{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:58:49Z","timestamp":1787795929939,"version":"build-2784847793"},"reference-count":67,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T00:00:00Z","timestamp":1578009600000},"content-version":"am","delay-in-days":365,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T00:00:00Z","timestamp":1546473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["NMRC0088\/2015"],"award-info":[{"award-number":["NMRC0088\/2015"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH\u201012\u20102\u20100012"],"award-info":[{"award-number":["W81XWH\u201012\u20102\u20100012"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P41 EB015902"],"award-info":[{"award-number":["P41 EB015902"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["awarded to OP"],"award-info":[{"award-number":["awarded to OP"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007333","name":"Alzheimer's Disease Neuroimaging Initiative","doi-asserted-by":"publisher","award":["U01 AG024904"],"award-info":[{"award-number":["U01 AG024904"]}],"id":[{"id":"10.13039\/100007333","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alterations in parietal and temporal white matter microstructure derived from diffusion tensor imaging occur in preclinical and clinical Alzheimer's disease. Amyloid beta (A\u03b2) deposition and such white matter alterations are two pathological hallmarks of Alzheimer's disease. However, the relationship between these pathologies is not yet understood, partly since conventional diffusion MRI methods cannot distinguish between cellular and extracellular processes. Thus, we studied A\u03b2\u2010associated longitudinal diffusion MRI changes in A\u03b2\u2010positive (<jats:italic>N<\/jats:italic>\u2009=\u200921) and A\u03b2\u2010negative (<jats:italic>N<\/jats:italic>\u2009=\u200951) cognitively normal elderly obtained from the Alzheimer's Disease Neuroimaging Initiative dataset using linear mixed models. A\u03b2\u2010positivity was based on Alzheimer's Disease Neuroimaging Initiative amyloid\u2010PET recommendations using a standardized uptake value ratio cut\u2010off of 1.11. We used free\u2010water imaging to distinguish cellular and extracellular changes. We found that A\u03b2\u2010positive subjects had increased baseline right uncinate fasciculus free\u2010water fraction (FW), associated with worse baseline Alzheimer's disease assessment scale scores. Furthermore, A\u03b2\u2010positive subjects showed faster decrease in fractional anisotropy (FW\u2010corrected) in the right uncinate fasciculus and faster age\u2010dependent right inferior longitudinal fasciculus FW increases over time. Right inferior longitudinal fasciculus FW increases were associated with greater memory decline. Importantly, these results remained significant after controlling for gray and white matter volume and hippocampal volume. This is the first study to illustrate the influence of A\u03b2 burden on early longitudinal (in addition to baseline) white matter changes in cognitively normal elderly individuals at\u2010risk of Alzheimer's disease, thus underscoring the importance of longitudinal studies in assessing microstructural alterations in individuals at risk of Alzheimer's disease prior to symptoms onset.<\/jats:p>","DOI":"10.1002\/hbm.24507","type":"journal-article","created":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T12:55:09Z","timestamp":1546520109000},"page":"2065-2075","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Amyloid burden accelerates white matter degradation in cognitively normal elderly individuals"],"prefix":"10.1002","volume":"40","author":[{"given":"Ashwati","family":"Vipin","sequence":"first","affiliation":[{"name":"Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program Duke\u2010National University of Singapore Graduate Medical School  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwun Kei","family":"Ng","sequence":"additional","affiliation":[{"name":"Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program Duke\u2010National University of Singapore Graduate Medical School  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Ji","sequence":"additional","affiliation":[{"name":"Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program Duke\u2010National University of Singapore Graduate Medical School  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Youn","family":"Shim","sequence":"additional","affiliation":[{"name":"Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program Duke\u2010National University of Singapore Graduate Medical School  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph K. W.","family":"Lim","sequence":"additional","affiliation":[{"name":"Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program Duke\u2010National University of Singapore Graduate Medical School  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofer","family":"Pasternak","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry and Radiology Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0180-8648","authenticated-orcid":false,"given":"Juan Helen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program Duke\u2010National University of Singapore Graduate Medical School  Singapore"},{"name":"Clinical Imaging Research Centre the Agency for Science, Technology and Research and National University of Singapore  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer's Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2014.04.008"},{"key":"e_1_2_8_3_1","volume-title":"ADNI 2 PET Technical Procedures Manual AV\u201045 (Florbetapir F 18) & FDG","author":"ADNI","year":"2011"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(00)00124-X"},{"key":"e_1_2_8_5_1","volume-title":"ADNI 2 Procedures Manual","author":"Alzheimer Disease Neuroimaging Initiative","year":"2008"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2011.04122.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-007-0029-0"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.10609"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5062-08.2009"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065175"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24711"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19971030)16:20<2349::AID-SIM667>3.0.CO;2-E"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.20563"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.01.021"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/111.6.1425"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00569-X"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2004.07.016"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhg087"},{"key":"e_1_2_8_19_1","first-page":"1327","article-title":"Age\u2010related total gray matter and white matter changes in normal adult brain. Part I: Volumetric MR imaging analysis","volume":"23","author":"Ge Y.","year":"2002","journal-title":"AJNR. American Journal of Neuroradiology"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.04.030"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-14-05900.2002"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31828ab35d"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.08.034"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2011.06.027"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.12.056"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70291-0"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0008-9"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000386"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-017-0292-4"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31822313dc"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.112.109009"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-014-2753-3"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.10.006"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2014.08.020"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.43"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.04.518"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-150897"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31827689e8"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.08.043"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.05.027"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.12.032"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.09.013"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00112"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.03.029"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01150-x"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.22055"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2904-12.2012"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2014.07.031"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt171"},{"key":"e_1_2_8_51_1","volume-title":"R: A language and environment for statistical computing","author":"R Core Team","year":"2014"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1155\/2009\/609839"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2014.02.001"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2015.01.014"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.02.084"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.03.016"},{"key":"e_1_2_8_57_1","volume-title":"RStudio: Integrated development environment for R","author":"RStudio Team","year":"2012"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/YCO.0b013e32835ed6e8"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.03.013"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720511795745375"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.003"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0156770"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2009.5"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq203"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.02.009"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2011.08.002"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.3389\/fninf.2011.00023"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.12.003"}],"container-title":["Human Brain Mapping"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhbm.24507","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hbm.24507","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hbm.24507","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/am-pdf\/10.1002\/hbm.24507","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hbm.24507","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T20:09:05Z","timestamp":1694203745000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hbm.24507"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,3]]},"references-count":67,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1002\/hbm.24507"],"URL":"https:\/\/doi.org\/10.1002\/hbm.24507","archive":["Portico"],"relation":{},"ISSN":["1065-9471","1097-0193"],"issn-type":[{"value":"1065-9471","type":"print"},{"value":"1097-0193","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,3]]},"assertion":[{"value":"2018-08-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}