{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:58:00Z","timestamp":1793055480155,"version":"4.5.0"},"reference-count":85,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["425899996"],"award-info":[{"award-number":["425899996"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["362321501"],"award-info":[{"award-number":["362321501"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["425899996"],"award-info":[{"award-number":["425899996"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["425899996"],"award-info":[{"award-number":["425899996"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["425899996"],"award-info":[{"award-number":["425899996"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["425899996"],"award-info":[{"award-number":["425899996"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["425899996"],"award-info":[{"award-number":["425899996"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["425899996"],"award-info":[{"award-number":["425899996"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["425899996"],"award-info":[{"award-number":["425899996"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["425899996"],"award-info":[{"award-number":["425899996"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["362321501"],"award-info":[{"award-number":["362321501"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["362321501"],"award-info":[{"award-number":["362321501"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["362321501"],"award-info":[{"award-number":["362321501"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen e.V. (DZNE) in der Helmholtz-Gemeinschaft","id":[{"id":"https:\/\/ror.org\/043j0f473","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["GeroScience"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Resistance to age-related pathological changes (brain maintenance), including Alzheimer\u2019s disease, cerebrovascular disease, and neurodegeneration may promote cognitive resilience in aging. However, how lifestyle and health profiles relate to successful cognitive and brain aging remains poorly understood. In a novel, deeply phenotyped cohort of 211 cognitively unimpaired older adults (age\u2009=\u200971.0\u2009\u00b1\u20097.4\u00a0years, 46% female), we characterized principal components of lifestyle and health using questionnaire, fitness, and blood data. We estimated cognitive age gap (CAG) based on comprehensive neuropsychological data and brain age gap (BAG) based on brain-pathology markers, including plasma biomarkers of Alzheimer\u2019s pathology (pTau\n                    <jats:sub>217<\/jats:sub>\n                    and A\u03b2\n                    <jats:sub>1-42<\/jats:sub>\n                    \/A\u03b2\n                    <jats:sub>1-40<\/jats:sub>\n                    ), MRI-based measures of white matter hyperintensities, perivascular spaces, and brain atrophy. Regression analyses tested how the observed lifestyle-health profiles were related to CAG and BAG. Seven principal components explained 49% of the variance in health and lifestyle. The second component, characterized by a mentally and physically active life and low cardiovascular risk, was associated with lower CAG (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2009= \u2212\u20090.66,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and BAG (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2009= \u2212\u20090.52,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.003), reflecting a younger-than-expected brain and cognitive age, respectively. The association of an active lifestyle and lower CAG was partially mediated by BAG. Higher CAG was also associated with other lifestyle components characterized by low mental stimulation. APOE-\u03b54 carriers exhibited higher BAG. In conclusion, a lifestyle combining low cardiovascular risk, high mental engagement throughout life and high physical activity\/fitness is jointly associated with less-than-expected brain pathology and better-than-expected cognitive performance, supporting its involvement in brain maintenance and cognitive resilience to aging.