Cognitive impairment, dementia and sarcopenia in geriatric patients - is there a relationship?

Currently, demographic aging of the population continues, and the frequency of various age-associated pathologies is increasing. Sarcopenia and cognitive impairment are often found in patients of older age groups, leading to the development of frailty, decreased quality of life, disability and premature death. There is an association between sarcopenia, frailty and cognitive impairment. Cognitive and physical frailty are interrelated: cognitive problems and dementia are more common in people with frailty, and people with cognitive impairment are more likely to become frail. Both frailty and cognitive decline share common pathogenesis mechanisms. The role of mediators of muscle origin (myokines) in the occurrence of cross-talk between muscles and brain is known. Sufficient physical activity plays an important role in maintaining not only skeletal muscles, but also cognitive functions. On the contrary, physical inactivity is one of the most important risk factors for sarcopenia, frailty and dementia. However, the relationship between sarcopenia and cognitive decline and the underlying mechanisms remain to be addressed. This is the focus of this literature review.

cognitive impairment, dementia, Alzheimer’s disease, sarcopenia, frailty, muscle protein synthesis, physical inactivity, neurological complications, ageing

1. Cruz-Jentoft A.J., Bahat G., Bauer J. et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(4):601. doi: 10.1093/ageing/afz046

2. Han D. S., Wu W. T., Hsu P. C. et al. Sarcopenia Is Associated With Increased Risks of Rotator Cuff Tendon Diseases Among Community-Dwelling Elders: A Cross-Sectional Quantitative Ultrasound Study. Front Med (Lausanne). 2021;8:630009. doi: 10.3389/fmed.2021.630009

3. Avgerinou C. Sarcopenia: why it matters in general practice. Br J Gen Pract. 2020;70(693):200-201. doi: 10.3399/bjgp20X709253

4. Delmonico M. J., Beck D. T. The Current Understanding of Sarcopenia: Emerging Tools and Interventional Possibilities. Am J Lifestyle Med. 2016;11(2):167-181. doi: 10.1177/1559827615594343

5. Kurmaev D. P., Bulgakova S. V., Zakharova N. O. What is primary: frailty or sarcopenia? (literature review) Advances in gerontology. 2021;34(6):848-856. (In Russ.) doi: 10.34922/AE.2021.34.6.005.@@ Курмаев Д. П., Булгакова С. В., Захарова Н. О. Что первично: старческая астения или саркопения? (обзор литературы). Успехи геронтологии. 2021;34(6): 848-856. doi: 10.34922/AE.2021.34.6.005. []

6. Tkacheva O. N., Kotovskaya Yu.V., Runikhina N. K. et al. Clinical guidelines on frailty.Russian Journal of Geriatric Medicine. 2020;(1):11-46. (In Russ.) doi: 10.37586/2686-8636-1-2020-11-46.@@ Ткачева О. Н., Котовская Ю. В., Рунихина Н. К. и др. Клинические рекомендации «Старческая астения». Российский журнал гериатрической медицины. 2020;(1):11-46. doi: 10.37586/2686-8636-1-2020-11-46.

7. García-Llorente A.M., Casimiro-Andújar A.J., Linhares D. G. et al. Multidomain interventions for sarcopenia and cognitive flexibility in older adults for promoting healthy aging: a systematic review and meta-analysis of randomized controlled trials. Aging Clin Exp Res. 2024;36(1):47. doi: 10.1007/s40520-024-02700-2

8. Kurmaev D. P., Bulgakova S. V., Treneva E. V. Sarcopenic obesity - a current problem of modern geriatrics.Russian Journal of Geriatric Medicine. 2022;(4):228-235. (In Russ.) doi: 10.37586/2686-8636-4-2022-228-235.@@ Курмаев Д. П., Булгакова С. В., Тренева Е. В. Саркопеническое ожирение - актуальная проблема современной гериатрии. Российский журнал гериатрической медицины. 2022;(4):228-235. doi: 10.37586/2686-8636-4-2022-228-235.

