{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:08:10Z","timestamp":1788858490009,"version":"build-2803163510"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001773","name":"University of New South Wales","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001773","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Brain Imaging and Behavior"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although the associations between cerebrovascular dysfunctions and Alzheimer\u2019s disease are increasingly appreciated, the relationship of cerebral blood flow and white matter hyperintensities with tau and amyloid-\u03b2 pathology remains unclear, particularly in the longitudinal context. This study investigated cross-sectional and longitudinal associations of cerebral blood flow and white matter hyperintensities with tau and amyloid-\u03b2 pathology using multimodal imaging and blood biomarkers in 179 participants from the ADNI3 cohort. Participants underwent structural (T1-weighted, T2-weighted FLAIR) and arterial spin labelling perfusion MRI, tau and amyloid-\u03b2 PET, and plasma assay tests for amyloid-\u03b2 42, amyloid-\u03b2 40, and phosphorylated tau-217. Tau from PET was negatively associated with cerebral blood flow both cross-sectionally and longitudinally in the posterior brain, independent of amyloid-\u03b2 quantified from PET. Higher white matter hyperintensities volumes were associated with higher levels of tau and amyloid-\u03b2 at baseline, but the associations were significantly attenuated after further adjusting for amyloid-\u03b2 and tau, respectively. Plasma amyloid-\u03b2 42\/40 ratio was negatively associated with white matter hyperintensity volumes both cross-sectionally and longitudinally. In conclusion, tau pathology showed spatially specific associations with cerebral hypoperfusion, independent of amyloid-\u03b2, particularly in posterior regions. The attenuation of associations of white matter hyperintensities with amyloid-\u03b2 and tau after adjustment may reflect shared disease-related variance rather than distinct independent effects.<\/jats:p>","DOI":"10.1007\/s11682-026-01187-x","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T07:13:20Z","timestamp":1785914000000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Associations of cerebral blood flow and white matter hyperintensities with tau and amyloid-beta across the Alzheimer\u2019s disease spectrum"],"prefix":"10.1007","volume":"20","author":[{"given":"Keshuo","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perminder S.","family":"Sachdev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"1187_CR1","doi-asserted-by":"publisher","first-page":"181","DOI":"10.3389\/fnagi.2017.00181","volume":"9","author":"KJ Bangen","year":"2017","unstructured":"Bangen, K. J., Clark, A. L., Edmonds, E. C., Evangelista, N. D., Werhane, M. L., Thomas, K. R., Locano, L. E., Tran, M., Zlatar, Z. Z., Nation, D. A., Bondi, M. W., & Delano-Wood, L. (2017). Cerebral Blood Flow and Amyloid-beta Interact to Affect Memory Performance in Cognitively Normal Older Adults. Frontiers In Aging Neuroscience, 9, 181. https:\/\/doi.org\/10.3389\/fnagi.2017.00181","journal-title":"Frontiers In Aging Neuroscience"},{"issue":"9","key":"1187_CR2","doi-asserted-by":"publisher","first-page":"2771","DOI":"10.1093\/brain\/awab114","volume":"144","author":"D