{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:43:31Z","timestamp":1787237011882,"version":"build-2736575974"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T00:00:00Z","timestamp":1616112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"<jats:p>One year after the start of the COVID-19 pandemic, its secondary impacts can be globally observed. Some of them result from physical distancing and severe social contact restrictions by policies still imposed to stop the fast spread of new variants of this infectious disease. People with Alzheimer's disease (AD) and other dementias can also be significantly affected by the reduction of their activity programs, the loss of partners, and social isolation. Searching for the closest translational scenario, the increased mortality rates in male 3xTg-AD mice modeling advanced stages of the disease can provide a scenario of \u201cnaturalistic isolation.\u201d Our most recent work has shown its impact worsening AD-cognitive and emotional profiles, AD-brain asymmetry, and eliciting hyperactivity and bizarre behaviors. Here, we further investigated the psychomotor function through six different psychomotor analysis in a set of 13-month-old 3xTg-AD mice and their non-transgenic counterparts with normal aging. The subgroup of male 3xTg-AD mice that lost their partners lived alone for the last 2\u20133 months after 10 months of social life. AD's functional limitations were shown as increased physical frailty phenotype, poor or deficient psychomotor performance, including bizarre behavior, in variables involving information processing and decision-making (exploratory activity and spontaneous gait), that worsened with isolation. Paradoxical muscular strength and better motor performance (endurance and learning) was shown in variables related to physical work and found enhanced by isolation, in agreement with the hyperactivity and the appearance of bizarre behaviors previously reported. Despite the isolation, a delayed appearance of motor deficits related to physical resistance and tolerance to exercise was found in the 3xTg-AD mice, probably because of the interplay of hyperactivity and mortality\/survivor bias. The translation of these results to the clinical setting offers a guide to generate flexible and personalized rehabilitation strategies adaptable to the restrictions of the COVID-19 pandemic.<\/jats:p>","DOI":"10.3389\/fragi.2021.648567","type":"journal-article","created":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T01:20:08Z","timestamp":1616116808000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Translational Modeling of Psychomotor Function in Normal and AD-Pathological Aging With Special Concerns on the Effects of Social Isolation"],"prefix":"10.3389","volume":"2","author":[{"given":"Lidia","family":"Castillo-Mariqueo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Gim\u00e9nez-Llort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"286","DOI":"10.3390\/healthcare8030286","article-title":"Impact of COVID-19 on Alzheimer's disease risk: viewpoint for research action","volume":"8","author":"Abate","year":"2020","journal-title":"Healthcare"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1093\/gerona\/gly031","article-title":"Sexual dimorphism in the behavioral responses and the immunoendocrine status in d-galactose-induced aging","volume":"73","author":"Baeta-Corral","year":"2018","journal-title":"J. Gerontol. A"},{"key":"B3","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.bbr.2013.10.017","article-title":"Bizarre behaviors and risk assessment in 3xTg-AD mice at early stages of the disease","volume":"258","author":"Baeta-Corral","year":"2014","journal-title":"Behav. Brain Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1037\/bne0000027","article-title":"Persistent hyperactivity and distinctive strategy features in the morris water maze in 3xTg-AD mice at advanced stages of disease","volume":"129","author":"Baeta-Corral","year":"2015","journal-title":"Behav. Neurosci"},{"key":"B5","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/j.amjmed.2017.11.051","article-title":"Gait disorders","volume":"131","author":"Baker","year":"2018","journal-title":"Am. J. Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/S0306-4530(02)00039-2","article-title":"Individual housing induces altered immuno-endocrine responses to psychological stress in male mice","volume":"28","author":"Bartolomucci","year":"2003","journal-title":"Psychoneuroendocrinology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1007\/s10549-015-3663-1.Progestin","article-title":"Poor gait performance and prediction of dementia: results from a meta-analysis","volume":"17","author":"Beauchet","year":"2016","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e12873","DOI":"10.1111\/acel.12873","article-title":"Temporal and regional progression of Alzheimer's disease-like pathology in 3xTg-AD mice","volume":"18","author":"Belfiore","year":"2019","journal-title":"Aging Cell"},{"key":"B9","doi-asserted-by":"publisher","first-page":"41","DOI":"10.3233\/JAD-200604","article-title":"The effects of confinement on neuropsychiatric symptoms in Alzheimer's disease during the COVID-19 crisis","volume":"76","author":"Boutoleau-Bretonni\u00e8re","year":"2020","journal-title":"J. Alzheimers. Dis"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1001\/archneurol.2009.240","article-title":"Association of muscle strength with the risk of Alzheimer disease and the rate of cognitive decline in community-dwelling older persons","volume":"66","author":"Boyle","year":"2009","journal-title":"Arch. Neurol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1016\/j.jagp.2020.04.010","article-title":"Anticipating and mitigating the impact of the COVID-19 pandemic on Alzheimer's disease and related dementias","volume":"28","author":"Brown","year":"2020","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"B12","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1101\/lm.473907","article-title":"The influence of visual ability on learning and memory performance in 13 strains of mice","volume":"14","author":"Brown","year":"2007","journal-title":"Learn. Mem"},{"key":"B13","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/0031-9384(95)02210-4","article-title":"The role of motor activity in diet-induced obesity in C57BL\/6J mice","volume":"60","author":"Brownlow","year":"1996","journal-title":"Physiol. Behav"},{"key":"B14","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1586\/ern.11.57","article-title":"Loss of motor function in preclinical Alzheimer's disease","volume":"11","author":"Buchman","year":"2011","journal-title":"Expert Rev Neurother"},{"key":"B15","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1212\/01.wnl.0000324864.81179.6a","article-title":"Physical frailty in older persons is associated with Alzheimer disease pathology","volume":"71","author":"Buchman","year":"2008","journal-title":"Neurology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1111\/jgs.16644","article-title":"Facing dementia during the COVID-19 outbreak","volume":"68","author":"Canevelli","year":"2020","journal-title":"J. Am. Geriatr. Soc"},{"key":"B17","doi-asserted-by":"publisher","first-page":"112229","DOI":"10.1016\/j.bbr.2019.112229","article-title":"Indexes for flotation and circling, two non-search behaviors in the water maze, sensitive to D-galactose\u2013induced accelerated aging and Alzheimer's disease","volume":"377","author":"Castillo-Mariqueo","year":"2019","journal-title":"Behav. Brain Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1017\/S1041610220003245","article-title":"Santa Isabel program for psychomotor function in normal and pathological aging during current times of COVID-19 confinement in a long-term care","volume":"32","author":"Castillo-Mariqueo","year":"2020","journal-title":"Int. Psychogeriatr"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e0202969","DOI":"10.1371\/journal.pone.0202969","article-title":"Sensory-specific impairment among older people. An investigation using both sensory thresholds and subjective measures across the five senses","volume":"13","author":"Cavazzana","year":"2018","journal-title":"PLoS ONE"},{"key":"B20","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1006\/exnr.1997.6708","article-title":"Gait analysis of adult paraplegic rats after spinal cord repair","volume":"148","author":"Cheng","year":"1997","journal-title":"Exp. Neurol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.nbd.2008.03.011","article-title":"Polyglutamine-expanded ataxin-3 causes cerebellar dysfunction of SCA3 transgenic mice by inducing transcriptional dysregulation","volume":"31","author":"Chou","year":"2008","journal-title":"Neurobiol. Dis"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e13093","DOI":"10.14814\/phy2.13093","article-title":"C57BL\/6J mice as a polygenic developmental model of diet-induced obesity","volume":"5","author":"Chu","year":"2017","journal-title":"Physiol. Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2967","DOI":"10.1128\/MCB.00230-16","article-title":"Mutation of the 3-phosphoinositide-dependent protein kinase 1 (PDK1) substrate-docking site in the developing brain causes microcephaly with abnormal brain morphogenesis independently of Akt, leading to impaired cognition and disruptive behaviors","volume":"36","author":"Cord\u00f3n-Barris","year":"2016","journal-title":"Mol. Cell. Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"507","DOI":"10.2174\/1567205011310050006","article-title":"Treadmill exercise prevents learning and memory impairment in Alzheimer's disease-like pathology","volume":"10","author":"Dao","year":"2013","journal-title":"Curr. Alzheimer Res"},{"key":"B25","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.neuroscience.2004.05.040","article-title":"Modulation of hippocampal cell proliferation, memory, and amyloid plaque deposition in APPsw (Tg2576) mutant mice by isolation stress","volume":"127","author":"Dong","year":"2004","journal-title":"Neuroscience"},{"key":"B26","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.neuroscience.2008.05.017","article-title":"Corticosterone and related receptor expression are associated with increased \u03b2-amyloid plaques in isolated Tg2576 mice","volume":"155","author":"Dong","year":"2008","journal-title":"Neuroscience"},{"key":"B27","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/j.apmr.2009.11.020","article-title":"Lower-extremity function in cognitively healthy aging, mild cognitive impairment, and Alzheimer's disease","volume":"91","author":"Eggermont","year":"2010","journal-title":"Arch. Phys. Med. Rehabil"},{"key":"B28","doi-asserted-by":"publisher","first-page":"113294","DOI":"10.1016\/j.psychres.2020.113294","article-title":"High depression and anxiety in people with Alzheimer's disease living in retirement homes during the covid-19 crisis","volume":"291","author":"El Haj","year":"2020","journal-title":"Psychiatry Res"},{"key":"B29","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.biopsych.2009.06.015","article-title":"Intraneuronal \u03b2-amyloid accumulation in the amygdala enhances fear and anxiety in Alzheimer's disease transgenic mice","volume":"67","author":"Espa\u00f1a","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"B30","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1079\/pns19950066","article-title":"Effects of exercise training in the elderly: impact of progressive-resistance training on skeletal muscle and whole-body protein metabolism","volume":"54","author":"Fielding","year":"1995","journal-title":"Proc. Nutr. Soc"},{"key":"B31","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1111\/j.1532-5415.1999.tb07240.x","article-title":"Equilibrium and limb coordination in mild cognitive impairment and mild Alzheimer's disease","volume":"47","author":"Franssen","year":"1999","journal-title":"J. Am. Geriatr. Soc"},{"key":"B32","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.bbr.2018.09.006","article-title":"Motor deficits in 16-month-old male and female 3xTg-AD mice","volume":"356","author":"Garvock-de Montbrun","year":"2019","journal-title":"Behav. Brain Res"},{"key":"B33","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.eurger.2010.10.001","article-title":"The snail and turtle effects: reflections on health care management in geriatric medicine","volume":"1","author":"Gim\u00e9nez-Llort","year":"2010","journal-title":"Eur. Geriatr. Med"},{"key":"B34","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1159\/000156475","article-title":"Gender-specific neuroimmunoendocrine aging in a triple-transgenic 3xTg-AD mouse model for Alzheimer's disease and its relation with longevity","volume":"15","author":"Gim\u00e9nez-Llort","year":"2008","journal-title":"Neuroimmunomodulation"},{"key":"B35","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.neubiorev.2006.07.007","article-title":"Modeling behavioral and neuronal symptoms of Alzheimer's disease in mice: a role for intraneuronal amyloid","volume":"31","author":"Gim\u00e9nez-Llort","year":"2007","journal-title":"Neurosci. Biobehav. Rev"},{"key":"B36","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1046\/j.1460-9568.2002.02122.x","article-title":"Mice lacking the adenosine A1 receptor are anxious and aggressive, but are normal learners with reduced muscle strength and survival rate","volume":"16","author":"Gim\u00e9nez-Llort","year":"2002","journal-title":"Eur. J. Neurosci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.3791\/1787","article-title":"A simple composite phenotype scoring system for evaluating mouse models of cerebellar ataxia","volume":"21","author":"Guyenet","year":"2010","journal-title":"J. Vis. Exp."