{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:57:26Z","timestamp":1790002646193,"version":"4.0.1"},"reference-count":79,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":296,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israeli Science Foundation","doi-asserted-by":"crossref","award":["ISF #1594\/14"],"award-info":[{"award-number":["ISF #1594\/14"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Reserve is a physiological capacity used under demanding situations. The concept was developed to account for the discrepancy between pathology and clinical manifestation. In neuroscience, motor, brain and cognitive reserves are abstract measures, conceptually defined yet elusive to quantify. Reserve is indirectly assessed using proxies such as years of education and brain volume, limiting its utility. Moreover, the dichotomy in definitions of cognitive and motor reserves is artificial, as daily function requires an intricate network of connections between these domains. Here, we assessed the validity of a newly developed graded motor cognitive \u2018stress test\u2019 to quantify the combined motor and cognitive reserve (MCR). The study included 144 participants (ages between 18 and 85, 50% women) with a range of reserve capacities (i.e. healthy young and older adults and individuals with Parkinson's disease, Alzheimer\u2019s disease, dementia with Lewy bodies and mild cognitive impairment). The assessment included walking on a treadmill while negotiating motor and cognitive challenges delivered using virtual reality. To establish an MCR index score, we used a semi-supervised machine learning algorithm. The model includes performance measures from completing the stress test and measures obtained from wearable sensors used during the test. Validation of the proposed MCR index was examined through: (i) model face validity\u2013reflecting decline of performance as challenge increased; (ii) known-groups validity\u2014classification of scores according to neurological status; (iii) construct validity (convergent)\u2014association with common MCRs proxies as well as MRI-derived regional brain volumes. The model's face validity revealed decreased performance with increased motor and cognitive challenges (both domains P &amp;lt; 0.001). The index accurately discriminated between healthy controls and those diagnosed with neurological conditions with an area under the curve of 0.89 [95% CI: 0.79\u20130.99] which was significantly higher than all other commonly used proxies. Statistically significant Spearman's \u03c1 correlations were observed with all commonly used motor and cognitive proxies (0.56 \u2264 r \u2264 0.79, after multiplicity correction all P &amp;lt; 0.05), reflecting construct validity. In addition, statistically significant correlations were observed between the MCR index and whole-brain grey matter and white matter volumes (r = 0.63 and 0.55), as well as the pre-defined left and right caudate nucleus (r = 0.56 and 0.68) and inferior-frontal gyrus (r = 0.47 and 0.58). This proof-of-concept study shows that the novel MCR index is valid, with high sensitivity to neurological deficits and is able to quantify reserve on an individual level. This new innovative tool can assist in screening for motor cognitive deficits and potentially, for predicting motor and cognitive decline associated with neurodegenerative disease.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf412","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T12:27:17Z","timestamp":1761222437000},"source":"Crossref","is-referenced-by-count":5,"title":["Quantifying motor\u2013cognitive reserve using a novel multi-modal stress test"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5690-4805","authenticated-orcid":false,"given":"Tal","family":"Kozlovski","sequence":"first","affiliation":[{"name":"Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel Aviv Sourasky Medical Center, Neurological Institute , Tel Aviv 6423906 ,","place":["Israel"]},{"name":"Department of Statistic and Operations Research, School of Mathematical Sciences, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inbal","family":"Maidan","sequence":"additional","affiliation":[{"name":"Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel Aviv Sourasky Medical Center, Neurological Institute , Tel Aviv 6423906 ,","place":["Israel"]},{"name":"Gray Faculty of Medicine and Health Sciences, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]},{"name":"Sagol School of Neuroscience, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eran","family":"Gazit","sequence":"additional","affiliation":[{"name":"Center of the Study of Movement, Cognition, and Mobility, Neurological Institute, Tel Aviv Sourasky Medical Center , Tel Aviv 6423906 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6182-0059","authenticated-orcid":false,"given":"Amgad","family":"Droby","sequence":"additional","affiliation":[{"name":"Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel Aviv Sourasky Medical Center, Neurological Institute , Tel Aviv 6423906 ,","place":["Israel"]},{"name":"Gray Faculty of Medicine and Health Sciences, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]},{"name":"Sagol School of Neuroscience, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avner","family":"Thaler","sequence":"additional","affiliation":[{"name":"Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel Aviv Sourasky Medical