{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T21:40:42Z","timestamp":1788730842489,"version":"build-2803163510"},"reference-count":41,"publisher":"MIT Press","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":313,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 EB028644"],"award-info":[{"award-number":["R01 EB028644"]}],"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":["S10 OD021480"],"award-info":[{"award-number":["S10 OD021480"]}],"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":["S10 OD028544"],"award-info":[{"award-number":["S10 OD028544"]}],"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":["P30 AG072958"],"award-info":[{"award-number":["P30 AG072958"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["direct.mit.edu"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neurodegeneration associated with Alzheimer\u2019s disease (AD) can start at the microstructural level years before cognitive symptoms; yet, it has been difficult to definitively detect these early changes to plan effective treatments. Using a cortical column-based analysis of high-resolution diffusion magnetic resonance imaging data, we aim to identify early microstructural neurodegeneration in the gray matter across different cortical depths and regions. We compared four groups of participants across a spectrum of cognitive decline (n = 60): cognitively normal amyloid-negative (normal controls), cognitively normal amyloid-positive (stage-1 AD), mild cognitive impairment (MCI), and AD dementia. Our results showed progressive increases in radial diffusivity across these groups in cortical regions associated with AD, and our analysis in individual asymptomatic stage-1 AD participants was able to differentiate such diffusivity increases to predict risk of impending cognitive decline in 2 participants who had cognitive decline and MCI diagnosis at their follow-up clinical examination and 11 participants who did not.<\/jats:p>","DOI":"10.1162\/imag.a.1037","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T23:53:52Z","timestamp":1762818832000},"update-policy":"https:\/\/doi.org\/10.1162\/mitpressjournals.corrections.policy","source":"Crossref","is-referenced-by-count":3,"title":["Predicting risk of impending cognitive decline in asymptomatic individuals with early Alzheimer\u2019s disease: Insights from cortical diffusion MRI"],"prefix":"10.1162","volume":"3","author":[{"given":"Devon K.","family":"Overson","sequence":"first","affiliation":[{"name":"Brain Imaging and Analysis Center, Duke University, Durham, NC, United States"},{"name":"Medical Physics Graduate Program, Duke University, Durham, NC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2699-1554","authenticated-orcid":false,"given":"Trong-Kha","family":"Truong","sequence":"additional","affiliation":[{"name":"Brain Imaging and Analysis Center, Duke University, Durham, NC, United States"},{"name":"Medical Physics Graduate Program, Duke University, Durham, NC, United States"},{"name":"Department of Radiology, Duke University Medical Center, Durham, NC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Petrella","sequence":"additional","affiliation":[{"name":"Brain Imaging and Analysis Center, Duke University, Durham, NC, United States"},{"name":"Medical Physics Graduate Program, Duke University, Durham, NC, United States"},{"name":"Department of Radiology, Duke University Medical Center, Durham, NC, United States"},{"name":"Duke Center for the Study of Aging and Human Development, Duke University, Durham, NC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Madden","sequence":"additional","affiliation":[{"name":"Brain Imaging and Analysis Center, Duke University, Durham, NC, United States"},{"name":"Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, United States"},{"name":"Department of Psychology and Neuroscience, Duke University, Durham, NC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Ma","sequence":"additional","affiliation":[{"name":"Brain Imaging and Analysis Center, Duke University, Durham, NC, United States"},{"name":"Medical Physics Graduate Program, Duke University, Durham, NC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim G.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, United States"},{"name":"Department of Neurology, Duke University, Durham, NC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy J.