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e323","DOI":"10.1016\/S2468-2667(18)30091-4","article-title":"Frailty and pre-frailty in middle-aged and older adults and its association with multimorbidity and mortality: a prospective analysis of 493 737 UK Biobank participants","volume":"3","author":"Hanlon","year":"2018","journal-title":"Lancet Public Health"},{"key":"B39","doi-asserted-by":"publisher","first-page":"172","DOI":"10.3389\/fnagi.2018.00172","article-title":"Sex differences in healthspan predict lifespan in the 3xTg-AD mouse model of Alzheimer's disease","volume":"10","author":"Kane","year":"2018","journal-title":"Front. Aging Neurosci"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e1000412","DOI":"10.1371\/journal.pbio.1000412","article-title":"Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research","volume":"8","author":"Kilkenny","year":"2010","journal-title":"PLoS Biol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.14814\/phy2.12708","article-title":"Similar degrees of obesity induced by diet or aging cause strikingly different immunologic and metabolic outcomes","volume":"4","author":"Krishna","year":"2016","journal-title":"Physiol. Rep"},{"key":"B42","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1515\/revneuro-2012-0041","article-title":"Neurologic and motor dysfunctions in APP transgenic mice","volume":"23","author":"Lalonde","year":"2012","journal-title":"Rev. Neurosci"},{"key":"B43","doi-asserted-by":"publisher","first-page":"7856823","DOI":"10.1155\/2018\/7856823","article-title":"The importance of physical activity exercise among older people","volume":"2018","author":"Langhammer","year":"2018","journal-title":"Biomed Res. Int"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1111\/ene.14339","article-title":"Neuropsychiatric symptoms and quality of life in Spanish patients with Alzheimer's disease during the COVID-19 lockdown","volume":"27","author":"Lara","year":"2020","journal-title":"Eur. J. Neurol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1001\/jama.300.9.1027","article-title":"Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease","volume":"300","author":"Lautenschlager","year":"2008","journal-title":"JAMA"},{"key":"B46","doi-asserted-by":"publisher","first-page":"M283","DOI":"10.1093\/gerona\/57.5.m283","article-title":"A conceptual framework of frailty: a review","volume":"57","author":"Li","year":"2002","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci"},{"key":"B47","doi-asserted-by":"publisher","first-page":"168","DOI":"10.3389\/fmed.2018.00168","article-title":"Editorial: dementia, frailty and aging","volume":"5","author":"Lim","year":"2018","journal-title":"Front. Med"},{"key":"B48","doi-asserted-by":"publisher","first-page":"S365","DOI":"10.3233\/JAD-179917","article-title":"Past to future: what animal models have taught us about Alzheimer's disease","volume":"64","author":"Martini","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"B49","doi-asserted-by":"publisher","first-page":"131","DOI":"10.3389\/fnins.2020.00131","article-title":"Relationship between exercise and Alzheimer's disease: a narrative literature review","volume":"14","author":"Meng","year":"2020","journal-title":"Front. Neurosci"},{"key":"B50","doi-asserted-by":"publisher","first-page":"290","DOI":"10.2522\/ptj.20160115","article-title":"Postural stability in older adults with alzheimer disease","volume":"97","author":"Mesbah","year":"2017","journal-title":"Phys. Ther"},{"key":"B51","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.3233\/JAD-190790","article-title":"Gait disorders in Alzheimer's disease and other dementias: there is something in the way you walk","volume":"71","author":"Montero-Odasso","year":"2019","journal-title":"J. Alzheimers