The multi-domain exercise intervention for memory and brain function in late middle-aged and older adults at risk for Alzheimer's disease: A protocol for Western-Eastern Brain Fitness Integration Training trial

Yu-Kai Chang, Kirk I Erickson, Sarah L Aghjayan, Feng-Tzu Chen, Ruei-Hong Li, Jia-Ru Shih, Shao-Hsi Chang, Chih-Mao Huang, Chien-Heng Chu, Yu-Kai Chang, Kirk I Erickson, Sarah L Aghjayan, Feng-Tzu Chen, Ruei-Hong Li, Jia-Ru Shih, Shao-Hsi Chang, Chih-Mao Huang, Chien-Heng Chu

Abstract

Background: Aging is associated with cognitive decline, increased risk for dementia, and deterioration of brain function. Modifiable lifestyle factors (e.g., exercise, meditation, and social interaction) have been proposed to benefit memory and brain function. However, previous studies have focused on a single exercise modality or a single lifestyle factor. Consequently, the effect of a more comprehensive exercise program that combines multiple exercise modalities and lifestyle factors, as well as examines potential mediators and moderators, on cognitive function and brain health in late middle-aged and older adults remains understudied. This study's primary aim is to examine the effect of a multi-domain exercise intervention on memory and brain function in cognitively healthy late middle-aged and older adults. In addition, we will examine whether apolipoprotein E (ApoE) genotypes, physical fitness (i.e., cardiovascular fitness, body composition, muscular fitness, flexibility, balance, and power), and brain-derived neurotrophic factor (BDNF) moderate and mediate the exercise intervention effects on memory and brain function.

Methods: The Western-Eastern Brain Fitness Integration Training (WE-BFit) is a single-blinded, double-arm, 6-month randomized controlled trial. One hundred cognitively healthy adults, aged 45-70 years, with different risks for Alzheimer's disease (i.e., ApoE genotype) will be recruited and randomized into either a multi-domain exercise group or an online educational course control group. The exercise intervention consists of one 90-min on-site and several online sessions up to 60 min per week for 6 months. Working memory, episodic memory, physical fitness, and BDNF will be assessed before and after the 6-month intervention. The effects of the WE-BFit on memory and brain function will be described and analyzed. We will further examine how ApoE genotype and changes in physical fitness and BDNF affect the effects of the intervention.

Discussion: WE-BFit is designed to improve memory and brain function using a multi-domain exercise intervention. The results will provide insight into the implementation of an exercise intervention with multiple domains to preserve memory and brain function in adults with genetic risk levels for Alzheimer's disease.

Clinical trial registration: ClinicalTrials.gov, identifier: NCT05068271.

Keywords: ApoE gene; BDNF; brain function; fitness; meditation; memory; social interaction.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Chang, Erickson, Aghjayan, Chen, Li, Shih, Chang, Huang and Chu.

Figures

Figure 1
Figure 1
The overall picture of the Western-Eastern Brain Fitness Integration Training (WE-BFit) Trial. ApoE, apolipoprotein E; BDNF, brain-derived neurotrophic factor; PF, physical fitness; exe., exercise.
Figure 2
Figure 2
Study flowchart. ApoE, apolipoprotein E; BDNF, brain-derived neurotrophic factor; fMRI, functional magnetic resonance imaging; rs-fMRI, resting-state functional magnetic resonance imaging.
Figure 3
Figure 3
Experimental timeline. ADay1, ADay2, ADay3, and ADay4, assessment day 1 to assessment day 4, respectively; BDNF, brain-derived neurotrophic factor; fMRI, functional magnetic resonance imaging; MDE, multi-domain exercise; PF, physical fitness assessments; PsySoc, psychosocial measures; rs-fMRI, resting-state functional magnetic resonance imaging.

