Promoting neuroplasticity and neuropsychological functioning in frailty through an app-based sensorimotor training: study protocol for a randomized trial

Florian Beier, Martin Löffler, Frauke Nees, Lucrezia Hausner, Lutz Frölich, Herta Flor, Florian Beier, Martin Löffler, Frauke Nees, Lucrezia Hausner, Lutz Frölich, Herta Flor

Abstract

Background: Frailty is characterized by an age-related decline in multiple physiological systems, leading to a high vulnerability to stressors, adverse health outcomes, and low quality of life. Neuroscientific models of pathological aging emphasize the loss of sensorimotor stimulation and reduced neuromodulatory capacities as core processes in age-related cognitive and bodily decline, which may be associated with maladaptive plastic changes in the brain. We plan to increase sensorimotor stimulation in frail persons through a newly developed app-based training program and link the training trials to biological and psychological correlates of age-associated vulnerability and health indices.

Methods: We will conduct a randomized trial, applying an app-based sensorimotor home training (N = 30) in people suffering from frailty. An app-based relaxation training will serve as an active control condition (N = 30). Both interventions will last for 90 days each. The sensorimotor training includes unimodal and multimodal sensory discrimination tasks in the visual, auditory, and tactile domain, as well as sensorimotor precision tasks. The tasks will be implemented using an adaptive training algorithm and enriched with motivational components embedded in a virtual training environment. We expect a pre-post reduction of frailty status and associated functional decline related to refinement of representational maps within the sensorimotor system and improved sensorimotor function such as extremity function. Secondary analyses will study the influence of BDNF genotype as moderating variable. Additional outcomes will include measures of perceptual and cognitive functioning, quality of life as well as BDNF serum levels. Measurements will take place before training (baseline), after 60 days (assessment 1), and at the end of the training after 90 days (assessment 2).

Discussion: In our randomized trial, we aim to characterize a multidimensional concept of frailty and to target maladaptive behaviors and neuroplasticity using an app-based sensorimotor training. This type of intervention might provide further knowledge and new possibilities for preventing decline and preserving function in older adults.

Trial registration: ClinicalTrials.gov NCT03666039 . Registered 11 September 2018 - Retrospectively registered. Protocol version: Version 4 revised (issue date: 19 May 2021).

Keywords: Aging; Frailty; Neuroplasticity; Sensorimotor functioning; Training app.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Expected flow of participants and study design

References

    1. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–762. doi: 10.1016/S0140-6736(12)62167-9.
    1. Morley JE, Vellas B, Abellan van Kan G, Anker SD, Bauer JM, Bernabei R, et al. Frailty consensus: a call to action. J Am Med Dir Assoc. 2013;14(6):392–397. doi: 10.1016/j.jamda.2013.03.022.
    1. Ferrucci L, Cavazzini C, Corsi A, Bartali B, Russo CR, Lauretani F, Ferrucci L, Cavazzini C, Corsi AM, Bartali B, Russo CR, Lauretani F, Bandinelli S, Bandinelli S, Guralnik JM. Biomarkers of frailty in older persons. J Endocrinol Investig. 2002;25(10 Suppl):10–15.
    1. Dinse HR. Cortical reorganization in the aging brain. Prog Brain Res. 2006;157:57–80. doi: 10.1016/S0079-6123(06)57005-0.
    1. Mahncke HW, Bronstone A, Merzenich MM. Brain plasticity and functional losses in the aged: scientific bases for a novel intervention. Prog Brain Res. 2006;157:81–109. doi: 10.1016/S0079-6123(06)57006-2.
    1. Rosano C, Studenski SA, Aizenstein HJ, Boudreau RM, Longstreth WT, Newman AB. Slower gait, slower information processing and smaller prefrontal area in older adults. Age Ageing. 2012;41(1):58–64. doi: 10.1093/ageing/afr113.
    1. Callisaya ML, Beare R, Phan TG, Chen J, Srikanth VK. Global and regional associations of smaller cerebral gray and white matter volumes with gait in older people. PLoS One. 2014;9(1):e84909. doi: 10.1371/journal.pone.0084909.
    1. Rodrigue KM, Raz N. Shrinkage of the entorhinal cortex over five years predicts memory performance in healthy adults. J Neurosci. 2004;24(4):956–963. doi: 10.1523/JNEUROSCI.4166-03.2004.
