{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T14:10:53Z","timestamp":1774102253146,"version":"3.50.1"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Disappointing results from clinical trials designed to delay structural brain decline and the accompanying increase in risk for dementia in older adults have precipitated a shift in testing promising interventions from late in life toward midlife before irreversible damage has accumulated. This shift, however, requires targeting midlife biomarkers that are associated with clinical changes manifesting only in late life. Here we explored possible links between one putative biomarker, distributed integrity of brain white matter, and two intervention targets, cardiovascular fitness and healthy lifestyle behaviors, in midlife. At age 45, fractional anisotropy (FA) derived from diffusion weighted MRI was used to estimate the microstructural integrity of distributed white matter tracts in a population-representative birth cohort. Age-45 cardiovascular fitness (VO<jats:sub>2<\/jats:sub>Max; <jats:italic>N<\/jats:italic> = 801) was estimated from heart rates obtained during submaximal exercise tests; age-45 healthy lifestyle behaviors were estimated using the Nyberg Health Index (<jats:italic>N<\/jats:italic> = 854). Ten-fold cross-validated elastic net predictive modeling revealed that estimated VO<jats:sub>2<\/jats:sub>Max was modestly associated with distributed FA. In contrast, there was no significant association between Nyberg Health Index scores and FA. Our findings suggest that cardiovascular fitness levels, but not healthy lifestyle behaviors, are associated with the distributed integrity of white matter in the brain in midlife. These patterns could help inform future clinical intervention research targeting ADRDs.<\/jats:p>","DOI":"10.3389\/fnagi.2021.652575","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T04:48:10Z","timestamp":1617684490000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Midlife Cardiovascular Fitness Is Reflected in the Brain's White Matter"],"prefix":"10.3389","volume":"13","author":[{"given":"Tracy","family":"d'Arbeloff","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxwell L.","family":"Elliott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annchen R.","family":"Knodt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Sison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy R.","family":"Melzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Ireland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandhya","family":"Ramrakha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richie","family":"Poulton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avshalom","family":"Caspi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terrie E.","family":"Moffitt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad R.","family":"Hariri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3065","DOI":"10.1093\/brain\/awy229","article-title":"White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer's disease","volume":"141","author":"Araque Caballero","year":"2018","journal-title":"Brain"},{"key":"B2","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1001\/archneur.63.2.246","article-title":"Association of white matter hyperintensity volume with decreased cognitive functioning: the framingham heart study","volume":"63","author":"Au","year":"2006","journal-title":"Arch. Neurol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3968393","DOI":"10.1155\/2016\/3968393","article-title":"Graded exercise testing protocols for the determination of VO2 max: historical perspectives, progress, and future considerations","volume":"2016","author":"Beltz","year":"2016","journal-title":"J. Sports Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.neuroscience.2013.11.026","article-title":"Disconnected aging: cerebral white matter integrity and age-related differences in cognition","volume":"276","author":"Bennett","year":"2014","journal-title":"Neuroscience"},{"key":"B5","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.neuroimage.2015.12.010","article-title":"Physical activity over a decade modifies age-related decline in perfusion, gray matter volume, and functional connectivity of the posterior default-mode network\u2014a multimodal approach","volume":"131","author":"Boraxbekk","year":"2016","journal-title":"Neuroimage"},{"key":"B6","doi-asserted-by":"publisher","first-page":"30","DOI":"10.7326\/M17-1528","article-title":"Physical activity interventions in preventing cognitive decline and alzheimer-type dementia: a systematic review","volume":"168","author":"Brasure","year":"2018","journal-title":"Ann. Intern. Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1016\/j.neuroimage.2008.03.039","article-title":"Reduced cortical thickness in hippocampal subregions among cognitively normal apolipoprotein E e4 carriers","volume":"41","author":"Burggren","year":"2008","journal-title":"Neuroimage"},{"key":"B8","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1212\/01.wnl.0000317094.86209.cb","article-title":"Cardiorespiratory fitness and brain atrophy in early Alzheimer disease","volume":"71","author":"Burns","year":"2008","journal-title":"Neurology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e159","DOI":"10.1016\/S2468-2667(19)30019-2","article-title":"Measuring population ageing: an analysis of the global burden of disease study 2017","volume":"4","author":"Chang","year":"2019","journal-title":"Lancet Public Health"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1016\/S0140-6736(09)61460-4","article-title":"Ageing populations: the challenges ahead","volume":"374","author":"Christensen","year":"2009","journal-title":"Lancet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"112042","DOI":"10.1016\/j.bbr.2019.112042","article-title":"Effect of aerobic exercise on white matter microstructure in the aging brain","volume":"373","author":"Clark","year":"2019","journal-title":"Behav. Brain Res"},{"key":"B12","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.tins.2017.10.001","article-title":"Predicting age using neuroimaging: innovative brain ageing biomarkers","volume":"40","author":"Cole","year":"2017","journal-title":"Trends Neurosci"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41380-020-00975-1","article-title":"Three major dimensions of human brain cortical ageing in relation to cognitive decline across the eighth decade of life","author":"Cox","year":"2021","journal-title":"Molecular Psychiatry"},{"key":"B14","first-page":"317","article-title":"Modification of the astrand-rhyming sub-maimal bicycle test for estimating VO2max of inactive men and women","volume":"20","author":"Cullinane","year":"1988","journal-title":"Med. Sci. Sports Exerc"},{"key":"B15","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/1471-244X-12-167","article-title":"Protocol for a randomized controlled trial evaluating the effect of physical activity on delaying the progression of white matter changes on MRI in older adults with memory complaints and mild cognitive impairment: the AIBL active trial","volume":"12","author":"Cyarto","year":"2012","journal-title":"BMC Psychiatry"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1007\/s11357-020-00244-7","article-title":"Cardiovascular fitness and structural brain integrity: an update on current evidence","volume":"42","author":"d'Arbeloff","year":"2020","journal-title":"GeroScience"},{"key":"B17","doi-asserted-by":"publisher","first-page":"fcz041","DOI":"10.1093\/braincomms\/fcz041","article-title":"White matter hyperintensities are common in midlife and already associated with cognitive decline","volume":"1","author":"d'Arbeloff","year":"2019","journal-title":"Brain Commun."},{"key":"B18","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1212\/01.wnl.0000199954.81900.e2","article-title":"White matter integrity and cognition in childhood and old age","volume":"66","author":"Deary","year":"2006","journal-title":"Neurology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1093\/bmb\/ldp033","article-title":"Age-associated cognitive decline","volume":"92","author":"Deary","year":"2009","journal-title":"Br. Med. Bull"},{"key":"B20","doi-asserted-by":"publisher","first-page":"729","DOI":"10.3233\/JAD-170415","article-title":"Cardiorespiratory fitness and white matter neuronal fiber integrity in mild cognitive impairment","volume":"61","author":"Ding","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e00625","DOI":"10.1002\/brb3.625","article-title":"Relationships between cardiorespiratory fitness, hippocampal volume, and episodic memory in a population at risk for Alzheimer's disease","volume":"7","author":"Dougherty","year":"2017","journal-title":"Brain Behav"},{"key":"B22","doi-asserted-by":"publisher","first-page":"101075","DOI":"10.1016\/j.arr.2020.101075","article-title":"MRI-based biomarkers of accelerated aging and dementia risk in midlife: how close are we?","volume":"61","author":"Elliott","year":"2020","journal-title":"Aging Res. Rev."},{"key":"B23","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1101\/681700","article-title":"What is the test-retest reliability of common task-functional MRI measures? New empirical evidence and a meta-analysis: psychological science","author":"Elliott","year":"2020","journal-title":"bioRxiv."},{"key":"B24","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/978-1-4939-3118-7_2","article-title":"Introduction to diffusion tensor imaging,","volume-title":"Diffusion Tensor Imaging: A Practical Handbook","author":"Emsell","year":"2016"},{"key":"B25","doi-asserted-by":"publisher","first-page":"S20","DOI":"10.1016\/j.neurobiolaging.2014.03.034","article-title":"Physical activity, fitness, and gray matter volume","volume":"35","author":"Erickson","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"B26","doi-asserted-by":"publisher","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. Sic. U.S.A."