{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:08:18Z","timestamp":1792181298464,"version":"4.4.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hypertens Res"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cognitive impairment is a frequent yet poorly understood complication of maintenance hemodialysis. We studied 162 thrice-weekly hemodialysis patients and 1858 community adults characterized previously with identical pressure-flow protocols. Group comparisons were conducted following propensity score matching and utilizing ANCOVA, adjusted for age, sex, educational attainment, body mass index, diabetes, and hypertension. On a mid-week non-dialysis day, synchronous applanation tonometry and Doppler ultrasound recorded ascending-aortic and common-carotid waveforms; mean hydraulic energy, pulsatile energy and the pulsatile energy fraction (PEF) were computed for each heartbeat. Global cognition was assessed with the Montreal Cognitive Assessment (MoCA), with scores\u2009&lt;\u200926 indicating impairment. Cognitive dysfunction was present in 39% of 152 hemodialysis patients versus 33% of community adults (Standardized Mean Difference\u2009=\u20090.134). Compared with the Community group, hemodialysis group exhibited a 45% increase in aortic PEF (0.16\u2009\u00b1\u20090.07 vs 0.11\u2009\u00b1\u20090.03), and a 74% increase in carotid PEF (0.080\u2009\u00b1\u20090.04 vs 0.046\u2009\u00b1\u20090.02). In multivariable models adjusted for age, sex, education level, and body-mass index, carotid PEF displayed the strongest inverse association with MoCA (standardized \u03b2\u2009=\u2009\u20130.287,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Introducing carotid PEF increased the model\u2019s explained variance and rendered pulse pressure and carotid\u2013femoral pulse-wave velocity non-significant. Conversely, higher steady mean carotid energy correlated positively with MoCA (\u03b2\u2009=\u2009+0.158,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.030). These findings indicate that cognitive performance in hemodialysis patients is governed less by conventional pressure or stiffness metrics than by the pulsatile energy transmitted to the carotids, positioning carotid PEF as a mechanistic marker and promising therapeutic target for preserving cognition in this vulnerable population.\n                  <\/jats:p>","DOI":"10.1038\/s41440-025-02438-y","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T09:17:31Z","timestamp":1762939051000},"page":"396-406","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Carotid pulsatile energy fraction surpasses traditional hemodynamic markers in explaining cognitive impairment among hemodialysis patients"],"prefix":"10.1038","volume":"49","author":[{"given":"Chih-Cheng","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieh-kai","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihchen","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru-Yin","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu-Yang","family":"Hsieh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Jiun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Yuan","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Min","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"2438_CR1","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1212\/WNL.0b013e31827f0f7f","volume":"80","author":"MJ Sarnak","year":"2013","unstructured":"Sarnak MJ, Tighiouart H, Scott TM, Lou KV, Sorensen EP, Giang LM, et al. Frequency of and risk factors for poor cognitive performance in hemodialysis patients. Neurology. 2013;80:471.","journal-title":"Neurology"},{"key":"2438_CR2","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1212\/01.wnl.0000225182.15532.40","volume":"67","author":"AM Murray","year":"2006","unstructured":"Murray AM, Tupper DE, Knopman DS, Gilbertson DT, Pederson SL, Li S, et al. Cognitive impairment in hemodialysis patients is common. Neurology. 