    1. Head D, Rodrigue KM, Kennedy KM, Raz N. Neuroanatomical and cognitive mediators of age-related differences in episodic memory. Neuropsychology. 2008;22(4):491–507. doi: 10.1037/0894-4105.22.4.491.
    1. Sullivan EV, Rohlfing T, Pfefferbaum A. Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: relations to timed performance. Neurobiol Aging. 2010;31(3):464–481. doi: 10.1016/j.neurobiolaging.2008.04.007.
    1. Davis SW, Dennis NA, Buchler NG, White LE, Madden DJ, Cabeza R. Assessing the effects of age on long white matter tracts using diffusion tensor tractography. Neuroimage. 2009;46(2):530–541. doi: 10.1016/j.neuroimage.2009.01.068.
    1. Park DC, Polk TA, Park R, Minear M, Savage A, Smith MR. Aging reduces neural specialization in ventral visual cortex. Proc Natl Acad Sci U S A. 2004;101(35):13091–13095. doi: 10.1073/pnas.0405148101.
    1. Du Y, Buchsbaum BR, Grady CL, Alain C. Increased activity in frontal motor cortex compensates impaired speech perception in older adults. Nat Commun. 2016;7:1–12.
    1. Carp J, Park J, Hebrank A, Park DC, Polk TA. Age-related neural dedifferentiation in the motor system. PLoS One. 2011;6(12):e29411. doi: 10.1371/journal.pone.0029411.
    1. Koen JD, Hauck N, Rugg MD. The relationship between age, neural differentiation, and memory performance. J Neurosci. 2019;39(1):149–162. doi: 10.1523/JNEUROSCI.1498-18.2018.
    1. Goh JO. Functional dedifferentiation and altered connectivity in older adults: neural accounts of cognitive aging. Aging Dis. 2011;2(1):30–48.
    1. Seidler RD, Bernard JA, Burutolu TB, Fling BW, Gordon MT, Gwin JT, Kwak Y, Lipps DB. Motor control and aging: links to age-related brain structural, functional, and biochemical effects. Neurosci Biobehav Rev. 2010;34(5):721–733. doi: 10.1016/j.neubiorev.2009.10.005.
    1. Sleimen-Malkoun R, Temprado JJ, Hong SL. Aging induced loss of complexity and dedifferentiation: consequences for coordination dynamics within and between brain, muscular and behavioral levels. Front Aging Neurosci. 2014;6:140140. doi: 10.3389/fnagi.2014.00140.
    1. Melendez RI, Gregory ML, Bardo MT, Kalivas PW. Impoverished rearing environment alters metabotropic glutamate receptor expression and function in the prefrontal cortex. Neuropsychopharmacology. 2004;29(11):1980–1987. doi: 10.1038/sj.npp.1300507.
    1. Beaulieu C, Colonnier M. Number and size of neurons and synapses in the motor cortex of cats raised in different environmental complexities. J Comp Neurol. 1989;289(1):178–187. doi: 10.1002/cne.902890115.
    1. Rolland Y, Abellan Van Kan G, Benetos A, Blain H, Bonnefoy M, Chassagne P, et al. Frailty, osteoporosis and hip fracture: causes, consequences and therapeutic perspectives. J Nutr Health Aging. 2008;12(5):335–346. doi: 10.1007/BF02982665.
    1. Flor H, Elbert T, Knecht S, Wienbruch C, Pantev C, Birbaumer N, et al. Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature. 1995;375(6531):482–484. doi: 10.1038/375482a0.
    1. Jabbour G, Iancu HD, Mauriège P, Joanisse DR, Martin LJ. High-intensity interval training improves performance in young and older individuals by increasing mechanical efficiency. Phys Rep. 2017;5(7):e13232. doi: 10.14814/phy2.13232.
    1. Lazarus NR, Izquierdo M, Higginson IJ, Harridge SDR. Exercise deficiency diseases of ageing: the primacy of exercise and muscle strengthening as first-line therapeutic agents to combat frailty. JJ Am Med Dir Assoc. 2018;19(9):741–743. doi: 10.1016/j.jamda.2018.04.014.
    1. Haider S, Grabovac I, Dorner TE. Effects of physical activity interventions in frail and prefrail community-dwelling people on frailty status, muscle strength, physical performance and muscle mass—a narrative review. Wien Klin Wochenschr. 2019;131(11–12):244–254. doi: 10.1007/s00508-019-1484-7.
