{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T13:27:43Z","timestamp":1767274063948,"version":"3.48.0"},"posted":{"date-parts":[[2025,12,11]]},"group-title":"Radiology and Imaging","reference-count":72,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Heart-brain interactions, including cardiac-induced brain pulsatility, are thought to support brain homeostasis, yet their alteration with aging and neurodegeneration remains poorly understood. Here, we used three-dimensional quantitative amplified MRI (q-aMRI) to visualize and quantify cardiac-induced pulsatile brain motion across healthy individuals and those on the Alzheimer\u2019s and Lewy body disease spectra. Expert evaluations revealed consistent distinctions between normal and abnormal motion patterns, which were further characterized using strain-based biomechanical features. Principal component analysis identified interpretable signatures of abnormal motion that emerged predominantly after midlife and were closely linked to chronological age. Even after accounting for age, these biomechanical features differentiated individuals with clinical and biomarker evidence of neurodegenerative disease. Together, these findings suggest that q-aMRI\u2013derived measures of cardiac-gated pulsatile brain motion may serve as imaging biomarkers of normal brain aging and dementia.<\/jats:p>","DOI":"10.64898\/2025.12.10.25341649","type":"posted-content","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T23:25:19Z","timestamp":1765495519000},"source":"Crossref","is-referenced-by-count":0,"title":["Pulsatile Brain Motion as a Marker of Brain Aging and Dementia: Insights from 3D q-aMRI"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6544-9138","authenticated-orcid":false,"given":"Itamar","family":"Terem","sequence":"first","affiliation":[{"name":"Electrical Engineering, Stanford University, Stanford, CA, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyan","family":"Younes","sequence":"additional","affiliation":[{"name":"Neurology & Neurological Sciences, Stanford University, Stanford, CA, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Skylar","family":"Weiss","sequence":"additional","affiliation":[{"name":"Neurology & Neurological Sciences, Stanford University, Stanford, CA, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Dreisbach","sequence":"additional","affiliation":[{"name":"Radiology, Stanford University, Stanford, CA, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hillary","family":"Vossler","sequence":"additional","affiliation":[{"name":"Neurology & Neurological Sciences, Stanford University, Stanford, CA, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eryn","family":"Kwon","sequence":"additional","affiliation":[{"name":"M\u0101tai Medical Research Institute, Tair\u0101whiti-Gisborne, New Zealand"},{"name":"Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand"},{"name":"Faculty of Medical & Health Science & Centre for Brain Research, University of Auckland, Auckland, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Cornfeld","sequence":"additional","affiliation":[{"name":"M\u0101tai Medical Research Institute, Tair\u0101whiti-Gisborne, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jet","family":"Wright","sequence":"additional","affiliation":[{"name":"M\u0101tai Medical Research Institute, Tair\u0101whiti-Gisborne, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Condron","sequence":"additional","affiliation":[{"name":"M\u0101tai Medical Research Institute, Tair\u0101whiti-Gisborne, New Zealand"},{"name":"Faculty of Medical & Health Science & Centre for Brain Research, University of Auckland, Auckland, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen L","family":"Poston","sequence":"additional","affiliation":[{"name":"Neurology & Neurological Sciences, Stanford University, Stanford, CA, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor W.","family":"Henderson","sequence":"additional","affiliation":[{"name":"Neurology & Neurological Sciences, Stanford University, Stanford, CA, United States"},{"name":"Department of Epidemiology and Population Health, Stanford University, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth C","family":"Mormino","sequence":"additional","affiliation":[{"name":"Neurology & Neurological Sciences, Stanford University, Stanford, CA, United States"},{"name":"Wu Tsai Neuroscience Institute, Stanford, California, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Holdsworth","sequence":"additional","affiliation":[{"name":"Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand"},{"name":"Faculty of Medical & Health Science & Centre for Brain Research, University of Auckland, Auckland, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kawin","family":"Setsompop","sequence":"additional","affiliation":[{"name":"Radiology, Stanford