\n                  <\/jats:p>","DOI":"10.1007\/s11357-025-01764-w","type":"journal-article","created":{"date-parts":[[2025,7,6]],"date-time":"2025-07-06T20:52:33Z","timestamp":1751835153000},"page":"1853-1873","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A physically and mentally active lifestyle relates to younger brain and cognitive age"],"prefix":"10.1007","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7947-9220","authenticated-orcid":false,"given":"Niklas","family":"Behrenbruch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2024-9236","authenticated-orcid":false,"given":"Svenja","family":"Schwarck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3530-5766","authenticated-orcid":false,"given":"Beate","family":"Schumann-Werner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7804-2214","authenticated-orcid":false,"given":"E\u00f3in N.","family":"Molloy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8585-6507","authenticated-orcid":false,"given":"Berta","family":"Garcia-Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Hochkeppler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9936-2954","authenticated-orcid":false,"given":"Larissa","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Therese","family":"B\u00fcchel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2014-4098","authenticated-orcid":false,"given":"Enise I.","family":"Incesoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3167-5134","authenticated-orcid":false,"given":"Jose","family":"Bernal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5915-2517","authenticated-orcid":false,"given":"Niklas","family":"Vockert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gusalija","family":"Behnisch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8174-9301","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Morgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5484-9710","authenticated-orcid":false,"given":"Hermann","family":"Esselmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7433-2716","authenticated-orcid":false,"given":"Constanze I.","family":"Seidenbecher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8237-4481","authenticated-orcid":false,"given":"Bj\u00f6rn H.","family":"Schott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henryk","family":"Barthel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6425-3504","authenticated-orcid":false,"given":"Osama","family":"Sabri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1492-5330","authenticated-orcid":false,"given":"Jens","family":"Wiltfang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5905-6015","authenticated-orcid":false,"given":"Michael C.","family":"Kreissl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-5388","authenticated-orcid":false,"given":"Emrah","family":"D\u00fczel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7889-795X","authenticated-orcid":false,"given":"Anne","family":"Maass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"1764_CR1","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1146\/annurev-psych-010418-103052","volume":"70","author":"L Nyberg","year":"2019","unstructured":"Nyberg L, Pudas S. Successful memory aging. Annu Rev Psychol. 2019;70:219\u201343.","journal-title":"Annu Rev Psychol"},{"key":"1764_CR2","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1126\/science.1254403","volume":"346","author":"U Lindenberger","year":"2014","unstructured":"Lindenberger U. Human cognitive aging: corriger la fortune? Science. 2014;346:572\u20138.","journal-title":"Science"},{"key":"1764_CR3","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/s41583-018-0068-2","volume":"19","author":"R Cabeza","year":"2018","unstructured":"Cabeza R, Albert M, Belleville S, et al. Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing. Nat Rev Neurosci. 2018;19:701\u201310.","journal-title":"Nat Rev Neurosci"},{"key":"1764_CR4","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s13195-020-00609-2","volume":"12","author":"EM Arenaza-Urquijo","year":"2020","unstructured":"Arenaza-Urquijo EM, Vemuri P. Improving the resistance and resilience framework for aging and dementia studies. Alzheimers Res Ther. 2020;12:41.","journal-title":"Alzheimers Res Ther"},{"key":"1764_CR5","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1016\/j.jalz.2018.07.219","volume":"16","author":"Y Stern","year":"2020","unstructured":"Stern Y, Arenaza-Urquijo EM, Bartr\u00e9s-Faz D, et al. Whitepaper: defining and investigating cognitive reserve, brain reserve, and brain maintenance. Alzheimers Dement. 2020;16:1305\u201311.","journal-title":"Alzheimers Dement"},{"key":"1764_CR6","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.neurobiolaging.2022.10.015","volume":"124","author":"Y Stern","year":"2023","unstructured":"Stern Y, Albert M, Barnes CA, et al. A framework for concepts of reserve and resilience in aging. Neurobiol Aging. 2023;124:100\u20133.","journal-title":"Neurobiol Aging"},{"key":"1764_CR7","doi-asserted-by":"publisher","first-page":"50","DOI":"10.3389\/fnagi.2013.00050","volume":"5","author":"PA Boyle","year":"2013","unstructured":"Boyle PA, Yu L, Wilson RS, et al. Relation of neuropathology with cognitive decline among older persons without dementia. Front Aging Neurosci. 