<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Consortium PSYCHIATRICUM</journal-id><journal-title-group><journal-title xml:lang="en">Consortium PSYCHIATRICUM</journal-title><trans-title-group xml:lang="ru"><trans-title>Consortium PSYCHIATRICUM</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2712-7672</issn><issn publication-format="electronic">2713-2919</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">15526</article-id><article-id pub-id-type="doi">10.17816/CP15526</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>REVIEW</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОБЗОР</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Mechanisms and functions of the cerebral-cognitive reserve in patients with Alzheimer's disease: a narrative review</article-title><trans-title-group xml:lang="ru"><trans-title>Механизмы и функции церебрально-когнитивного резерва при болезни Альцгеймера: нарративный обзор литературы</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5142-3992</contrib-id><name-alternatives><name xml:lang="en"><surname>Sidenkova</surname><given-names>Alena P.</given-names></name><name xml:lang="ru"><surname>Сиденкова</surname><given-names>Алена Петровна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Dr. Sci (Med.), Head of the Department of Psychiatry, Psychotherapy and Narcology</p></bio><email>sidenkovs@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0004-3691-5787</contrib-id><name-alternatives><name xml:lang="en"><surname>Litvinenko</surname><given-names>Vasilisa V.</given-names></name><name xml:lang="ru"><surname>Литвиненко</surname><given-names>Василиса Владимировна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Student, Department of pediatrics</p></bio><email>sidenkovs@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0966-9571</contrib-id><name-alternatives><name xml:lang="en"><surname>Bazarny</surname><given-names>Vladimir  V.</given-names></name><name xml:lang="ru"><surname>Базарный</surname><given-names>Владимир Викторович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Dr. Sci (Med.), Professor, Chief Researcher</p></bio><email>sidenkovs@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8665-5299</contrib-id><name-alternatives><name xml:lang="en"><surname>Rezaikin</surname><given-names>Alexei  V.</given-names></name><name xml:lang="ru"><surname>Резайкин</surname><given-names>Алексей  Васильевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci (Med.), Associate Professor of the Department of Medical Physics and Digital Technologies</p></bio><email>sidenkovs@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4004-7474</contrib-id><name-alternatives><name xml:lang="en"><surname>Zakharov</surname><given-names>Alexander V.</given-names></name><name xml:lang="ru"><surname>Захаров</surname><given-names>Александр Владимирович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci (Med.), Director of Samara State Medical University</p></bio><email>sidenkovs@mail.ru</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0009-6878-5071</contrib-id><name-alternatives><name xml:lang="en"><surname>Baranskaya</surname><given-names>Lyudmila  T.</given-names></name><name xml:lang="ru"><surname>Баранская</surname><given-names>Людмила  Тимофеевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Dr. Sci (Psychol.), Professor, Department of Psychiatry, Psychotherapy and Narcology</p></bio><email>sidenkovs@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0002-1692-4198</contrib-id><name-alternatives><name xml:lang="en"><surname>Babushkina</surname><given-names>Ekaterina Ivanovna</given-names></name><name xml:lang="ru"><surname>Бабушкина</surname><given-names>Екатерина И.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci (Med.), Associate Professor of the Department of Psychiatry, Psychotherapy and Narcology</p></bio><email>sidenkovs@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Ural State Medical University</institution></aff><aff><institution xml:lang="ru">Уральский государственный медицинский университет</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Samara State Medical University</institution></aff><aff><institution xml:lang="ru">Самарский государственный медицинский университет</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2024-08-28" publication-format="electronic"><day>28</day><month>08</month><year>2024</year></pub-date><pub-date date-type="pub" iso-8601-date="2024-10-08" publication-format="electronic"><day>08</day><month>10</month><year>2024</year></pub-date><volume>5</volume><issue>3</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>17</fpage><lpage>29</lpage><history><date date-type="received" iso-8601-date="2024-03-26"><day>26</day><month>03</month><year>2024</year></date><date date-type="accepted" iso-8601-date="2024-07-11"><day>11</day><month>07</month><year>2024</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2024, Sidenkova A.P., Litvinenko V.V., Bazarny V.V., Rezaikin A.V., Zakharov A.V., Baranskaya L.T., Babushkina E.I.