University, Stanford, CA, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026010105262493000_2025.12.10.25341649v1.1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.185.3.1438741"},{"key":"2026010105262493000_2025.12.10.25341649v1.2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910350516"},{"key":"2026010105262493000_2025.12.10.25341649v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROIMAGE.2020.116581"},{"key":"2026010105262493000_2025.12.10.25341649v1.4","doi-asserted-by":"crossref","first-page":"118078","DOI":"10.1016\/j.neuroimage.2021.118078","article-title":"Strain Tensor Imaging: Cardiac-induced brain tissue deformation in humans quantified with high-field MRI","volume":"236","year":"2021","journal-title":"Neuroimage"},{"key":"2026010105262493000_2025.12.10.25341649v1.5","doi-asserted-by":"publisher","DOI":"10.1098\/rsfs.2024.0058"},{"key":"2026010105262493000_2025.12.10.25341649v1.6","doi-asserted-by":"publisher","DOI":"10.1098\/rsfs.2024.0041"},{"key":"2026010105262493000_2025.12.10.25341649v1.7","doi-asserted-by":"crossref","first-page":"110278","DOI":"10.1016\/j.ijmecsci.2025.110278","article-title":"Blood\u2013brain mechanics: How brain tissue responds to pulsatile blood flow dynamics","volume":"296","year":"2025","journal-title":"International Journal of Mechanical Sciences"},{"key":"2026010105262493000_2025.12.10.25341649v1.8","doi-asserted-by":"publisher","DOI":"10.1101\/2025.06.20.660588"},{"key":"2026010105262493000_2025.12.10.25341649v1.9","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/57\/22\/7275"},{"key":"2026010105262493000_2025.12.10.25341649v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07318-3"},{"key":"2026010105262493000_2025.12.10.25341649v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01327-2"},{"key":"2026010105262493000_2025.12.10.25341649v1.12","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2023.0288"},{"key":"2026010105262493000_2025.12.10.25341649v1.13","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/s43587-022-00219-7","article-title":"Deep learning-based brain age prediction in normal aging and dementia","volume":"2","year":"2022","journal-title":"Nat Aging"},{"key":"2026010105262493000_2025.12.10.25341649v1.14","doi-asserted-by":"crossref","first-page":"e70059","DOI":"10.1002\/alz.70059","article-title":"The impact of arteriolosclerosis on cognitive impairment in decedents without severe dementia from the National Alzheimer\u2019s Coordinating Center","volume":"21","year":"2025","journal-title":"Alzheimers Dement"},{"key":"2026010105262493000_2025.12.10.25341649v1.15","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.25891"},{"key":"2026010105262493000_2025.12.10.25341649v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROIMAGE.2021.117889"},{"key":"2026010105262493000_2025.12.10.25341649v1.17","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.22707"},{"key":"2026010105262493000_2025.12.10.25341649v1.18","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/B978-0-12-804766-8.00009-1","article-title":"Epidemiology of aging and associated cognitive disorders: Prevalence and incidence of Alzheimer\u2019s disease and other dementias","volume":"167","year":"2019","journal-title":"Handb Clin Neurol"},{"key":"2026010105262493000_2025.12.10.25341649v1.19","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000271090.28148.24"},{"key":"2026010105262493000_2025.12.10.25341649v1.20","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001831"},{"key":"2026010105262493000_2025.12.10.25341649v1.21","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-014-0082-1"},{"key":"2026010105262493000_2025.12.10.25341649v1.22","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002480"},{"key":"2026010105262493000_2025.12.10.25341649v1.23","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1093\/brain\/awad154","article-title":"The pathotome and precision health","volume":"146","year":"2023","journal-title":"Brain"},{"key":"2026010105262493000_2025.12.10.25341649v1.24","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","year":"2024","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"2026010105262493000_2025.12.10.25341649v1.25","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004058"},{"key":"2026010105262493000_2025.12.10.25341649v1.26","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26142"},{"key":"2026010105262493000_2025.12.10.25341649v1.27","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.27236"},{"key":"2026010105262493000_2025.12.10.25341649v1.28","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.28797"},{"key":"2026010105262493000_2025.12.10.25341649v1.29","doi-asserted-by":"crossref","first-page":"100022","DOI":"10.1016\/j.brain.2021.100022","article-title":"Development, calibration, and testing of 3D amplified MRI (aMRI) for the quantification of intrinsic brain motion","volume":"2","year":"2021","journal-title":"Brain