2013;5:50.","journal-title":"Front Aging Neurosci"},{"key":"1764_CR8","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1146\/annurev-physiol-021119-034338","volume":"82","author":"TM De Silva","year":"2020","unstructured":"De Silva TM, Faraci FM. Contributions of aging to cerebral small vessel disease. Annu Rev Physiol. 2020;82:275\u201395.","journal-title":"Annu Rev Physiol"},{"key":"1764_CR9","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/S1474-4422(17)30077-7","volume":"16","author":"CR Jack Jr","year":"2017","unstructured":"Jack CR Jr, Wiste HJ, Weigand SD, et al. Age-specific and sex-specific prevalence of cerebral \u03b2-amyloidosis, tauopathy, and neurodegeneration in cognitively unimpaired individuals aged 50\u201395 years: a cross-sectional study. Lancet Neurol. 2017;16:435\u201344.","journal-title":"Lancet Neurol"},{"key":"1764_CR10","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/s41582-020-0312-z","volume":"16","author":"JM Wardlaw","year":"2020","unstructured":"Wardlaw JM, Benveniste H, Nedergaard M, et al. Perivascular spaces in the brain: anatomy, physiology and pathology. Nat Rev Neurol. 2020;16:137\u201353.","journal-title":"Nat Rev Neurol"},{"key":"1764_CR11","doi-asserted-by":"publisher","first-page":"9815","DOI":"10.1038\/s41467-024-53360-9","volume":"15","author":"N Vockert","year":"2024","unstructured":"Vockert N, Machts J, Kleineidam L, et al. Cognitive reserve against Alzheimer\u2019s pathology is linked to brain activity during memory formation. Nat Commun. 2024;15:9815.","journal-title":"Nat Commun"},{"key":"1764_CR12","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.neuroimage.2018.05.033","volume":"178","author":"Y Stern","year":"2018","unstructured":"Stern Y, Gazes Y, Razlighi Q, et al. A task-invariant cognitive reserve network. Neuroimage. 2018;178:36\u201345.","journal-title":"Neuroimage"},{"key":"1764_CR13","doi-asserted-by":"publisher","first-page":"5003","DOI":"10.1038\/s41467-024-49262-5","volume":"15","author":"M Bloomberg","year":"2024","unstructured":"Bloomberg M, Muniz-Terrera G, Brocklebank L, Steptoe A. Healthy lifestyle and cognitive decline in middle-aged and older adults residing in 14 European countries. Nat Commun. 2024;15:5003.","journal-title":"Nat Commun"},{"key":"1764_CR14","doi-asserted-by":"publisher","first-page":"S114","DOI":"10.1016\/S0140-6736(16)32350-9","volume":"388","author":"Y-T Wu","year":"2016","unstructured":"Wu Y-T, Teale J, Matthews FE, et al. Lifestyle factors, cognitive reserve, and cognitive function: results from the Cognitive Function and Ageing Study Wales, a population-based cohort. Lancet. 2016;388:S114.","journal-title":"Lancet"},{"key":"1764_CR15","doi-asserted-by":"publisher","first-page":"101551","DOI":"10.1016\/j.arr.2021.101551","volume":"74","author":"S Song","year":"2022","unstructured":"Song S, Stern Y, Gu Y. Modifiable lifestyle factors and cognitive reserve: a systematic review of current evidence. Ageing Res Rev. 2022;74:101551.","journal-title":"Ageing Res Rev"},{"key":"1764_CR16","doi-asserted-by":"publisher","unstructured":"Rolandi E, Rossi M, Colombo M, et al (2024) Lifestyle, cognitive, and psychological factors associated with a resilience phenotype in aging: a multidimensional approach on a population-based sample of oldest-old (80+). J Gerontol B Psychol Sci Soc Sci 79.: https:\/\/doi.org\/10.1093\/geronb\/gbae132","DOI":"10.1093\/geronb\/gbae132"},{"key":"1764_CR17","doi-asserted-by":"publisher","first-page":"1794","DOI":"10.2337\/dc24-0860","volume":"47","author":"A Dove","year":"2024","unstructured":"Dove A, Wang J, Huang H, et al. Diabetes, prediabetes, and brain aging: the role of healthy lifestyle. Diabetes Care. 2024;47:1794\u2013802.","journal-title":"Diabetes Care"},{"key":"1764_CR18","doi-asserted-by":"publisher","first-page":"e14435","DOI":"10.1002\/alz.14435","volume":"21","author":"A Marseglia","year":"2025","unstructured":"Marseglia A, Dartora C, Samuelsson J, et al. Biological brain age and resilience in cognitively unimpaired 70-year-old individuals. Alzheimers Dement. 2025;21:e14435.","journal-title":"Alzheimers Dement"},{"key":"1764_CR19","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1002\/alz.13459","volume":"20","author":"S Halloway","year":"2024","unstructured":"Halloway S, Wagner M, Tangney C, et al. Profiles of lifestyle health behaviors and cognitive decline in older adults. Alzheimers Dement. 