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Duke University, Durham, NC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Neurology, Duke University, Durham, NC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather E.","family":"Whitson","sequence":"additional","affiliation":[{"name":"Duke Center for the Study of Aging and Human Development, Duke University, Durham, NC, United States"},{"name":"Department of Neurology, Duke University, Durham, NC, United States"},{"name":"Department of Medicine, Duke University, Durham, NC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen W.","family":"Song","sequence":"additional","affiliation":[{"name":"Brain Imaging and Analysis Center, Duke University, Durham, NC, United States"},{"name":"Medical Physics Graduate Program, Duke University, Durham, NC, United States"},{"name":"Department of Radiology, Duke University Medical Center, Durham, NC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"281","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"issue":"2","key":"2025112414560665100_IMAG.a.1037-b1","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/S1053-8119(03)00336-7","article-title":"How to correct susceptibility distortions in spin-echo echo-planar images: Application to diffusion tensor imaging","volume":"20","author":"Andersson","year":"2003","journal-title":"NeuroImage"},{"key":"2025112414560665100_IMAG.a.1037-b2","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.neuroimage.2015.10.019","article-title":"An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging","volume":"125","author":"Andersson","year":"2016","journal-title":"NeuroImage"},{"issue":"6","key":"2025112414560665100_IMAG.a.1037-b3","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1016\/j.neuropsychologia.2007.10.026","article-title":"Mapping progressive brain structural changes in early Alzheimer\u2019s disease and mild cognitive impairment","volume":"46","author":"Apostolova","year":"2008","journal-title":"Neuropsychologia"},{"issue":"12","key":"2025112414560665100_IMAG.a.1037-b4","doi-asserted-by":"crossref","first-page":"2468","DOI":"10.1002\/alz.12580","article-title":"Neurodegeneration and astrogliosis in the entorhinal cortex in Alzheimer\u2019s disease: Stereological layer-specific assessment and proteomic analysis","volume":"18","author":"Astillero-Lopez","year":"2022","journal-title":"Alzheimer\u2019s & Dementia"},{"issue":"1","key":"2025112414560665100_IMAG.a.1037-b5","doi-asserted-by":"crossref","first-page":"395","DOI":"10.3233\/JAD-210406","article-title":"Sex differences in Alzheimer\u2019s disease revealed by free-water diffusion tensor imaging and voxel-based morphometry","volume":"85","author":"Bergamino","year":"2022","journal-title":"Journal of Alzheimer\u2019s Disease"},{"key":"2025112414560665100_IMAG.a.1037-b6","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.neuroimage.2013.01.038","article-title":"A robust multi-shot scan strategy for high-resolution diffusion weighted MRI enabled by multiplexed sensitivity-encoding (MUSE)","volume":"72","author":"Chen","year":"2013","journal-title":"NeuroImage"},{"key":"2025112414560665100_IMAG.a.1037-b7","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.neuroimage.2019.06.039","article-title":"Complex diffusion-weighted image estimation via matrix recovery under general noise models","volume":"200","author":"Cordero-Grande","year":"2019","journal-title":"NeuroImage"},{"issue":"12","key":"2025112414560665100_IMAG.a.1037-b8","doi-asserted-by":"crossref","first-page":"e48121","DOI":"10.1371\/journal.pone.0048121","article-title":"The connectome mapper: An open-source processing pipeline to map connectomes with MRI","volume":"7","author":"Daducci","year":"2012","journal-title":"PLoS One"},{"issue":"3","key":"2025112414560665100_IMAG.a.1037-b9","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.neuroimage.2006.01.021","article-title":"An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest","volume":"31","author":"Desikan","year":"2006","journal-title":"NeuroImage"},{"issue":"Suppl. 5","key":"2025112414560665100_IMAG.a.1037-b10","doi-asserted-by":"crossref","first-page":"e055657","DOI":"10.1002\/alz.055657","article-title":"Clinical validation of the lumipulse G \u03b2-amyloid ratio (1-42\/1-40) in a subset of ADNI CSF samples","volume":"17","author":"Esquivel","year":"2021","journal-title":"Alzheimer\u2019s Dementia"},{"issue":"2","key":"2025112414560665100_IMAG.a.1037-b11","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.neuroimage.2012.01.021","article-title":"FreeSurfer","volume":"62","author":"Fischl","year":"2012","journal-title":"NeuroImage"},{"issue":"20","key":"2025112414560665100_IMAG.a.1037-b12","doi-asserted-by":"crossref","first-page":"11050","DOI":"10.1073\/pnas.200033797","article-title":"Measuring the thickness of the human cerebral cortex from magnetic resonance images","volume":"97","author":"Fischl","year":"2000","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"1","key":"2025112414560665100_IMAG.a.1037-b13","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s43856-023-00324-7","article-title":"Cortical microstructural changes predict tau accumulation and episodic memory decline in older adults harboring amyloid","volume":"3","author":"Gagliardi","year":"2023","journal-title":"Communications Medicine"},{"issue":"14","key":"2025112414560665100_IMAG.a.1037-b14","doi-asserted-by":"crossref","first-page":"4491","DOI":"10.1523\/JNEUROSCI.16-14-04491.1996","article-title":"Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer\u2019s