{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T13:50:17Z","timestamp":1773064217153,"version":"3.50.1"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R21AG074146"],"award-info":[{"award-number":["R21AG074146"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["GeroScience"],"DOI":"10.1007\/s11357-025-01805-4","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T12:23:10Z","timestamp":1753100590000},"page":"2505-2522","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advancing clinical trial readiness in white matter disease and related dementias: key steps for future research progress"],"prefix":"10.1007","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5160-2509","authenticated-orcid":false,"given":"Pradoldej","family":"Sompol","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory A.","family":"Jicha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason D.","family":"Hinman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam M.","family":"Brickman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven M.","family":"Greenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantinos","family":"Arfanakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion S.","family":"Buckwalter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene Lorenzo","family":"Llorente","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeff D.","family":"Williamson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael S.","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric E.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aditi","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret E.","family":"Flanagan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel A.","family":"Vazquez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey M.","family":"Burns","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Thomas","family":"Carmichael","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank C.","family":"Barone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"issue":"1","key":"1805_CR1","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1186\/s13195-020-00669-4","volume":"12","author":"A Garnier-Crussard","year":"2020","unstructured":"Garnier-Crussard A, et al. White matter hyperintensities across the adult lifespan: relation to age, Abeta load, and cognition. Alzheimers Res Ther. 2020;12(1):127.","journal-title":"Alzheimers Res Ther"},{"key":"1805_CR2","doi-asserted-by":"publisher","first-page":"617927","DOI":"10.4061\/2011\/617927","volume":"2011","author":"YY Xiong","year":"2011","unstructured":"Xiong YY, Mok V. Age-related white matter changes. J Aging Res. 2011;2011: 617927.","journal-title":"J Aging Res"},{"issue":"4","key":"1805_CR3","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1002\/hbm.20586","volume":"30","author":"W Wen","year":"2009","unstructured":"Wen W, et al. White matter hyperintensities in the forties: their prevalence and topography in an epidemiological sample aged 44\u201348. Hum Brain Mapp. 2009;30(4):1155\u201367.","journal-title":"Hum Brain Mapp"},{"issue":"9","key":"1805_CR4","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1007\/s002340050820","volume":"41","author":"R Mantyla","year":"1999","unstructured":"Mantyla R, et al. The prevalence and distribution of white-matter changes on different MRI pulse sequences in a post-stroke cohort. Neuroradiology. 1999;41(9):657\u201365.","journal-title":"Neuroradiology"},{"issue":"3","key":"1805_CR5","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1161\/STROKEAHA.109.563502","volume":"41","author":"J Jimenez-Conde","year":"2010","unstructured":"Jimenez-Conde J, et al. Hyperlipidemia and reduced white matter hyperintensity volume in patients with ischemic stroke. Stroke. 2010;41(3):437\u201342.","journal-title":"Stroke"},{"issue":"1\u20132","key":"1805_CR6","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.jns.2009.02.314","volume":"283","author":"M Targosz-Gajniak","year":"2009","unstructured":"Targosz-Gajniak M, et al. Cerebral white matter lesions in patients with dementia - from MCI to severe Alzheimer\u2019s disease. J Neurol Sci. 2009;283(1\u20132):79\u201382.","journal-title":"J Neurol Sci"},{"issue":"2","key":"1805_CR7","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1212\/01.WNL.0000103289.03648.AD","volume":"62","author":"FE de Leeuw","year":"2004","unstructured":"de Leeuw FE, Barkhof F, Scheltens P. White matter lesions and hippocampal atrophy in Alzheimer\u2019s disease. Neurology. 