Dis"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1007\/s10072-018-3505-0","article-title":"Muscle profile and cognition in patients with Alzheimer's disease dementia","volume":"39","author":"Moon","year":"2018","journal-title":"Neurol. Sci"},{"key":"B53","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1159\/000500718","article-title":"Muscle strength is independently related to brain atrophy in patients with Alzheimer's disease","volume":"47","author":"Moon","year":"2019","journal-title":"Dement. Geriatr. Cogn. Disord"},{"key":"B54","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.gaitpost.2011.08.014","article-title":"Gait assessment in mild cognitive impairment and Alzheimer's disease: the effect of dual-task challenges across the cognitive spectrum","volume":"35","author":"Muir","year":"2012","journal-title":"Gait Posture"},{"key":"B55","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1097\/WAD.0b013e3181c78a20","article-title":"Gait and balance impairments in alzheimer disease patients","volume":"24","author":"Munoz","year":"2010","journal-title":"Alzheimer Dis. Assoc. Disord"},{"key":"B56","doi-asserted-by":"publisher","first-page":"572583","DOI":"10.3389\/fpsyt.2020.572583","article-title":"Impact of social isolation on the behavioral, functional profiles, and hippocampal atrophy asymmetry in dementia in times of coronavirus pandemic (COVID-19): a translational neuroscience approach","volume":"11","author":"Muntsant","year":"","journal-title":"Front. Psychiatry"},{"key":"B57","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1017\/S1041610220002720","article-title":"419\u2013Brain atrophy asymmetry in dementia is worsened by social isolation: a translational neuroscience approach in times of coronavirus pandemic (COVID-19)","volume":"32","author":"Muntsant","year":"","journal-title":"Int. Psychogeriatr."},{"key":"B58","doi-asserted-by":"publisher","first-page":"111","DOI":"10.3390\/biomedicines9020111","article-title":"Sex-dependent end-of-life mental and vascular scenarios for compensatory mechanisms in mice with normal and AD-neurodegenerative aging","volume":"9","author":"Muntsant","year":"2021","journal-title":"Biomedicines"},{"key":"B59","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/S0896-6273(03)00434-3","article-title":"Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular A\u03b2 and synaptic dysfunction","volume":"39","author":"Oddo","year":"2003","journal-title":"Neuron"},{"key":"B60","doi-asserted-by":"publisher","first-page":"e12538","DOI":"10.1111\/gbb.12538","article-title":"Age-related deterioration of motor function in male and female 5xFAD mice from 3 to 16 months of age","volume":"19","author":"O'Leary","year":"2020","journal-title":"Genes Brain Behav"},{"key":"B61","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.bbr.2017.09.009","article-title":"Motor function deficits in the 12 month-old female 5xFAD mouse model of Alzheimer's disease","volume":"337","author":"O'Leary","year":"2018","journal-title":"Behav. Brain Res"},{"key":"B62","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/S0031-9384(01)00494-2","article-title":"Social stress in mice: gender differences and effects of estrous cycle and social dominance","volume":"73","author":"Palanza","year":"2001","journal-title":"Physiol. Behav"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1007\/s40520-020-01601-4","article-title":"The potential long-term impact of the COVID-19 outbreak on patients with non-communicable diseases in Europe: consequences for healthy ageing","volume":"32","author":"Palmer","year":"2020","journal-title":"Aging Clin. Exp. Res"},{"key":"B64","doi-asserted-by":"publisher","first-page":"e58","DOI":"10.1016\/s2666-7568(20)30007-6","article-title":"Associations between physical frailty and dementia incidence: a prospective study from UK Biobank","volume":"1","author":"Petermann-Rocha","year":"2020","journal-title":"Lancet Health Longev"},{"key":"B65","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/s00508-016-1096-4","article-title":"Gait disorders in adults and the elderly: a clinical guide","volume":"129","author":"Pirker","year":"2017","journal-title":"Wien. Klin. Wochenschr"},{"key":"B66","doi-asserted-by":"publisher","first-page":"830.e1","DOI":"10.1016\/j.neurobiolaging.2011.07.005","article-title":"3xTgAD mice exhibit altered behavior and elevated A\u03b2 after chronic mild social