disease","volume":"16","author":"G\u00f3mez-Isla","year":"1996","journal-title":"The Journal of Neuroscience"},{"issue":"1","key":"2025112414560665100_IMAG.a.1037-b15","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.neuroimage.2009.06.060","article-title":"Accurate and robust brain image alignment using boundary-based registration","volume":"48","author":"Greve","year":"2009","journal-title":"NeuroImage"},{"issue":"8","key":"2025112414560665100_IMAG.a.1037-b16","doi-asserted-by":"crossref","first-page":"5143","DOI":"10.1002\/alz.13859","article-title":"Revised criteria for diagnosis and staging of Alzheimer\u2019s disease: Alzheimer\u2019s Association Workgroup","volume":"20","author":"Jack","year":"2024","journal-title":"Alzheimer\u2019s Dementia"},{"issue":"4","key":"2025112414560665100_IMAG.a.1037-b17","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA research framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimer\u2019s Dementia"},{"issue":"3","key":"2025112414560665100_IMAG.a.1037-b18","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1002\/alz.13651","article-title":"Comparison of plasma biomarkers and amyloid PET for predicting memory decline in cognitively unimpaired individuals","volume":"20","author":"Jack","year":"2024","journal-title":"Alzheimer\u2019s & Dementia"},{"issue":"5","key":"2025112414560665100_IMAG.a.1037-b19","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1002\/mrm.26054","article-title":"Gibbs-ringing artifact removal based on local subvoxel-shifts","volume":"76","author":"Kellner","year":"2016","journal-title":"Magnetic Resonance in Medicine"},{"issue":"9","key":"2025112414560665100_IMAG.a.1037-b20","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1016\/j.cortex.2012.11.015","article-title":"Layer-specific diffusion weighted imaging in human primary visual cortex in vitro","volume":"49","author":"Kleinnijenhuis","year":"2013","journal-title":"Cortex"},{"key":"2025112414560665100_IMAG.a.1037-b21","doi-asserted-by":"crossref","first-page":"119993","DOI":"10.1016\/j.neuroimage.2023.119993","article-title":"Column-based cortical depth analysis of the diffusion anisotropy and radiality in submillimeter whole-brain diffusion tensor imaging of the human cortical gray matter in vivo","volume":"270","author":"Ma","year":"2023","journal-title":"NeuroImage"},{"issue":"3","key":"2025112414560665100_IMAG.a.1037-b22","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.jalz.2017.09.013","article-title":"Cortical microstructural changes along the Alzheimer\u2019s disease continuum","volume":"14","author":"Montal","year":"2018","journal-title":"Alzheimer\u2019s & Dementia"},{"issue":"4","key":"2025112414560665100_IMAG.a.1037-b23","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The Montreal Cognitive Assessment, MoCA: A brief screening tool for mild cognitive impairment","volume":"53","author":"Nasreddine","year":"2005","journal-title":"Journal of the American Geriatrics Society"},{"key":"2025112414560665100_IMAG.a.1037-b24","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3389\/fnagi.2013.00071","article-title":"Sex dimorphism of cortical water diffusion in normal aging measured by magnetic resonance imaging","volume":"5","author":"Ng","year":"2013","journal-title":"Frontiers in Aging Neuroscience"},{"key":"2025112414560665100_IMAG.a.1037-b25","doi-asserted-by":"crossref","first-page":"101311","DOI":"10.1016\/j.arr.2021.101311","article-title":"Region-specific vulnerability in neurodegeneration: Lessons from normal ageing","volume":"67","author":"Pandya","year":"2021","journal-title":"Ageing Research Reviews"},{"issue":"1","key":"2025112414560665100_IMAG.a.1037-b26","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/alzrt62","article-title":"Amyloid imaging and memory change for prediction of cognitive impairment","volume":"3","author":"Resnick","year":"2011","journal-title":"Alzheimer\u2019s Research & Therapy"},{"issue":"12","key":"2025112414560665100_IMAG.a.1037-b27","doi-asserted-by":"crossref","first-page":"7813","DOI":"10.1038\/s41380-021-01290-z","article-title":"Association of cortical microstructure with amyloid-\u03b2 and tau: Impact on cognitive decline, neurodegeneration, and clinical progression in older adults","volume":"26","author":"Rodriguez-Vieitez","year":"2021","journal-title":"Molecular Psychiatry"},{"key":"2025112414560665100_IMAG.a.1037-b28","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/978-1-4419-9863-7_223","article-title":"False discovery rate (FDR)","volume-title":"Encyclopedia of systems biology","author":"Rouam","year":"2013"},{"key":"2025112414560665100_IMAG.a.1037-b29","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.nicl.2016.05.017","article-title":"A large-scale comparison of cortical thickness and volume methods for measuring Alzheimer\u2019s disease severity","volume":"11","author":"Schwarz","year":"2016","journal-title":"NeuroImage Clinical"},{"issue":"Suppl. 