Ключевые слова
старение
деменция
генетические факторы
Как цитировать
Аннотация
Статья посвящена изучению механизмов формирования когнитивных нарушений и влиянию физической активности на снижение риска их развития. Когнитивные функции, такие как память, внимание и скорость обработки информации, критически важны для повседневной жизни, но могут ухудшаться с возрастом и при различных заболеваниях, что повышает риск развития когнитивных расстройств и деменции. Обзор освещает патогенетические механизмы когнитивных нарушений, включая хроническое нейровоспаление, дисбаланс нейротрансмиттеров, накопление амилоидных бляшек, нарушения микроциркуляции и нейронных сетей, а также генетические и эпигенетические факторы. Особое внимание уделяется роли физической активности. Анализируются клинические исследования, подтверждающие положительное влияние физической активности на когнитивные функции пожилых людей, а также на пациентов с болезнью Альцгеймера. Обсуждаются механизмы, посредством которых физические упражнения оказывают своё воздействие, включая снижение нейровоспаления, улучшение кровоснабжения мозга, стимуляцию нейрогенеза, увеличение уровня нейротрофических факторов, и влияние на метаболические процессы. Рассматривается роль экзеркинов, выделяемых мышцами, в улучшении когнитивных функций. Авторы приходят к выводу о важности физической активности для поддержания когнитивного здоровья и необходимости дальнейших исследований для разработки оптимальных протоколов физических упражнений для разных групп населения.Литература
Kanaya A.M. et al. Total and regional adiposity and cognitive change in older adults: The Health, Aging and Body Composition (ABC) study // Archives of Neurology. – 2009. – V. 66, № 3. – P. 329–335. DOI: 10.1001/archneurol.2008.570.
Hassing L.B. et al. Overweight in midlife is related to lower cognitive function 30 years later: a prospective study with longitudinal assessments // Dementia and Geriatric Cognitive Disorders. – 2010. – V. 29. – P. 543–552. DOI: 10.1159/000314874.
Wu Z. et al. Distinct cognitive trajectories in late life and associated predictors and outcomes: a systematic review // Journal of Alzheimer’s Disease Reports. – 2020. – V. 4. – P. 459–478. DOI: 10.3233/ADR-200232.
Dominguez L.J. et al. Nutrition, Physical Activity, and Other Lifestyle Factors in the Prevention of Cognitive Decline and Dementia // Nutrients. – 2021. – V. 13, № 11. – Article 4080. DOI: 10.3390/nu13114080.
Клинические рекомендации Министерства здравоохранения РФ «Когнитивные расстройства у лиц пожилого и старческого возраста». – 2020. [Klinicheskie rekomendatsii Ministerstva zdravookhraneniya RF “Kognitivnye rasstroystva u lits pozhilogo i starcheskogo vozrasta”. – 2020. In Russian].
Яхно Н.Н., и др. Предумеренные (субъективные и лёгкие) когнитивные расстройства // Неврологический журнал. – 2017. – Т. 22, № 4. – С. 198–204. DOI: 10.18821/1560-9545-2017-22-4-198-204. [Yakhno N.N. et al. “Predumerennye” (sub’yektivnye i legkiye) kognitivnye rasstroystva. Neurological Journal. – 2017. – V. 22, No. 4. – P. 198–204. In Russian].
Barrios H. et al. Quality of life in patients with mild cognitive impairment // Aging & Mental Health. – 2013. – V. 17. – P. 287–292. DOI: 10.1080/13607863.2012.747083.
Falck R.S. et al. International depiction of the cost of functional independence limitations among older adults living in the community: A systematic review and cost-of-impairment study // BMC Geriatrics. – 2022. – V. 22. – Article 815. DOI: 10.1186/s12877-022-03466-w.
Caspersen C.J., Powell K.E., Christenson G.M. Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research // Public Health Reports. – 1985.
Li J. et al. Editorial: Neuroinflammation and cognitive impairment // Frontiers in Aging Neuroscience. – 2024. – V. 16. – Article 1453772. DOI: 10.3389/fnagi.2024.1453772.
Ajami B. et al. Single-cell mass cytometry reveals distinct populations of brain myeloid cells in mouse neuroinflammation and neurodegeneration models // Nature Neuroscience. – 2018. – V. 21. – P. 541–551. DOI: 10.1038/s41593-018-0100-x.