    1. Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 2002;25(6):295–301. doi: 10.1016/S0166-2236(02)02143-4.
    1. Lu B, Nagappan G, Guan X, Nathan PJ, Wren P. BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases. Nat Rev Neurosci. 2013;14(6):401401–401416. doi: 10.1038/nrn3505.
    1. Coelho FM, Pereira DS, Lustosa LP, Silva JP, Dias JMD, Dias RCD, Queiroz BZ, Teixeira AL, Teixeira MM, Pereira LSM. Physical therapy intervention (PTI) increases plasma brain-derived neurotrophic factor (BDNF) levels in non-frail and pre-frail elderly women. Arch Gerontol Geriatr. 2012;54(3):415–420. doi: 10.1016/j.archger.2011.05.014.
    1. Puts MTE, Toubasi S, Andrew MK, Ashe MC, Ploeg J, Atkinson E, Ayala AP, Roy A, Rodríguez Monforte M, Bergman H, McGilton K. Interventions to prevent or reduce the level of frailty in community-dwelling older adults: a scoping review of the literature and international policies. Age Ageing. 2017;46(3):383–392. doi: 10.1093/ageing/afw247.
    1. Theou O, Stathokostas L, Roland KP, Jakobi JM, Patterson C, Vandervoort AA, et al. The effectiveness of exercise interventions for the management of frailty: a systematic review. J Aging Res. 2011;2011:569194. doi: 10.4061/2011/569194.
    1. de Labra C, Guimaraes-Pinheiro C, Maseda A, Lorenzo T, Millán-Calenti JC. Effects of physical exercise interventions in frail older adults: a systematic review of randomized controlled trials. BMC Geriatr. 2015;15(1):154. doi: 10.1186/s12877-015-0155-4.
    1. Mahncke HW, Connor BB, Appelman J, Ahsanuddin ON, Hardy JL, Wood RA, Joyce NM, Boniske T, Atkins SM, Merzenich MM. Memory enhancement in healthy older adults using a brain plasticity-based training program: a randomized, controlled study. Proc Natl Acad Sci U S A. 2006;103(33):12523–12528. doi: 10.1073/pnas.0605194103.
    1. Shah T, Verdile G, Sohrabi H, Campbell A, Putland E, Cheetham C, Dhaliwal S, Weinborn M, Maruff P, Darby D, Martins RN. A combination of physical activity and computerized brain training improves verbal memory and increases cerebral glucose metabolism in the elderly. Transl Psychiatry. 2014;4(12):e487. doi: 10.1038/tp.2014.122.
    1. Anguera JA, Boccanfuso J, Rintoul JL, Al-Hashimi O, Faraji F, Janowich J, et al. Video game training enhances cognitive control in older adults. Nature. 2013;501(7465):97–101. doi: 10.1038/nature12486.
    1. Scheibe S, Carstensen LL. Emotional aging: recent findings and future trends. J Gerontol B Psychol Sci Soc Sci. 2010;65B(2):135–144. doi: 10.1093/geronb/gbp132.
    1. Coyle H, Traynor V, Solowij N. Computerized and virtual reality cognitive training for individuals at high risk of cognitive decline: systematic review of the literature. Am J Geriatr Psychiatry. 2015;23(4):335–359. doi: 10.1016/j.jagp.2014.04.009.
    1. Bekrater-Bodmann R, Löffler A, Silvoni S, Frölich L, Hausner L, Desch S, Kleinböhl D, Flor H. Tablet-based sensorimotor home-training system for amnestic mild cognitive impairments in the elderly: design of a randomised clinical trial. BMJ Open. 2019;9(8):e028632. doi: 10.1136/bmjopen-2018-028632.
    1. Nascimento CM, Pereira JR, Pires de Andrade L, Garuffi M, Ayan C, Kerr DS, Talib LL, et al. Physical exercise improves peripheral BDNF levels and cognitive functions in mild cognitive impairment elderly with different bdnf Val66Met genotypes. J Alzheimers Dis. 2015;43(1):81–91. doi: 10.3233/JAD-140576.
    1. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol Med Sci. 2001;56(3):146–156. doi: 10.1093/gerona/56.3.M146.