References

    1. Alzheimer's Association . (2021). 2021 Alzheimer's disease facts and figures. Alzheimers. Dement. 17, 327–406. 10.1002/alz.12328
    1. American College of Sports Medicine . (2018). ACSM's Guidelines for Exercise Testing and Prescription. Philadelphia, PA: Wolters Kluwer.
    1. Baddeley A. (2012). Working memory: theories, models, and controversies. Annu. Rev. Psychol. 63, 1–29. 10.1146/annurev-psych-120710-100422
    1. Basso J. C., Mchale A., Ende V., Oberlin D. J., andSuzuki W. A. (2019). Brief, daily meditation enhances attention, memory, mood, and emotional regulation in non-experienced meditators. Behav. Brain Res. 356, 208–220. 10.1016/j.bbr.2018.08.023
    1. Benarroch E. E. (2015). Brain-derived neurotrophic factor: regulation, effects, and potential clinical relevance. Neurology 84, 1693–1704. 10.1212/WNL.0000000000001507
    1. Berkman L. F., Glass T., Brissette I., Seeman T. E. (2000). From social integration to health: Durkheim in the new millennium. Soc. Sci. Med. 51, 843–857. 10.1016/S0277-9536(00)00065-4
    1. Boots E. A., Schultz S. A., Oh J. M., Larson J., Edwards D., Cook D. B., et al. . (2015). Cardiorespiratory fitness is associated with brain structure, cognition, and mood in a middle-aged cohort at risk for Alzheimer's disease. Brain Imaging Behav. 9, 639–649. 10.1007/s11682-014-9325-9
    1. Borba E. M., Duarte J. A., Bristot G., Scotton E., Camozzato A. L., Chaves M. L. F. (2016). Brain-derived neurotrophic factor serum levels and hippocampal volume in mild cognitive impairment and dementia due to Alzheimer disease. Dement. Geriatr. Cogn. Dis. Extra 6, 559–567. 10.1159/000450601
    1. Bramham C. R., Messaoudi E. (2005). BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis. Prog. Neurobiol. 76, 99–125. 10.1016/j.pneurobio.2005.06.003
    1. Brown K. W., Ryan R. M. (2003). The benefits of being present: mindfulness and its role in psychological well-being. J. Pers. Soc. Psychol. 84, 822–848. 10.1037/0022-3514.84.4.822
    1. Caspersen C. J., Powell K. E., Christenson G. M. (1985). Physical activity, exercise, and physical fitness: Definitions and distinctions for health-related research. Public Health Rep. 100, 126–131.
    1. Castells-Sánchez A., Roig-Coll F., Lamonja-Vicente N., Altés-Magret M., Torán-Monserrat P., Via M., et al. . (2019). Effects and mechanisms of cognitive, aerobic exercise, and combined training on cognition, health, and brain outcomes in physically inactive older adults: the projecte moviment protocol. Front. Aging Neurosci. 11, 216. 10.3389/fnagi.2019.00216
    1. Chai W. J., Abd Hamid A. I., Abdullah J. M. (2018). Working memory from the psychological and neurosciences perspectives: a review. Front. Psychol. 9, 401. 10.3389/fpsyg.2018.00401
    1. Chan J. S. Y., Deng K., Wu J., Yan J. H. (2019). Effects of meditation and mind-body exercises on older adults' cognitive performance: a meta-analysis. Gerontologist 59, e782–e790. 10.1093/geront/gnz022
    1. Chang J.-H., Lin Y.-C., Huang C.-L. (2011). Psychometric properties of the Chinese translation of mindful attention awareness scale (CMAAS). Psychol. Test 58, 235–260. 10.7108/PT.201104.0090