stress","volume":"33","author":"Rothman","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"B67","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.neubiorev.2006.11.007","article-title":"Gait in ageing and associated dementias; its relationship with cognition","volume":"31","author":"Scherder","year":"2007","journal-title":"Neurosci. Biobehav. Rev"},{"key":"B68","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1159\/000083365","article-title":"Aging effects on vestibulo-ocular responses in C57BL\/6 mice: comparison with alteration in auditory function","volume":"10","author":"Shiga","year":"2005","journal-title":"Audiol. Neurotol"},{"key":"B69","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.bbr.2014.11.046","article-title":"Analysis of motor function in 6-month-old male and female 3xTg-AD mice","volume":"281","author":"Stover","year":"2015","journal-title":"Behav. Brain Res"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.2522\/ptj.20130298","article-title":"Relationships between balance and cognition in patients with subjective cognitive impairment, mild cognitive impairment, and Alzheimer disease","volume":"94","author":"Tangen","year":"2014","journal-title":"Phys. Ther"},{"key":"B71","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1136\/postgradmedj-2012-131366","article-title":"Physical activity is medicine for older adults","volume":"90","author":"Taylor","year":"2014","journal-title":"Postgrad. Med. J"},{"key":"B72","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.jalz.2013.03.009","article-title":"Cognition and gait show a distinct pattern of association in the general population","volume":"10","author":"Verlinden","year":"2014","journal-title":"Alzheimers Dement"},{"key":"B73","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1007\/s00335-015-9556-0","article-title":"Vestibular dysfunction, altered macular structure and trait localization in A\/J inbred mice","volume":"26","author":"Vijayakumar","year":"2015","journal-title":"Mamm. Genome"},{"key":"B74","doi-asserted-by":"publisher","first-page":"107","DOI":"10.3389\/fnbeh.2019.00107","article-title":"Analysis of motor function in the Tg4-42 mouse model of alzheimer's disease","volume":"13","author":"Wagner","year":"2019","journal-title":"Front. Behav. Neurosci"},{"key":"B75","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.dadm.2018.05.002","article-title":"Relationship between frailty and Alzheimer's disease biomarkers: a scoping review","volume":"10","author":"Wallace","year":"2018","journal-title":"Alzheimer Dement. Diagn. Assess. Dis. Monit"},{"key":"B76","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1016\/S0140-6736(20)30755-8","article-title":"Dementia care during COVID-19","volume":"365","author":"Wang","year":"2020","journal-title":"Lancet"},{"key":"B77","doi-asserted-by":"publisher","first-page":"e2854","DOI":"10.7717\/peerj.2854","article-title":"Gait disorder as a predictor of spatial learning and memory impairment in aged mice","volume":"5","author":"Wang","year":"2017","journal-title":"PeerJ"},{"key":"B78","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1097\/HCO.0000000000000437","article-title":"Health benefits of physical activity","volume":"32","author":"Warburton","year":"2017","journal-title":"Curr. Opin. Cardiol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1046\/j.1440-1681.2003.t01-1-03808.x","article-title":"Diet-induced obesity and cardiovascular regulation in C57BL\/6J mice","volume":"30","author":"Williams","year":"2003","journal-title":"Clin. Exp. Pharmacol. Physiol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/0165-6147(91)90529-2","article-title":"Animal models as simulations of depression","volume":"12","author":"Willner","year":"1991","journal-title":"Trends Pharmacol. Sci"}],"container-title":["Frontiers in Aging"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fragi.2021.648567\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T01:20:10Z","timestamp":1616116810000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fragi.2021.648567\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,19]]},"references-count":80,"alternative-id":["10.3389\/fragi.2021.648567"],"URL":"https:\/\/doi.org\/10.3389\/fragi.2021.648567","relation":{},"ISSN":["2673-6217"],"issn-type":[{"value":"2673-6217","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,19]]},"article-number":"648567"}}