    1. Chen X, Mao G, Leng SX. Frailty syndrome: an overview. Clin Interv Aging. 2014;9:433–441. doi: 10.2147/CIA.S45300.
    1. Gill TM, Gahbauer EA, Allore HG, Han L. Transitions between frailty states among community-living older persons. Arch Intern Med. 2006;166(4):418–423. doi: 10.1001/archinte.166.4.418.
    1. Borkovec TD, Nau SD. Credibility of analogue therapy rationales. J Behav Ther Exp Psychiatry. 1972;3(4):257–260. doi: 10.1016/0005-7916(72)90045-6.
    1. Faul F, Erdfelder E, Lang AG, Buchner A. G*power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39(2):175–191. doi: 10.3758/BF03193146.
    1. Paraskevopoulos E, Herholz SC. Multisensory integration and neuroplasticity in the human cerebral cortex. Transl Neurosci. 2013;4(3):337–348. doi: 10.2478/s13380-013-0134-1.
    1. Wallace MT, Stevenson RA. The construct of the multisensory temporal binding window and its dysregulation in developmental disabilities. Neuropsychologia. 2014;64:105–123. doi: 10.1016/j.neuropsychologia.2014.08.005.
    1. Darainy M, Vahdat S, Ostry DJ. Perceptual learning in sensorimotor adaptation. J Neurophysiol. 2013;110(9):2152–2162. doi: 10.1152/jn.00439.2013.
    1. Censor N, Sagi D, Cohen LG. Common mechanisms of human perceptual and motor learning. Nat Rev Neurosci. 2012;13(9):658–664. doi: 10.1038/nrn3315.
    1. Shmuelof L, Yang J, Caffo B, Mazzoni P, Krakauer JW. The neural correlates of learned motor acuity. J Neurophysiol. 2014;112(4):971–980. doi: 10.1152/jn.00897.2013.
    1. Brehmer Y, Kalpouzos G, Wenger E, Lövdén M. Plasticity of brain and cognition in older adults. Psychol Res. 2014;78(6):790–802. doi: 10.1007/s00426-014-0587-z.
    1. Krohne HW, Egloff B, Kohlmann C-W, Tausch A. Untersuchungen mit einer deutschen version der “positive and negative affect schedule” (PANAS). [studies with a German version of the “positive and negative affect schedule” (PANAS)] Diagnostica. 1996;42(2):139–156.
    1. Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988;54(6):1063–1070. doi: 10.1037/0022-3514.54.6.1063.
    1. Mitnitski AB, Graham JE, Mogilner AJ, Rockwood K. Frailty, fitness and late-life mortality in relation to chonological and biological age. BMC Geriatr. 2002;2(1):1. doi: 10.1186/1471-2318-2-1.
    1. Searle SD, Mitnitski A, Gahbauer EA, Gill TM, Rockwood K. A standard procedure for creating a frailty index. BMC Geriatr. 2008;8:24. doi: 10.1186/1471-2318-8-24.
    1. Malmstrom TK, Miller DK, Morley JE. A comparison of four frailty models. J Am Geriatr Soc. 2014;62(4):721–726. doi: 10.1111/jgs.12735.
    1. Woo J, Leung J, Morley JE. Comparison of frailty indicators based on clinical phenotype and the multiple deficit approach in predicting mortality and physical limitation. J Am Geriatr Soc. 2012;60(8):1478–1486. doi: 10.1111/j.1532-5415.2012.04074.x.
    1. Blodgett J, Theou O, Kirkland S, Andreou P, Rockwood K. Frailty in NHANES: comparing the frailty index and phenotype. Arch Gerontol Geriatr. 2015;60(3):464–470. doi: 10.1016/j.archger.2015.01.016.
    1. de Vries NM, Staal JB, van Ravensberg CD, Hobbelen JSM, Olde Rikkert MGM. Nijhuis-van der Sanden MWG. Outcome instruments to measure frailty: a systematic review. Ageing Res Rev. 2011;10(1):104–114. doi: 10.1016/j.arr.2010.09.001.
    1. Cesari M, Gambassi G, Van Kan GA, Vellas B. The frailty phenotype and the frailty index: different instruments for different purposes. Age Ageing. 2014;43(1):10–12. doi: 10.1093/ageing/aft160.