Berron","year":"2021","unstructured":"Berron, D., Vogel, J. W., Insel, P. S., Pereira, J. B., Xie, L., Wisse, L. E. M., Yushkevich, P. A., Palmqvist, S., Mattsson-Carlgren, N., Stomrud, E., Smith, R., Strandberg, O., & Hansson, O. (2021). Early stages of tau pathology and its associations with functional connectivity, atrophy and memory. Brain, 144(9), 2771\u20132783. https:\/\/doi.org\/10.1093\/brain\/awab114","journal-title":"Brain"},{"issue":"S5","key":"1187_CR4","doi-asserted-by":"publisher","first-page":"e054189","DOI":"10.1002\/alz.054189","volume":"17","author":"M Bilgel","year":"2021","unstructured":"Bilgel, M., Wong, D. F., & Resnick, S. M. (2021). Tau pathology mediates the effects of amyloid on cerebral blood flow and propagation of tau. Alzheimer\u2019s & Dementia, 17(S5), e054189. https:\/\/doi.org\/10.1002\/alz.054189","journal-title":"Alzheimer\u2019s & Dementia"},{"issue":"4","key":"1187_CR3","doi-asserted-by":"publisher","first-page":"fcac193","DOI":"10.1093\/braincomms\/fcac193","volume":"4","author":"M Bilgel","year":"2022","unstructured":"Bilgel, M., Wong, D. F., Moghekar, A. R., Ferrucci, L., Resnick, S. M., & Alzheimer\u2019s Disease Neuroimaging, I. (2022). Causal links among amyloid, tau, and neurodegeneration. Brain Commun, 4(4), fcac193. https:\/\/doi.org\/10.1093\/braincomms\/fcac193","journal-title":"Brain Commun"},{"issue":"3","key":"1187_CR6","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/0197-4580(95)00021-6","volume":"16","author":"H Braak","year":"1995","unstructured":"Braak, H., & Braak, E. (1995). Staging of Alzheimer\u2019s disease-related neurofibrillary changes. Neurobiology Of Aging, 16(3), 271\u2013278. https:\/\/doi.org\/10.1016\/0197-4580(95)00021-6. discussion 278\u2013284.","journal-title":"Neurobiology Of Aging"},{"issue":"4","key":"1187_CR5","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s00401-006-0127-z","volume":"112","author":"H Braak","year":"2006","unstructured":"Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H., & Del Tredici, K. (2006). Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathologica, 112(4), 389\u2013404. https:\/\/doi.org\/10.1007\/s00401-006-0127-z","journal-title":"Acta Neuropathologica"},{"issue":"1","key":"1187_CR7","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/s13195-023-01296-5","volume":"15","author":"S Bun","year":"2023","unstructured":"Bun, S., Ito, D., Tezuka, T., Kubota, M., Ueda, R., Takahata, K., Moriguchi, S., Kurose, S., Momota, Y., Suzuki, N., Morimoto, A., Hoshino, Y., Seki, M., Mimura, Y., Shikimoto, R., Yamamoto, Y., Hoshino, T., Sato, Y., Tabuchi, H., & Mimura, M. (2023). Performance of plasma Abeta42\/40, measured using a fully automated immunoassay, across a broad patient population in identifying amyloid status. Alzheimer\u2019S Research & Therapy, 15(1), 149. https:\/\/doi.org\/10.1186\/s13195-023-01296-5","journal-title":"Alzheimer\u2019S Research & Therapy"},{"issue":"1","key":"1187_CR8","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13195-024-01417-8","volume":"16","author":"WJ Cha","year":"2024","unstructured":"Cha, W. J., Yi, D., Ahn, H., Byun, M. S., Chang, Y. Y., Choi, J. M., Kim, K., Choi, H., Jung, G., Kang, K. M., Sohn, C. H., Lee, Y. S., Kim, Y. K., & Lee, D. Y. (2024). Association between brain amyloid deposition and longitudinal changes of white matter hyperintensities. Alzheimer\u2019S Research & Therapy, 16(1), 50. https:\/\/doi.org\/10.1186\/s13195-024-01417-8","journal-title":"Alzheimer\u2019S Research & Therapy"},{"key":"1187_CR9","doi-asserted-by":"publisher","unstructured":"Chappell, M. A., Kirk, T. F., Craig, M. S., McConnell, F. A. K., Zhao, M. Y., MacIntosh, B. J., Okell, T. W., & Woolrich, M. W. (2023). BASIL: A toolbox for perfusion quantification using arterial spin labelling. Imaging Neurosci (Camb), 1. https:\/\/doi.org\/10.1162\/imag_a_00041","DOI":"10.1162\/imag_a_00041"},{"issue":"10","key":"1187_CR10","doi-asserted-by":"publisher","first-page":"6810","DOI":"10.1002\/alz.14126","volume":"20","author":"A de Havenon","year":"2024","unstructured":"de Havenon, A., Gottesman, R. F., Willamson, J. D., Rost, N., Sharma, R., Li, V., Littig, L., Stulberg, E., Falcone, G. J., Prabhakaran, S., Schneider, A. L. C., Sheth, K. N., Pajewski, N. M., & Brickman, A. M. (2024). White matter hyperintensity on MRI and plasma Abeta42\/40 ratio additively increase the risk of cognitive impairment in hypertensive adults. Alzheimers Dement, 20(10), 6810\u20136819. https:\/\/doi.org\/10.1002\/alz.14126","journal-title":"Alzheimers Dement"},{"issue":"1","key":"1187_CR11","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","volume":"14","author":"MA DeTure","year":"2019","unstructured":"DeTure, M. A., & Dickson, D. W. (2019). The neuropathological diagnosis of Alzheimer\u2019s disease. Mol Neurodegener, 14(1), 32. https:\/\/doi.org\/10.1186\/s13024-019-0333-5","journal-title":"Mol Neurodegener"},{"issue":"1","key":"1187_CR12","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., Bougacha, S., Wirth, M., Andre, C., Delarue, M., Landeau, B., Mezenge, F., Kuhn, E., Gonneaud, J., Chocat, A., Quillard, A., Ferrand-Devouge, E., de La Sayette, V., Vivien, D., Krolak-Salmon, P., & Chetelat, G. (2020). White matter hyperintensities across the adult lifespan: relation to age, Abeta load, and cognition. Alzheimer\u2019S Research & Therapy, 12(1), 127. https:\/\/doi.org\/10.1186\/s13195-020-00669-4","journal-title":"Alzheimer\u2019S Research & Therapy"},{"issue":"8","key":"1187_CR13","doi-asserted-by":"publisher","first-page":"3738","DOI":"10.1002\/alz.13057","volume":"19","author":"A Garnier-Crussard","year":"2023","unstructured":"Garnier-Crussard, A., Cotton, F., Krolak-Salmon, P., & Chetelat, G. (2023). White matter hyperintensities in Alzheimer\u2019s disease: Beyond vascular contribution. Alzheimers Dement, 19(8), 3738\u20133748. https:\/\/doi.org\/10.1002\/alz.13057","journal-title":"Alzheimers Dement"},{"issue":"8","key":"1187_CR14","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.1093\/brain\/awz162","volume":"142","author":"J Graff-Radford","year":"2019","unstructured":"Graff-Radford, J., Arenaza-Urquijo, E. M., Knopman, D. S., Schwarz, C. G., Brown, R. D., Rabinstein, A. A., Gunter, J. L., Senjem, M. L., Przybelski, S. A., Lesnick, T., Ward, C., Mielke, M. M., Lowe, V. J., Petersen, R. C., Kremers, W. K., Kantarci, K., Jack, C. R., & Vemuri, P. (2019). White matter hyperintensities: relationship to amyloid and tau burden. Brain, 142(8), 2483\u20132491. https:\/\/doi.org\/10.1093\/brain\/awz162","journal-title":"Brain"},{"issue":"7","key":"1187_CR15","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1111\/febs.14004","volume":"284","author":"J Hardy","year":"2017","unstructured":"Hardy, J. (2017). The discovery of Alzheimer-causing mutations in the APP gene and the formulation of the amyloid cascade hypothesis. Febs Journal, 284(7), 1040\u20131044. https:\/\/doi.org\/10.1111\/febs.14004","journal-title":"Febs