9. Berns S. A., Sheptulina A. F., Mamutova E. M. et al. Sarcopenic obesity: epidemiology, pathogenesis and diagnostic criteria. Cardiovascular Therapy and Prevention. 2023;22(6):3576. (In Russ.) doi: 10.15829/1728-8800-2023-3576.@@ Бернс С. А., Шептулина А. Ф., Мамутова Э. М. и др. Саркопеническое ожирение: эпидемиология, патогенез и особенности диагностики. Кардиоваскулярная терапия и профилактика. 2023;22(6):3576. doi: 10.15829/1728-8800-2023-3576.

10. Shirolapov I. V., Zakharov A. V., Smirnova D. A. et al. The Role of the Glymphatic Clearance System in the Mechanisms of the Interactions of the Sleep-Waking Cycle and the Development of Neurodegenerative Processes. Neuroscience and Behavioral Physiology. 2024;54(2):199-204. doi: 10.1007/s11055-024-01585-y.

11. Shirolapov I. V., Zakharov A. V., Smirnova D. A. et al. The significance of the glymphatic pathway in the relationship between the sleep - wake cycle and neurodegenerative diseases. S. S. Korsakov Journal of Neurology and Psychiatry. 2023;123(9):31-36. (In Russ.) doi: 10.17116/jnevro202312309131.@@ Широлапов И. В., Захаров А. В., Смирнова Д. А. и др. Роль глимфатического клиренса в механизмах взаимосвязи цикла «сон - бодрствование» и развития нейродегенеративных процессов. Журнал неврологии и психиатрии им. С. С. Корсакова. 2023;123(9):31-36. doi: 10.17116/jnevro202312309131.

12. Hull R., Martin R. C., Beier M. E. et al. Executive function in older adults: a structural equation modeling approach. Neuropsychology. 2008;22(4):508-522. doi: 10.1037/0894-4105.22.4.508.

13. Halil M., Cemal Kizilarslanoglu M., Emin Kuyumcu M. et al. Cognitive aspects of frailty: mechanisms behind the link between frailty and cognitive impairment. J Nutr Health Aging. 2015;19(3):276-283. doi: 10.1007/s12603-014-0535-z.

14. De la Rosa A., Olaso-Gonzalez G., Arc-Chagnaud C. et al. Physical exercise in the prevention and treatment of Alzheimer’s disease. J Sport Health Sci. 2020;9(5):394-404. doi: 10.1016/j.jshs.2020.01.004.

15. Gonzalez-Freire M., de Cabo R., Studenski S. A., Ferrucci L. The neuromuscular junction: Aging at the crossroad between nerves and muscle. Front. Aging Neurosci. 2014;6:208. doi: 10.3389/fnagi.2014.00208.

16. Pratt J., De Vito G., Narici M., Boreham C. Neuromuscular junction aging: A role for biomarkers and exercise. J. Gerontol. A Biol. Sci. Med. Sci. 2021;76:576-585. doi: 10.1093/gerona/glaa207.

17. Arosio B., Calvani R., Ferri E. et al. Sarcopenia and Cognitive Decline in Older Adults: Targeting the Muscle-Brain Axis. Nutrients. 2023 Apr 12;15(8):1853. doi: 10.3390/nu15081853.

18. Calvani R., Picca A., Marini F. et al. Identification of biomarkers for physical frailty and sarcopenia through a new multi-marker approach: Results from the BIOSPHERE study. GeroScience. 2020;43:727-740. doi: 10.1007/s11357-020-00197-x.

19. Beeri M. S., Leugrans S. E., Delbono O. et al. Sarcopenia is associated with incident Alzheimer’s dementia, mild cognitive impairment, and cognitive decline. J Am Geriatr Soc. 2021;69(7):1826-1835. doi: 10.1111/jgs.17206.

20. Scisciola L., Fontanella R. A., Surina. et al. Sarcopenia and Cognitive Function: Role of Myokines in Muscle Brain Cross-Talk. Life (Basel). 2021;11(2):173. doi: 10.3390/life11020173.