Hoogland I.C. et al. Systemic inflammation and microglial activation: systematic review of animal experiments // Journal of Neuroinflammation. – 2015. – V. 12. – Article 114. DOI: 10.1186/s12974-015-0332-6.
Gao C. et al. Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets // Signal Transduction and Targeted Therapy. – 2023. – V. 8. – Article 359. DOI: 10.1038/s41392-023-01588-0.
Sadeghdoust M., Das A., Kaushik D.K. Fueling neurodegeneration: metabolic insights into microglia functions // Journal of Neuroinflammation. – 2024. – V. 21. – Article 300. DOI: 10.1186/s12974-024-03296-0.
Davis I., Liu A. What is the tryptophan kynurenine pathway and why is it important to neurotherapy? // Expert Review of Neurotherapeutics. – 2015. – V. 15, № 7. – P. 719–721. DOI: 10.1586/14737175.2015.1049999.
Colabroy K.L., Begley T.P. Tryptophan catabolism: identification and characterization.
Ramos-Chávez L.A. et al. Relevance of Alternative Routes of Kynurenic Acid Production in the Brain // Oxidative Medicine and Cellular Longevity. – 2018. – Article 5272741. DOI: 10.1155/2018/5272741.
Hengerer B., Kolassa I.T., von Arnim C.A.F. Novel blood-based biomarkers of cognition, stress, and physical or cognitive training in older adults at risk of dementia: preliminary evidence for a role of BDNF, Irisin, and the kynurenine pathway // Journal of Alzheimer’s Disease. – 2017. – V. 59, № 3. – P. 1097–1111. DOI: 10.3233/JAD-170447.
Campos C. et al. Exercise-induced neuroprotective effects on neurodegenerative diseases: the key role of trophic factors // Expert Review of Neurotherapeutics. – 2016. – V. 16. – P. 723–734. DOI: 10.1080/14737175.2016.1179582.
MohanKumar S.M.J. et al. Role of cytokines and reactive oxygen species in brain aging // Mechanisms of Ageing and Development. – 2023. – V. 214. – Article 111855. DOI: 10.1016/j.mad.2023.111855.
Mohamed A.R. et al. Alzheimer’s disease: A molecular view of beta-amyloid induced morbific events // Biomedicines. – 2021. – V. 9. – Article 1126. DOI: 10.3390/biomedicines9091126.
Iadecola C., Gottesman R.F. Neurovascular and cognitive dysfunction in hypertension // Circulation Research. – 2019. – V. 124, № 7. – P. 1025–1044. DOI: 10.1161/CIRCRESAHA.118.313260.
Monteiro A. et al. Cerebral blood flow regulation and cognitive performance in hypertension // Journal of Cerebral Blood Flow & Metabolism. – 2024. – V. 44, № 11. – P. 1277–1287. DOI: 10.1177/0271678X241254680.
Sun Y. et al. Hippocampal iron overload and spatial reference memory impairment: insights from a rat model // Neuroscience Letters. – 2024. – V. 843. – Article 138014. DOI: 10.1016/j.neulet.2024.138014. Erratum in: Neuroscience Letters. – 2025. – V. 851. – Article 138133. DOI: 10.1016/j.neulet.2025.138133.
Ouerchefani R. et al. Role of the prefrontal cortex and executive functions in basic emotions recognition: evidence from patients with focal damage to the prefrontal cortex // Cognitive Neuroscience. – 2023. – V. 14, № 3. – P. 75–95. DOI: 10.1080/17588928.2023.2211345.
Bartoli E. et al. Default mode network electrophysiological dynamics and causal role in creative thinking // Brain. – 2024. – V. 147, № 10. – P. 3409–3425. DOI: 10.1093/brain/awae199.
Anacker C., Hen R. Adult hippocampal neurogenesis and cognitive flexibility — linking memory and mood // Nature Reviews Neuroscience. – 2017. – V. 18, № 6. – P. 335–346. DOI: 10.1038/nrn.2017.45.
Kim T.A. et al. Adult hippocampal neurogenesis and its impairment in Alzheimer’s disease // Zoological Research. – 2022. – V. 43, № 3. – P. 481–496. DOI: 10.24272/j.issn.2095-8137.2021.479.