2004;62(2):310\u20132.","journal-title":"Neurology"},{"issue":"6","key":"1805_CR8","first-page":"505","volume":"42","author":"J Slawek","year":"2008","unstructured":"Slawek J, et al. The influence of vascular risk factors and white matter hyperintensities on the degree of cognitive impairment in Parkinson\u2019s disease. Neurol Neurochir Pol. 2008;42(6):505\u201312.","journal-title":"Neurol Neurochir Pol"},{"issue":"2","key":"1805_CR9","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.archger.2008.09.005","volume":"49","author":"SJ Lee","year":"2009","unstructured":"Lee SJ, et al. The severity of leukoaraiosis correlates with the clinical phenotype of Parkinson\u2019s disease. Arch Gerontol Geriatr. 2009;49(2):255\u20139.","journal-title":"Arch Gerontol Geriatr"},{"issue":"1","key":"1805_CR10","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s12883-020-02037-z","volume":"21","author":"TC Chang","year":"2021","unstructured":"Chang TC, et al. Systemic oxidative stress and cognitive function in Parkinson\u2019s disease with different PWMH or DWMH lesions. BMC Neurol. 2021;21(1):16.","journal-title":"BMC Neurol"},{"issue":"3","key":"1805_CR11","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/S1474-4422(15)00393-2","volume":"15","author":"M Filippi","year":"2016","unstructured":"Filippi M, et al. MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol. 2016;15(3):292\u2013303.","journal-title":"Lancet Neurol"},{"issue":"4","key":"1805_CR12","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nrneurol.2018.39","volume":"14","author":"R Geraldes","year":"2018","unstructured":"Geraldes R, et al. The current role of MRI in differentiating multiple sclerosis from its imaging mimics. Nat Rev Neurol. 2018;14(4):213.","journal-title":"Nat Rev Neurol"},{"issue":"5","key":"1805_CR13","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1097\/00005072-198809000-00003","volume":"47","author":"SM de la Monte","year":"1988","unstructured":"de la Monte SM, Vonsattel JP, Richardson EP Jr. Morphometric demonstration of atrophic changes in the cerebral cortex, white matter, and neostriatum in Huntington\u2019s disease. J Neuropathol Exp Neurol. 1988;47(5):516\u201325.","journal-title":"J Neuropathol Exp Neurol"},{"issue":"8","key":"1805_CR14","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1002\/mds.28109","volume":"35","author":"C Casella","year":"2020","unstructured":"Casella C, et al. A critical review of white matter changes in Huntington\u2019s disease. Mov Disord. 2020;35(8):1302\u201311.","journal-title":"Mov Disord"},{"key":"1805_CR15","doi-asserted-by":"publisher","first-page":"103204","DOI":"10.1016\/j.nicl.2022.103204","volume":"36","author":"M Dadar","year":"2022","unstructured":"Dadar M, et al. White matter hyperintensity distribution differences in aging and neurodegenerative disease cohorts. Neuroimage Clin. 2022;36: 103204.","journal-title":"Neuroimage Clin"},{"issue":"12","key":"1805_CR16","doi-asserted-by":"publisher","first-page":"2262","DOI":"10.1161\/01.STR.27.12.2262","volume":"27","author":"D Liao","year":"1996","unstructured":"Liao D, et al. Presence and severity of cerebral white matter lesions and hypertension, its treatment, and its control. The ARIC Study. Atherosclerosis Risk in Communities Study. Stroke. 1996;27(12):2262\u201370.","journal-title":"Stroke"},{"issue":"3","key":"1805_CR17","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1159\/000368814","volume":"16","author":"D Liao","year":"1997","unstructured":"Liao D, et al. The prevalence and severity of white matter lesions, their relationship with age, ethnicity, gender, and cardiovascular disease risk factors: the ARIC Study. Neuroepidemiology. 