Journal"},{"issue":"3","key":"1187_CR16","doi-asserted-by":"publisher","first-page":"977","DOI":"10.3233\/JAD-170458","volume":"60","author":"S Hilal","year":"2017","unstructured":"Hilal, S., Akoudad, S., van Duijn, C. M., Niessen, W. J., Verbeek, M. M., Vanderstichele, H., Stoops, E., Ikram, M. A., & Vernooij, M. W. (2017). Plasma Amyloid-beta Levels, Cerebral Small Vessel Disease, and Cognition: The Rotterdam Study. Journal Of Alzheimer\u2019S Disease, 60(3), 977\u2013987. https:\/\/doi.org\/10.3233\/JAD-170458","journal-title":"Journal Of Alzheimer\u2019S Disease"},{"key":"1187_CR17","doi-asserted-by":"publisher","first-page":"859873","DOI":"10.3389\/fnagi.2022.859873","volume":"14","author":"SL Holmqvist","year":"2022","unstructured":"Holmqvist, S. L., Thomas, K. R., Brenner, E. K., Edmonds, E. C., Calcetas, A., Edwards, L., Bordyug, M., & Bangen, K. J. (2022). Longitudinal Intraindividual Cognitive Variability Is Associated With Reduction in Regional Cerebral Blood Flow Among Alzheimer\u2019s Disease Biomarker-Positive Older Adults. Frontiers In Aging Neuroscience, 14, 859873. https:\/\/doi.org\/10.3389\/fnagi.2022.859873","journal-title":"Frontiers In Aging Neuroscience"},{"key":"1187_CR18","doi-asserted-by":"publisher","first-page":"119474","DOI":"10.1016\/j.neuroimage.2022.119474","volume":"260","author":"A Hoopes","year":"2022","unstructured":"Hoopes, A., Mora, J. S., Dalca, A. V., Fischl, B., & Hoffmann, M. (2022). SynthStrip: skull-stripping for any brain image. Neuroimage, 260, 119474. https:\/\/doi.org\/10.1016\/j.neuroimage.2022.119474","journal-title":"Neuroimage"},{"issue":"1","key":"1187_CR19","doi-asserted-by":"publisher","first-page":"2367","DOI":"10.1038\/s41467-023-37840-y","volume":"14","author":"SA Hussong","year":"2023","unstructured":"Hussong, S. A., Banh, A. Q., Van Skike, C. E., Dorigatti, A. O., Hernandez, S. F., Hart, M. J., Ferran, B., Makhlouf, H., Gaczynska, M., Osmulski, P. A., McAllen, S. A., Dineley, K. T., Ungvari, Z., Perez, V. I., Kayed, R., & Galvan, V. (2023). Soluble pathogenic tau enters brain vascular endothelial cells and drives cellular senescence and brain microvascular dysfunction in a mouse model of tauopathy. Nature Communications, 14(1), 2367. https:\/\/doi.org\/10.1038\/s41467-023-37840-y","journal-title":"Nature Communications"},{"issue":"3","key":"1187_CR20","doi-asserted-by":"publisher","first-page":"426","DOI":"10.14283\/jpad.2023.43","volume":"10","author":"L Iaccarino","year":"2023","unstructured":"Iaccarino, L., Burnham, S. C., Dell\u2019Agnello, G., Dowsett, S. A., & Epelbaum, S. (2023). Diagnostic biomarkers of amyloid and tau pathology in alzheimer\u2019s disease: an overview of tests for clinical practice in the United States and Europe. J Prev Alzheimers Dis, 10(3), 426\u2013442. https:\/\/doi.org\/10.14283\/jpad.2023.43","journal-title":"J Prev Alzheimers Dis"},{"issue":"Pt 6","key":"1187_CR21","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1093\/brain\/awn016","volume":"131","author":"MD Ikonomovic","year":"2008","unstructured":"Ikonomovic, M. D., Klunk, W. E., Abrahamson, E. E., Mathis, C. A., Price, J. C., Tsopelas, N. D., Lopresti, B. J., Ziolko, S., Bi, W., Paljug, W. R., Debnath, M. L., Hope, C. E., Isanski, B. A., Hamilton, R. L., & DeKosky, S. T. (2008). Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer\u2019s disease. Brain, 131(Pt 6), 1630\u20131645. https:\/\/doi.org\/10.1093\/brain\/awn016","journal-title":"Brain"},{"issue":"5","key":"1187_CR23","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1212\/WNL.0000000000002923","volume":"87","author":"CR Jack Jr","year":"2016","unstructured":"Jack, C. R. Jr., Bennett, D. A., Blennow, K., Carrillo, M. C., Feldman, H. H., Frisoni, G. B., Hampel, H., Jagust, W. J., Johnson, K. A., Knopman, D. S., Petersen, R. C., Scheltens, P., Sperling, R. A., & Dubois, B. (2016). A\/T\/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology, 87(5), 539\u2013547. https:\/\/doi.org\/10.1212\/WNL.0000000000002923","journal-title":"Neurology"},{"issue":"3","key":"1187_CR24","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.jalz.2016.08.005","volume":"13","author":"CR Jack Jr","year":"2017","unstructured":"Jack, C. R. Jr., Wiste, H. J., Weigand, S. D., Therneau, T. M., Lowe, V. J., Knopman, D. S., Gunter, J. L., Senjem, M. L., Jones, D. T., Kantarci, K., Machulda, M. M., Mielke, M. M., Roberts, R. O., Vemuri, P., Reyes, D. A., & Petersen, R. C. (2017). Defining imaging biomarker cut points for brain aging and Alzheimer\u2019s disease. Alzheimers Dement, 13(3), 205\u2013216. https:\/\/doi.org\/10.1016\/j.jalz.2016.08.005","journal-title":"Alzheimers Dement"},{"key":"1187_CR22","doi-asserted-by":"publisher","unstructured":"Jack, C. R., Jr., Arani, A., Borowski, B. J., Cash, D. M., Crawford, K., Das, S. R., DeCarli, C., Fletcher, E., Fox, N. C., Gunter, J. L., Ittyerah, R., Harvey, D. J., Jahanshad, N., Maillard, P., Malone, I. B., Nir, T. M., Reid, R. I., Reyes, D. A., Schwarz, C. G., . . . Alzheimer's Disease Neuroimaging, I. (2024). Overview of ADNI MRI. Alzheimers Dement, 20(10), 7350\u20137360. https:\/\/doi.org\/10.1002\/alz.14166","DOI":"10.1002\/alz.14166"},{"key":"1187_CR25","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.neuroimage.2018.03.050","volume":"174","author":"J Jiang","year":"2018","unstructured":"Jiang, J., Liu, T., Zhu, W., Koncz, R., Liu, H., Lee, T., Sachdev, P. S., & Wen, W. (2018). UBO Detector - A cluster-based, fully automated pipeline for extracting white matter hyperintensities. Neuroimage, 174, 539\u2013549. https:\/\/doi.org\/10.1016\/j.neuroimage.2018.03.050","journal-title":"Neuroimage"},{"issue":"6","key":"1187_CR26","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1007\/s00401-020-02215-w","volume":"140","author":"N Korte","year":"2020","unstructured":"Korte, N., Nortley, R., & Attwell, D. (2020). Cerebral blood flow decrease as an early pathological mechanism in Alzheimer\u2019s disease. Acta Neuropathologica, 140(6), 793\u2013810. https:\/\/doi.org\/10.1007\/s00401-020-02215-w","journal-title":"Acta Neuropathologica"},{"key":"1187_CR27","doi-asserted-by":"publisher","unstructured":"La Joie, R., Visani, A. V., Baker, S. L., Brown, J. A., Bourakova, V., Cha, J., Chaudhary, K., Edwards, L., Iaccarino, L., Janabi, M., Lesman-Segev, O. H., Miller, Z. A., Perry, D. C., O\u2019Neil, J. P., Pham, J., Rojas, J. C., Rosen, H. J., Seeley, W. W., Tsai, R. M., & Rabinovici, G. D. (2020). Prospective longitudinal atrophy in Alzheimer\u2019s disease correlates with the intensity and topography of baseline tau-PET. Science Translational Medicine, 12(524). https:\/\/doi.org\/10.1126\/scitranslmed.aau5732","DOI":"10.1126\/scitranslmed.aau5732"},{"issue":"1","key":"1187_CR28","doi-asserted-by":"publisher","first-page":"e14378","DOI":"10.1002\/alz.14378","volume":"21","author":"SM