Geigenmüller J.N. et al. The relationship between adult hippocampal neurogenesis and cognitive impairment in Alzheimer’s disease // Alzheimer’s & Dementia. – 2024. – V. 20, № 10. – P. 7369–7383. DOI: 10.1002/alz.14179.
Raulin A.C. et al. ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies // Molecular Neurodegeneration. – 2022. – V. 17, № 1. – Article 72. DOI: 10.1186/s13024-022-00574-4.
Liampas I. et al. Apolipoprotein E gene in α-synucleinopathies: a narrative review // International Journal of Molecular Sciences. – 2024. – V. 25, № 3. – Article 1795. DOI: 10.3390/ijms25031795.
Jackson R.J., Hyman B.T., Serrano-Pozo A. Multifaceted roles of APOE in Alzheimer disease // Nature Reviews Neurology. – 2024. – V. 20, № 8. – P. 457–474. DOI: 10.1038/s41582-024-00988-2.
Ghosh P., Saadat A. Neurodegeneration and epigenetics: a review // Neurologia (English Edition). – 2023. – V. 38, № 6. – P. e62–e68. DOI: 10.1016/j.nrleng.2023.05.001.
De Plano L.M. et al. Epigenetic changes in Alzheimer’s disease: DNA methylation and histone modification // Cells. – 2024. – V. 13, № 8. – Article 719. DOI: 10.3390/cells13080719.
Behl T. et al. Epigenetic biomarkers in Alzheimer’s disease: diagnostic and prognostic relevance // Ageing Research Reviews. – 2024. – V. 102. – Article 102556. DOI: 10.1016/j.arr.2024.102556.
Demurtas J. et al. Physical activity and exercise in mild cognitive impairment and dementia: an umbrella review of intervention and observational studies // Journal of the American Medical Directors Association. – 2020. – V. 21, № 10. – P. 1415–1422.e6. DOI: 10.1016/j.jamda.2020.08.031.
De Labra C. et al. Effects of physical exercise interventions in frail older adults: a systematic review of randomized controlled trials // BMC Geriatrics. – 2015. – V. 15, № 1. – Article 154. DOI: 10.1186/s12877-015-0155-4.
Rogers C.E., Larkey L.K., Keller C. A review of clinical trials of tai chi and qigong in older adults // Western Journal of Nursing Research. – 2009. – V. 31, № 2. – P. 245–279. DOI: 10.1177/0193945908327529.
Chang Y.-K. et al. Effect of resistance-exercise training on cognitive function in healthy older adults: a review // Journal of Aging and Physical Activity. – 2012. – V. 20, № 4. – P. 497–517. DOI: 10.1123/japa.20.4.497.
Blondell S.J., Hammersley-Mather R., Veerman J.L. Does physical activity prevent cognitive decline and dementia?: a systematic review and meta-analysis of longitudinal studies // BMC Public Health. – 2014. – V. 14, № 1. – Article 510. DOI: 10.1186/1471-2458-14-510.
Erickson K.I. et al. 2018 Physical Activity Guidelines Advisory Committee. Physical activity, cognition, and brain outcomes: a review of the 2018 physical activity guidelines // Medicine & Science in Sports & Exercise. – 2019. – V. 51, № 6. – P. 1242–1251. DOI: 10.1249/MSS.0000000000001936.
Blondell S.J., Hammersley-Mather R., Veerman J.L. Does physical activity prevent cognitive decline and dementia: a systematic review and meta-analysis of longitudinal studies // BMC Public Health. – 2014. – V. 14. – Article 510. DOI: 10.1186/1471-2458-14-510.
Guure C.B. et al. Impact of physical activity on cognitive decline, dementia, and its subtypes: meta-analysis of prospective studies // BioMed Research International. – 2017. – Article 9016924. DOI: 10.1155/2017/9016924.
Colcombe S., Kramer A.F. Fitness effects on the cognitive function of older adults: a meta-analytic study // Psychological Science. – 2003. – V. 14, № 2. – P. 125–130.
Northey J.M. et al. Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis // British Journal of Sports Medicine. – 2018. – V. 52, № 3. – P. 154–160.