    1. Caproni S, Muti M, Principi M, Ottaviano P, Frondizi D, Capocchi G, Floridi P, Rossi A, Calabresi P, Tambasco N. Complexity of motor sequences and cortical reorganization in Parkinson’s disease: a functional MRI Study. PLoS One. 2013;8(6):e66834. doi: 10.1371/journal.pone.0066834.
    1. Bekrater-Bodmann R, Foell J, Diers M, Kamping S, Rance M, Kirsch P, Trojan J, Fuchs X, Bach F, Çakmak HK, Maaß H, Flor H. The importance of synchrony and temporal order of visual and tactile input for illusory limb ownership experiences - an FMRI study applying virtual reality. PLoS One. 2014;9(1):e87013. doi: 10.1371/journal.pone.0087013.
    1. Kolasinski J, Makin TR, Jbabdi S, Clare S, Stagg CJ, Johansen-Berg H. Investigating the stability of fine-grain digit Somatotopy in individual human participants. J Neurosci. 2016;36(4):1113–1127. doi: 10.1523/JNEUROSCI.1742-15.2016.
    1. Oliviero A, Profice P, Tonali PA, Pilato F, Saturno E, Dileone M, Ranieri F, di Lazzaro V. Effects of aging on motor cortex excitability. Neurosci Res. 2006;55(1):74–77. doi: 10.1016/j.neures.2006.02.002.
    1. Bhandari A, Radhu N, Farzan F, Mulsant BH, Rajji TK, Daskalakis ZJ, Blumberger DM. A meta-analysis of the effects of aging on motor cortex neurophysiology assessed by transcranial magnetic stimulation. Clin Neurophysiol. 2016;127(8):2834–2845. doi: 10.1016/j.clinph.2016.05.363.
    1. McGregor KM, Carpenter H, Kleim E, Sudhyadhom A, White KD, Butler AJ, et al. Motor map reliability and aging: a TMS/fMRI study. Exp Brain Res. 2012;219(1):97–106. doi: 10.1007/s00221-012-3070-3.
    1. Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, Scherr PA, Wallace RB. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol Med Sci. 1994;49(2):M85–M94. doi: 10.1093/geronj/49.2.M85.
    1. Kiely DK, Cupples LA, Lipsitz LA. Validation and comparison of two frailty indexes: the MOBILIZE Boston study. J Am Geriatr Soc. 2009;57(9):1532–1539. doi: 10.1111/j.1532-5415.2009.02394.x.
    1. Study Investigators LIFE, Pahor M, Blair SN, Espeland M, Fielding R, Gill TM, et al. Effects of a physical activity intervention on measures of physical performance: results of the lifestyle interventions and independence for elders pilot (LIFE-P) study. J Gerontol A Biol Sci Med Sci. 2006;61(11):1157–1165. doi: 10.1093/gerona/61.11.1157.
    1. Shumway-Cook A, Horak F. Assessing the influence of sensory interaction of balance. Phys Ther. 1986;66(10):1548–1550. doi: 10.1093/ptj/66.10.1548.
    1. Tiffin J, Asher EJ. The Purdue pegboard; norms and studies of reliability and validity. J Appl Psychol. 1948;32(3):234–247. doi: 10.1037/h0061266.
    1. Desrosiers J, Hébert R, Bravo G, Dutil E. The purdue pegboard test: normative data for people aged 60 and over. Disabil Rehabil. 1995;17(5):217–224. doi: 10.3109/09638289509166638.
    1. Brown M, Sinacore DR, Binder EF, Kohrt WM. Physical and performance measures for the identification of mild to moderate frailty. J Gerontol A Biol Sci Med Sci. 2000;55(6):M350–M355. doi: 10.1093/gerona/55.6.M350.
    1. Bach M. The Freiburg visual acuity test - automatic measurement of visual acuity. Optom Vis Sci. 1996;73(1):49–53. doi: 10.1097/00006324-199601000-00008.
    1. Bach M. The Freiburg visual acuity test-variability unchanged by post-hoc re-analysis. Graefes Arch Clin Exp Ophthalmol. 2007;245(7):965–971. doi: 10.1007/s00417-006-0474-4.
    1. Bell-Krotoski JA, Fess EE, Figarola JH, Hiltz D. Threshold detection and Semmes-Weinstein monofilaments. J Hand Ther. 1995;8(2):155–162. doi: 10.1016/S0894-1130(12)80314-0.
