{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:57:34Z","timestamp":1768568254167,"version":"3.49.0"},"posted":{"date-parts":[[2024,8,16]]},"group-title":"Neurology","reference-count":68,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T00:00:00Z","timestamp":1723766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,8,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Excessive daytime sleepiness (EDS) is a disabling symptom of Lewy body disorders (LBD). The hypothalamus is a key sleep-wake regulator, but its contribution to EDS in LBD remains unclear.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Use diffusion MRI to evaluate the relationship of hypothalamic microstructure to EDS symptoms in LBD.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We studied 102 patients with clinically-defined LBD (Parkinson\u2019s disease, n=93; Parkinson\u2019s disease dementia, n=4; and dementia with Lewy bodies, n=5) and Epworth Sleepiness Scale (ESS) within 2 years of MRI. Mean diffusivity (MD) was compared between EDS+ (ESS\u226510, n=37) and EDS- (ESS&lt;10, n=65) groups in the whole hypothalamus and three subregions, covarying for age and sex. Secondary analyses tested correlations between subregion MD and continuous ESS, global cognition, and motor scores; and between subregion volume and continuous ESS.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    MD was increased in EDS+ compared to EDS-only in the inferior tuberal subregion (Cohen\u2019s d=0.43, p=0.043, \u03b2=0.117\u00b10.057), with trend level differences in the whole hypothalamus (Cohen\u2019s d=0.39, p=0.064, \u03b2=0.070\u00b10.037) and superior tuberal subregion (Cohen\u2019s d=0.38, p=0.073, \u03b2=0.063\u00b10.035). No difference was seen in the posterior subregion (Cohen\u2019s d=0.1, p=0.628, \u03b2=0.019\u00b10.038). Significant correlations with continuous ESS were seen in MD of whole hypothalamus (r\n                    <jats:sup>2<\/jats:sup>\n                    =0.074, p=0.0057), superior tuberal (r\n                    <jats:sup>2<\/jats:sup>\n                    =0.081, p=0.0038), and inferior tuberal (r\n                    <jats:sup>2<\/jats:sup>\n                    =0.073, p=0.0059) subregions. There was no correlation of hypothalamic MD with global cognition or motor scores, and no correlation of whole\/subregional hypothalamic volumes with ESS.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Daytime sleepiness associates with increased MD in the inferior tuberal hypothalamus in an LBD cohort. This suggests degeneration within this region could contribute to EDS symptoms.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.08.16.24312102","type":"posted-content","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T17:40:17Z","timestamp":1723830017000},"source":"Crossref","is-referenced-by-count":0,"title":["Microstructural changes in the inferior tuberal hypothalamus correlate with daytime sleepiness in Lewy body disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2554-5181","authenticated-orcid":false,"given":"Jesse S.","family":"Cohen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamsanandini","family":"Radhakrishnan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher A.","family":"Olm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandhitsu R.","family":"Das","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip A.","family":"Cook","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Wolk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0633-7168","authenticated-orcid":false,"given":"Daniel","family":"Weintraub","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Irwin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7581-6405","authenticated-orcid":false,"given":"Corey T.","family":"McMillan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024081907450729000_2024.08.16.24312102v1.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah4968"},{"key":"2024081907450729000_2024.08.16.24312102v1.2","doi-asserted-by":"publisher","DOI":"10.1002\/gps.3799"},{"key":"2024081907450729000_2024.08.16.24312102v1.3","doi-asserted-by":"publisher","DOI":"10.1002\/gps.1709"},{"key":"2024081907450729000_2024.08.16.24312102v1.4","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870130606"},{"key":"2024081907450729000_2024.08.16.24312102v1.5","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp263"},{"key":"2024081907450729000_2024.08.16.24312102v1.6","doi-asserted-by":"crossref","first-page":"333","DOI":"10.31887\/DCNS.2004.6.3\/imckeith","article-title":"Dementia with Lewy bodies","volume":"6","year":"2004","journal-title":"Dialogues Clin Neurosci"},{"key":"2024081907450729000_2024.08.16.24312102v1.7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2869.2005.00462.x"},{"key":"2024081907450729000_2024.08.16.24312102v1.8","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.10.1544"},{"key":"2024081907450729000_2024.08.16.24312102v1.9","doi-asserted-by":"publisher","DOI":"10.1177\/089198879100400405"},{"key":"2024081907450729000_2024.08.16.24312102v1.10","doi-asserted-by":"publisher","DOI":"10.1007\/BF01321316"},{"key":"2024081907450729000_2024.08.16.24312102v1.11","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410030207"},{"key":"2024081907450729000_2024.08.16.24312102v1.12","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1212\/WNL.34.5.672","article-title":"Biochemistry