2024;20:472\u201382.","journal-title":"Alzheimers Dement"},{"key":"1764_CR20","doi-asserted-by":"publisher","first-page":"148668","DOI":"10.1016\/j.brainres.2023.148668","volume":"1823","author":"LK Soumya Kumari","year":"2024","unstructured":"Soumya Kumari LK, Sundarrajan R. A review on brain age prediction models. Brain Res. 2024;1823:148668.","journal-title":"Brain Res"},{"key":"1764_CR21","doi-asserted-by":"publisher","first-page":"789","DOI":"10.3389\/fneur.2019.00789","volume":"10","author":"K Franke","year":"2019","unstructured":"Franke K, Gaser C. Ten years of as a neuroimaging biomarker of brain aging: what insights have we gained? Front Neurol. 2019;10:789.","journal-title":"Front Neurol"},{"key":"1764_CR22","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1002\/alz.13438","volume":"20","author":"S Pezzoli","year":"2024","unstructured":"Pezzoli S, Giorgio J, Martersteck A, et al. Successful cognitive aging is associated with thicker anterior cingulate cortex and lower tau deposition compared to typical aging. Alzheimers Dement. 2024;20:341\u201355.","journal-title":"Alzheimers Dement"},{"key":"1764_CR23","doi-asserted-by":"crossref","unstructured":"Pezzoli S, Giorgio J, Chen X, et al (2025) Cognitive aging outcomes are related to both tau pathology and maintenance of cingulate cortex structure. Alzheimers Dement e14515","DOI":"10.1002\/alz.14515"},{"key":"1764_CR24","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1002\/hbm.25316","volume":"42","author":"M Anat\u00fcrk","year":"2021","unstructured":"Anat\u00fcrk M, Kaufmann T, Cole JH, et al. Prediction of brain age and cognitive age: quantifying brain and cognitive maintenance in aging. Hum Brain Mapp. 2021;42:1626\u201340.","journal-title":"Hum Brain Mapp"},{"key":"1764_CR25","doi-asserted-by":"publisher","first-page":"3829","DOI":"10.1038\/s41380-019-0626-7","volume":"26","author":"ML Elliott","year":"2021","unstructured":"Elliott ML, Belsky DW, Knodt AR, et al. Brain-age in midlife is associated with accelerated biological aging and cognitive decline in a longitudinal birth cohort. Mol Psychiatry. 2021;26:3829\u201338.","journal-title":"Mol Psychiatry"},{"key":"1764_CR26","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/s43587-022-00219-7","volume":"2","author":"J Lee","year":"2022","unstructured":"Lee J, Burkett BJ, Min H-K, et al. Deep learning-based brain age prediction in normal aging and dementia. Nat Aging. 2022;2:412\u201324.","journal-title":"Nat Aging"},{"key":"1764_CR27","doi-asserted-by":"publisher","first-page":"e67346","DOI":"10.1371\/journal.pone.0067346","volume":"8","author":"C Gaser","year":"2013","unstructured":"Gaser C, Franke K, Kl\u00f6ppel S, et al. BrainAGE in mild cognitive impaired patients: predicting the conversion to Alzheimer\u2019s disease. PLoS ONE. 2013;8:e67346.","journal-title":"PLoS ONE"},{"key":"1764_CR28","doi-asserted-by":"crossref","unstructured":"Feng Y, Villal\u00f3n-Reina JE, Nir TM, et al (2024) Predicting white matter age using along-tract microstructural profiles from diffusion MRI. bioRxiv","DOI":"10.1101\/2024.08.16.608347"},{"key":"1764_CR29","doi-asserted-by":"publisher","unstructured":"Millar PR, Gordon BA, Luckett PH, et al (2023) Multimodal brain age estimates relate to Alzheimer disease biomarkers and cognition in early stages: a cross-sectional observational study. Elife 12. https:\/\/doi.org\/10.7554\/eLife.81869","DOI":"10.7554\/eLife.81869"},{"key":"1764_CR30","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","volume":"9","author":"C-C Liu","year":"2013","unstructured":"Liu C-C, Liu C-C, Kanekiyo T, et al. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013;9:106\u201318.","journal-title":"Nat Rev Neurol"},{"key":"1764_CR31","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41582-024-00988-2","volume":"20","author":"RJ Jackson","year":"2024","unstructured":"Jackson RJ, Hyman BT, Serrano-Pozo A. Multifaceted roles of APOE in Alzheimer disease. Nat Rev Neurol. 2024;20:457\u201374.","journal-title":"Nat Rev Neurol"},{"key":"1764_CR32","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1016\/j.tins.2023.06.003","volume":"46","author":"JM Palmer","year":"2023","unstructured":"Palmer JM, Huentelman M, Ryan L. More than just risk for Alzheimer\u2019s disease: APOE \u03b54\u2019s impact on the aging brain. Trends Neurosci. 2023;46:750\u201363.","journal-title":"Trends Neurosci"},{"key":"1764_CR33","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1001\/archneur.56.3.303","volume":"56","author":"RC Petersen","year":"1999","unstructured":"Petersen RC, Smith GE, Waring SC, et al. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56:303\u20138.","journal-title":"Arch Neurol"},{"key":"1764_CR34","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1007\/s00406-014-0571-z","volume":"265","author":"P Mistridis","year":"2015","unstructured":"Mistridis P, Egli SC, Iverson GL, et al. Considering the base rates of low performance in cognitively healthy older adults improves the accuracy to identify neurocognitive impairment with the Consortium to Establish a Registry for Alzheimer\u2019s Disease-Neuropsychological Assessment Battery (CERAD-NAB). Eur Arch Psychiatry Clin Neurosci. 2015;265:407\u201317.","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"1764_CR35","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1097\/JGP.0b013e31819431d5","volume":"17","author":"AJ Jak","year":"2009","unstructured":"Jak AJ, Bondi MW, Delano-Wood L, et al. Quantification of five neuropsychological approaches to defining mild cognitive impairment. Am J Geriatr Psychiatry. 2009;17:368\u201375.","journal-title":"Am J Geriatr Psychiatry"},{"key":"1764_CR36","first-page":"21","volume":"141","author":"C Helmstaedter","year":"1990","unstructured":"Helmstaedter C, Durwen HF. The verbal learning and retention test. A useful and differentiated tool in evaluating verbal memory performance. Schweiz Arch Neurol Psychiatr. 1990;141:21\u201330.","journal-title":"Schweiz Arch Neurol Psychiatr"},{"key":"1764_CR37","unstructured":"Wechsler D (1987) Wechsler Memory Scale-Revised: Manual. Psychological Corporation"},{"key":"1764_CR38","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1080\/01688638408401233","volume":"6","author":"H Buschke","year":"1984","unstructured":"Buschke H. Cued recall in amnesia. J Clin Neuropsychol. 1984;6:433\u201340.","journal-title":"J Clin Neuropsychol"},{"key":"1764_CR39","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1080\/13854049508402059","volume":"9","author":"JE Meyers","year":"1995","unstructured":"Meyers JE, Meyers KR. Rey complex figure test under four different administration procedures. Clin Neuropsychol. 1995;9:63\u20137.","journal-title":"Clin Neuropsychol"},{"key":"1764_CR40","unstructured":"Smith A (2016) Symbol digit modalities test. PsycTESTS Dataset"},{"key":"1764_CR41","unstructured":"Zimmermann P, Fimm B (2009) Testbatterie zur Aufmerksamkeitspr\u00fcfung : TAP"},{"key":"1764_CR42","volume-title":"Regensburger Wortfl\u00fcssigkeits-Test: RWT","author":"S Aschenbrenner","year":"2000","unstructured":"Aschenbrenner S, Tucha O, Lange KW. Regensburger Wortfl\u00fcssigkeits-Test: RWT. Verlag f\u00fcr Psychologie: Hogrefe; 2000."},{"key":"1764_CR43","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-023-01751-2","author":"B Morgado","year":"2024","unstructured":"Morgado B, Klafki H-W, Bauer C, et al. Assessment of immunoprecipitation with subsequent immunoassays for the blood-based diagnosis of Alzheimer\u2019s disease. Eur Arch Psychiatry Clin Neurosci. 2024. https:\/\/doi.org\/10.1007\/s00406-023-01751-2.","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"1764_CR44","doi-asserted-by":"publisher","unstructured":"Klasson N, Olsson E, Eckerstr\u00f6m C, et al (2018) Estimated intracranial volume from FreeSurfer is biased by total brain volume. Eur Radiol Exp 2.: https:\/\/doi.org\/10.1186\/s41747-018-0055-4","DOI":"10.1186\/s41747-018-0055-4"},{"key":"1764_CR45","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1186\/s13195-024-01603-8","volume":"16","author":"I Menze","year":"2024","unstructured":"Menze I, Bernal J, Kaya P, et al. Perivascular space enlargement accelerates in ageing and Alzheimer\u2019s disease pathology: evidence from a three-year longitudinal multicenter study. Alzheimers Res Ther. 2024;16:242.","journal-title":"Alzheimers Res Ther"},{"key":"1764_CR46","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez M del CV, Piper RJ, Wang X, et al (2013) Towards the automatic computational assessment of enlarged perivascular spaces on brain magnetic resonance images: a systematic review. J Magn Reson Imaging 38:774\u2013785","DOI":"10.1002\/jmri.24047"},{"key":"1764_CR47","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1111\/ijs.12054","volume":"10","author":"GM Potter","year":"2015","unstructured":"Potter GM, Doubal FN, Jackson CA, et al. Enlarged perivascular spaces and cerebral small vessel disease. Int J Stroke. 2015;10:376\u201381.","journal-title":"Int J Stroke"},{"key":"1764_CR48","doi-asserted-by":"publisher","DOI":"10.1300\/J018v01n01_06","author":"TL Brink","year":"1982","unstructured":"Brink TL, Yesavage JA, Lum O, et al. Screening tests for geriatric depression. Clin Gerontol. 