},{"key":"B27","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.brainresrev.2006.01.002","article-title":"A meta-regression to examine the relationship between aerobic fitness and cognitive performance","volume":"52","author":"Etnier","year":"2006","journal-title":"Brain Res. Rev"},{"key":"B28","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/B978-1-4160-6231-8.10101-1","article-title":"Chapter 101\u2013exercise for successful aging,","volume-title":"Brocklehurst's Textbook of Geriatric Medicine and Gerontology","author":"Evans","year":"2010"},{"key":"B29","unstructured":"Alzheimer's Disease and Dementia.2020"},{"key":"B30","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1080\/13607863.2018.1455804","article-title":"Aging, cognition, and the brain: effects of age-related variation in white matter integrity on neuropsychological function","volume":"23","author":"Fan","year":"2019","journal-title":"Aging Ment. Health"},{"key":"B31","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.scispo.2018.02.011","article-title":"Effect of physical exercise on hippocampal volume in adults: systematic review and meta-analysis","volume":"33","author":"Feter","year":"2018","journal-title":"Sci. Sports"},{"key":"B32","doi-asserted-by":"publisher","first-page":"110","DOI":"10.3389\/fnhum.2017.00110","article-title":"No evidence that short-term cognitive or physical training programs or lifestyles are related to changes in white matter integrity in older adults at risk of dementia","volume":"11","author":"Fissler","year":"2017","journal-title":"Front. Hum. Neurosci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"15462","DOI":"10.1073\/pnas.1508831112","article-title":"Development and aging of cortical thickness correspond to genetic organization patterns","volume":"112","author":"Fjell","year":"2015","journal-title":"Proc. Natl. Acad. Sic. U.S.A."},{"key":"B34","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.pneurobio.2014.02.004","article-title":"What is normal in normal aging? Effects of aging, amyloid and Alzheimer's disease on the cerebral cortex and the hippocampus","volume":"117","author":"Fjell","year":"2014","journal-title":"Progr. Neurobiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"3137","DOI":"10.1001\/jama.288.24.3137","article-title":"Recent trends in disability and functioning among older adults in the united states: a systematic review","volume":"288","author":"Freedman","year":"2002","journal-title":"JAMA"},{"key":"B36","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1177\/2515245919847202","article-title":"Evaluating effect size in psychological research: sense and nonsense","volume":"2","author":"Funder","year":"2019","journal-title":"Adv. Methods Pract. Psychol. Sci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1089\/rej.2014.1623","article-title":"Exercise attenuates the major hallmarks of aging","volume":"18","author":"Garatachea","year":"2015","journal-title":"Rejuvenation Res"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1212\/WNL.0000000000003764","article-title":"Corpus callosal atrophy and associations with cognitive impairment in Parkinson disease","volume":"88","author":"Goldman","year":"2017","journal-title":"Neurology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3389\/fninf.2018.00025","article-title":"Resting-state brain functional hyper-network construction based on elastic net and group lasso methods","volume":"12","author":"Guo","year":"2018","journal-title":"Front. Neuroinform"},{"key":"B40","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.dadm.2018.02.002","article-title":"Regional tract-specific white matter hyperintensities are associated with patterns of aging-related brain atrophy via vascular risk factors, but also independently","volume":"10","author":"Habes","year":"2018","journal-title":"Alzheimers Dement."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1093\/geronb\/gby010","article-title":"Accelerometer physical activity is associated with greater gray matter volumes in older adults without dementia or mild cognitive impairment","volume":"74","author":"Halloway","year":"2018","journal-title":"J. Gerontol. Ser. B"},{"key":"B42","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1152\/physiol.00029.2016","article-title":"Physical activity, aging, and physiological function","volume":"32","author":"Harridge","year":"2017","journal-title":"Physiology"},{"key":"B43","doi-asserted-by":"publisher","first-page":"285","DOI":"10.3389\/fnhum.2020.00285","article-title":"Diffusion tensor imaging revealing the relation of age-related differences in the corpus callosum with cognitive style","volume":"14","author":"Hsieh","year":"2020","journal-title":"Front. Hum. Neurosci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1159\/000362872","article-title":"Age effects on cortical thickness in cognitively normal elderly individuals","volume":"4","author":"Hurtz","year":"2014","journal-title":"Dement. Geriatr. Cogn. Dis. Extra"},{"key":"B45","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/j.neuroimage.2013.04.061","article-title":"Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: a pilot project of the ENIGMA\u2013DTI working group","volume":"81","author":"Jahanshad","year":"2013","journal-title":"Neuroimage"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e0236986","DOI":"10.1371\/journal.pone.0236986","article-title":"Cardiorespiratory fitness diminishes the effects of age on white matter hyperintensity volume","volume":"15","author":"Johnson","year":"2020","journal-title":"PLoS ONE"},{"key":"B47","doi-asserted-by":"publisher","first-page":"336","DOI":"10.3389\/fnagi.2016.00336","article-title":"Aerobic