Galle S.A. et al. The effects of a moderate physical activity intervention on physical fitness and cognition in healthy elderly with low levels of physical activity: a randomized controlled trial // Alzheimer’s Research & Therapy. – 2023. – V. 15, № 1. – Article 12. DOI: 10.1186/s13195-022-01123-3.
Langa K.M., Levine D.A. The diagnosis and management of mild cognitive impairment: a clinical review // JAMA – Journal of the American Medical Association. – 2014. – V. 312, № 23. – P. 2551–2561. DOI: 10.1001/jama.2014.13806.
Blumenthal J.A. et al. Lifestyle and neurocognition in older adults with cognitive impairments: a randomized trial // Neurology. – 2019. – V. 92, № 3. – P. e212–e223. DOI: 10.1212/WNL.0000000000006784.
Andrade-Guerrero J. et al. Advancing Alzheimer’s therapeutics: exploring the impact of physical exercise in animal models and patients // Cells. – 2023. – V. 12, № 21. – Article 2531. DOI: 10.3390/cells12212531.
Du Z. et al. Physical activity can improve cognition in patients with Alzheimer’s disease: a systematic review and meta-analysis of randomized controlled trials // Clinical Interventions in Aging. – 2018. – V. 13. – P. 1593–1603. DOI: 10.2147/CIA.S169565.
Panza G.A. et al. Can exercise improve cognitive symptoms of Alzheimer’s disease? // Journal of the American Geriatrics Society. – 2018. – V. 66. – P. 487–495. DOI: 10.1111/jgs.15241.
Demurtas J. et al. Physical activity and exercise in mild cognitive impairment and dementia: an umbrella review of intervention and observational studies // Journal of the American Medical Directors Association. – 2020. – V. 21. – P. 1415–1422.e1416. DOI: 10.1016/j.jamda.2020.08.031.
De la Rosa A. et al. Physical exercise in the prevention and treatment of Alzheimer’s disease // Journal of Sport and Health Science. – 2020. – V. 9. – P. 394–404. DOI: 10.1016/j.jshs.2020.01.004.
Villemagne V.L. et al. Effect of a 24-month physical activity program on brain changes in older adults at risk of Alzheimer’s disease: the AIBL active trial // Neurobiology of Aging. – 2020. – V. 89. – P. 132–141. DOI: 10.1016/j.neurobiolaging.2019.02.030.
Aguera Sanchez M.A., Barbancho M.M.A., Garcia-Casares N. Effect of physical exercise on Alzheimer’s disease: a systematic review // Atención Primaria. – 2020. – V. 52. – P. 307–318. DOI: 10.1016/j.aprim.2018.09.010.
Nascimento C.M.C. et al. Efectos del ejercicio físico y pautas básicas para su prescripción en la enfermedad de Alzheimer // Revista Andaluza de Medicina del Deporte. – 2016. – V. 9. – P. 32–40. DOI: 10.1016/j.ramd.2015.02.003.
Li B. et al. An integrative review of exercise interventions among community-dwelling adults with Alzheimer’s disease // International Journal of Older People Nursing. – 2020. – V. 15. – Article e12287. DOI: 10.1111/opn.12287.
Ohia-Nwoko O. et al. Long-term treadmill exercise attenuates tau pathology in P301S tau transgenic mice // Molecular Neurodegeneration. – 2014. – V. 9. – Article 54. DOI: 10.1186/1750-1326-9-54.
Leem Y.H. et al. Repression of tau hyperphosphorylation by chronic endurance exercise in aged transgenic mouse model of tauopathies // Journal of Neuroscience Research. – 2009. – V. 87. – P. 2561–2570. DOI: 10.1002/jnr.22075.
Stojanovic M. et al. Physical exercise and longitudinal trajectories in Alzheimer disease biomarkers and cognitive functioning // Alzheimer Disease and Associated Disorders. – 2020. – V. 34. – P. 212–219. DOI: 10.1097/WAD.0000000000000385.
Yokoyama H. et al. The effect of cognitive-motor dual-task training on cognitive function and plasma amyloid β peptide 42/40 ratio in healthy elderly persons: a randomized controlled trial // BMC Geriatrics. – 2015. – V. 15, № 1. – Article 60. DOI: 10.1186/s12877-015-0058-4.
