{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:22:28Z","timestamp":1792621348611,"version":"4.5.0"},"reference-count":37,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,9,12]]},"abstract":"<jats:p>Background: Emerging evidence suggests that age-related changes in cerebral health may be sensitive to vascular risk modifiers, such as physical activity and sleep. Objective: We examine whether cardiorespiratory fitness modifies the association of obstructive sleep apnea (OSA) severity with MRI-assessed measures of cerebral structure and perfusion. Methods: Using data from a cross-sectional sample of participants (n\u200a=\u200a129, 51% female, age range 49.6-85.3 years) in the Wisconsin Sleep Cohort study, we estimated linear models of MRI-assessed total and regional gray matter (GM) and white matter (WM) volumes, WM hyperintensity (WMH:ICV ratio), total lesion volume, and arterial spin labeling (ASL) cerebral blood flow (CBF), using an estimated measure of cardiorespiratory fitness (CRF) and OSA severity as predictors. Participants\u2019 sleep was assessed using overnight in-laboratory polysomnography, and OSA severity was measured using the apnea-hypopnea index (AHI), or the mean number of recorded apnea and hypopnea events per hour of sleep. The mean\u00b1SD time difference between PSG data collection and MRI data collection was 1.7\u00b11.5 years (range: [0, 4.9 years]). Results: OSA severity was associated with reduced total GM volume (\u03b2=-0.064; SE\u200a=\u200a0.023; p\u200a=\u200a0.007), greater total WM lesion volume (interaction p\u200a=\u200a0.023), and greater WMHs (interaction p\u200a=\u200a0.017) in less-fit subjects. Perfusion models revealed significant differences in the association of AHI and regional CBF between fitness groups (interaction ps\u200a&lt;\u200a0.05). Conclusion: This work provides new evidence for the protective role of cardiorespiratory fitness against the deleterious effects of OSA on brain aging in late-middle age to older adults.<\/jats:p>","DOI":"10.3233\/jad-220910","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T12:39:56Z","timestamp":1691152796000},"page":"427-435","source":"Crossref","is-referenced-by-count":5,"title":["Cardiorespiratory Fitness Attenuates the Deleterious Effects of Sleep Apnea on Cerebral Structure and Perfusion in the Wisconsin Sleep Cohort Study"],"prefix":"10.1177","volume":"95","author":[{"given":"Kyle J.","family":"Edmunds","sequence":"first","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Driscoll","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"},{"name":"Psychology Department, University of Wisconsin-Milwaukee, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika W.","family":"Hagen","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodi H.","family":"Barnet","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurel A.","family":"Ravelo","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Plante","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian M.","family":"Gait\u00e1n","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah R.","family":"Lose","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Motovylyak","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara B.","family":"Bendlin","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Institute, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozioma C.","family":"Okonkwo","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E.","family":"Peppard","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-220910_ref1","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1093\/brain\/awu043","article-title":"Association of brain amyloid-\u03b2 with cerebral perfusion and structure in Alzheimer\u2019s disease and mild cognitive impairment","volume":"137","author":"Mattsson","year":"2014","journal-title":"Brain"},{"key":"10.3233\/JAD-220910_ref2","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1093\/cercor\/bhs381","article-title":"Cerebral blood flow is diminished in asymptomatic middle-aged adults with maternal history of Alzheimer\u2019s disease","volume":"24","author":"Okonkwo","year":"2014","journal-title":"Cereb Cortex"},{"key":"10.3233\/JAD-220910_ref3","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1177\/0271678X211021313","article-title":"Impact of sex and APOE \u025b4 on age-related cerebral perfusion trajectories in cognitively asymptomatic middle-aged and older adults: A longitudinal study","volume":"41","author":"Wang","year":"2021","journal-title":"J Cereb Blood Flow Metab"},{"key":"10.3233\/JAD-220910_ref4","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.neubiorev.2016.11.023","article-title":"Cerebral blood flow measured by arterial spin labeling MRI at resting state in normal aging and Alzheimer\u2019s disease","volume":"72","author":"Zhang","year":"2017","journal-title":"Neurosci Biobehav Rev"},{"key":"10.3233\/JAD-220910_ref5","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1212\/WNL.0000000000000964","article-title":"Physical