exercise intervention, cognitive performance, and brain structure: results from the physical influences on brain in aging (PHIBRA) study","volume":"8","author":"Jonasson","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"B48","volume-title":"Predictive Analytics and Data Mining","author":"Kotu","year":"2015"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v028.i05","article-title":"Building predictive models in R using the caret package","volume":"28","author":"Kuhn","year":"2008","journal-title":"J. Stat. Softw"},{"key":"B50","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.neuroscience.2015.05.049","article-title":"Tract-based analysis of white matter degeneration in Alzheimer's disease","volume":"301","author":"Lee","year":"2015","journal-title":"Neuroscience"},{"key":"B51","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.arr.2016.11.006","article-title":"Aging of cerebral white matter","volume":"34","author":"Liu","year":"2017","journal-title":"Ageing Res. Rev"},{"key":"B52","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1080\/00913847.2020.1758545","article-title":"The effects of aerobic exercise on corpus callosum integrity: systematic review","volume":"48","author":"Loprinzi","year":"2020","journal-title":"Phys. Sportsmed"},{"key":"B53","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1097\/JES.0b013e31825b34a0","article-title":"Improving self-reports of active and sedentary behaviors in large epidemiologic studies","volume":"40","author":"Matthews","year":"2012","journal-title":"Exerc. Sport Sci. Rev"},{"key":"B54","doi-asserted-by":"publisher","first-page":"e1172","DOI":"10.1038\/tp.2017.135","article-title":"Effects of aerobic exercise on brain metabolism and grey matter volume in older adults: results of the randomised controlled SMART trial","volume":"7","author":"Matura","year":"2017","journal-title":"Transl. Psychiatry"},{"key":"B55","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s10548-011-0198-6","article-title":"Age-Related changes in the thickness of cortical zones in humans","volume":"24","author":"McGinnis","year":"2011","journal-title":"Brain Topogr"},{"key":"B56","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1093\/brain\/awx355","article-title":"Fibre-specific white matter reductions in Alzheimer's disease and mild cognitive impairment","volume":"141","author":"Mito","year":"2018","journal-title":"Brain"},{"key":"B57","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1093\/gerona\/glw191","article-title":"The longitudinal study of aging in human young adults: knowledge gaps and research agenda","volume":"72","author":"Moffitt","year":"2017","journal-title":"J. Gerontol. A Biol. Sci. Med. Sic"},{"key":"B58","unstructured":"MoriS.\n            WakanaS.\n            Van ZijlP. C.\n            Nagae-PoetscherL. M.\n          MRI Atlas of Human White Matter. Elsevier Science2005"},{"key":"B59","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1001\/jamaneurol.2020.4478","article-title":"Possible consequences of the approval of a disease-modifying therapy for alzheimer disease","volume":"78","author":"Musiek","year":"2020","journal-title":"JAMA Neurol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"331","DOI":"10.3233\/JAD-200246","article-title":"Cortical complexity analyses and their cognitive correlate in alzheimer's disease and frontotemporal dementia","volume":"76","author":"Nicastro","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"B61","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1001\/jamainternmed.2020.0618","article-title":"Association of healthy lifestyle with years lived without major chronic diseases","volume":"180","author":"Nyberg","year":"2020","journal-title":"JAMA Intern. Med"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1038\/mp.2012.66","article-title":"Brain white matter tract integrity as a neural foundation for general intelligence","volume":"17","author":"Penke","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"B63","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1007\/s11682-015-9431-3","article-title":"Cardiorespiratory fitness and white matter integrity in Alzheimer's disease","volume":"10","author":"Perea","year":"2016","journal-title":"Brain Imaging Behav"},{"key":"B64","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1007\/s00127-015-1048-8","article-title":"The dunedin multidisciplinary health and development study: overview of the first 40 years, with an eye to the future","volume":"50","author":"Poulton","year":"2015","journal-title":"Soc. Psychiatry Psychiatr. Epidemiol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/s41562-019-0810-4","article-title":"Clustering of health, crime and social-welfare inequality in 4 million citizens from 2 nations","volume":"4","author":"Richmond-Rakerd","year":"2020","journal-title":"Nat. Hum. Behav"},{"key":"B66","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/B978-0-12-396460-1.00006-8","volume-title":"Diffusion MRI.","author":"Seunarine","year":"2014"},{"key":"B67","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.neuroimage.2015.09.071","article-title":"A systematic review of MRI studies examining the