21. Dost F. S., Ates Bulut E., Dokuzlar O. et al. Sarcopenia is as common in older patients with dementia with Lewy bodies as it is in those with Alzheimer’s disease. Geriatr Gerontol Int. 2022;22(5):418-424. doi: 10.1111/ggi.14383.

22. Raleigh S. M., Orchard K. J.A. Sarcopenia as a Risk Factor for Alzheimer’s Disease: Genetic and Epigenetic Perspectives. Genes (Basel). 2024;15(5):561. doi: 10.3390/genes15050561.

23. Nishii K., Aizu N., Yamada K. Review of the health-promoting effects of exercise and the involvement of myokines. Fujita Med J. 2023 Aug;9(3):171-178. doi: 10.20407/fmj.2022-020.

24. Castro R., Taetzsch T., Vaughan S. K. et al. Specific labeling of synaptic schwann cells reveals unique cellular and molecular features. eLife. 2020;9: e56935. doi: 10.7554/eLife.56935.

25. Sugiura Y., Lin W. Neuron-glia interactions: The roles of Schwann cells in neuromuscular synapse formation and function. Biosci. Rep. 2011;31:295-302. doi: 10.1042/BSR20100107.

26. Casati M., Costa A. S., Capitanio D. et al. The biological foundations of sarcopenia: Established and promising markers. Front. Med. 2019;6:184. doi: 10.3389/fmed.2019.00184.

27. Landi F., Calvani R., Lorenzi M. et al. Serum levels of C-terminal agrin fragment (CAF) are associated with sarcopenia in older multimorbid community-dwellers: Results from the ilSIRENTE study. Exp Gerontol. 2016;79:31-36. doi: 10.1016/j.exger.2016.03.012.

28. Sartori R., Romanello V., Sandri M. Mechanisms of muscle atrophy and hypertrophy: Implications in health and disease. Nat.Commun. 2021;12:330. doi: 10.1038/s41467-020-20123-1.

29. Vainshtein A., Sandri M. Signaling pathways that control muscle mass.Int. J. Mol. Sci. 2020;21:4759. doi: 10.3390/ijms21134759.

30. Ham D. J., Börsch A., Lin S. et al. The neuromuscular junction is a focal point of mTORC1 signaling in sarcopenia. Nat.Commun. 2020;11:4510. doi: 10.1038/s41467-020-18140-1.

31. Baraldo M., Geremia A., Pirazzini M. et al. Skeletal muscle mTORC1 regulates neuromuscular junction stability. J. Cachexia Sarcopenia Muscle. 2020;11:208-225. doi: 10.1002/jcsm.12496.

32. Coelho-Junior H.J., Picca A., Calvani R. et al. If my muscle could talk: Myokines as a biomarker of frailty. Exp. Gerontol. 2019;127:110715. doi: 10.1016/j.exger.2019.110715.

33. Moon H. Y., Becke A., Berron D. et al.Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function. Cell Metab. 2016;24(2):332-340. doi: 10.1016/j.cmet.2016.05.025.

34. Sartori C. R., Vieira A. S., Ferrari E. M. et al. The antidepressive effect of the physical exercise correlates with increased levels of mature BDNF, and proBDNF proteolytic cleavage-related genes, p11 and tPA. Neuroscience. 2011;180:9-18. doi: 10.1016/j.neuroscience.2011.02.055.

35. Nagase T., Tohda C. Skeletal muscle atrophy-induced hemopexin accelerates onset of cognitive impairment in Alzheimer’s disease. J Cachexia Sarcopenia Muscle. 2021;12(6):2199-2210. doi: 10.1002/jcsm.12830.

36. Huang Y., Mahley R. W. Apolipoprotein E: structure and function in lipid metabolism, neurobiology, and Alzheimer’s diseases. Neurobiol Dis. 2014;72 Pt A:3-12. doi: 10.1016/j.nbd.2014.08.025.