1997;16(3):149\u201362.","journal-title":"Neuroepidemiology"},{"issue":"5\u20136","key":"1805_CR18","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1159\/000091536","volume":"21","author":"AM Basile","year":"2006","unstructured":"Basile AM, et al. Age, hypertension, and lacunar stroke are the major determinants of the severity of age-related white matter changes. The LADIS (Leukoaraiosis and Disability in the Elderly) Study. Cerebrovasc Dis. 2006;21(5\u20136):315\u201322.","journal-title":"Cerebrovasc Dis"},{"issue":"3","key":"1805_CR19","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1111\/j.1751-7176.2009.00234.x","volume":"12","author":"LH Kuller","year":"2010","unstructured":"Kuller LH, et al. Relationship of hypertension, blood pressure, and blood pressure control with white matter abnormalities in the Women\u2019s Health Initiative Memory Study (WHIMS)-MRI trial. J Clin Hypertens (Greenwich). 2010;12(3):203\u201312.","journal-title":"J Clin Hypertens (Greenwich)"},{"issue":"7","key":"1805_CR20","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1212\/WNL.56.7.921","volume":"56","author":"C Dufouil","year":"2001","unstructured":"Dufouil C, et al. Longitudinal study of blood pressure and white matter hyperintensities: the EVA MRI Cohort. Neurology. 2001;56(7):921\u20136.","journal-title":"Neurology"},{"issue":"2","key":"1805_CR21","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1159\/000323810","volume":"31","author":"M Vuorinen","year":"2011","unstructured":"Vuorinen M, et al. Changes in vascular risk factors from midlife to late life and white matter lesions: a 20-year follow-up study. Dement Geriatr Cogn Disord. 2011;31(2):119\u201325.","journal-title":"Dement Geriatr Cogn Disord"},{"issue":"7","key":"1805_CR22","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1001\/archneur.1988.00520310025011","volume":"45","author":"J Aharon-Peretz","year":"1988","unstructured":"Aharon-Peretz J, Cummings JL, Hill MA. Vascular dementia and dementia of the Alzheimer type. Cognition, ventricular size, and leuko-araiosis. Arch Neurol. 1988;45(7):719\u201321.","journal-title":"Arch Neurol"},{"key":"1805_CR23","doi-asserted-by":"publisher","first-page":"595962","DOI":"10.3389\/fendo.2020.595962","volume":"11","author":"DQ Wang","year":"2020","unstructured":"Wang DQ, et al. Relationship between type 2 diabetes and white matter hyperintensity: a systematic review. Front Endocrinol (Lausanne). 2020;11: 595962.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"1805_CR24","doi-asserted-by":"publisher","first-page":"1096206","DOI":"10.3389\/fnagi.2023.1096206","volume":"15","author":"FR Sharp","year":"2023","unstructured":"Sharp FR, et al. White matter injury, cholesterol dysmetabolism, and APP\/Abeta dysmetabolism interact to produce Alzheimer\u2019s disease (AD) neuropathology: a hypothesis and review. Front Aging Neurosci. 2023;15:1096206.","journal-title":"Front Aging Neurosci"},{"issue":"11","key":"1805_CR25","doi-asserted-by":"publisher","first-page":"e1168","DOI":"10.1212\/WNL.0000000000007093","volume":"92","author":"A de Havenon","year":"2019","unstructured":"de Havenon A, et al. Blood pressure, glycemic control, and white matter hyperintensity progression in type 2 diabetics. Neurology. 2019;92(11):e1168\u201375.","journal-title":"Neurology"},{"issue":"10 Pt B","key":"1805_CR26","doi-asserted-by":"publisher","first-page":"2614","DOI":"10.1016\/j.bbadis.2017.05.020","volume":"1863","author":"M Braun","year":"2017","unstructured":"Braun M, et al. White matter damage after traumatic brain injury: a role for damage associated molecular patterns. Biochim Biophys Acta Mol Basis Dis. 2017;1863(10 Pt B):2614\u201326.","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"2","key":"1805_CR27","doi-asserted-by":"publisher","first-page":"345","DOI":"10.3233\/JAD-180287","volume":"65","author":"CM Filley","year":"2018","unstructured":"Filley CM, Kelly JP. White matter and cognition in traumatic brain injury. J Alzheimers Dis. 2018;65(2):345\u201362.","journal-title":"J Alzheimers Dis"},{"issue":"3 Suppl","key":"1805_CR28","first-page":"S20","volume":"40","author":"GA Rosenberg","year":"2009","unstructured":"Rosenberg GA. Inflammation and white matter damage in vascular cognitive impairment. Stroke. 