Center, Neurological Institute , Tel Aviv 6423906 ,","place":["Israel"]},{"name":"Gray Faculty of Medicine and Health Sciences, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]},{"name":"Sagol School of Neuroscience, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3855-3423","authenticated-orcid":false,"given":"Jeffrey M","family":"Hausdorff","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medicine and Health Sciences, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]},{"name":"Sagol School of Neuroscience, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]},{"name":"Center of the Study of Movement, Cognition, and Mobility, Neurological Institute, Tel Aviv Sourasky Medical Center , Tel Aviv 6423906 ,","place":["Israel"]},{"name":"Rush Alzheimer\u2019s Disease Center and Department of Orthopaedic Surgery, Rush University Medical Center , Chicago, IL 60612 ,","place":["USA"]},{"name":"Department of Physical Therapy, Gray Faculty of Medicine and Health Sciences, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nir","family":"Giladi","sequence":"additional","affiliation":[{"name":"Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel Aviv Sourasky Medical Center, Neurological Institute , Tel Aviv 6423906 ,","place":["Israel"]},{"name":"Gray Faculty of Medicine and Health Sciences, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]},{"name":"Sagol School of Neuroscience, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]},{"name":"Center of the Study of Movement, Cognition, and Mobility, Neurological Institute, Tel Aviv Sourasky Medical Center , Tel Aviv 6423906 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoav","family":"Benjamini","sequence":"additional","affiliation":[{"name":"Department of Statistic and Operations Research, School of Mathematical Sciences, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]},{"name":"Edmond J. Safra Center for Bioinformatics, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anat","family":"Mirelman","sequence":"additional","affiliation":[{"name":"Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel Aviv Sourasky Medical Center, Neurological Institute , Tel Aviv 6423906 ,","place":["Israel"]},{"name":"Gray Faculty of Medicine and Health Sciences, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]},{"name":"Sagol School of Neuroscience, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]},{"name":"Center of the Study of Movement, Cognition, and Mobility, Neurological Institute, Tel Aviv Sourasky Medical Center , Tel Aviv 6423906 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"issue":"2","key":"2025112901530417900_fcaf412-B1","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1002\/j.2040-4603.2012.tb00425.x","article-title":"Lack of exercise is a major cause of chronic diseases","volume":"2","author":"Booth","year":"2012","journal-title":"Compr Physiol"},{"issue":"3","key":"2025112901530417900_fcaf412-B2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1136\/hrt.79.3.289","article-title":"Physiological cardiac reserve: Development of a non-invasive method and first estimates in man","volume":"79","author":"Cooke","year":"1998","journal-title":"Heart"},{"issue":"12","key":"2025112901530417900_fcaf412-B3","doi-asserted-by":"crossref","first-page":"3190","DOI":"10.1161\/01.CIR.94.12.3190","article-title":"Right ventricular performance and contractile reserve in patients with severe heart failure: Assessment by pressure-area relations and association with outcome","volume":"94","author":"Gorcsan","year":"1996","journal-title":"Circulation"},{"issue":"6","key":"2025112901530417900_fcaf412-B4","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/0002-9343(83)90873-2","article-title":"Renal functional reserve in humans: Effect of protein intake on glomerular filtration rate","volume":"75","author":"Bosch","year":"1983","journal-title":"Am J Med"},{"issue":"6","key":"2025112901530417900_fcaf412-B5","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1038\/ki.1994.217","article-title":"Renal functional reserve in cyclosporin-treated recipients of kidney transplant","volume":"45","author":"Ader","year":"1994","journal-title":"Kidney Int"},{"issue":"1","key":"2025112901530417900_fcaf412-B6","doi-asserted-by":"crossref","first-page":"18","DOI":"10.5414\/CN108497","article-title":"Optimizing a kidney stress test to evaluate renal functional reserve","volume":"86","author":"Sharma","year":"2016","journal-title":"Clin Nephrol"},{"issue":"5","key":"2025112901530417900_fcaf412-B7","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/0002-8703(90)90122-E","article-title":"Early assessment of coronary reserve after bypass surgery by dipyridamole transesophageal echocardiographic stress test","volume":"120","author":"Biagini","year":"1990","journal-title":"Am Heart J"},{"issue":"3","key":"2025112901530417900_fcaf412-B8","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/ehjci\/jes078","article-title":"Quantitation of the diastolic stress test: Filling pressure vs. diastolic reserve","volume":"14","author":"Gibby","year":"2013","journal-title":"Eur Hear Journal--Cardiovascular Imaging"},{"issue":"5","key":"2025112901530417900_fcaf412-B9","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.neurobiolaging.2013.11.015","article-title":"A comparative study of Parkinson\u2019s disease and leucine-rich repeat kinase 2 p. 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