Longobardi A. et al. Cerebrospinal fluid EV concentration and size are altered in Alzheimer’s disease and dementia with Lewy bodies // Cells. – 2022. – V. 11, № 3. – Article 462. DOI: 10.3390/cells11030462.
Wang M. et al. Exercise suppresses neuroinflammation for alleviating Alzheimer’s disease // Journal of Neuroinflammation. – 2023. – V. 20. – Article 76. DOI: 10.1186/s12974-023-02753-6.
Bo H., Kang W., Jiang N., Wang X., Zhang Y., Ji L.L. Exercise-induced neuroprotection of hippocampus in APP/PS1 transgenic mice via upregulation of mitochondrial 8-oxoguanine DNA glycosylase // Oxidative Medicine and Cellular Longevity. – 2014. – Article 834502. DOI: 10.1155/2014/834502.
Sylow L. et al. Exercise-stimulated glucose uptake — regulation and implications for glycaemic control // Nature Reviews Endocrinology. – 2017. – V. 13. – P. 133–148. DOI: 10.1038/nrendo.2016.162.
H.J., Rhie S.J., Shim I. The effects of physical exercise therapy on weight control: its regulation of adipocyte physiology and metabolic capacity // Journal of Exercise Rehabilitation. – 2023. – V. 19. – P. 141–148. DOI: 10.12965/jer.2346232.116.
Erickson K.I., Leckie R.L., Weinstein A.M. Physical activity, fitness, and gray matter volume // Neurobiology of Aging. – 2014. – V. 35, Suppl. 2. – P. S20–S28. DOI: 10.1016/j.neurobiolaging.2014.03.034.
Thomas A.G. et al. The effects of aerobic activity on brain structure // Frontiers in Psychology. – 2012. – V. 3. – Article 86. DOI: 10.3389/fpsyg.2012.00086.
Frederiksen K.S. et al.. Effects of physical exercise on Alzheimer’s disease biomarkers: a systematic review of intervention studies // Journal of Alzheimer’s Disease. – 2018. – V. 61. – P. 359–372. DOI: 10.3233/JAD-170567.
Maliszewska-Cyna E. et al. P1-015: Evaluation of effects of physical exercise on vascular and cerebral pathology, plasticity and function in a mouse model of Alzheimer’s disease // Alzheimer’s & Dementia. – 2016. – V. 12. – P. P404–P405. DOI: 10.1016/j.jalz.2016.06.762.
Pedrinolla A. et al. Exercise training improves vascular function in patients with Alzheimer’s disease // European Journal of Applied Physiology. – 2020. – V. 120. – P. 2233–2245. DOI: 10.1007/s00421-020-04447-w.
Thomas B.P. et al. Brain perfusion change in patients with mild cognitive impairment after 12 months of aerobic exercise training // Journal of Alzheimer’s Disease. – 2020. – V. 75. – P. 617–631. DOI: 10.3233/JAD-190977.
Liang Y.Y. et al. All roads lead to Rome – a review of the potential mechanisms by which exerkines exhibit neuroprotective effects in Alzheimer’s disease // Neural Regeneration Research. – 2022. – V. 17. – P. 1210–1227. DOI: 10.4103/1673-5374.325012.
Vints W. et al. Myokines as mediators of exercise-induced cognitive changes in older adults: protocol for a comprehensive living systematic review and meta-analysis // Frontiers in Aging Neuroscience. – 2023. – V. 15. – Article 1213057. DOI: 10.3389/fnagi.2023.1213057.
Sanford J.A. et al. Molecular transducers of physical activity consortium (MoTrPAC): mapping the dynamic responses to exercise // Cell. – 2020. – V. 181. – P. 1464–1474. DOI: 10.1016/j.cell.2020.06.004.
Pedersen B.K. et al. Searching for the exercise factor: is IL-6 a candidate? // Journal of Muscle Research and Cell Motility. – 2003. – V. 24. – P. 113–119. DOI: 10.1023/A:1026070911202.
Chen W. et al. Myokines mediate the cross talk between skeletal muscle and other organs // Journal of Cellular Physiology. – 2021. – V. 236. – P. 2393–2412. DOI: 10.1002/jcp.30033.
Scisciola L. et al. Sarcopenia and cognitive function: role of myokines in muscle–brain cross-talk // Life. – 2021. – V. 11. – Article 173. DOI: 10.3390/life11020173.