2009;40(3 Suppl):S20\u20133.","journal-title":"Stroke"},{"key":"1805_CR29","doi-asserted-by":"publisher","first-page":"786840","DOI":"10.3389\/fneur.2021.786840","volume":"12","author":"CJ Huang","year":"2021","unstructured":"Huang CJ, et al. Contribution of inflammation and hypoperfusion to white matter hyperintensities-related cognitive impairment. Front Neurol. 2021;12: 786840.","journal-title":"Front Neurol"},{"issue":"1","key":"1805_CR30","first-page":"e12091","volume":"12","author":"M Dadar","year":"2020","unstructured":"Dadar M, et al. The temporal relationships between white matter hyperintensities, neurodegeneration, amyloid beta, and cognition. Alzheimers Dement (Amst). 2020;12(1): e12091.","journal-title":"Alzheimers Dement (Amst)"},{"key":"1805_CR31","doi-asserted-by":"publisher","first-page":"117560","DOI":"10.1016\/j.neuroimage.2020.117560","volume":"226","author":"Q Wen","year":"2021","unstructured":"Wen Q, et al. Tau-related white-matter alterations along spatially selective pathways. Neuroimage. 2021;226: 117560.","journal-title":"Neuroimage"},{"issue":"12","key":"1805_CR32","doi-asserted-by":"publisher","first-page":"e0144431","DOI":"10.1371\/journal.pone.0144431","volume":"10","author":"Y Gao","year":"2015","unstructured":"Gao Y, et al. Homocysteine level is associated with white matter hyperintensity locations in patients with acute ischemic stroke. PLoS ONE. 2015;10(12): e0144431.","journal-title":"PLoS ONE"},{"issue":"1","key":"1805_CR33","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1111\/j.1469-7580.2010.01339.x","volume":"219","author":"C Matute","year":"2011","unstructured":"Matute C. Glutamate and ATP signalling in white matter pathology. J Anat. 2011;219(1):53\u201364.","journal-title":"J Anat"},{"key":"1805_CR34","unstructured":"Sharma R, Sekhon S, Cascella M. White matter lesions: StatPearls. Treasure Island (FL): StatPealrs Publishing; 2023."},{"issue":"25","key":"1805_CR35","doi-asserted-by":"publisher","first-page":"6132","DOI":"10.1523\/JNEUROSCI.0877-17.2017","volume":"37","author":"P Sompol","year":"2017","unstructured":"Sompol P, et al. Calcineurin\/NFAT signaling in activated astrocytes drives network hyperexcitability in abeta-bearing mice. J Neurosci. 2017;37(25):6132\u201348.","journal-title":"J Neurosci"},{"issue":"10","key":"1805_CR36","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1523\/JNEUROSCI.1333-22.2023","volume":"43","author":"P Sompol","year":"2023","unstructured":"Sompol P, et al. Targeting astrocyte signaling alleviates cerebrovascular and synaptic function deficits in a diet-based mouse model of small cerebral vessel disease. J Neurosci. 2023;43(10):1797\u2013813.","journal-title":"J Neurosci"},{"issue":"5","key":"1805_CR37","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1523\/JNEUROSCI.1930-15.2016","volume":"36","author":"JL Furman","year":"2016","unstructured":"Furman JL, et al. Blockade of astrocytic calcineurin\/NFAT signaling helps to normalize hippocampal synaptic function and plasticity in a rat model of traumatic brain injury. J Neurosci. 2016;36(5):1502\u201315.","journal-title":"J Neurosci"},{"issue":"1","key":"1805_CR38","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/s40478-019-0783-6","volume":"7","author":"EY Hayden","year":"2019","unstructured":"Hayden EY, et al. Ischemic axonal injury up-regulates MARK4 in cortical neurons and primes tau phosphorylation and aggregation. Acta Neuropathol Commun. 2019;7(1):135.","journal-title":"Acta Neuropathol Commun"},{"issue":"6","key":"1805_CR39","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1097\/WCO.0000000000000149","volume":"27","author":"JD Hinman","year":"2014","unstructured":"Hinman JD. The back and forth of axonal injury and repair after stroke. Curr Opin Neurol. 2014;27(6):615\u201323.","journal-title":"Curr Opin Neurol"},{"issue":"9","key":"1805_CR40","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.4103\/1673-5374.191203","volume":"11","author":"G Xiao","year":"2016","unstructured":"Xiao G, Hinman JD. Concepts and opportunities for repair in cerebral microvascular disease and white matter stroke. Neural Regen Res. 2016;11(9):1398\u2013400.","journal-title":"Neural Regen Res"},{"issue":"8","key":"1805_CR41","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1136\/jnnp-2012-303645","volume":"84","author":"SD Makin","year":"2013","unstructured":"Makin SD, et al. Cognitive impairment after lacunar stroke: systematic review and meta-analysis of incidence, prevalence and comparison with other stroke subtypes. J Neurol Neurosurg Psychiatry. 