    1. Chang Y. K., Alderman B. L., Chu C. H., Wang C. C., Song T. F., Chen F. T. (2017a). Acute exercise has a general facilitative effect on cognitive function: a combined ERP temporal dynamics and BDNF study. Psychophysiology 54, 289–300. 10.1111/psyp.12784
    1. Chang Y. K., Chu I. H., Liu J. H., Wu C. H., Chu C. H., Yang K. T., et al. . (2017b). Exercise modality is differentially associated with neurocognition in older adults. Neural Plast. 2017, 3480413. 10.1155/2017/3480413
    1. Chang Y. K., Nien Y. H., Chen A. G., Yan J. (2014). Tai Ji Quan, the brain, and cognition in older adults. J. Sport Health. Sci. 3, 36–42. 10.1016/j.jshs.2013.09.003
    1. Chang Y. K., Nien Y. H., Tsai C. L., Etnier J. L. (2010). Physical activity and cognition in older adults: the potential of Tai Chi Chuan. J. Aging Phys. Act. 18, 451–472. 10.1123/japa.18.4.451
    1. Chen F. T., Chen Y. P., Schneider S., Kao S. C., Huang C. M., Chang Y. K. (2019). Effects of exercise modes on neural processing of working memory in late middle-aged adults: An fMRI study. Front. Aging Neurosci. 11, 224. 10.3389/fnagi.2019.00224
    1. Chen F. T., Etnier J. L., Chan K. H., Chiu P. K., Hung T. M., Chang Y. K. (2020a). Effects of exercise training interventions on executive function in older adults: a systematic review and meta-analysis. Sports Med. 50, 1451–1467. 10.1007/s40279-020-01292-x
    1. Chen F. T., Hopman R. J., Huang C. J., Chu C. H., Hillman C. H., Hung T. M., et al. . (2020b). The effect of exercise training on brain structure and function in older adults: a systematic review based on evidence from randomized control trials. J. Clin. Med. 9, 914. 10.3390/jcm9040914
    1. Cole R. C., Hazeltine E., Weng T. B., Wharff C., Dubose L. E., Schmid P., et al. . (2020). Cardiorespiratory fitness and hippocampal volume predict faster episodic associative learning in older adults. Hippocampus 30, 143–155. 10.1002/hipo.23151
    1. Cotier F. A., Zhang R., Lee T. M. C. (2017). A longitudinal study of the effect of short-term meditation training on functional network organization of the aging brain. Sci. Rep. 7, 598. 10.1038/s41598-017-00678-8
    1. Deeny S. P., Poeppel D., Zimmerman J. B., Roth S. M., Brandauer J., Witkowski S., et al. . (2008). Exercise, ApoE, and working memory: MEG and behavioral evidence for benefit of exercise in epsilon4 carriers. Biol. Psychol. 78, 179–187. 10.1016/j.biopsycho.2008.02.007
    1. Dinoff A., Herrmann N., Swardfager W., Liu C. S., Sherman C., Chan S., et al. . (2016). The effect of exercise training on resting concentrations of peripheral brain-derived neurotrophic factor (BDNF): a meta-analysis. PLoS ONE 11, e0163037. 10.1371/journal.pone.0163037
    1. Dougherty R. J., Schultz S. A., Boots E. A., Ellingson L. D., Meyer J. D., Van Riper S., et al. . (2017). Relationships between cardiorespiratory fitness, hippocampal volume, and episodic memory in a population at risk for Alzheimer's disease. Brain Behav. 7, e00625. 10.1002/brb3.625
    1. Erickson K. I., Grove G. A., Burns J. M., Hillman C. H., Kramer A. F., Mcauley E., et al. . (2019). Investigating gains in neurocognition in an intervention trial of exercise (IGNITE): Protocol. Contemp. Clin. Trials 85, 105832. 10.1016/j.cct.2019.105832