2006;67:216.","journal-title":"Neurology"},{"key":"2438_CR3","doi-asserted-by":"publisher","first-page":"e0304762","DOI":"10.1371\/journal.pone.0304762","volume":"19","author":"J Zhang","year":"2024","unstructured":"Zhang J, Wu L, Wang P, Pan Y, Dong X, Jia L, et al. Prevalence of cognitive impairment and its predictors among chronic kidney disease patients: a systematic review and meta-analysis. PLoS One. 2024;19:e0304762.","journal-title":"PLoS One"},{"key":"2438_CR4","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1053\/j.ajkd.2010.07.003","volume":"56","author":"K Griva","year":"2010","unstructured":"Griva K, Stygall J, Hankins M, Davenport A, Harrison M, Newman SP. Cognitive impairment and 7-year mortality in dialysis patients. Am J Kidney Dis. 2010;56:693\u2013703.","journal-title":"Am J Kidney Dis"},{"key":"2438_CR5","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1053\/j.ajkd.2011.12.029","volume":"60","author":"EP Sorensen","year":"2012","unstructured":"Sorensen EP, Sarnak MJ, Tighiouart H, Scott T, Giang LM, Kirkpatrick B, et al. The kidney disease quality of life cognitive function subscale and cognitive performance in maintenance hemodialysis patients. Am J Kidney Dis. 2012;60:417\u201326.","journal-title":"Am J Kidney Dis"},{"key":"2438_CR6","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.3389\/fcvm.2020.00096","volume":"7","author":"M Miglinas","year":"2020","unstructured":"Miglinas M, Cesniene U, Janusaite MM, Vinikovas A. Cerebrovascular disease and cognition in chronic kidney disease patients. Front Cardiovasc Med. 2020;7:2020.","journal-title":"Front Cardiovasc Med"},{"key":"2438_CR7","doi-asserted-by":"publisher","first-page":"S140","DOI":"10.1046\/j.1523-1755.2000.07618.x","volume":"58","author":"F Meeus","year":"2000","unstructured":"Meeus F, Kourilsky O, Guerin AP, Gaudry C, Marchais SJ, London GM. Pathophysiology of cardiovascular disease in hemodialysis patients. Kidney Int. 2000;58:S140\u2013S7.","journal-title":"Kidney Int"},{"key":"2438_CR8","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-024-03905-8","volume":"24","author":"B Aimagambetova","year":"2024","unstructured":"Aimagambetova B, Ariko T, Merritt S, Rundek T. Arterial stiffness measured by pulse wave velocity correlated with cognitive decline in hypertensive individuals: a systematic review. BMC Neurol. 2024;24:393.","journal-title":"BMC Neurol"},{"key":"2438_CR9","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1016\/j.ekir.2017.07.013","volume":"2","author":"ED Kim","year":"2017","unstructured":"Kim ED, Meoni LA, Jaar BG, Shafi T, Linda Kao WH, Estrella MM, et al. Association of arterial stiffness and central pressure with cognitive function in incident hemodialysis patients: the PACE study. Kidney Int Rep. 2017;2:1149\u201359.","journal-title":"Kidney Int Rep"},{"key":"2438_CR10","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1111\/j.1542-4758.2012.00718.x","volume":"17","author":"LM Giang","year":"2013","unstructured":"Giang LM, Tighiouart H, Lou KV, Agganis B, Drew DA, Shaffi K, et al. Measures of blood pressure and cognition in dialysis patients. Hemodial Int Int Symp Home Hemodial. 2013;17:24\u201331.","journal-title":"Hemodial Int Int Symp Home Hemodial"},{"key":"2438_CR11","doi-asserted-by":"publisher","first-page":"2262","DOI":"10.1038\/s41440-024-01735-2","volume":"47","author":"HM Cheng","year":"2024","unstructured":"Cheng HM, Wang JJ, Chuang SY, Lin CH, Mitchell GF, Huang CJ, et al. Dissecting the vascular-cognitive nexus: energetic vs. conventional hemodynamic parameters. Hypertens Res. 2024;47:2262\u201374.","journal-title":"Hypertens Res"},{"key":"2438_CR12","first-page":"668","volume":"100","author":"CJ Yeh","year":"2001","unstructured":"Yeh CJ, Pan WH, Jong YS, Kuo YY, Lo CH. Incidence and predictors of isolated systolic hypertension and isolated diastolic hypertension in Taiwan. J Formos Med Assoc. 2001;100:668\u201375.","journal-title":"J Formos Med Assoc"},{"key":"2438_CR13","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.apnu.2016.01.015","volume":"30","author":"JC Tsai","year":"2016","unstructured":"Tsai JC, Chen CW, Chu H, Yang HL, Chung MH, Liao YM, et al. Comparing the sensitivity, specificity, and predictive values of the montreal cognitive assessment and mini-mental state examination when screening people for mild cognitive impairment and dementia in Chinese population. Arch Psychiatr Nurs. 2016;30:486\u201391.","journal-title":"Arch Psychiatr Nurs"},{"key":"2438_CR14","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","volume":"12","author":"MF Folstein","year":"1975","unstructured":"Folstein MF, Folstein SE, McHugh PR. \u201cMini-mental state\u201d. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189\u201398.","journal-title":"J Psychiatr Res"},{"key":"2438_CR15","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","volume":"53","author":"ZS Nasreddine","year":"2005","unstructured":"Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53:695\u20139.","journal-title":"J Am Geriatr Soc"},{"key":"2438_CR16","first-page":"693","volume":"64","author":"YP Lin","year":"2001","unstructured":"Lin YP, Chen CH, Hsu TL, Yang WC, Ding PY. Sequential tonometry as a practical method to estimate truncal pulse wave velocity. Zhonghua Yi Xue Za Zhi. 2001;64:693\u2013702.","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"2438_CR17","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.1161\/01.CIR.95.7.1827","volume":"95","author":"CH Chen","year":"1997","unstructured":"Chen CH, Nevo E, Fetics B, Pak PH, Yin FC, Maughan WL, et al. Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure. Validation of generalized transfer function. Circulation. 1997;95:1827\u201336.","journal-title":"Circulation"},{"key":"2438_CR18","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1016\/j.jacc.2013.06.029","volume":"62","author":"HM Cheng","year":"2013","unstructured":"Cheng HM, Chuang SY, Sung SH, Yu WC, Pearson A, Lakatta EG, et al. Derivation and validation of diagnostic thresholds for central blood pressure measurements based on long-term cardiovascular risks. J Am Coll Cardiol. 2013;62:1780\u20137.","journal-title":"J Am Coll Cardiol"},{"key":"2438_CR19","doi-asserted-by":"publisher","first-page":"2262","DOI":"10.1161\/STROKEAHA.116.013207","volume":"47","author":"SY Chuang","year":"2016","unstructured":"Chuang SY, Cheng HM, Bai CH, Yeh WT, Chen JR, Pan WH. Blood pressure, carotid flow pulsatility, and the risk of stroke: a community-based study. Stroke. 2016;47:2262\u20138.","journal-title":"Stroke"},{"key":"2438_CR20","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1007\/s12975-020-00836-7","volume":"12","author":"SY Chuang","year":"2021","unstructured":"Chuang SY, Wang PN, Chen LK, Chou KH, Chung CP, Chen CH, et al. Associations of blood pressure and carotid flow velocity with brain volume and cerebral small vessel disease in a community-based population. Transl Stroke Res. 2021;12:248\u201358.","journal-title":"Transl Stroke Res"},{"key":"2438_CR21","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1161\/HYPERTENSIONAHA.120.16696","volume":"77","author":"MA Haidar","year":"2021","unstructured":"Haidar MA, van Buchem MA, Sigurdsson S, Gotal JD, Gudnason V, Launer LJ, et al. Wave reflection at the origin of a first-generation branch artery and target organ protection: the AGES-Reykjavik study. Hypertension. 2021;77:1169\u201377.","journal-title":"Hypertension"},{"key":"2438_CR22","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.762437","volume":"12","author":"SF Vatner","year":"2021","unstructured":"Vatner SF, Zhang J, Vyzas C, Mishra K, Graham RM, Vatner DE. Vascular stiffness in aging and disease. Front Physiol. 2021;12:762437.","journal-title":"Front Physiol"},{"key":"2438_CR23","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/S0140-6736(16)30508-6","volume":"388","author":"C Wanner","year":"2016","unstructured":"Wanner C, Amann K, Shoji T. The heart and vascular system in dialysis. Lancet. 2016;388:276\u201384.","journal-title":"Lancet"},{"key":"2438_CR24","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1161\/01.HYP.27.2.159","volume":"27","author":"GL Baumbach","year":"1996","unstructured":"Baumbach GL. Effects of increased pulse pressure on cerebral arterioles. Hypertension. 1996;27:159\u201367.","journal-title":"Hypertension"},{"key":"2438_CR25","doi-asserted-by":"publisher","first-page":"2614","DOI":"10.1177\/0271678X16672482","volume":"37","author":"F Garcia-Polite","year":"2017","unstructured":"Garcia-Polite F, Martorell J, Del Rey-Puech P, Melgar-Lesmes P, O\u2019Brien CC, Roquer J, et al. Pulsatility and high shear stress deteriorate barrier phenotype in brain microvascular endothelium. J Cereb Blood Flow Metab. 