1982. https:\/\/doi.org\/10.1300\/J018v01n01_06.","journal-title":"Clin Gerontol"},{"key":"1764_CR49","unstructured":"Spielberger CD, Gorsuch RL, Lushene RE (1970) STAI Manual for the State-trait Anxiety Inventory (\u201cSelf-evaluation Questionnaire\u201d)"},{"key":"1764_CR50","unstructured":"Spielberger CD, Sydeman SJ (1994) State-trait anxiety inventory and state-trait anger expression inventory. In: Maruish ME (ed) The use of psychological testing for treatment planning and outcomes assessment. Lawrence Erlbaum Associates, Inc., pp 292\u2013332"},{"key":"1764_CR51","volume-title":"Das State-Trait-Angstinventar. Theoretische Grundlagen und Handanweisung","author":"L Laux","year":"1981","unstructured":"Laux L, Glanzmann P, Schaffner P, Spielberger CD. Das State-Trait-Angstinventar. Theoretische Grundlagen und Handanweisung. Weinheim: Beltz Test GmbH; 1981."},{"key":"1764_CR52","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/0165-1781(89)90047-4","volume":"28","author":"DJ Buysse","year":"1989","unstructured":"Buysse DJ, Reynolds CF 3rd, Monk TH, et al. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28:193\u2013213.","journal-title":"Psychiatry Res"},{"key":"1764_CR53","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1093\/sleep\/14.6.540","volume":"14","author":"MW Johns","year":"1991","unstructured":"Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14:540\u20135.","journal-title":"Sleep"},{"key":"1764_CR54","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/1475-2891-9-36","volume":"9","author":"M Haftenberger","year":"2010","unstructured":"Haftenberger M, Heuer T, Heidemann C, et al. Relative validation of a food frequency questionnaire for national health and nutrition monitoring. Nutr J. 2010;9:36.","journal-title":"Nutr J"},{"key":"1764_CR55","doi-asserted-by":"publisher","first-page":"740005","DOI":"10.3389\/fnagi.2021.740005","volume":"13","author":"V Ourry","year":"2021","unstructured":"Ourry V, Marchant NL, Schild A-K, et al. Harmonisation and between-country differences of the lifetime of experiences questionnaire in older adults. Front Aging Neurosci. 2021;13:740005.","journal-title":"Front Aging Neurosci"},{"key":"1764_CR56","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1017\/S003329170600938X","volume":"37","author":"MJ Valenzuela","year":"2007","unstructured":"Valenzuela MJ, Sachdev P. Assessment of complex mental activity across the lifespan: development of the Lifetime of Experiences Questionnaire (LEQ). Psychol Med. 2007;37:1015\u201325.","journal-title":"Psychol Med"},{"key":"1764_CR57","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1097\/00005650-198807000-00007","volume":"26","author":"AL Stewart","year":"1988","unstructured":"Stewart AL, Hays RD, Ware JE Jr. The MOS short-form general health survey. Reliability and validity in a patient population. Med Care. 1988;26:724\u201335.","journal-title":"Med Care"},{"key":"1764_CR58","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1016\/0277-9536(95)00115-N","volume":"41","author":"M Bullinger","year":"1995","unstructured":"Bullinger M. German translation and psychometric testing of the SF-36 Health Survey: preliminary results from the IQOLA Project. International Quality of Life Assessment. Soc Sci Med. 1995;41:1359\u201366.","journal-title":"Soc Sci Med"},{"key":"1764_CR59","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/BF01667127","volume":"44","author":"I Frey","year":"1999","unstructured":"Frey I, Berg A, Grathwohl D, Keul J. Freiburg Questionnaire of physical activity\u2013development, evaluation and application. Soz Praventivmed. 1999;44:55\u201364.","journal-title":"Soz Praventivmed"},{"key":"1764_CR60","doi-asserted-by":"publisher","first-page":"S498","DOI":"10.1097\/00005768-200009001-00009","volume":"32","author":"BE Ainsworth","year":"2000","unstructured":"Ainsworth BE, Haskell WL, Whitt MC, et al. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc. 2000;32:S498-504.","journal-title":"Med Sci Sports Exerc"},{"key":"1764_CR61","doi-asserted-by":"publisher","unstructured":"Lange C, Manz K, Rommel A, et al (2016) Alkoholkonsum von Erwachsenen in Deutschland: Riskante Trinkmengen, Folgen und Ma\u00dfnahmen. https:\/\/doi.org\/10.17886\/RKI-GBE-2016-025","DOI":"10.17886\/RKI-GBE-2016-025"},{"key":"1764_CR62","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40795-022-00636-2","volume":"9","author":"R Thieleking","year":"2023","unstructured":"Thieleking R, Schneidewind L, Kanyamibwa A, et al. Nutrient scoring for the DEGS1-FFQ - from food intake to nutrient intake. BMC Nutr. 2023;9:12.","journal-title":"BMC Nutr"},{"key":"1764_CR63","unstructured":"Kuhn D-A (2018) Entwicklung eines Index zur Bewertung der Ern\u00e4hrungsqualit\u00e4t in der Studie zur Gesundheit Erwachsener in Deutschland (DEGS1). Robert Koch-Institut"},{"key":"1764_CR64","doi-asserted-by":"publisher","first-page":"102063","DOI":"10.1016\/j.nicl.2019.102063","volume":"24","author":"I