    1. Erickson K. I., Prakash R. S., Voss M. W., Chaddock L., Heo S., Mclaren M., et al. . (2010). Brain-derived neurotrophic factor is associated with age-related decline in hippocampal volume. J. Neurosci. 30, 5368–5375. 10.1523/JNEUROSCI.6251-09.2010
    1. Erickson K. I., Voss M. W., Prakash R. S., Basak C., Szabo A., Chaddock L., et al. . (2011). Exercise training increases size of hippocampus and improves memory. Proc. Natl. Acad. Sci. USA. 108, 3017–3022. 10.1073/pnas.1015950108
    1. Evans I. E. M., Martyr A., Collins R., Brayne C., Clare L. (2019). Social isolation and cognitive function in later life: a systematic review and meta-analysis. J. Alzheimers. Dis. 70, S119–S144. 10.3233/JAD-180501
    1. Fissler P., Muller H. P., Kuster O. C., Laptinskaya D., Thurm F., Woll A., et al. . (2017). No evidence that short-term cognitive or physical training programs or lifestyles are related to changes in white matter integrity in older adults at risk of dementia. Front. Hum. Neurosci. 11, 110. 10.3389/fnhum.2017.00110
    1. Fletcher G. F., Balady G. J., Amsterdam E. A., Chaitman B., Eckel R., Fleg J., et al. . (2001). Exercise standards for testing and training: a statement for healthcare professionals from the American Heart Association. Circulation 104, 1694–1740. 10.1161/hc3901.095960
    1. Fox K. C., Nijeboer S., Dixon M. L., Floman J. L., Ellamil M., Rumak S. P., et al. . (2014). Is meditation associated with altered brain structure? A systematic review and meta-analysis of morphometric neuroimaging in meditation practitioners. Neurosci. Biobehav. Rev. 43, 48–73. 10.1016/j.neubiorev.2014.03.016
    1. Freudenberger P., Petrovic K., Sen A., Töglhofer A. M., Fixa A., Hofer E., et al. . (2016). Fitness and cognition in the elderly: the Austrian stroke prevention study. Neurology 86, 418–424. 10.1212/WNL.0000000000002329
    1. Froeliger B., Garland E. L., Kozink R. V., Modlin L. A., Chen N. K., Mcclernon F. J., et al. . (2012). Meditation-state functional connectivity (msFC): strengthening of the dorsal attention network and beyond. Evid. Based Complement. Alternat. Med. 2012, 680407. 10.1155/2012/680407
    1. Gaitán J. M., Moon H. Y., Stremlau M., Dubal D. B., Cook D. B., Okonkwo O. C., et al. . (2021). Effects of aerobic exercise training on systemic biomarkers and cognition in late middle-aged adults at risk for Alzheimer's disease. Front. Endocrinol. 12, 660181. 10.3389/fendo.2021.660181
    1. Gajewski P. D., Falkenstein M. (2018). ERP and behavioral effects of physical and cognitive training on working memory in aging: a randomized controlled study. Neural Plast. 2018, 3454835. 10.1155/2018/3454835
    1. Gallant S. N. (2016). Mindfulness meditation practice and executive functioning: breaking down the benefit. Conscious. Cogn. 40, 116–130. 10.1016/j.concog.2016.01.005
    1. Gellish R. L., Goslin B. R., Olson R. E., Mcdonald A., Russi G. D., Moudgil V. K. (2007). Longitudinal modeling of the relationship between age and maximal heart rate. Med. Sci. Sports Exerc. 39, 822–829. 10.1097/mss.0b013e31803349c6
    1. Golding L. A., Myers C. R., Sinning W. E. (1989). The Y's Way to Physical Fitness. Champaign, IL: Human Kinetics Publishers.