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2024, Сиденкова А.П., Литвиненко В.В., Базарный В.В., Резайкин А.В., Захаров А.В., Баранская Л.Т., Бабушкина Е.И.</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="en">Sidenkova A.P., Litvinenko V.V., Bazarny V.V., Rezaikin A.V., Zakharov A.V., Baranskaya L.T., Babushkina E.I.</copyright-holder><copyright-holder xml:lang="ru">Сиденкова А.П., Литвиненко В.В., Базарный В.В., Резайкин А.В., Захаров А.В., Баранская Л.Т., Бабушкина Е.И.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc-nd/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://consortium-psy.com/jour/article/view/15526">https://consortium-psy.com/jour/article/view/15526</self-uri><abstract xml:lang="en"><p><bold>BACKGROUND:<italic> </italic></bold>The need for scientific knowledge about aging is predicated on the demand of modern society to extend the active life of a person. To maintain intellectual longevity, it is necessary to take into account not only the pathological, but also compensatory mechanisms that arise during aging. The cerebral-cognitive reserve (CCR) influences the rate of transition from pre-phenomenological stages to the clinical stage of the disease, thereby changing the prognosis of Alzheimer’s disease (AD).</p> <p><bold>AIM: </bold>The aim of this work was to review meta-analyses from studies that have examined the principles and functions of the CCR in people with AD.</p> <p><bold>METHODS:<italic> </italic></bold>The work included 83 scientific publications devoted to the issues of the CCR in neurodegenerative diseases such as AD. The Results and Discussion sections of this article provide reviews of the results of 12 meta-analyses published from 2012 to 2024 and selected from the PubMed and eLibrary databases using the following keywords in English and Russian: “cerebral reserve”, “cognitive “reserve”, and “Alzheimer’s disease”. The scope of the definition was not limited, since the goal here was to determine the terminological boundaries of the concepts of “cognitive reserve” and “single brain reserve”.</p> <p><bold>RESULTS: </bold>The modern understanding of AD as a biological continuum covering the preclinical, prodromal, and clinical phases of the disease makes it possible to infer that insufficiency of protective factors underlies the progression of AD. The cognitive reserve is involved in the sanogenetic protective mechanism during neurodegeneration. The cognitive reserve is a theoretical concept that reflects modern research’s understanding of how the integrative functioning of the brain (cerebral) and cognitive reserves extend the period of active intellectual longevity through energy-saving mechanisms. It considers these mechanisms as central to healthy mental activity and in slowing the progression of neurodegenerative diseases. At some point, an increase in excess interneuronal activity that reflects the hypercompensatory function of the reserve would accelerate the depletion of brain structures and contribute to clinical and psychopathological manifestations of AD.</p> <p><bold>CONCLUSION:<italic> </italic></bold>The concept of the CCR puts the spotlight on the need to determine the compensatory indicators of cognitive deficit in AD, assess the architecture and volume of the reserve, and develop and follow protocols for its maintenance. It appears just as crucial to adopt measures to prevent the Reserve’s depletion as early as at the preclinical stages of the disease. Elaborating protective and compensatory mechanisms that help to maintain the functional activity of the brain in conditions of neurodegeneration, that is, CCR, require further research and can form a conceptual basis for the prevention of AD, starting from the preclinical stages of the disease.</p></abstract><trans-abstract xml:lang="ru"><p><bold>ВВЕДЕНИЕ:</bold> Необходимость научного познания старения мозга обусловлена запросами современного общества на продление активной жизни человека. Для поддержания интеллектуального долголетия необходимо учитывать не только патологические, но и компенсаторные механизмы, участвующие в старении. Церебро-когнитивный резерв (ЦКР) оказывает влияние на скорость перехода дофеноменологического этапа к клиническому этапу болезни, тем самым изменяя прогноз болезни Альцгеймера (БА).</p> <p><bold>ЦЕЛЬ:</bold> Произвести обзор научных публикаций, посвященных изучению механизмов и функций ЦКР у лиц, страдающих БА.