37. Di Battista A. M., Heinsinger N. M., Rebeck G. W. Alzheimer’s Disease Genetic Risk Factor APOE-ε4 Also Affects Normal Brain Function. Curr Alzheimer Res. 2016;13(11):1200-1207. doi: 10.2174/1567205013666160401115127.

38. Dalle S., Rossmeislova L., Koppo K. The Role of Inflammation in Age-Related Sarcopenia. Front Physiol. 2017;8:1045. doi: 10.3389/fphys.2017.01045.

39. Doi T., Shimada H., Makizako H. et al. Apolipoprotein E genotype and physical function among older people with mild cognitive impairment. Geriatr Gerontol Int. 2015;15(4):422-427. doi: 10.1111/ggi.12291.

40. Boyle P. A., Buchman A. S., Wilson R. S. et al. Association of muscle strength with the risk of Alzheimer disease and the rate of cognitive decline in community-dwelling older persons. Arch Neurol. 2009;66(11):1339-1344. doi: 10.1001/archneurol.2009.240.

41. Cabett Cipolli G., Sanches Yassuda M., Aprahamian I. Sarcopenia Is Associated with Cognitive Impairment in Older Adults: A Systematic Review and Meta-Analysis. J Nutr Health Aging. 2019;23(6):525-531. doi: 10.1007/s12603-019-1188-8.

42. Peng T. C., Chen W. L., Wu L. W. et al. Sarcopenia and cognitive impairment: A systematic review and meta-analysis. Clin Nutr. 2020;39(9):2695-2701. doi: 10.1016/j.clnu.2019.12.014.

43. Chen W. L., Peng T. C., Sun Y. S. et al. Examining the Association Between Quadriceps Strength and Cognitive Performance in the Elderly. Medicine (Baltimore). 2015;94(32): e1335. doi: 10.1097/MD.0000000000001335.

44. Cai Z., Wang X., Wang Q. Does muscle strength predict working memory? A cross-sectional fNIRS study in older adults. Front Aging Neurosci. 2023;15:1243283. doi: 10.3389/fnagi.2023.1243283.

45. Ogawa Y., Kaneko Y., Sato T. et al. Sarcopenia and Muscle Functions at Various Stages of Alzheimer Disease. Front Neurol. 2018;9:710. doi: 10.3389/fneur.2018.00710.

46. Liu S. W., Li M., Zhu J. T. et al. [Correlation of muscle strength with cognitive function and medial temporal lobe atrophy in patients with mild to moderate Alzheimer’s disease]. Zhonghua Yi Xue Za Zhi. 2022;102(35):2786-2792. Chinese. doi: 10.3760/cma.j.cn112137-20220406-00715.

47. Amini N., Ibn Hach M., Lapauw L. et al. Meta-analysis on the interrelationship between sarcopenia and mild cognitive impairment, Alzheimer’s disease and other forms of dementia. J Cachexia Sarcopenia Muscle. 2024. doi: 10.1002/jcsm.13485.

48. Duchowny K. A., Ackley S. F., Brenowitz W. D. et al. Associations Between Handgrip Strength and Dementia Risk, Cognition, and Neuroimaging Outcomes in the UK Biobank Cohort Study. JAMA Netw Open. 2022;5(6): e2218314. doi: 10.1001/jamanetworkopen.2022.18314.

49. Gurholt T. P., Borda M. G., Parker N. et al. Linking sarcopenia, brain structure and cognitive performance: a large-scale UK Biobank study. Brain Commun. 2024;6(2): fcae083. doi: 10.1093/braincomms/fcae083.

50. Ye C., Kong L., Wang Y. et al. Causal associations of sarcopenia-related traits with cardiometabolic disease and Alzheimer’s disease and the mediating role of insulin resistance: A Mendelian randomization study. Aging Cell. 2023;22(9): e13923. doi: 10.1111/acel.13923.

51. Sun M., Lu Z., Chen W. M., Wu S. Y., Zhang J. Sarcopenia and diabetes-induced dementia risk. Brain Commun. 2023;6(1): fcad347. doi: 10.1093/braincomms/fcad347.