    1. Boyle PA, Buchman AS, Wilson RS, Leurgans SE, Bennett DA. Physical frailty is associated with incident mild cognitive impairment in community-based older persons. J Am Geriatr Soc. 2010;58(2):248–255. doi: 10.1111/j.1532-5415.2009.02671.x.
    1. Brigola AG, Rossetti ES, dos Santos BR, Neri AL, Zazzetta MS, Inouye K, et al. Relationship between cognition and frailty in elderly. Dement Neuropsychol. 2015;9(2):110–119. doi: 10.1590/1980-57642015DN92000005.
    1. Gross AL, Xue QL, Bandeen-Roche K, Fried LP, Varadhan R, McAdams-DeMarco MA, et al. Declines and impairment in executive function predict onset of physical frailty. J Gerontol A Biol Sci Med Sci. 2016;71(12):1624–1630. doi: 10.1093/gerona/glw067.
    1. O’Halloran AM, Finucane C, Savva GM, Robertson IH, Kenny RA. Sustained attention and frailty in the older adult population. J Gerontol B Psychol Sci Soc Sci. 2014;69(2):147–156. doi: 10.1093/geronb/gbt009.
    1. Gloth FM, Walston J, Meyer J, Pearson J. Reliability and validity of the frail elderly functional assessment questionnaire. Am J Phys Med Rehabil. 1995;74(1):45–53. doi: 10.1097/00002060-199501000-00008.
    1. Gloth FM, Scheve AA, Shah S, Ashton R, McKinney R. The frail elderly functional assessment questionnaire: its responsiveness and validity in alternative settings. Arch Phys Med Rehabil. 1999;80(12):1572–1576. doi: 10.1016/S0003-9993(99)90332-5.
    1. Hautzinger M, Bailer M, Hofmeister D, Keller F. Allgemeine Depressionsskala. 2. Göttingen: Hogrefe; 2012.
    1. Radloff LS. The CES-D scale: a self report depression scale for research in the general population. Appl Psychol Meas. 1977;1(3):385–401. doi: 10.1177/014662167700100306.
    1. Ware JE, Sherbourne CD. The MOS 36-ltem short-form health survey (SF-36) Med Care. 1992;30(6):473–483. doi: 10.1097/00005650-199206000-00002.
    1. Brooks R. EuroQol: the current state of play. Health Policy. 1996;37(1):53–72. doi: 10.1016/0168-8510(96)00822-6.
    1. Gauggel S, Peleska B, Bode RK. Relationship between cognitive impairments and rated activity restrictions stroke patients. J Head Trauma Rehabil. 2000;15(1):710–723. doi: 10.1097/00001199-200002000-00009.
    1. Tinetti ME, Richman D, Powell L. Falls efficacy as a measure of fear of falling. J Gerontol. 1990;45(6):P239–P243. doi: 10.1093/geronj/45.6.P239.
    1. McGee M, Jensen GL. Mini nutritional assessment (MNA): research and practice in the elderly. Am J Clin Nutr. 1999;71(1):158. doi: 10.1093/ajcn/71.1.158.
    1. Rochat S, Cumming RG, Blyth F, Creasey H, Handelsman D, Le Couteur DG, et al. Frailty and use of health and community services by community-dwelling older men: the Concord health and ageing in men project. Age Ageing. 2010;39(2):228–233. doi: 10.1093/ageing/afp257.
    1. Sánchez-García S, Sánchez-Arenas R, García-Peña C, Rosas-Carrasco O, Ávila-Funes JA, Ruiz-Arregui L, Juárez-Cedillo T. Frailty among community-dwelling elderly Mexican people: prevalence and association with sociodemographic characteristics, health state and the use of health services. Geriatr Gerontol Int. 2014;14(2):395–402. doi: 10.1111/ggi.12114.
    1. Cesari M, Vellas B, Hsu FC, Newman AB, Doss H, King AC, Manini TM, Church T, Gill TM, Miller ME, Pahor M, for the LIFE Study Group A physical activity intervention to treat the frailty syndrome in older persons - results from the LIFE-P study. J Gerontol A Biol Sci Med Sci. 2015;70(2):216–222. doi: 10.1093/gerona/glu099.
    1. Yamada M, Arai H, Sonoda T, Aoyama T. Community-based exercise program is cost-effective by preventing care and disability in Japanese frail older adults. J Am Med Dir Assoc. 2012;13(6):507–511. doi: 10.1016/j.jamda.2012.04.001.