of the hypothalamus in Parkinson\u2019s disease","volume":"34","year":"1984","journal-title":"Neurology"},{"key":"2024081907450729000_2024.08.16.24312102v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)91761-2"},{"key":"2024081907450729000_2024.08.16.24312102v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(85)90132-6"},{"key":"2024081907450729000_2024.08.16.24312102v1.15","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410180507"},{"key":"2024081907450729000_2024.08.16.24312102v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00065-9"},{"key":"2024081907450729000_2024.08.16.24312102v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/nature04284"},{"key":"2024081907450729000_2024.08.16.24312102v1.18","doi-asserted-by":"crossref","first-page":"26782","DOI":"10.1038\/srep26782","article-title":"Structural Brain Alterations Associated with Rapid Eye Movement Sleep Behavior Disorder in Parkinson\u2019s Disease","volume":"6","year":"2016","journal-title":"Scientific Reports"},{"key":"2024081907450729000_2024.08.16.24312102v1.19","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26592"},{"key":"2024081907450729000_2024.08.16.24312102v1.20","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1002\/mds.27814","article-title":"Morphological MRI investigations of the hypothalamus in 232 individuals with Parkinson\u2019s disease","volume":"34","year":"2019","journal-title":"Mov Disord"},{"key":"2024081907450729000_2024.08.16.24312102v1.21","doi-asserted-by":"crossref","first-page":"106472","DOI":"10.1016\/j.nbd.2024.106472","article-title":"Microstructural alterations of the hypothalamus in Parkinson\u2019s disease and probable REM sleep behavior disorder","volume":"194","year":"2024","journal-title":"Neurobiology of Disease"},{"key":"2024081907450729000_2024.08.16.24312102v1.22","doi-asserted-by":"publisher","DOI":"10.1006\/jmrb.1996.0086"},{"key":"2024081907450729000_2024.08.16.24312102v1.23","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abq2923"},{"key":"2024081907450729000_2024.08.16.24312102v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.07.001"},{"key":"2024081907450729000_2024.08.16.24312102v1.25","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.nicl.2018.09.027","article-title":"Microstructural brain changes track cognitive decline in mild cognitive impairment","volume":"20","year":"2018","journal-title":"Neuroimage Clin"},{"key":"2024081907450729000_2024.08.16.24312102v1.26","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.parkreldis.2021.06.003","article-title":"Progressive microstructural alterations in subcortical nuclei in Parkinson\u2019s disease: A diffusion magnetic resonance imaging study","volume":"88","year":"2021","journal-title":"Parkinsonism & Related Disorders"},{"key":"2024081907450729000_2024.08.16.24312102v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2013.06.003"},{"key":"2024081907450729000_2024.08.16.24312102v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2010.08.233"},{"key":"2024081907450729000_2024.08.16.24312102v1.29","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21507"},{"key":"2024081907450729000_2024.08.16.24312102v1.30","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26424"},{"key":"2024081907450729000_2024.08.16.24312102v1.31","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.56.1.33"},{"key":"2024081907450729000_2024.08.16.24312102v1.32","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004058"},{"key":"2024081907450729000_2024.08.16.24312102v1.33","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000187889.17253.b1"},{"key":"2024081907450729000_2024.08.16.24312102v1.34","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/14.6.540"},{"key":"2024081907450729000_2024.08.16.24312102v1.35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2869.2007.00570.x"},{"key":"2024081907450729000_2024.08.16.24312102v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/S1087-0792(98)90050-8"},{"key":"2024081907450729000_2024.08.16.24312102v1.37","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.parkreldis.2018.02.003","article-title":"Daytime sleepiness in dementia with Lewy bodies is associated with neuronal depletion of the nucleus basalis of Meynert","volume":"50","year":"2018","journal-title":"Parkinsonism Relat Disord"},{"key":"2024081907450729000_2024.08.16.24312102v1.38","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.2147\/NSS.S340950","article-title":"Reliability and Efficacy of the Epworth Sleepiness Scale: Is There Still a Place for It?","volume":"14","year":"2022","journal-title":"Nat Sci Sleep"},{"key":"2024081907450729000_2024.08.16.24312102v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.117287"},{"key":"2024081907450729000_2024.08.16.24312102v1.40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.200033797"},{"key":"2024081907450729000_2024.08.16.24312102v1.41","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/s41592-021-01185-5","article-title":"QSIPrep: an integrative platform for preprocessing and reconstructing diffusion MRI