relationship between physical fitness and activity and the white matter of the ageing brain","volume":"131","author":"Sexton","year":"2016","journal-title":"Neuroimage"},{"key":"B68","doi-asserted-by":"publisher","first-page":"112923","DOI":"10.1016\/j.physbeh.2020.112923","article-title":"The effects of an aerobic training intervention on cognition, grey matter volumes and white matter microstructure","volume":"223","author":"Sexton","year":"2020","journal-title":"Physiol. Behav"},{"key":"B69","doi-asserted-by":"publisher","first-page":"2885","DOI":"10.1093\/brain\/awl256","article-title":"Spatial patterns of cortical thinning in mild cognitive impairment and Alzheimer's disease","volume":"129","author":"Singh","year":"2006","journal-title":"Brain"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1016\/j.neuroimage.2006.02.024","article-title":"Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data","volume":"31","author":"Smith","year":"2006","journal-title":"Neuroimage"},{"key":"B71","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1016\/j.neuron.2014.10.038","article-title":"The evolution of preclinical Alzheimer's disease: implications for prevention trials","volume":"84","author":"Sperling","year":"2014","journal-title":"Neuron"},{"key":"B72","doi-asserted-by":"publisher","first-page":"489","DOI":"10.3233\/JAD-190875","article-title":"Cerebral white matter integrity in amnestic mild cognitive impairment: a 1-year randomized controlled trial of aerobic exercise training","volume":"73","author":"Tarumi","year":"2020","journal-title":"J. Alzheimers. Dis."},{"key":"B73","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1016\/j.neuroimage.2006.07.047","article-title":"Multivariate network analysis of fiber tract integrity in Alzheimer's disease","volume":"34","author":"Teipel","year":"2007","journal-title":"Neuroimage"},{"key":"B74","doi-asserted-by":"publisher","first-page":"615","DOI":"10.3233\/JAD-191125","article-title":"Cerebellar white matter disruption in alzheimer's disease patients: a diffusion tensor imaging study","volume":"74","author":"Toniolo","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"B75","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.neuroimage.2015.10.044","article-title":"Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging","volume":"131","author":"Voss","year":"2016","journal-title":"Neuroimage"},{"key":"B76","doi-asserted-by":"publisher","first-page":"1850055","DOI":"10.1142\/S0129065718500557","article-title":"Cortical thickness and surface area networks in healthy aging, alzheimer's disease and behavioral variant fronto-temporal dementia","volume":"29","author":"Vuksanovi,\u0107","year":"2019","journal-title":"Int. J. Neur. Syst."},{"key":"B77","doi-asserted-by":"publisher","first-page":"270","DOI":"10.3389\/fgene.2013.00270","article-title":"Evaluation of the lasso and the elastic net in genome-wide association studies","volume":"4","author":"Waldmann","year":"2013","journal-title":"Front. Genet"},{"key":"B78","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.neurobiolaging.2019.04.006","article-title":"Associations between modifiable risk factors and white matter of the aging brain: insights from diffusion tensor imaging studies","volume":"80","author":"Wassenaar","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"B79","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.dadm.2019.06.003","article-title":"White matter alterations in early-stage Alzheimer's disease: a tract-specific study","volume":"11","author":"Wen","year":"2019","journal-title":"Alzheimers Dement."},{"key":"B80","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1016\/j.neuroimage.2016.10.033","article-title":"Cardiorespiratory fitness is differentially associated with cortical thickness in young and older adults","volume":"146","author":"Williams","year":"2017","journal-title":"NeuroImage"},{"key":"B81","doi-asserted-by":"publisher","first-page":"143","DOI":"10.3389\/fnagi.2016.00143","article-title":"The association of aging with white matter integrity and functional connectivity hubs","volume":"8","author":"Yang","year":"2016","journal-title":"Front. Aging Neurosci."},{"key":"B82","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1212\/WNL.0000000000001658","article-title":"Cardiorespiratory fitness and brain volume and white matter integrity: the CARDIA study","volume":"84","author":"Zhu","year":"2015","journal-title":"Neurology"},{"key":"B83","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1111\/j.1467-9868.2005.00503.x","article-title":"Regularization and variable selection via the elastic net","volume":"67","author":"Zou","year":"2005","journal-title":"J. R. Stat. Soc. Ser. B"}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2021.652575\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T04:48:19Z","timestamp":1617684499000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2021.652575\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,6]]},"references-count":83,"alternative-id":["10.3389\/fnagi.2021.652575"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2021.652575","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,6]]},"article-number":"652575"}}