52. Mignardot J. B., Beauchet O., Annweiler C. et al. Postural sway, falls, and cognitive status: a cross-sectional study among older adults. J Alzheimers Dis. 2014;41(2):431-439. doi: 10.3233/JAD-132657.

53. Gago M. F., Fernandes V., Ferreira J. et al. Postural stability analysis with inertial measurement units in Alzheimer’s disease. Dement Geriatr Cogn Dis Extra. 2014;4(1):22-30. doi: 10.1159/000357472.

54. Tsutsumimoto K., Doi T., Makizako H. et al. Cognitive Frailty is Associated with Fall-Related Fracture among Older People. J Nutr Health Aging. 2018;22(10):1216-1220. doi: 10.1007/s12603-018-1131-4.

55. Özkal Ö., Kara M., Topuz S. et al. Assessment of core and lower limb muscles for static/dynamic balance in the older people: An ultrasonographic study. Age Ageing. 2019;48(6):881-887. doi: 10.1093/ageing/afz079.

56. Johansson J., Jarocka E., Westling G. et al. Predicting incident falls: Relationship between postural sway and limits of stability in older adults. Hum Mov Sci. 2019;66:117-123. doi: 10.1016/j.humov.2019.04.004.

57. Yoon B., Choi S. H., Jeong J. H. et al. Balance and Mobility Performance Along the Alzheimer’s Disease Spectrum. J Alzheimers Dis. 2020;73(2):633-644. doi: 10.3233/JAD-190601.

58. Güner Oytun M., Topuz S., Baş A. O. et al. Relationships of Fall Risk With Frailty, Sarcopenia, and Balance Disturbances in Mild-to-Moderate Alzheimer’s Disease. J Clin Neurol. 2023;19(3):251-259. doi: 10.3988/jcn.2022.0219.

59. Severinsen M. C.K., Pedersen B. K. Muscle-Organ Crosstalk: The Emerging Roles of Myokines. Endocr. Rev. 2020;41:594-609. doi: 10.1210/endrev/bnaa016.

60. Pedersen B. K. Physical activity and muscle-brain cross-talk. Nat. Rev. Endocrinol. 2019;15:383-392. doi: 10.1038/s41574-019-0174-x.

61. Kim S., Choi J. Y., Moon S. et al. Roles of myokines in exercise-induced improvement of neuropsychiatric function. Pflugers Arch. 2019;471(3):491-505. doi: 10.1007/s00424-019-02253-8.

62. Voss M. W., Erickson K. I., Prakash R. S. et al. Neurobiological markers of exercise-related brain plasticity in older adults. Brain Behav Immun. 2013;28:90-99. doi: 10.1016/j.bbi.2012.10.021.

63. Vreugdenhil A., Cannell J., Davies A., Razay G. A community-based exercise programme to improve functional ability in people with Alzheimer’s disease: a randomized controlled trial. Scand J Caring Sci. 2012;26(1):12-19. doi: 10.1111/j.1471-6712.2011.00895.x.

64. Mokhtarzade M., Motl R., Negaresh R. et al. Exercise-induced changes in neurotrophic factors and markers of blood-brain barrier permeability are moderated by weight status in multiple sclerosis. Neuropeptides. 2018;70:93-100. doi: 10.1016/j.npep.2018.05.010.

65. Adcock M., Fankhauser M., Post J. et al. Effects of an In-home Multicomponent Exergame Training on Physical Functions, Cognition, and Brain Volume of Older Adults: A Randomized Controlled Trial. Front Med (Lausanne). 2020;6:321. doi: 10.3389/fmed.2019.00321.

66. Jones L., Ekkekakis P. Affect and prefrontal hemodynamics during exercise under immersive audiovisual stimulation: Improving the experience of exercise for overweight adults. J Sport Health Sci. 2019;8(4):325-338. doi: 10.1016/j.jshs.2019.03.003.