    1. Gutierrez-Garralda J. M., Hernandez-Castillo C. R., Barrios F. A., Pasaye E. H., Fernandez-Ruiz J. (2014). Neural correlates of spatial working memory manipulation in a sequential Vernier discrimination task. Neuroreport 25, 1418–1423. 10.1097/WNR.0000000000000280
    1. Hamer M., Chida Y. (2009). Physical activity and risk of neurodegenerative disease: a systematic review of prospective evidence. Psychol. Med. 39, 3–11. 10.1017/S0033291708003681
    1. Hayes S. M., Forman D. E., Verfaellie M. (2016). Cardiorespiratory fitness is associated with cognitive performance in older but not younger adults. J. Gerontol. B Psychol. Sci. Soc. Sci. 71, 474–482. 10.1093/geronb/gbu167
    1. Heinze K., Cumming J., Dosanjh A., Palin S., Poulton S., Bagshaw A. P., et al. . (2020). Neurobiological evidence of longer-term physical activity interventions on mental health outcomes and cognition in young people: a systematic review of randomised controlled trials. Neurosci. Biobehav. Rev. 120, 431–441. 10.1016/j.neubiorev.2020.10.014
    1. Hong C. J., Liu T. Y., Liu H. C., Wang S. J., Fuh J. L., Chi C. W., et al. . (1996). Epsilon 4 allele of apolipoprotein E increases risk of Alzheimer's disease in a Chinese population. Neurology 46, 1749–1751. 10.1212/WNL.46.6.1749
    1. Huo L., Li R., Wang P., Zheng Z., Li J. (2018). The default mode network supports episodic memory in cognitively unimpaired elderly individuals: different contributions to immediate recall and delayed recall. Front. Aging Neurosci. 10, 6. 10.3389/fnagi.2018.00006
    1. Kelly M. E., Duff H., Kelly S., Mchugh Power J. E., Brennan S., Lawlor B. A., et al. . (2017). The impact of social activities, social networks, social support and social relationships on the cognitive functioning of healthy older adults: a systematic review. Syst. Rev. 6, 259. 10.1186/s13643-017-0632-2
    1. Kirova A. M., Bays R. B., Lagalwar S. (2015). Working memory and executive function decline across normal aging, mild cognitive impairment, and Alzheimer's disease. Biomed Res. Int. 2015, 748212. 10.1155/2015/748212
    1. Klusmann V., Evers A., Schwarzer R., Schlattmann P., Reischies F. M., Heuser I., et al. . (2010). Complex mental and physical activity in older women and cognitive performance: a 6-month randomized controlled trial. J. Gerontol. A Biol. Sci. Med. Sci. 65, 680–688. 10.1093/gerona/glq053
    1. Kramer A. F., Colcombe S. (2018). Fitness effects on the cognitive function of older adults: a meta-analytic study-revisited. Perspect. Psychol. Sci. 13, 213–217. 10.1177/1745691617707316
    1. Levi U., Rosenstreich E. (2019). Mindfulness and memory: a review of findings and a potential model. J. Cogn. Enhanc. 3, 302–314. 10.1007/s41465-018-0099-7
    1. Li L., Men W. W., Chang Y. K., Fan M. X., Ji L., Wei G. X. (2014). Acute aerobic exercise increases cortical activity during working memory: a functional MRI study in female college students. PLoS ONE 9, e99222. 10.1371/journal.pone.0099222
    1. Li X., Wang Y., Wang W., Huang W., Chen K., Xu K., et al. . (2020). Age-related decline in the topological efficiency of the brain structural connectome and cognitive aging. Cereb. Cortex. 30:4651–4661. 10.1093/cercor/bhaa066
    1. Lim C. Y., In J. (2019). Randomization in clinical studies. Korean J. Anesthesiol. 72, 221–232. 10.4097/kja.19049
    1. Linde K., Alfermann D. (2014). Single versus combined cognitive and physical activity effects on fluid cognitive abilities of healthy older adults: a 4-month randomized controlled trial with follow-up. J. Aging Phys. Act. 22, 302–313. 10.1123/JAPA.2012-0149