activity attenuates age-related biomarker alterations in preclinical AD","volume":"83","author":"Okonkwo","year":"2014","journal-title":"Neurology"},{"key":"10.3233\/JAD-220910_ref6","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3233\/JAD-180291","article-title":"Cardiorespiratory fitness modifies influence of sleep problems on cerebrospinal fluid biomarkers in an at-risk cohort","volume":"69","author":"Law","year":"2019","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220910_ref7","doi-asserted-by":"crossref","first-page":"709","DOI":"10.5665\/sleep.2632","article-title":"Obstructive sleep apnea as a risk factor for cerebral white matter change in a middle-aged and older general population","volume":"36","author":"Kim","year":"2013","journal-title":"Sleep"},{"key":"10.3233\/JAD-220910_ref8","first-page":"4909","article-title":"Associations between severity and duration of sleep-disordered breathing and brain tissue volume, PA","volume":"48","author":"Hagen","year":"2016","journal-title":"Eur Respir J"},{"key":"10.3233\/JAD-220910_ref9","first-page":"328","article-title":"ACSM\u2019s guidelines for exercise testing and prescription 9th Ed. 2014","volume":"58","author":"Ferguson","year":"2014","journal-title":"J Can Chiropr Assoc"},{"key":"10.3233\/JAD-220910_ref10","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s13195-018-0429-0","article-title":"Cardiorespiratory fitness attenuates age-associated aggregation of white matter hyperintensities in an at-risk cohort","volume":"10","author":"Vesperman","year":"2018","journal-title":"Alzheimers Res Ther"},{"key":"10.3233\/JAD-220910_ref11","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s11682-014-9325-9","article-title":"Cardiorespiratory fitness is associated with brain structure, cognition, and mood in a middle-aged cohort at risk for Alzheimer\u2019s disease","volume":"9","author":"Boots","year":"2015","journal-title":"Brain Imaging Behav"},{"key":"10.3233\/JAD-220910_ref12","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1037\/a0022733","article-title":"Cardiorespiratory fitness, hippocampal volume, and frequency of forgetting in older adults","volume":"25","author":"Szabo","year":"2011","journal-title":"Neuropsychology"},{"key":"10.3233\/JAD-220910_ref13","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.autneu.2019.01.007","article-title":"Control of the cardiovascular and respiratory systems during sleep","volume":"218","author":"Benarroch","year":"2019","journal-title":"Auton Neurosci"},{"key":"10.3233\/JAD-220910_ref14","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1164\/rccm.200609-1271OC","article-title":"Effects of continuous positive airway pressure on cerebral vascular response to hypoxia in patients with obstructive sleep apnea","volume":"175","author":"Foster","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"10.3233\/JAD-220910_ref15","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.amepre.2005.06.004","article-title":"Assessing cardiorespiratory fitness without performing exercise testing","volume":"29","author":"Jurca","year":"2005","journal-title":"Am J Prev Med"},{"key":"10.3233\/JAD-220910_ref16","first-page":"1071","article-title":"Sleep disordered breathing and mortality: Eighteen-year follow-up of the Wisconsin sleep cohort","volume":"31","author":"Young","year":"2008","journal-title":"Sleep"},{"key":"10.3233\/JAD-220910_ref17","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1056\/NEJM199304293281704","article-title":"The occurrence of sleep-disordered breathing among middle-aged adults","volume":"328","author":"Young","year":"1993","journal-title":"N Engl J Med"},{"key":"10.3233\/JAD-220910_ref18","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1177\/019459988108900522","article-title":"Sleep and breathing disturbance secondary to nasal obstruction","volume":"89","author":"Olsen","year":"1981","journal-title":"Otolaryngol Head Neck Surg"},{"key":"10.3233\/JAD-220910_ref19","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1164\/rccm.201201-0130OC","article-title":"Sleep-disordered breathing and cancer mortality: Results from the Wisconsin Sleep Cohort Study","volume":"186","author":"Nieto","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"10.3233\/JAD-220910_ref20","first-page":"120","article-title":"Obstructive sleep apnea diagnosis and management","volume":"114","author":"Goyal","year":"2017","journal-title":"Mo Med"},{"key":"10.3233\/JAD-220910_ref21","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1006\/nimg.1998.0396","article-title":"Cortical surface-based analysis: II: Inflation, flattening, and a surface-based coordinate system","volume":"9","author":"Fischl","year":"1999","journal-title":"Neuroimage"},{"key":"10.3233\/JAD-220910_ref22","doi-asserted-by":"crossref","first-page":"3774","DOI":"10.1016\/j.neuroimage.2011.11.032","article-title":"An automated tool for detection of FLAIR-hyperintense white-matter lesions in multiple