K.A.D., R.V., C.A.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7498-0396","authenticated-orcid":true,"given":"Niema M.","family":"Pahlevan","sequence":"additional","affiliation":[{"name":"Department of Aerospace and Mechanical Engineering (N.M.P.), University of Southern California, Los Angeles."},{"name":"Division of Cardiovascular Medicine, Keck School of Medicine (N.M.P.), University of Southern California, Los Angeles."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4449-2468","authenticated-orcid":true,"given":"Kevin S.","family":"King","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Barrow Neurological Institute, Phoenix, AZ (K.S.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7010-2318","authenticated-orcid":true,"given":"Matthew T.","family":"Borzage","sequence":"additional","affiliation":[{"name":"Fetal and Neonatal Institute, Division of Neonatology, Children\u2019s Hospital Los Angeles, Keck School of Medicine (B.L.S., H.E.W., S.R., M.T.B.), University of Southern California, Los Angeles."},{"name":"Alfred E. Mann Department of Biomedical Engineering, Viterbi School of Engineering (B.X., J.C.W., M.T.B.), University of Southern California, Los Angeles."},{"name":"Department of Regulatory and Quality Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences (M.T.B.), University of Southern California, Los Angeles."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith","family":"Braskie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Barber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonggang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Nandy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick","family":"McColl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Mason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Christian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Large","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Badri","family":"Vardarajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Rivera Mindt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrita","family":"Cheema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Mapstone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Kind","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozioma","family":"Okonkwo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Vintimilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Donohue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rema","family":"Raman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Borzage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Mielke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beau","family":"Ances","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh","family":"Babulal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Llibre-Guerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocky","family":"Vig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","article-title":"Fast facts: health and economic costs of chronic conditions.","author":"CDC","year":"2024","unstructured":"CDC. Fast facts: health and economic costs of chronic conditions. Chronic Disease; 2024. https:\/\/www.cdc.gov\/chronic-disease\/data-research\/facts-stats\/index.html","journal-title":"Chronic Disease"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001123"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.121.034814"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25564"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/MS9.0000000000001177"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/jon.12606"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2023.105140"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.07.007"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/1179069518785151"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.03.033"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.145"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010133"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.08.059"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.22044"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.06.010"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.08.018"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.29.7.1311"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.29.5.963"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.643468"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.656746"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12202"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39335.541782.AD"},{"key":"e_1_3_4_24_2","unstructured":"R Core Team. R: a language and environment for statistical computing; 2023. Accessed November 7 2023. https:\/\/www.R-project.org\/"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giae049"},{"key":"e_1_3_4_26_2","volume-title":"Statistical Parametric Mapping: The Analysis of Functional Brain Images","author":"Friston KJ","year":"2006","unstructured":"Friston KJ, Ashburner JT, Kiebel SJ, Nichols TE, Penny WD, editors. Statistical Parametric Mapping: The Analysis of Functional Brain Images. 1st ed. Academic Press; 2006."},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.06.060"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1053-8119(02)91132-8"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2016.03.001"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007963824710"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2001.0931"},{"key":"e_1_3_4_32_2","volume-title":"Non-Linear Registration, aka Spatial Normalisation","author":"Andersson JLR","year":"2010","unstructured":"Andersson JLR, Jenkinson M, Smith S. Non-Linear Registration, aka Spatial Normalisation. FMRIB Centre, Oxford; 2010. https:\/\/www.fmrib.ox.ac.uk\/datasets\/techrep\/"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2023.120448"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.01.021"},{"key":"e_1_3_4_35_2","unstructured":"Lenth RV. emmeans: estimated marginal means aka least-squares means; 2024. Accessed May 19 2024. https:\/\/CRAN.R-project.org\/package=emmeans"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2012.11.002"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X231219568"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X19828327"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.66"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00228.2022"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.2020.34.s1.06725"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.194"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2022.02.006"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2006.06.009"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.7758\/rsf.2016.2.4.01"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000000941"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0257815"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2016.09.007"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1183\/20734735.009817"},{"key":"e_1_3_4_50_2","volume-title":"Physiology, Respiratory Drive","author":"Brinkman JE","year":"2024","unstructured":"Brinkman JE, Toro F, Sharma S. Physiology, Respiratory Drive. StatPearls Publishing. 2024. Accessed August 16, 2024. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK482414\/"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.608475"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.125.051026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T15:09:17Z","timestamp":1754579357000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.125.051026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":50,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1161\/STROKEAHA.125.051026"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.125.051026","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2025-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-17","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}