    1. Liu C. C., Liu C. C., Kanekiyo T., Xu H., Bu G. (2013). Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat. Rev. Neurol. 9, 106–118. 10.1038/nrneurol.2012.263
    1. Liu C. Y., Lu C. H., Yu S., Yang Y. Y. (1998). Correlations between scores on Chinese versions of long and short forms of the Geriatric Depression Scale among elderly Chinese. Psychol. Rep. 82, 211–214. 10.2466/pr0.1998.82.1.211
    1. Livingston G., Huntley J., Sommerlad A., Ames D., Ballard C., Banerjee S., et al. . (2020). Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet 396, 413–446. 10.1016/S0140-6736(20)30367-6
    1. Lommatzsch M., Zingler D., Schuhbaeck K., Schloetcke K., Zingler C., Schuff-Werner P., et al. . (2005). The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol. Aging 26, 115–123. 10.1016/j.neurobiolaging.2004.03.002
    1. Martins C. A., Oulhaj A., De Jager C. A., Williams J. H. (2005). ApoE alleles predict the rate of cognitive decline in Alzheimer disease: a nonlinear model. Neurology 65, 1888–1893. 10.1212/01.wnl.0000188871.74093.12
    1. Mehta D., Jackson R., Paul G., Shi J., Sabbagh M. (2017). Why do trials for Alzheimer's disease drugs keep failing? A discontinued drug perspective for 2010-2015. Expert. Opin. Investig. Drugs 26, 735–739. 10.1080/13543784.2017.1323868
    1. Miranda M., Morici J. F., Zanoni M. B., Bekinschtein P. (2019). Brain-derived neurotrophic factor: a key molecule for memory in the healthy and the pathological brain. Front. Cell. Neurosci. 13, 363. 10.3389/fncel.2019.00363
    1. Mrazek M. D., Franklin M. S., Phillips D. T., Baird B., Schooler J. W. (2013). Mindfulness training improves working memory capacity and GRE performance while reducing mind wandering. Psychol. Sci. 24, 776–781. 10.1177/0956797612459659
    1. Murer M. G., Yan Q., Raisman-Vozari R. (2001). Brain-derived neurotrophic factor in the control human brain, and in Alzheimer's disease and Parkinson's disease. Prog. Neurobiol. 63, 71–124. 10.1016/S0301-0082(00)00014-9
    1. Netz Y. (2019). Is there a preferred mode of exercise for cognition enhancement in older age? A narrative review. Front. Med. 6, 57. 10.3389/fmed.2019.00057
    1. Nien J. T., Wu C. H., Yang K. T., Cho Y. M., Chu C. H., Chang Y. K., et al. . (2020). Mindfulness training enhances endurance performance and executive functions in athletes: an event-related potential study. Neural Plast. 2020, 8213710. 10.1155/2020/8213710
    1. Northey J. M., Cherbuin N., Pumpa K. L., Smee D. J., Rattray B. (2018). Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis. Br. J. Sports Med. 52, 154–160. 10.1136/bjsports-2016-096587
    1. Nyhus E., Engel W. A., Pitfield T. D., Vakkur I. M. W. (2019). Increases in theta oscillatory activity during episodic memory retrieval following mindfulness meditation training. Front. Hum. Neurosci. 13, 311–311. 10.3389/fnhum.2019.00311
    1. Penninkilampi R., Casey A. N., Singh M. F., Brodaty H. (2018). The association between social engagement, loneliness, and risk of dementia: a systematic review and meta-analysis. J. Alzheimers. Dis. 66, 1619–1633. 10.3233/JAD-180439
    1. Piccoli T., Valente G., Linden D. E., Re M., Esposito F., Sack A. T., et al. . (2015). The default mode network and the working memory network are not anti-correlated during all phases of a working memory task. PLoS ONE 10, e0123354. 10.1371/journal.pone.0123354