2013;84(8):893\u2013900.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"1","key":"1805_CR42","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1097\/WCO.0000000000000783","volume":"33","author":"KP Doyle","year":"2020","unstructured":"Doyle KP, Buckwalter MS. Immunological mechanisms in poststroke dementia. Curr Opin Neurol. 2020;33(1):30\u20136.","journal-title":"Curr Opin Neurol"},{"key":"1805_CR43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbi.2016.08.009","volume":"64","author":"KP Doyle","year":"2017","unstructured":"Doyle KP, Buckwalter MS. Does B lymphocyte-mediated autoimmunity contribute to post-stroke dementia? Brain Behav Immun. 2017;64:1\u20138.","journal-title":"Brain Behav Immun"},{"issue":"5","key":"1805_CR44","doi-asserted-by":"publisher","first-page":"2133","DOI":"10.1523\/JNEUROSCI.4098-14.2015","volume":"35","author":"KP Doyle","year":"2015","unstructured":"Doyle KP, et al. B-lymphocyte-mediated delayed cognitive impairment following stroke. J Neurosci. 2015;35(5):2133\u201345.","journal-title":"J Neurosci"},{"issue":"1","key":"1805_CR45","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1186\/s12883-020-01897-9","volume":"20","author":"LL Drag","year":"2020","unstructured":"Drag LL, et al. A longitudinal study of the post-stroke immune response and cognitive functioning: the StrokeCog study protocol. BMC Neurol. 2020;20(1):313.","journal-title":"BMC Neurol"},{"key":"1805_CR46","doi-asserted-by":"crossref","unstructured":"Al-Janabi OM et al. White matter hyperintensity regression: comparison of brain atrophy and cognitive profiles with progression and stable groups. Brain Sci. 2019;9(7):170.","DOI":"10.3390\/brainsci9070170"},{"key":"1805_CR47","doi-asserted-by":"publisher","first-page":"109270","DOI":"10.1016\/j.jneumeth.2021.109270","volume":"360","author":"AA Bahrani","year":"2021","unstructured":"Bahrani AA, et al. Development of a protocol to assess within-subject, regional white matter hyperintensity changes in aging and dementia. J Neurosci Methods. 2021;360: 109270.","journal-title":"J Neurosci Methods"},{"key":"1805_CR48","doi-asserted-by":"publisher","first-page":"102768","DOI":"10.1016\/j.nicl.2021.102768","volume":"31","author":"N Makkinejad","year":"2021","unstructured":"Makkinejad N, et al. ARTS: A novel In-vivo classifier of arteriolosclerosis for the older adult brain. Neuroimage Clin. 2021;31: 102768.","journal-title":"Neuroimage Clin"},{"issue":"3","key":"1805_CR49","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.3233\/JAD-180663","volume":"66","author":"OM Al-Janabi","year":"2018","unstructured":"Al-Janabi OM, et al. Distinct white matter changes associated with cerebrospinal fluid amyloid-beta1-42 and hypertension. J Alzheimers Dis. 2018;66(3):1095\u2013104.","journal-title":"J Alzheimers Dis"},{"issue":"7","key":"1805_CR50","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1016\/j.neurobiolaging.2014.01.144","volume":"35","author":"RJ Dawe","year":"2014","unstructured":"Dawe RJ, et al. Ex vivo T2 relaxation: associations with age-related neuropathology and cognition. Neurobiol Aging. 2014;35(7):1549\u201361.","journal-title":"Neurobiol Aging"},{"issue":"10","key":"1805_CR51","doi-asserted-by":"publisher","first-page":"2798","DOI":"10.1016\/j.neurobiolaging.2015.06.025","volume":"36","author":"A Kotrotsou","year":"2015","unstructured":"Kotrotsou A, et al. Neuropathologic correlates of regional brain volumes in a community cohort of older adults. Neurobiol Aging. 