sclerosis","volume":"59","author":"Schmidt","year":"2012","journal-title":"Neuroimage"},{"key":"10.3233\/JAD-220910_ref23","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/j.neuroimage.2010.01.064","article-title":"A robust method to estimate the intracranial volume across MRI field strengths (1.5 T and 3T)","volume":"50","author":"Keihaninejad","year":"2010","journal-title":"Neuroimage"},{"key":"10.3233\/JAD-220910_ref24","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.neurobiolaging.2013.10.072","article-title":"Regional white matter hyperintensities: Aging, Alzheimer\u2019s disease risk, and cognitive function","volume":"35","author":"Birdsill","year":"2014","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-220910_ref25","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/1522-2594(200007)44:1<92::AID-MRM14>3.0.CO;2-M","article-title":"Noise reduction in 3D perfusion imaging by attenuating the static signal in arterial spin tagging (ASSIST)","volume":"44","author":"Ye","year":"2000","journal-title":"Magn Reson Med"},{"key":"10.3233\/JAD-220910_ref26","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/mrm.20556","article-title":"Efficiency of inversion pulses for background suppressed arterial spin labeling","volume":"54","author":"Garcia","year":"2005","journal-title":"Magn Reson Med"},{"key":"10.3233\/JAD-220910_ref27","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s11325-011-0557-2","article-title":"Coexistence of obstructive sleep apnoea and metabolic syndrome is independently associated with left ventricular hypertrophy and diastolic dysfunction","volume":"16","author":"Usui","year":"2012","journal-title":"Sleep Breath"},{"key":"10.3233\/JAD-220910_ref28","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.5665\/sleep.5828","article-title":"Effects of obstructive sleep apnea and obesity on cardiac remodeling: The Wisconsin sleep cohort study","volume":"39","author":"Korcarz","year":"2016","journal-title":"Sleep"},{"key":"10.3233\/JAD-220910_ref29","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s11910-018-0855-1","article-title":"Sleep apnea is a risk factor for stroke and vascular dementia","volume":"18","author":"Culebras","year":"2018","journal-title":"Curr Neurol Neurosci Rep"},{"key":"10.3233\/JAD-220910_ref30","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.1073\/pnas.1015950108","article-title":"Exercise training increases size of hippocampus and improves memory","volume":"108","author":"Erickson","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-220910_ref31","doi-asserted-by":"crossref","first-page":"5638","DOI":"10.1073\/pnas.0611721104","article-title":"An correlate of exercise-induced neurogenesis in the adult dentate gyrus","volume":"104","author":"Pereira","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-220910_ref32","first-page":"1695","article-title":"Using network science to evaluate exercise-associated brain changes in older adults","volume":"2","author":"Burdette","year":"2010","journal-title":"Front Aging Neurosci"},{"key":"10.3233\/JAD-220910_ref33","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/1479-5868-5-56","article-title":"A comparison of direct versus self-report measures for assessing physical activity in adults: A systematic review","volume":"5","author":"Prince","year":"2008","journal-title":"Int J Behav Nutr Phys Act"},{"key":"10.3233\/JAD-220910_ref34","doi-asserted-by":"crossref","first-page":"601","DOI":"10.3233\/JAD-170576","article-title":"An objective methodto accurately measure cardiorespiratory fitness in older adults who cannot satisfy widely used oxygen consumption criteria","volume":"61","author":"Dougherty","year":"2018","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220910_ref35","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1161\/CIRCRESAHA.118.312669","article-title":"Sedentary behavior, exercise, and cardiovascular health","volume":"124","author":"Lavie","year":"2019","journal-title":"Circ Res"},{"key":"10.3233\/JAD-220910_ref36","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1093\/oxfordjournals.aje.a112608","article-title":"Physical activity as an index of heart attack risk in college alumni","volume":"108","author":"Paffenbarger","year":"1978","journal-title":"Am J Epidemiol"},{"key":"10.3233\/JAD-220910_ref37","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1097\/EDE.0b013e3181ba333c","article-title":"On the distinction between interaction and effect modification","volume":"20","author":"Vander Weele","year":"2009","journal-title":"Epidemiology"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-220910","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:08:20Z","timestamp":1777370900000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-220910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,12]]},"references-count":37,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3233\/jad-220910","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,12]]}}}