    1. Ragland J. D., Ranganath C., Barch D. M., Gold J. M., Haley B., Macdonald A. W. 3rd, et al. . (2012). Relational and item-specific encoding (RISE): task development and psychometric characteristics. Schizophr. Bull. 38, 114–124. 10.1093/schbul/sbr146
    1. Ragland J. D., Ranganath C., Harms M. P., Barch D. M., Gold J. M., Layher E., et al. . (2015). Functional and neuroanatomic specificity of episodic memory dysfunction in schizophrenia: a functional magnetic resonance imaging study of the relational and item-specific encoding task. JAMA Psychiatry 72, 909–916. 10.1001/jamapsychiatry.2015.0276
    1. Rathore A., Lom B. (2017). The effects of chronic and acute physical activity on working memory performance in healthy participants: a systematic review with meta-analysis of randomized controlled trials. Syst. Rev. 6, 124. 10.1186/s13643-017-0514-7
    1. Roberts L. R., Schuh H., Sherzai D., Belliard J. C., Montgomery S. B. (2015). Exploring experiences and perceptions of aging and cognitive decline across diverse racial and ethnic groups. Gerontol. Geriatr. Med. 1, 2333721415596101. 10.1177/2333721415596101
    1. Robiner W. N. (2005). Enhancing adherence in clinical research. Contemp. Clin. Trials 26, 59–77. 10.1016/j.cct.2004.11.015
    1. Saito T., Murata C., Saito M., Takeda T., Kondo K. (2018). Influence of social relationship domains and their combinations on incident dementia: a prospective cohort study. J. Epidemiol. Community Health 72, 7–12. 10.1136/jech-2017-209811
    1. Salthouse T. A. (2019). Trajectories of normal cognitive aging. Psychol. Aging 34, 17–24. 10.1037/pag0000288
    1. Sheikh J. I., Yesavage J. A. (1986). Geriatric Depression Scale (GDS): recent evidence and development of a shorter version. Clin. Gerontol. 5, 165–173. 10.1300/J018v05n01_09
    1. Smith J. C., Nielson K. A., Woodard J. L., Seidenberg M., Durgerian S., Antuono P., et al. . (2011). Interactive effects of physical activity and ApoE-ε4 on BOLD semantic memory activation in healthy elders. NeuroImage 54, 635–644. 10.1016/j.neuroimage.2010.07.070
    1. Sommerlad A., Sabia S., Singh-Manoux A., Lewis G., Livingston G. (2019). Association of social contact with dementia and cognition: 28-year follow-up of the Whitehall II cohort study. PLoS Med. 16, e1002862. 10.1371/journal.pmed.1002862
    1. Song J. H., Yu J. T., Tan L. (2015). Brain-derived neurotrophic factor in Alzheimer's disease: risk, mechanisms, and therapy. Mol. Neurobiol. 52, 1477–1493. 10.1007/s12035-014-8958-4
    1. Sundström A., Adolfsson A. N., Nordin M., Adolfsson R. (2020). Loneliness increases the risk of all-cause dementia and Alzheimer's disease. J. Gerontol. B Psychol. Sci. Soc. Sci. 75, 919–926. 10.1093/geronb/gbz139
    1. Sungkarat S., Boripuntakul S., Kumfu S., Lord S. R., Chattipakorn N. (2018). Tai Chi improves cognition and plasma BDNF in older adults with mild cognitive impairment: a randomized controlled trial. Neurorehabil. Neural Repair 32, 142–149. 10.1177/1545968317753682
    1. Szuhany K. L., Bugatti M., Otto M. W. (2015). A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. J. Psychiatr. Res. 60, 56–64. 10.1016/j.jpsychires.2014.10.003
    1. Tao J., Liu J., Egorova N., Chen X., Sun S., Xue X., et al. . (2016). Increased hippocampus-medial prefrontal cortex resting-state functional connectivity and memory function after Tai Chi Chuan practice in elder adults. Front. Aging Neurosci. 8, 25. 10.3389/fnagi.2016.00025
    1. Toepper M., Markowitsch H. J., Gebhardt H., Beblo T., Bauer E., Woermann F. G., et al. . (2014). The impact of age on prefrontal cortex integrity during spatial working memory retrieval. Neuropsychologia 59, 157–168. 10.1016/j.neuropsychologia.2014.04.020