    1. Kim H, Suzuki T, Kim M, Kojima N, Ota N, Shimotoyodome A, Hase T, Hosoi E, Yoshida H. Effects of exercise and milk fat globule membrane (MFGM) supplementation on body composition, physical function, and hematological parameters in community-dwelling frail Japanese women: a randomized double blind, placebo-controlled, follow-up trial. PLoS One. 2015;10(2):e0116256. doi: 10.1371/journal.pone.0116256.
    1. Kwon J, Yoshida Y, Yoshida H, Kim H, Suzuki T, Lee Y. Effects of a combined physical training and nutrition intervention on physical performance and health-related quality of life in prefrail older women living in the community: A randomized controlled trial. J Am Med Dir Assoc. 2015;16(3):263.e1–263.e2638. doi: 10.1016/j.jamda.2014.12.005.
    1. Ng TP, Feng L, Nyunt MSZ, Feng L, Niti M, Tan BY, Chan G, Khoo SA, Chan SM, Yap P, Yap KB. Nutritional, physical, cognitive, and combination interventions and frailty reversal among older adults: a randomized controlled trial. Am J Med. 2015;128(11):1225–1236. doi: 10.1016/j.amjmed.2015.06.017.
    1. Li CM, Chen CY, Li CY, Wang WD, Wu SC. The effectiveness of a comprehensive geriatric assessment intervention program for frailty in community-dwelling older people: a randomized, controlled trial. Arch Gerontol Geriatr. 2010;50(Suppl 1):S39–S42. doi: 10.1016/S0167-4943(10)70011-X.
    1. Mazya AL, Garvin P, Ekdahl AW. Outpatient comprehensive geriatric assessment: effects on frailty and mortality in old people with multimorbidity and high health care utilization. Aging Clin Exp Res. 2019;31(4):519–525. doi: 10.1007/s40520-018-1004-z.
    1. Chen WT, Chou KH, Liu LK, Lee PL, Lee WJ, Chen LK, Wang PN, Lin CP. Reduced cerebellar gray matter is a neural signature of physical frailty. Hum Brain Mapp. 2015;36(9):3666–3676. doi: 10.1002/hbm.22870.
    1. Ryberg C, Rostrup E, Stegmann MB, Barkhof F, Scheltens P, van Straaten ECW, Fazekas F, Schmidt R, Ferro JM, Baezner H, Erkinjuntti T, Jokinen H, Wahlund LO, O'brien J, Basile AM, Pantoni L, Inzitari D, Waldemar G, LADIS study group Clinical significance of corpus callosum atrophy in a mixed elderly population. Neurobiol Aging. 2007;28(6):955–963. doi: 10.1016/j.neurobiolaging.2006.04.008.
    1. Doba N, Tokuda Y, Goldstein NE, Kushiro T, Hinohara S. A pilot trial to predict frailty syndrome: the Japanese Health Research volunteer Study. Exp Gerontol. 2012;47(8):638–643. doi: 10.1016/j.exger.2012.05.016.
    1. Raji MA, Al Snih S, Ostir GV, Markides KS, Ottenbacher KJ. Cognitive status and future risk of frailty in older Mexican Americans. J Gerontol A Biol Sci Med Sci. 2010;65(11):1228–1234. doi: 10.1093/gerona/glq121.
    1. Park H, Poo MM. Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci. 2013;14(1):7–23. doi: 10.1038/nrn3379.
    1. Schäbitz WR, Steigleder T, Cooper-Kuhn CM, Schwab S, Sommer C, Schneider A, et al. Intravenous brain-derived neurotrophic factor enhances poststroke sensorimotor recovery and stimulates neurogenesis. Stroke. 2007;38(7):2165–2172. doi: 10.1161/STROKEAHA.106.477331.
    1. Walston J, Hadley EC, Ferrucci L, Guralnik JM, Newman AB, Studenski SA, Ershler WB, Harris T, Fried LP. Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/National Institute on Aging research conference on frailty in older adults. J Am Geriatr Soc. 2006;54(6):991–1001. doi: 10.1111/j.1532-5415.2006.00745.x.
    1. Panza F, Lozupone M, Logroscino G. Understanding frailty to predict and prevent dementia. Lancet Neurol. 2019;18(2):133–134. doi: 10.1016/S1474-4422(18)30446-0.

Source: PubMed

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