data","volume":"18","year":"2021","journal-title":"Nat Methods"},{"key":"2024081907450729000_2024.08.16.24312102v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(75)90026-6"},{"key":"2024081907450729000_2024.08.16.24312102v1.43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2005.53221.x"},{"key":"2024081907450729000_2024.08.16.24312102v1.44","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26062"},{"key":"2024081907450729000_2024.08.16.24312102v1.45","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22340"},{"key":"2024081907450729000_2024.08.16.24312102v1.46","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-199001000-00010"},{"key":"2024081907450729000_2024.08.16.24312102v1.47","unstructured":"Cohen J. Statistical Power Analysis for the Behavioral Sciences (2nd ed.): Routledge, 1988."},{"key":"2024081907450729000_2024.08.16.24312102v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2010.06.004"},{"key":"2024081907450729000_2024.08.16.24312102v1.49","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-011-0631-8"},{"key":"2024081907450729000_2024.08.16.24312102v1.50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.181330998"},{"key":"2024081907450729000_2024.08.16.24312102v1.51","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1002\/mds.26287","article-title":"Histaminergic tuberomammillary neuron loss in multiple system atrophy and dementia with Lewy bodies","volume":"30","year":"2015","journal-title":"Mov Disord"},{"key":"2024081907450729000_2024.08.16.24312102v1.52","first-page":"1","article-title":"Neuroanatomy and pathology of sporadic Parkinson\u2019s disease","volume":"201","year":"2009","journal-title":"Adv Anat Embryol Cell Biol"},{"key":"2024081907450729000_2024.08.16.24312102v1.53","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870080310"},{"key":"2024081907450729000_2024.08.16.24312102v1.54","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1212\/WNL.46.6.1693","article-title":"Large neurons in the tuberomammillary nucleus in patients with Parkinson\u2019s disease and multiple system atrophy","volume":"46","year":"1996","journal-title":"Neurology"},{"key":"2024081907450729000_2024.08.16.24312102v1.55","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2000.7362"},{"key":"2024081907450729000_2024.08.16.24312102v1.56","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1016\/j.neurobiolaging.2011.01.004","article-title":"Neuronal histamine production remains unaltered in Parkinson\u2019s disease despite the accumulation of Lewy bodies and Lewy neurites in the tuberomamillary nucleus","volume":"33","year":"2012","journal-title":"Neurobiol Aging"},{"key":"2024081907450729000_2024.08.16.24312102v1.57","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.00871.x"},{"key":"2024081907450729000_2024.08.16.24312102v1.58","doi-asserted-by":"crossref","first-page":"e2216247120","DOI":"10.1073\/pnas.2216247120","article-title":"Ameliorating parkinsonian motor dysfunction by targeting histamine receptors in entopeduncular nucleus-thalamus circuitry","volume":"120","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024081907450729000_2024.08.16.24312102v1.59","doi-asserted-by":"publisher","DOI":"10.1172\/JCI99986"},{"key":"2024081907450729000_2024.08.16.24312102v1.60","doi-asserted-by":"crossref","first-page":"5201","DOI":"10.1172\/JCI124777","article-title":"Histamine and deep brain stimulation: the pharmacology of regularizing a brain","volume":"128","year":"2018","journal-title":"J Clin Invest"},{"key":"2024081907450729000_2024.08.16.24312102v1.61","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24019"},{"key":"2024081907450729000_2024.08.16.24312102v1.62","doi-asserted-by":"crossref","first-page":"709","DOI":"10.2147\/NSS.S264140","article-title":"Pitolisant to Treat Excessive Daytime Sleepiness and Cataplexy in Adults with Narcolepsy: Rationale and Clinical Utility","volume":"12","year":"2020","journal-title":"Nat Sci Sleep"},{"key":"2024081907450729000_2024.08.16.24312102v1.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2003.09.032"},{"key":"2024081907450729000_2024.08.16.24312102v1.64","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0117593"},{"key":"2024081907450729000_2024.08.16.24312102v1.65","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0742-6"},{"key":"2024081907450729000_2024.08.16.24312102v1.66","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2021.02.016"},{"key":"2024081907450729000_2024.08.16.24312102v1.67","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000443"},{"key":"2024081907450729000_2024.08.16.24312102v1.68","doi-asserted-by":"crossref","unstructured":"Khodai T , Luckman SM . Ventromedial Nucleus of the Hypothalamus Neurons Under the Magnifying Glass. Endocrinology 2021;162.","DOI":"10.1210\/endocr\/bqab141"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.08.16.24312102","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:09:29Z","timestamp":1768507769000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2024.08.16.24312102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,16]]},"references-count":68,"URL":"https:\/\/doi.org\/10.1101\/2024.08.16.24312102","relation":{},"subject":[],"published":{"date-parts":[[2024,8,16]]},"subtype":"preprint"}}