Beheshti","year":"2019","unstructured":"Beheshti I, Nugent S, Potvin O, Duchesne S. Bias-adjustment in neuroimaging-based brain age frameworks: a robust scheme. Neuroimage Clin. 2019;24:102063.","journal-title":"Neuroimage Clin"},{"key":"1764_CR65","doi-asserted-by":"publisher","first-page":"3113","DOI":"10.1002\/hbm.25837","volume":"43","author":"A-MG de Lange","year":"2022","unstructured":"de Lange A-MG, Anat\u00fcrk M, Rokicki J, et al. Mind the gap: performance metric evaluation in brain-age prediction. Hum Brain Mapp. 2022;43:3113\u201329.","journal-title":"Hum Brain Mapp"},{"key":"1764_CR66","doi-asserted-by":"publisher","first-page":"3143","DOI":"10.1002\/hbm.24588","volume":"40","author":"H Liang","year":"2019","unstructured":"Liang H, Zhang F, Niu X. Investigating systematic bias in brain age estimation with application to post-traumatic stress disorders. Hum Brain Mapp. 2019;40:3143\u201352.","journal-title":"Hum Brain Mapp"},{"key":"1764_CR67","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/S0140-6736(24)01296-0","volume":"404","author":"G Livingston","year":"2024","unstructured":"Livingston G, Huntley J, Liu KY, et al. Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. Lancet. 2024;404:572\u2013628.","journal-title":"Lancet"},{"key":"1764_CR68","doi-asserted-by":"publisher","first-page":"847938","DOI":"10.3389\/fpubh.2022.847938","volume":"10","author":"D Olajide","year":"2022","unstructured":"Olajide D, Eberth B, Ludbrook A. Analysis of multiple health risky behaviours and associated disease outcomes using Scottish linked hospitalisation data. Front Public Health. 2022;10:847938.","journal-title":"Front Public Health"},{"key":"1764_CR69","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.amepre.2004.04.017","volume":"27","author":"LJ Fine","year":"2004","unstructured":"Fine LJ, Philogene GS, Gramling R, et al. Prevalence of multiple chronic disease risk factors. 2001 National Health Interview Survey. Am J Prev Med. 2004;27:18\u201324.","journal-title":"Am J Prev Med"},{"key":"1764_CR70","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.ypmed.2015.07.003","volume":"81","author":"N Noble","year":"2015","unstructured":"Noble N, Paul C, Turon H, Oldmeadow C. Which modifiable health risk behaviours are related? A systematic review of the clustering of Smoking, Nutrition, Alcohol and Physical activity (\u2018SNAP\u2019) health risk factors. Prev Med. 2015;81:16\u201341.","journal-title":"Prev Med"},{"key":"1764_CR71","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.neurobiolaging.2020.03.014","volume":"92","author":"JH Cole","year":"2020","unstructured":"Cole JH. Multimodality neuroimaging brain-age in UK biobank: relationship to biomedical, lifestyle, and cognitive factors. Neurobiol Aging. 2020;92:34\u201342.","journal-title":"Neurobiol Aging"},{"key":"1764_CR72","doi-asserted-by":"publisher","first-page":"3015","DOI":"10.1038\/s41591-024-03144-x","volume":"30","author":"Z Yang","year":"2024","unstructured":"Yang Z, Wen J, Erus G, et al. Brain aging patterns in a large and diverse cohort of 49,482 individuals. Nat Med. 2024;30:3015\u201326.","journal-title":"Nat Med"},{"key":"1764_CR73","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1038\/s41467-022-28735-5","volume":"13","author":"R Daviet","year":"2022","unstructured":"Daviet R, Aydogan G, Jagannathan K, et al. Associations between alcohol consumption and gray and white matter volumes in the UK Biobank. Nat Commun. 2022;13:1175.","journal-title":"Nat Commun"},{"key":"1764_CR74","doi-asserted-by":"publisher","first-page":"103066","DOI":"10.1016\/j.nicl.2022.103066","volume":"35","author":"A Topiwala","year":"2022","unstructured":"Topiwala A, Ebmeier KP, Maullin-Sapey T, Nichols TE. Alcohol consumption and MRI markers of brain structure and function: cohort study of 25,378 UK Biobank participants. NeuroImage Clin. 2022;35:103066.","journal-title":"NeuroImage Clin"},{"key":"1764_CR75","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1038\/mp.2014.187","volume":"20","author":"S Karama","year":"2015","unstructured":"Karama S, Ducharme S, Corley J, et al. Cigarette smoking and thinning of the brain\u2019s cortex. Mol Psychiatry. 2015;20:778\u201385.","journal-title":"Mol Psychiatry"},{"key":"1764_CR76","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.neurobiolaging.2023.07.023","volume":"131","author":"N Demnitz","year":"2023","unstructured":"Demnitz N, Hulme OJ, Siebner HR, et al. Characterising the covariance pattern between lifestyle factors and structural brain measures: a multivariable replication study of two independent ageing cohorts. Neurobiol Aging. 