    1. Tomporowski P., Pesce C. (2019). Exercise, sports, and performance arts benefit cognition via a common process. Psychol. Bull. 145, 929–951. 10.1037/bul0000200
    1. Tsai P.-S., Wang S.-Y., Wang M.-Y., Su C.-T., Yang T.-T., Huang C.-J., et al. . (2005). Psychometric evaluation of the Chinese Version of the Pittsburgh Sleep Quality Index (CPSQI) in primary insomnia and control subjects. Qual. Life Res. 14, 1943–1952. 10.1007/s11136-005-4346-x
    1. Tulving E. (2002). Episodic memory: from mind to brain. Annu. Rev. Psychol. 53, 1–25. 10.1146/annurev.psych.53.100901.135114
    1. United Nations . (2019). “World Population Ageing 2019: Highlights”, (ed.) P.D. Department of Economic and Social Affairs. New York, NY: United Nations. 10.18356/9df3caed-en
    1. Valenzuela P. L., Castillo-García A., Morales J. S., De La Villa P., Hampel H., Emanuele E., et al. . (2020). Exercise benefits on Alzheimer's disease: State-of-the-science. Ageing Res. Rev. 62, 101108. 10.1016/j.arr.2020.101108
    1. Van Vugt M. K., Hitchcock P., Shahar B., Britton W. (2012). The effects of mindfulness-based cognitive therapy on affective memory recall dynamics in depression: a mechanistic model of rumination. Front. Hum. Neurosci. 6, 257. 10.3389/fnhum.2012.00257
    1. Voelcker-Rehage C., Godde B., Staudinger U. M. (2010). Physical and motor fitness are both related to cognition in old age. Eur. J. Neurosci. 31, 167–176. 10.1111/j.1460-9568.2009.07014.x
    1. Wang P. N., Hong C. J., Lin K. N., Liu H. C., Chen W. T. (2011). ApoE ε4 increases the risk of progression from amnestic mild cognitive impairment to Alzheimer's disease among ethnic Chinese in Taiwan. J. Neurol. Neurosurg. Psychiatry 82, 165–169. 10.1136/jnnp.2010.209122
    1. Ward A., Crean S., Mercaldi C. J., Collins J. M., Boyd D., Cook M. N., et al. . (2012). Prevalence of apolipoprotein E4 genotype and homozygotes (ApoE e4/4) among patients diagnosed with Alzheimer's disease: a systematic review and meta-analysis. Neuroepidemiology 38, 1–17. 10.1159/000334607
    1. Yang S.-W., Kim T.-H., Choi H.-M. (2018). The reproducibility and validity verification for body composition measuring devices using bioelectrical impedance analysis in Korean adults. J. Exerc. Rehabil. 14, 621–627. 10.12965/jer.1836284.142
    1. Yao G., Chien C.-C., Chang Y.-C., Lin W.-L., Wang J.-D., Hsieh C.-L., et al. . (2017). Development and validation of the WHOQOL-OLD in Taiwan. Taiwan J. Public Health 36, 239–258. 10.6288/TJPH201736106018
    1. Ye M., Wang L., Xiong J., Zheng G. (2021). The effect of mind–body exercise on memory in older adults: a systematic review and meta-analysis. Aging Clin. Exp. Res. 33, 1163–1173. 10.1007/s40520-020-01557-5
    1. Yin J. J., Liao L. M., Luo D. X., Xu K., Ma S. H., Wang Z. X., et al. . (2013). Spatial working memory impairment in subclinical hypothyroidism: an FMRI study. Neuroendocrinology 97, 260–270. 10.1159/000343201
    1. Yonelinas A. P., Ranganath C., Ekstrom A. D., Wiltgen B. J. (2019). A contextual binding theory of episodic memory: systems consolidation reconsidered. Nat. Rev. Neurosci. 20, 364–375. 10.1038/s41583-019-0150-4
    1. Zou L., Loprinzi P. D., Yeung A. S., Zeng N., Huang T. (2019). The beneficial effects of mind-body exercises for people with mild cognitive impairment: a systematic review with meta-analysis. Arch. Phys. Med. Rehabil. 100, 1556–1573. 10.1016/j.apmr.2019.03.009

Source: PubMed

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