Multiphys"},{"key":"2026010105262493000_2025.12.10.25341649v1.30","doi-asserted-by":"publisher","DOI":"10.1098\/rsfs.2024.0049"},{"key":"2026010105262493000_2025.12.10.25341649v1.31","doi-asserted-by":"crossref","first-page":"fcz021","DOI":"10.1093\/braincomms\/fcz021","article-title":"Novel strain analysis informs about injury susceptibility of the corpus callosum to repeated impacts","volume":"1","year":"2019","journal-title":"Brain Commun"},{"key":"2026010105262493000_2025.12.10.25341649v1.32","doi-asserted-by":"crossref","first-page":"100100","DOI":"10.1016\/j.brain.2024.100100","article-title":"Increased hindbrain motion in Chiari I malformation patients measured through 3D amplified MRI (3D aMRI)","volume":"7","year":"2024","journal-title":"Brain Multiphysics"},{"key":"2026010105262493000_2025.12.10.25341649v1.33","first-page":"449","volume-title":"Advances in Magnetic Resonance Technology and Applications","volume":"6","year":"2022"},{"key":"2026010105262493000_2025.12.10.25341649v1.34","doi-asserted-by":"publisher","DOI":"10.1136\/jnis-2025-023486"},{"key":"2026010105262493000_2025.12.10.25341649v1.35","doi-asserted-by":"crossref","first-page":"4113","DOI":"10.1109\/TMI.2020.3012932","article-title":"Amplified Flow Imaging (aFlow): A Novel MRI-Based Tool to Unravel the Coupled Dynamics Between the Human Brain and Cerebrovasculature","volume":"39","year":"2020","journal-title":"IEEE Trans Med Imaging"},{"key":"2026010105262493000_2025.12.10.25341649v1.36","doi-asserted-by":"publisher","DOI":"10.1098\/rsfs.2024.0039"},{"key":"2026010105262493000_2025.12.10.25341649v1.37","doi-asserted-by":"crossref","first-page":"851","DOI":"10.3390\/bioengineering11080851","article-title":"3D Quantitative-Amplified Magnetic Resonance Imaging (3D q-aMRI)","volume":"11","year":"2024","journal-title":"Bioengineering"},{"key":"2026010105262493000_2025.12.10.25341649v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.021"},{"key":"2026010105262493000_2025.12.10.25341649v1.39","first-page":"2233","article-title":"Tau PET imaging with 18F-PI-2620 in aging and neurodegenerative diseases","volume":"48","year":"2020","journal-title":"European Journal of Nuclear Medicine and Molecular Imaging"},{"key":"2026010105262493000_2025.12.10.25341649v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.media.2023.102789"},{"key":"2026010105262493000_2025.12.10.25341649v1.41","first-page":"3","article-title":"Magnetic resonance imaging of the pulsing brain: a systematic review","volume":"36","year":"2023","journal-title":"MAGMA"},{"key":"2026010105262493000_2025.12.10.25341649v1.42","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.24163"},{"key":"2026010105262493000_2025.12.10.25341649v1.43","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/56\/13\/N02"},{"key":"2026010105262493000_2025.12.10.25341649v1.44","unstructured":"Website. Cardillo G. (2007) Fleiss\u2019es kappa: compute the Fleiss\u2019es kappa for multiple raters. http:\/\/www.mathworks.com\/matlabcentral\/fileexchange\/15426."},{"key":"2026010105262493000_2025.12.10.25341649v1.45","doi-asserted-by":"crossref","first-page":"igz036","DOI":"10.1093\/geroni\/igz036","article-title":"Effect Size Guidelines, Sample Size Calculations, and Statistical Power in Gerontology","volume":"3","year":"2019","journal-title":"Innov Aging"},{"key":"2026010105262493000_2025.12.10.25341649v1.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.01.010"},{"key":"2026010105262493000_2025.12.10.25341649v1.47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023451"},{"key":"2026010105262493000_2025.12.10.25341649v1.48","doi-asserted-by":"crossref","first-page":"bpae086","DOI":"10.1093\/biomethods\/bpae086","article-title":"MRI-based whole-brain elastography and volumetric measurements to predict brain age","volume":"10","year":"2025","journal-title":"Biol Methods Protoc"},{"key":"2026010105262493000_2025.12.10.25341649v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)90878-9"},{"key":"2026010105262493000_2025.12.10.25341649v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.06.017"},{"key":"2026010105262493000_2025.12.10.25341649v1.51","doi-asserted-by":"crossref","first-page":"fcae116","DOI":"10.1093\/braincomms\/fcae116","article-title":"Caudate functional networks influence brain structural changes with aging","volume":"6","year":"2024","journal-title":"Brain Commun"},{"key":"2026010105262493000_2025.12.10.25341649v1.52","doi-asserted-by":"crossref","first-page":"e2318153","DOI":"10.1001\/jamanetworkopen.2023.18153","article-title":"Characterization of Brain Volume Changes in Aging Individuals With Normal Cognition Using Serial Magnetic Resonance Imaging","volume":"6","year":"2023","journal-title":"JAMA Netw Open"},{"key":"2026010105262493000_2025.12.10.25341649v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.07.043"},{"key":"2026010105262493000_2025.12.10.25341649v1.54","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn278"},{"key":"2026010105262493000_2025.12.10.25341649v1.55","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp007"},{"key":"2026010105262493000_2025.12.10.25341649v1.56","first-page":"816","article-title":"Amidst