2015;36(10):2798\u2013805.","journal-title":"Neurobiol Aging"},{"issue":"1","key":"1805_CR52","doi-asserted-by":"publisher","first-page":"333","DOI":"10.3233\/JAD-190687","volume":"73","author":"K Arfanakis","year":"2020","unstructured":"Arfanakis K, et al. Neuropathologic correlates of white matter hyperintensities in a community-based cohort of older adults. J Alzheimers Dis. 2020;73(1):333\u201345.","journal-title":"J Alzheimers Dis"},{"issue":"9","key":"1805_CR53","doi-asserted-by":"publisher","first-page":"2825","DOI":"10.1161\/STROKEAHA.120.029388","volume":"51","author":"C Javierre-Petit","year":"2020","unstructured":"Javierre-Petit C, et al. Neuropathologic and cognitive correlates of enlarged perivascular spaces in a community-based cohort of older adults. Stroke. 2020;51(9):2825\u201333.","journal-title":"Stroke"},{"key":"1805_CR54","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.neurobiolaging.2022.05.009","volume":"117","author":"M Tazwar","year":"2022","unstructured":"Tazwar M, et al. Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is associated with lower R(2) relaxation rate: an ex-vivo MRI and pathology investigation. Neurobiol Aging. 2022;117:128\u201338.","journal-title":"Neurobiol Aging"},{"issue":"1","key":"1805_CR55","doi-asserted-by":"publisher","first-page":"e12261","DOI":"10.1002\/dad2.12261","volume":"14","author":"P Maillard","year":"2022","unstructured":"Maillard P, et al. Instrumental validation of free water, peak-width of skeletonized mean diffusivity, and white matter hyperintensities: MarkVCID neuroimaging kits. Alzheimers Dement (Amst). 2022;14(1): e12261.","journal-title":"Alzheimers Dement (Amst)"},{"issue":"8","key":"1805_CR56","doi-asserted-by":"publisher","first-page":"5281","DOI":"10.1002\/alz.13888","volume":"20","author":"P Liu","year":"2024","unstructured":"Liu P, et al. Cerebrovascular reactivity MRI as a biomarker for cerebral small vessel disease-related cognitive decline: multi-site validation in the MarkVCID Consortium. Alzheimers Dement. 2024;20(8):5281\u20139.","journal-title":"Alzheimers Dement"},{"key":"1805_CR57","doi-asserted-by":"publisher","first-page":"118754","DOI":"10.1016\/j.neuroimage.2021.118754","volume":"245","author":"P Liu","year":"2021","unstructured":"Liu P, et al. Multi-vendor and multisite evaluation of cerebrovascular reactivity mapping using hypercapnia challenge. Neuroimage. 2021;245: 118754.","journal-title":"Neuroimage"},{"issue":"8","key":"1805_CR58","doi-asserted-by":"publisher","first-page":"3519","DOI":"10.1002\/alz.12974","volume":"19","author":"JD Hinman","year":"2023","unstructured":"Hinman JD, et al. Placental growth factor as a sensitive biomarker for vascular cognitive impairment. Alzheimers Dement. 2023;19(8):3519\u201327.","journal-title":"Alzheimers Dement"},{"key":"1805_CR59","doi-asserted-by":"publisher","first-page":"7590997","DOI":"10.1155\/2022\/7590997","volume":"2022","author":"P Liu","year":"2022","unstructured":"Liu P, et al. PTBP1 is a novel poor prognostic factor for glioma. Biomed Res Int. 2022;2022:7590997.","journal-title":"Biomed Res Int"},{"issue":"12","key":"1805_CR60","doi-asserted-by":"publisher","first-page":"8374","DOI":"10.1002\/alz.14265","volume":"20","author":"A Watts","year":"2024","unstructured":"Watts A, et al. LEAP! Rx: a randomized trial of a pragmatic approach to lifestyle medicine. Alzheimers Dement. 2024;20(12):8374\u201386.","journal-title":"Alzheimers Dement"},{"issue":"2","key":"1805_CR61","doi-asserted-by":"publisher","first-page":"IV","DOI":"10.1177\/23969873211027002","volume":"6","author":"JM Wardlaw","year":"2021","unstructured":"Wardlaw JM, et al. ESO Guideline on covert cerebral small vessel disease. Eur Stroke J. 2021;6(2):IV.","journal-title":"Eur Stroke J"},{"issue":"11","key":"1805_CR62","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1001\/jamaneurol.2022.2262","volume":"79","author":"HS Markus","year":"2022","unstructured":"Markus HS, et al. Framework for Clinical Trials in Cerebral Small Vessel Disease (FINESSE): A Review. JAMA Neurol. 2022;79(11):1187\u201398.","journal-title":"JAMA Neurol"},{"issue":"10","key":"1805_CR63","doi-asserted-by":"publisher","first-page":"e040466","DOI":"10.1136\/bmjopen-2020-040466","volume":"10","author":"A Ganesh","year":"2020","unstructured":"Ganesh A, et al. Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol. BMJ Open. 2020;10(10): e040466.","journal-title":"BMJ Open"},{"issue":"10","key":"1805_CR64","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s11883-019-0799-1","volume":"21","author":"A de Havenon","year":"2019","unstructured":"de Havenon A, et al. Subclinical cerebrovascular disease: epidemiology and treatment. Curr Atheroscler Rep. 2019;21(10):39.","journal-title":"Curr Atheroscler Rep"},{"issue":"6","key":"1805_CR65","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1001\/jama.2018.21442","volume":"321","author":"SMIftSR Group","year":"2019","unstructured":"Group SMIftSR, et al. Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial. JAMA. 2019;321(6):553\u201361.","journal-title":"JAMA"},{"issue":"Suppl 2","key":"1805_CR66","first-page":"S1","volume":"68 Suppl 2","author":"SL Mitchell","year":"2020","unstructured":"Mitchell SL, et al. Embedded pragmatic trials in dementia care: realizing the vision of the NIA IMPACT collaboratory. J Am Geriatr Soc. 2020;68 Suppl 2(Suppl 2):S1\u20137.","journal-title":"J Am Geriatr Soc"},{"issue":"Suppl 2","key":"1805_CR67","first-page":"S43","volume":"68 Suppl 2","author":"L Tuzzio","year":"2020","unstructured":"Tuzzio L, et al. Transforming dementia care through pragmatic clinical trials embedded in learning healthcare systems. J Am Geriatr Soc. 2020;68 Suppl 2(Suppl 2):S43\u20138.","journal-title":"J Am Geriatr Soc"},{"issue":"7","key":"1805_CR68","doi-asserted-by":"publisher","first-page":"2594","DOI":"10.1161\/STROKEAHA.109.552554","volume":"40","author":"JL Saver","year":"2009","unstructured":"Saver JL, et al. Stroke Therapy Academic Industry Roundtable (STAIR) recommendations for extended window acute stroke therapy trials. Stroke. 2009;40(7):2594\u2013600.","journal-title":"Stroke"},{"issue":"9","key":"1805_CR69","doi-asserted-by":"publisher","first-page":"11753","DOI":"10.3390\/ijms130911753","volume":"13","author":"J Minnerup","year":"2012","unstructured":"Minnerup J, et al. Neuroprotection for stroke: current status and future perspectives. Int J Mol Sci. 2012;13(9):11753\u201372.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"1805_CR70","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s13024-023-00667-8","volume":"18","author":"KE Foley","year":"2023","unstructured":"Foley KE, Weekman EM, Wilcock DM. Mechanisms of ARIA: is it time to focus on the unique immune environment of the neurovascular unit? Mol Neurodegener. 2023;18(1):76.","journal-title":"Mol Neurodegener"},{"key":"1805_CR71","doi-asserted-by":"crossref","unstructured":"Khaw J et al. Current update on the clinical utility of MMSE and MoCA for stroke patients in Asia: a systematic review. Int J Environ Res Public Health. 2021;18(17):8962.","DOI":"10.3390\/ijerph18178962"},{"issue":"4","key":"1805_CR72","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1002\/alz.12215","volume":"17","author":"D Wilcock","year":"2021","unstructured":"Wilcock D, et al. MarkVCID cerebral small vessel consortium: I. Enrollment, clinical, fluid protocols. Alzheimers Dement. 2021;17(4):704\u201315.","journal-title":"Alzheimers Dement"},{"key":"1805_CR73","doi-asserted-by":"crossref","unstructured":"Wang G et al. Know-Me: a toolkit for designing personalised dementia care. Int J Environ Res Public Health. 2021;18(11):5662.","DOI":"10.3390\/ijerph18115662"}],"container-title":["GeroScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-025-01805-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11357-025-01805-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-025-01805-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:04:12Z","timestamp":1773050652000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11357-025-01805-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,21]]},"references-count":73,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["1805"],"URL":"https:\/\/doi.org\/10.1007\/s11357-025-01805-4","relation":{},"ISSN":["2509-2723"],"issn-type":[{"value":"2509-2723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,21]]},"assertion":[{"value":"3 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable. Ethics approval and consent to participate statements can be found in the individual authors\u2019 publications.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}