2023;131:115\u201323.","journal-title":"Neurobiol Aging"},{"key":"1764_CR77","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1002\/hbm.25680","volume":"43","author":"D Beck","year":"2022","unstructured":"Beck D, de Lange A-MG, Pedersen ML, et al. Cardiometabolic risk factors associated with brain age and accelerate brain ageing. Hum Brain Mapp. 2022;43:700\u201320.","journal-title":"Hum Brain Mapp"},{"key":"1764_CR78","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1212\/WNL.0000000000002939","volume":"87","author":"L Chang","year":"2016","unstructured":"Chang L, Douet V, Bloss C, et al. Gray matter maturation and cognition in children with different APOE \u03b5 genotypes. Neurology. 2016;87:585\u201394.","journal-title":"Neurology"},{"key":"1764_CR79","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1212\/01.wnl.0000238079.00472.3a","volume":"67","author":"HA Wishart","year":"2006","unstructured":"Wishart HA, Saykin AJ, McAllister TW, et al. Regional brain atrophy in cognitively intact adults with a single APOE epsilon4 allele. Neurology. 2006;67:1221\u20134.","journal-title":"Neurology"},{"key":"1764_CR80","doi-asserted-by":"publisher","first-page":"162","DOI":"10.3109\/11038128.2015.1102320","volume":"23","author":"M Fallahpour","year":"2016","unstructured":"Fallahpour M, Borell L, Luborsky M, Nyg\u00e5rd L. Leisure-activity participation to prevent later-life cognitive decline: a systematic review. Scand J Occup Ther. 2016;23:162\u201397.","journal-title":"Scand J Occup Ther"},{"key":"1764_CR81","doi-asserted-by":"publisher","first-page":"e374","DOI":"10.1016\/S2666-7568(23)00079-X","volume":"4","author":"M Garo-Pascual","year":"2023","unstructured":"Garo-Pascual M, Gaser C, Zhang L, et al. Brain structure and phenotypic profile of superagers compared with age-matched older adults: a longitudinal analysis from the Vallecas Project. Lancet Healthy Longev. 2023;4:e374\u201385.","journal-title":"Lancet Healthy Longev"},{"key":"1764_CR82","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.neurobiolaging.2022.03.006","volume":"114","author":"C-L Chen","year":"2022","unstructured":"Chen C-L, Kuo M-C, Chen P-Y, et al. Validation of neuroimaging-based brain age gap as a mediator between modifiable risk factors and cognition. Neurobiol Aging. 2022;114:61\u201372.","journal-title":"Neurobiol Aging"},{"key":"1764_CR83","doi-asserted-by":"publisher","first-page":"101184","DOI":"10.1016\/j.arr.2020.101184","volume":"64","author":"L Nyberg","year":"2020","unstructured":"Nyberg L, Boraxbekk C-J, S\u00f6rman DE, et al. Biological and environmental predictors of heterogeneity in neurocognitive ageing: evidence from Betula and other longitudinal studies. Ageing Res Rev. 2020;64:101184.","journal-title":"Ageing Res Rev"},{"key":"1764_CR84","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/j.bbi.2020.05.014","volume":"88","author":"KB Casaletto","year":"2020","unstructured":"Casaletto KB, Lindbergh C, Memel M, et al. Sexual dimorphism of physical activity on cognitive aging: role of immune functioning. Brain Behav Immun. 2020;88:699\u2013710.","journal-title":"Brain Behav Immun"},{"key":"1764_CR85","doi-asserted-by":"publisher","first-page":"5695","DOI":"10.1002\/alz.13844","volume":"20","author":"EM Arenaza-Urquijo","year":"2024","unstructured":"Arenaza-Urquijo EM, Boyle R, Casaletto K, et al. Sex and gender differences in cognitive resilience to aging and Alzheimer\u2019s disease. Alzheimers Dement. 2024;20:5695\u2013719.","journal-title":"Alzheimers Dement"}],"container-title":["GeroScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-025-01764-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11357-025-01764-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-025-01764-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T22:02:24Z","timestamp":1773093744000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11357-025-01764-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,7]]},"references-count":85,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["1764"],"URL":"https:\/\/doi.org\/10.1007\/s11357-025-01764-w","relation":{},"ISSN":["2509-2723"],"issn-type":[{"value":"2509-2723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,7]]},"assertion":[{"value":"9 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study design and protocol were approved by the local Ethics Committee of the Medical Faculty, Otto-von-Guericke University Magdeburg (200\/19) and were carried out in accordance with the code of ethics of the World Medical Association (Declaration of Helsinki, 1967). Written informed consent was obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}