1","key":"2025112414560665100_IMAG.a.1037-b30","doi-asserted-by":"crossref","first-page":"S208","DOI":"10.1016\/j.neuroimage.2004.07.051","article-title":"Advances in functional and structural MR image analysis and implementation as FSL","volume":"23","author":"Smith","year":"2004","journal-title":"NeuroImage"},{"issue":"3","key":"2025112414560665100_IMAG.a.1037-b31","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.neuron.2014.10.038","article-title":"The evolution of preclinical Alzheimer\u2019s disease: Implications for prevention trials","volume":"84","author":"Sperling","year":"2014","journal-title":"Neuron"},{"issue":"3","key":"2025112414560665100_IMAG.a.1037-b32","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1093\/brain\/awad428","article-title":"Diffusion MRI tracks cortical microstructural changes during the early stages of Alzheimer\u2019s disease","volume":"147","author":"Spotorno","year":"2024","journal-title":"Brain"},{"issue":"10","key":"2025112414560665100_IMAG.a.1037-b33","doi-asserted-by":"crossref","first-page":"7048","DOI":"10.1002\/alz.14176","article-title":"Spatial and temporal patterns of cortical mean diffusivity in Alzheimer\u2019s disease and suspected non-Alzheimer\u2019s disease pathophysiology","volume":"20","author":"Sun","year":"2024","journal-title":"Alzheimer\u2019s & Dementia"},{"issue":"2","key":"2025112414560665100_IMAG.a.1037-b34","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.neuroscience.2008.03.077","article-title":"Posterior parahippocampal gyrus pathology in Alzheimer\u2019s disease","volume":"154","author":"Thangavel","year":"2008","journal-title":"Neuroscience"},{"key":"2025112414560665100_IMAG.a.1037-b35","doi-asserted-by":"crossref","first-page":"116137","DOI":"10.1016\/j.neuroimage.2019.116137","article-title":"MRtrix3: A fast, flexible and open software framework for medical image processing and visualisation","volume":"202","author":"Tournier","year":"2019","journal-title":"NeuroImage"},{"issue":"1","key":"2025112414560665100_IMAG.a.1037-b36","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in early Alzheimer\u2019s disease","volume":"388","author":"van Dyck","year":"2023","journal-title":"New England Journal of Medicine"},{"issue":"3","key":"2025112414560665100_IMAG.a.1037-b37","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2174\/1567205013666151218150322","article-title":"Defining the earliest pathological changes of Alzheimer\u2019s disease","volume":"13","author":"Vickers","year":"2016","journal-title":"Current Alzheimer Research"},{"issue":"1","key":"2025112414560665100_IMAG.a.1037-b38","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13195-015-0132-3","article-title":"Diffusion imaging changes in grey matter in Alzheimer\u2019s disease: A potential marker of early neurodegeneration","volume":"7","author":"Weston","year":"2015","journal-title":"Alzheimer\u2019s Research & Therapy"},{"issue":"1","key":"2025112414560665100_IMAG.a.1037-b39","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13195-020-00679-2","article-title":"Measuring cortical mean diffusivity to assess early microstructural cortical change in presymptomatic familial Alzheimer\u2019s disease","volume":"12","author":"Weston","year":"2020","journal-title":"Alzheimer\u2019s Research & Therarpy"},{"issue":"Suppl. 4","key":"2025112414560665100_IMAG.a.1037-b40","doi-asserted-by":"crossref","first-page":"e046006","DOI":"10.1002\/alz.046006","article-title":"Prediction of amyloid PET status using the LUMIPULSE G \u03b2-amyloid ratio (1-42\/1-40)","volume":"16","author":"Willemse","year":"2020","journal-title":"Alzheimer\u2019s Dementia"},{"issue":"7","key":"2025112414560665100_IMAG.a.1037-b41","doi-asserted-by":"crossref","first-page":"e70222","DOI":"10.1002\/hbm.70222","article-title":"Layer-dependent effect of A\u03b2-pathology on cortical microstructure with ex vivo human brain diffusion MRI at 7 tesla","volume":"46","author":"Zhao","year":"2025","journal-title":"Human Brain Mapping"}],"container-title":["Imaging Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/direct.mit.edu\/imag\/article-pdf\/doi\/10.1162\/IMAG.a.1037\/2563662\/imag.a.1037.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/direct.mit.edu\/imag\/article-pdf\/doi\/10.1162\/IMAG.a.1037\/2563662\/imag.a.1037.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T19:56:19Z","timestamp":1764014179000},"score":1,"resource":{"primary":{"URL":"https:\/\/direct.mit.edu\/imag\/article\/doi\/10.1162\/IMAG.a.1037\/133931\/Predicting-risk-of-impending-cognitive-decline-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":41,"URL":"https:\/\/doi.org\/10.1162\/imag.a.1037","relation":{},"ISSN":["2837-6056"],"issn-type":[{"value":"2837-6056","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025]]},"published":{"date-parts":[[2025]]},"article-number":"IMAG.a.1037"}}