Landau","year":"2025","unstructured":"Landau, S. M., Harrison, T. M., Baker, S. L., Boswell, M. S., Lee, J., Taggett, J., Ward, T. J., Chadwick, T., Murphy, A., DeCarli, C., Schwarz, C. G., Vemuri, P., Jack, C. R. Jr., Koeppe, R. A., Jagust, W. J., & Group, U. S. P. S. (2025). Positron emission tomography harmonization in the Alzheimer\u2019s Disease Neuroimaging Initiative: A scalable and rigorous approach to multisite amyloid and tau quantification. Alzheimers Dement, 21(1), e14378. https:\/\/doi.org\/10.1002\/alz.14378. for the Alzheimer\u2019s Disease Neuroimaging.","journal-title":"Alzheimers Dement"},{"issue":"5","key":"1187_CR29","doi-asserted-by":"publisher","first-page":"e0195838","DOI":"10.1371\/journal.pone.0195838","volume":"13","author":"S Lee","year":"2018","unstructured":"Lee, S., Zimmerman, M. E., Narkhede, A., Nasrabady, S. E., Tosto, G., Meier, I. B., Benzinger, T. L. S., Marcus, D. S., Fagan, A. M., Fox, N. C., Cairns, N. J., Holtzman, D. M., Buckles, V., Ghetti, B., McDade, E., Martins, R. N., Saykin, A. J., Masters, C. L., & Ringman, J. M. (2018). White matter hyperintensities and the mediating role of cerebral amyloid angiopathy in dominantly-inherited Alzheimer\u2019s disease. PLoS One, 13(5), e0195838. https:\/\/doi.org\/10.1371\/journal.pone.0195838. Dominantly Inherited Alzheimer, N.","journal-title":"PLoS One"},{"issue":"5","key":"1187_CR30","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1093\/brain\/awu043","volume":"137","author":"N Mattsson Jr.","year":"2014","unstructured":"Mattsson, N., Tosun, D., Insel, P. S., Simonson, A., Jack, C. R., Jr., Beckett, L. A., Donohue, M., Jagust, W., Schuff, N., Weiner, M. W., & Alzheimer's Disease Neuroimaging, I. (2014). Association of brain amyloid-beta with cerebral perfusion and structure in Alzheimer\u2019s disease and mild cognitive impairment. Brain, 137(5), 1550\u20131561. https:\/\/doi.org\/10.1093\/brain\/awu043","journal-title":"Brain"},{"key":"1187_CR31","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s40478-015-0240-0","volume":"3","author":"KE McAleese","year":"2015","unstructured":"McAleese, K. E., Firbank, M., Dey, M., Colloby, S. J., Walker, L., Johnson, M., Beverley, J. R., Taylor, J. P., Thomas, A. J., O\u2019Brien, J. T., & Attems, J. (2015). Cortical tau load is associated with white matter hyperintensities. Acta Neuropathol Commun, 3, 60. https:\/\/doi.org\/10.1186\/s40478-015-0240-0","journal-title":"Acta Neuropathol Commun"},{"issue":"3","key":"1187_CR32","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/nrneurol.2015.10","volume":"11","author":"ND Prins","year":"2015","unstructured":"Prins, N. D., & Scheltens, P. (2015). White matter hyperintensities, cognitive impairment and dementia: an update. Nat Rev Neurol, 11(3), 157\u2013165. https:\/\/doi.org\/10.1038\/nrneurol.2015.10","journal-title":"Nat Rev Neurol"},{"issue":"1","key":"1187_CR33","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s13195-021-00836-1","volume":"13","author":"SK Royse","year":"2021","unstructured":"Royse, S. K., Minhas, D. S., Lopresti, B. J., Murphy, A., Ward, T., Koeppe, R. A., Bullich, S., DeSanti, S., Jagust, W. J., Landau, S. M., & Alzheimer\u2019s Disease Neuroimaging, I. (2021). Validation of amyloid PET positivity thresholds in centiloids: a multisite PET study approach. Alzheimer\u2019S Research & Therapy, 13(1), 99. https:\/\/doi.org\/10.1186\/s13195-021-00836-1","journal-title":"Alzheimer\u2019S Research & Therapy"},{"key":"1187_CR34","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.neurobiolaging.2021.02.003","volume":"102","author":"A Rubinski","year":"2021","unstructured":"Rubinski, A., Tosun, D., Franzmeier, N., Neitzel, J., Frontzkowski, L., Weiner, M., & Ewers, M. (2021). Lower cerebral perfusion is associated with tau-PET in the entorhinal cortex across the Alzheimer\u2019s continuum. Neurobiology Of Aging, 102, 111\u2013118. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2021.02.003","journal-title":"Neurobiology Of Aging"},{"issue":"6","key":"1187_CR35","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1161\/STROKEAHA.116.012532","volume":"47","author":"PS Sachdev","year":"2016","unstructured":"Sachdev, P. S., Thalamuthu, A., Mather, K. A., Ames, D., Wright, M. J., Wen, W., & Team, O. C. R. (2016). White Matter Hyperintensities Are Under Strong Genetic Influence. Stroke, 47(6), 1422\u20131428. https:\/\/doi.org\/10.1161\/STROKEAHA.116.012532","journal-title":"Stroke"},{"issue":"13","key":"1187_CR37","doi-asserted-by":"publisher","first-page":"3165","DOI":"10.1007\/s00259-020-04831-w","volume":"47","author":"D Visser","year":"2020","unstructured":"Visser, D., Wolters, E. E., Verfaillie, S. C. J., Coomans, E. M., Timmers, T., Tuncel, H., Reimand, J., Boellaard, R., Windhorst, A. D., Scheltens, P., van der Flier, W. M., Ossenkoppele, R., & van Berckel, B. N. M (2020). Tau pathology and relative cerebral blood flow are independently associated with cognition in Alzheimer\u2019s disease. European Journal Of Nuclear Medicine And Molecular Imaging, 47(13), 3165\u20133175. https:\/\/doi.org\/10.1007\/s00259-020-04831-w","journal-title":"European Journal Of Nuclear Medicine And Molecular Imaging"},{"issue":"8","key":"1187_CR36","doi-asserted-by":"publisher","first-page":"2409","DOI":"10.1007\/s00259-023-06196-2","volume":"50","author":"D Visser","year":"2023","unstructured":"Visser, D., Verfaillie, S. C. J., Bosch, I., Brouwer, I., Tuncel, H., Coomans, E. M., Rikken, R. M., Mastenbroek, S. E., Golla, S. S. V., Barkhof, F., van de Giessen, E., van Berckel, B. N. M., van der Flier, W. M., & Ossenkoppele, R. (2023). Tau pathology as determinant of changes in atrophy and cerebral blood flow: a multi-modal longitudinal imaging study. European Journal Of Nuclear Medicine And Molecular Imaging, 50(8), 2409\u20132419. https:\/\/doi.org\/10.1007\/s00259-023-06196-2","journal-title":"European Journal Of Nuclear Medicine And Molecular Imaging"},{"issue":"6","key":"1187_CR38","doi-asserted-by":"publisher","first-page":"001140","DOI":"10.1161\/JAHA.114.001140","volume":"4","author":"JM Wardlaw","year":"2015","unstructured":"Wardlaw, J. M., Hernandez, V., M. C., & Munoz-Maniega, S. (2015). What are white matter hyperintensities made of? Relevance to vascular cognitive impairment. J Am Heart Assoc, 4(6), 001140. https:\/\/doi.org\/10.1161\/JAHA.114.001140","journal-title":"J Am Heart Assoc"},{"issue":"1","key":"1187_CR39","doi-asserted-by":"publisher","first-page":"fcz046","DOI":"10.1093\/braincomms\/fcz046","volume":"2","author":"AJ Weigand","year":"2020","unstructured":"Weigand, A. J., Bangen, K. J., Thomas, K. R., Delano-Wood, L., Gilbert, P. E., Brickman, A. M., Bondi, M. W., & Alzheimer\u2019s Disease Neuroimaging, I. (2020). Is tau in the absence of amyloid on the Alzheimer\u2019s continuum? A study of discordant PET positivity. Brain Commun, 2(1), fcz046. https:\/\/doi.org\/10.1093\/braincomms\/fcz046","journal-title":"Brain