an amygdala renaissance in Alzheimer\u2019s disease","volume":"147","year":"2023","journal-title":"Brain"},{"key":"2026010105262493000_2025.12.10.25341649v1.57","doi-asserted-by":"crossref","first-page":"e638","DOI":"10.1002\/mco2.638","article-title":"Cerebellum in Alzheimer\u2019s disease and other neurodegenerative diseases: an emerging research frontier","volume":"5","year":"2024","journal-title":"MedComm"},{"key":"2026010105262493000_2025.12.10.25341649v1.58","doi-asserted-by":"crossref","first-page":"e14428","DOI":"10.1002\/alz.14428","article-title":"Neuropathological correlates of vulnerability and resilience in the cerebellum in Alzheimer\u2019s disease","volume":"21","year":"2025","journal-title":"Alzheimers Dement"},{"key":"2026010105262493000_2025.12.10.25341649v1.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2014.02.002"},{"key":"2026010105262493000_2025.12.10.25341649v1.60","doi-asserted-by":"crossref","first-page":"1486775","DOI":"10.3389\/fnagi.2025.1486775","article-title":"Cerebral pulsatility might be a driver of neurofunctional reorganization in the aging brain: an MRI and NIRS study","volume":"17","year":"2025","journal-title":"Front. Aging Neurosci"},{"key":"2026010105262493000_2025.12.10.25341649v1.61","doi-asserted-by":"crossref","first-page":"fcab211","DOI":"10.1093\/braincomms\/fcab211","article-title":"The enigma and implications of brain hemispheric asymmetry in neurodegenerative diseases","volume":"3","year":"2021","journal-title":"Brain Commun"},{"key":"2026010105262493000_2025.12.10.25341649v1.62","doi-asserted-by":"crossref","first-page":"8232","DOI":"10.1038\/s41467-025-63564-2","article-title":"Hemispheric asymmetry of tau pathology is related to asymmetric amyloid deposition in Alzheimer\u2019s Disease","volume":"16","year":"2025","journal-title":"Nat Commun"},{"key":"2026010105262493000_2025.12.10.25341649v1.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2024.05.002"},{"key":"2026010105262493000_2025.12.10.25341649v1.64","doi-asserted-by":"crossref","first-page":"103327","DOI":"10.1016\/j.nicl.2023.103327","article-title":"Hippocampal subfield viscoelasticity in amnestic mild cognitive impairment evaluated with MR elastography","volume":"37","year":"2023","journal-title":"Neuroimage Clin"},{"key":"2026010105262493000_2025.12.10.25341649v1.65","doi-asserted-by":"crossref","first-page":"fcz049","DOI":"10.1093\/braincomms\/fcz049","article-title":"Mechanical property alterations across the cerebral cortex due to Alzheimer\u2019s disease","volume":"2","year":"2020","journal-title":"Brain Commun"},{"key":"2026010105262493000_2025.12.10.25341649v1.66","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.nicl.2013.09.006","article-title":"Cerebral magnetic resonance elastography in supranuclear palsy and idiopathic Parkinson\u2019s disease","volume":"3","year":"2013","journal-title":"Neuroimage Clin"},{"key":"2026010105262493000_2025.12.10.25341649v1.67","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.06.018"},{"key":"2026010105262493000_2025.12.10.25341649v1.68","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-022-00376-2"},{"key":"2026010105262493000_2025.12.10.25341649v1.69","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2463\/mrms.mp.2017-0014","article-title":"Cardiac-driven Pulsatile Motion of Intracranial Cerebrospinal Fluid Visualized Based on a Correlation Mapping Technique","volume":"17","year":"2018","journal-title":"Magn Reson Med Sci"},{"key":"2026010105262493000_2025.12.10.25341649v1.70","doi-asserted-by":"crossref","first-page":"110530","DOI":"10.1016\/j.mri.2025.110530","article-title":"Cardiac-induced brain tissue motion in Chiari Malformation type 1 subjects and its relationship to symptomatology, morphometrics, and surgical outcomes","volume":"124","year":"2025","journal-title":"Magn. Reson. Imaging"},{"key":"2026010105262493000_2025.12.10.25341649v1.71","unstructured":"Margetis, K. & Baker, S. Physiology, Cerebral Spinal Fluid. in StatPearls [Internet] (StatPearls Publishing, 2025)."},{"key":"2026010105262493000_2025.12.10.25341649v1.72","doi-asserted-by":"crossref","first-page":"104987","DOI":"10.1016\/j.isci.2022.104987","article-title":"The glymphatic system: Current understanding and modeling","volume":"25","year":"2022","journal-title":"iScience"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2025.12.10.25341649","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T13:26:39Z","timestamp":1767273999000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2025.12.10.25341649"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,11]]},"references-count":72,"URL":"https:\/\/doi.org\/10.64898\/2025.12.10.25341649","relation":{},"subject":[],"published":{"date-parts":[[2025,12,11]]},"subtype":"preprint"}}