2017;37:2614\u201325.","journal-title":"J Cereb Blood Flow Metab"},{"key":"2438_CR26","doi-asserted-by":"publisher","first-page":"245","DOI":"10.3389\/fnagi.2020.00245","volume":"12","author":"AC Conley","year":"2020","unstructured":"Conley AC, Karayanidis F, Jolly TAD, Yang MH, Hsieh S. Cerebral arterial pulsatility and global white matter microstructure impact spatial working memory in older adults with and without cardiovascular risk factors. Front Aging Neurosci. 2020;12:245.","journal-title":"Front Aging Neurosci"},{"key":"2438_CR27","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1161\/01.HYP.31.1.125","volume":"31","author":"JJ Cheng","year":"1998","unstructured":"Cheng JJ, Wung BS, Chao YJ, Wang DL. Cyclic strain-induced reactive oxygen species involved in ICAM-1 gene induction in endothelial cells. Hypertension. 1998;31:125\u201330.","journal-title":"Hypertension"},{"key":"2438_CR28","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1161\/CIRCRESAHA.123.321752","volume":"132","author":"C Baaten","year":"2023","unstructured":"Baaten C, Vondenhoff S, Noels H. Endothelial cell dysfunction and increased cardiovascular risk in patients with chronic kidney disease. Circ Res. 2023;132:970\u201392.","journal-title":"Circ Res"},{"key":"2438_CR29","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1007\/s40620-020-00745-w","volume":"33","author":"C Loutradis","year":"2020","unstructured":"Loutradis C, Papagianni A, Ekart R, Theodorakopoulou M, Minopoulou I, Pagourelias E, et al. Excess volume removal following lung ultrasound evaluation decreases central blood pressure and pulse wave velocity in hemodialysis patients: a LUST sub-study. J Nephrol. 2020;33:1289\u2013300.","journal-title":"J Nephrol"},{"key":"2438_CR30","doi-asserted-by":"publisher","unstructured":"Lim S, Kook H, Yu CW, Kim JH, Cha JJ, Joo HJ, et al. Differential effects of antihypertensive drugs on central blood pressure: a randomized comparison between nebivolol and telmisartan. Am J Hypertens. 2025;20250610, https:\/\/doi.org\/10.1093\/ajh\/hpaf098.","DOI":"10.1093\/ajh\/hpaf098"},{"key":"2438_CR31","doi-asserted-by":"publisher","first-page":"H1567","DOI":"10.1152\/ajpheart.00622.2009","volume":"297","author":"P Lacolley","year":"2009","unstructured":"Lacolley P, Safar ME, Regnault V, Frohlich ED. Angiotensin II, mechanotransduction, and pulsatile arterial hemodynamics in hypertension. Am J Physiol Heart Circ Physiol. 2009;297:H1567\u201375.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2438_CR32","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.niox.2013.10.001","volume":"35","author":"AH Liu","year":"2013","unstructured":"Liu AH, Bondonno CP, Croft KD, Puddey IB, Woodman RJ, Rich L, et al. Effects of a nitrate-rich meal on arterial stiffness and blood pressure in healthy volunteers. Nitric Oxide. 2013;35:123\u201330.","journal-title":"Nitric Oxide"},{"key":"2438_CR33","doi-asserted-by":"publisher","first-page":"163","DOI":"10.5301\/jva.5000196","volume":"15","author":"RH Vaes","year":"2014","unstructured":"Vaes RH, Tordoir JH, Scheltinga MR. Systemic effects of a high-flow arteriovenous fistula for hemodialysis. J Vasc Access. 2014;15:163\u20138.","journal-title":"J Vasc Access"}],"container-title":["Hypertension Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41440-025-02438-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41440-025-02438-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41440-025-02438-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T07:05:35Z","timestamp":1768979135000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41440-025-02438-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,12]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["2438"],"URL":"https:\/\/doi.org\/10.1038\/s41440-025-02438-y","relation":{},"ISSN":["0916-9636","1348-4214"],"issn-type":[{"value":"0916-9636","type":"print"},{"value":"1348-4214","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,12]]},"assertion":[{"value":"10 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 November 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}