Commun"},{"key":"1187_CR40","doi-asserted-by":"publisher","first-page":"100153","DOI":"10.1016\/j.cccb.2022.100153","volume":"3","author":"AJ Weigand","year":"2022","unstructured":"Weigand, A. J., Hamlin, A. M., Breton, J., & Clark, A. L. (2022). Cerebral blood flow, tau imaging, and memory associations in cognitively unimpaired older adults. Cereb Circ Cogn Behav, 3, 100153. https:\/\/doi.org\/10.1016\/j.cccb.2022.100153","journal-title":"Cereb Circ Cogn Behav"},{"issue":"5","key":"1187_CR41","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.jalz.2016.10.006","volume":"13","author":"MW Weiner Jr.","year":"2017","unstructured":"Weiner, M. W., Veitch, D. P., Aisen, P. S., Beckett, L. A., Cairns, N. J., Green, R. C., Harvey, D., Jack, C. R., Jr., Jagust, W., Morris, J. C., Petersen, R. C., Salazar, J., Saykin, A. J., Shaw, L. M., Toga, A. W., Trojanowski, J. Q., & Alzheimer's Disease Neuroimaging, I. (2017). The Alzheimer\u2019s disease neuroimaging initiative 3: Continued innovation for clinical trial improvement. Alzheimers Dement, 13(5), 561\u2013571. https:\/\/doi.org\/10.1016\/j.jalz.2016.10.006","journal-title":"Alzheimers Dement"}],"container-title":["Brain Imaging and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11682-026-01187-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11682-026-01187-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11682-026-01187-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:18:11Z","timestamp":1788855491000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11682-026-01187-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":41,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["1187"],"URL":"https:\/\/doi.org\/10.1007\/s11682-026-01187-x","relation":{},"ISSN":["1931-7565"],"issn-type":[{"value":"1931-7565","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]},"assertion":[{"value":"8 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"ADNI obtained ethics approval from the Institutional Review Board (IRB) of the University of Southern California and from the IRBs of all participating institutions. Written informed consent was obtained from all participants or their authorized representatives. The full list of participating IRBs and ethics committees is provided in the Supplementary Text.","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All participants provided written informed consent, and data collection procedures adhered to established ethical standards with subsequent de-identification of all participant data.","order":3,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"PSS reports receiving research funding from the National Health and Medical Research Council of Australia (APP1169489) and the National Institutes of Health, USA (grants 1RF1AG057531\u201301 and 2R01AG057531-02A1), with all payments made to his institution. He received an honorarium from Alkem Labs for a lecture as part of the Frontiers of Psychiatry 2023 seminar in Mumbai, India. He has served on the Medical Advisory Committees of Biogen Australia (2020\u20132021), Roche Australia (2022), Eli Lilly (2025) and Novo Nordisk (2025), with payment received for participation in meetings. He also holds unpaid leadership roles with the International Neuropsychiatric Association (Executive Board Member) and the World Psychiatric Association (Planning Committee Member). KL and JJ declare no conflicts of interest.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"117"}}