67. Han X., Song L., Li Y. et al. Accelerometer-Measured Sedentary Behavior Patterns, Brain Structure, and Cognitive Function in Dementia-Free Older Adults: A Population-Based Study. J Alzheimers Dis. 2023;96(2):657-668. doi: 10.3233/JAD-230575.

68. Dillon K., Morava A., Prapavessis H. et al. Total Sedentary Time and Cognitive Function in Middle-Aged and Older Adults: A Systematic Review and Meta-analysis. Sports Med Open. 2022;8(1):127. doi: 10.1186/s40798-022-00507-x.

69. Li S., Wang P., Cai Z. et al. Correlates of physical activity levels, muscle strength, working memory, and cognitive function in older adults. Front Aging Neurosci. 2023;15:1283864. doi: 10.3389/fnagi.2023.1283864.

70. Kim D., Ko Y., Jung A. Longitudinal effects of exercise according to the World Health Organization guidelines on cognitive function in middle-aged and older adults. Front Public Health. 2022;10:1009775. doi: 10.3389/fpubh.2022.1009775.

71. Kondratiev A. N., Tsentsiper L. M. Glymphatic system of the brain: structure and practical significance.Russian Journal of Anesthesiology and Reanimatology. 2019;(6):72-80. (In Russ.) doi: 10.17116/anaesthesiology201906172.@@ Кондратьев А. Н., Ценципер Л. М. Глимфатическая система мозга: строение и практическая значимость. Анестезиология и реаниматология. 2019;6:72-80. doi: 10.17116/anaesthesiology201906172.

72. Shirolapov I. V., Zakharov A. V., Smirnova D. A. et al. The significance of glymphatic pathway in the relationship between the sleep - wake cycle and neurodegenerative diseases. S. S. Korsakov Journal of Neurology and Psychiatry. 2023;123(10):42-47. (In Russ.) doi: 10.17116/jnevro202312310142.@@ Широлапов И. В., Захаров А. В., Смирнова Д. А. и др. Роль глимфатического клиренса в механизмах связи цикла «сон - бодрствование» и развития нейродегенеративных процессов. Журнал неврологии и психиатрии им. С. С. Корсакова. 2023;123(10):42-47. doi: 10.17116/jnevro202312310142.

73. Shirolapov I. V., Zakharov A. V., Bulgakova S. V. et al. Glymphatic dysfunction in the pathogenesis of neurodegenerative diseases and pathological aging. Genes & Cells. 2023;18(4):309-322. (In Russ.) doi: 10.23868/gc546022.@@ Широлапов И. В., Захаров А. В., Булгакова С. В. и др. Глимфатическая дисфункция в патогенезе нейродегенеративных заболеваний и патологического старения. Гены и Клетки. 2023;18(4):309-322. doi: 10.23868/gc546022.

74. Olegário R. L., Nóbrega O. T., Camargos E. F. The newly discovered glymphatic system: the missing link between physical exercise and brain health?. Front Integr Neurosci. 2024;18:1349563. doi: 10.3389/fnint.2024.1349563.

75. Piatin V. F., Shirolapov I. V., Nikitin O. L. Vibrational physical exercises as the rehabilitation in gerontology. Adv Gerontol. 2009;22(2):337-342. (In Russ). PMID: 19947400.@@ Пятин В. Ф., Широлапов И. В., Никитин О. Л. Реабилитационные возможности вибрационной физической нагрузки в геронтологии. Успехи геронтологии. 2009;22(2):337-342.

76. Shirolapov I. V., Zakharov A. V., Shishkina A. A., et al. Efficiency of computerized cognitive training for prevention of cognitive impairments and stimulation of neuroplasticity. Adv Gerontol. 2024;37(3):221-229. (In Russ.). doi: 10.34922/AE.2024.37.3.007.@@ Широлапов И. В., Захаров А. В., Шишкина А. А., и др. Эффективность компьютеризированного когнитивного тренинга для профилактики когнитивных нарушений и стимуляции нейропластичности. Успехи геронтологии. 2024;37(3):221-229. doi: 10.34922/AE.2024.37.3.007.