</p> <p><bold>МЕТОДЫ: </bold>В работу было взято 83 публикации по проблеме ЦКР при нейродегенеративном заболевании на примере БА. В обзор вошли 12 метаанализов, опубликованных с 2012 по 2024 год, отобранных в базе данных PubMed и электронной библиотеке eLIBRARY по следующим ключевым словам на русском и английском языке: «церебральный резерв», «когнитивный резерв», «болезнь Альцгеймера». Глубину поиска не ограничивали, поскольку одной из задач работы было определение терминологических границ понятий «когнитивный резерв» и «церебральный резерв».</p> <p><bold>РЕЗУЛЬТАТЫ: </bold>Современное представление о БА как о биологическом континууме, охватывающем доклиническую, продромальную и клиническую фазу заболевания, позволяет понять, что недостаточность протективных механизмов лежит в основе прогредиентности БА. Когнитивный резерв является примером саногенетического защитного механизма при нейродегенерации. Когнитивный резерв — это теоретическая концепция, отражающая представления современных исследователей об интегративном функционировании мозгового (церебрального) и когнитивного резервов, пролонгирующих период активного интеллектуального долголетия за счет энергосберегающих стратегий, лежащих в основе здоровой психической активности и снижающих прогредиентность нейродегенеративной болезни. На этапах развернутого заболевания чрезмерная межнейронная активность, отражающая гиперкомпенсаторную функцию резерва, способствует ускоренному истощению мозговых структур, облегчая клинико-психопатологические проявления БА.</p> <p><bold>ЗАКЛЮЧЕНИЕ: </bold>Концепция ЦКР делает актуальным вопрос поиска компенсаторных механизмов когнитивного дефицита при БА, а также оценку структуры и объема резерва, разработку и реализацию программ его поддержания, профилактику его истощения, начиная с доклинического этапа болезни. Защитно-компенсаторные механизмы поддержания функциональной активности головного мозга в условиях нейродегенерации, то есть ЦКР, требуют дальнейшего изучения и могут составить концептуальную основу профилактики БА, начиная с доклинических стадий заболевания.</p></trans-abstract><kwd-group xml:lang="en"><kwd>cerebral reserve</kwd><kwd>cognitive reserve</kwd><kwd>Alzheimer’s disease</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>церебральный резерв</kwd><kwd>когнитивный резерв</kwd><kwd>болезнь Альцгеймера</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Pristrom MS, Pristrom SL, Semenenkov II. [Aging is physiological and premature. A modern view of the problem]. Mezhdunarodnye obzory: klinicheskaja praktika i zdorov'e. 2017;(5-6):40–64. Russian.</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Stern Y, Arenaza-Urquijo EM, Bartrés-Faz D, et al. Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenance. Alzheimers Dement. 2020;16(9):1305–1311. doi: 10.1016/j.jalz.2018.07.219</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Weiler M, Casseb RF, de Campos BM, et al. Cognitive Reserve Relates to Functional Network Efficiency in Alzheimer's Disease. Front Aging Neurosci. 2018;10:255. doi: 10.3389/fnagi.2018.00255</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Arenaza-Urquijo EM, Vemuri P. Improving the resistance and resilience framework for aging and dementia studies. Alzheimers Res Ther. 2020;12(1):41. doi: 10.1186/s13195-020-00609-2</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Arenaza-Urquijo EM, Vemuri P. Resistance vs resilience to Alzheimer disease: Clarifying terminology for preclinical studies. Neurology. 2018;90(15):695–703. doi: 10.1212/WNL.0000000000005303</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Dawe RJ, Yu L, Schneider JA, et al. Postmortem brain MRI is related to cognitive decline, independent of cerebral vessel disease in older adults. Neurobiol Aging. 2018;69:177–184. doi: 10.1016/j.neurobiolaging.2018.05.020</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Katzman R, Terry R, DeTeresa R, et al. Clinical pathological and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Ann Neurol. 1988;23(2):138–144. doi: 10.1002/ana.410230206</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Tret'jakova VD. [Age-related changes in the brain and the factors influencing them]. Bjulleten' nauki i praktiki. 2022;8(7):151–191. Russian.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Sidenkova AP. [Aging of the brain. Cognitive continuum: cognitive norm – subjective cognitive decline – cognitive disorder]. Social'naja i klinicheskaja psihiatrija. 2023;33(3):88–94. Russian.</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Sidenkova A, Calabrese V, Tomasello M, et al Subjective cognitive decline and cerebral-cognitive reserve in late age. Translational Medicine of Aging. 2023;(7):137–147.</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Naumenko AA, Preobrazhenskaja IS. [Pathogenesis, diagnosis and therapy of Alzheimer's disease]. Medicinskij Sovet. 2015;(5):46–54. Russian. doi: 10.21518/2079-701X-2015-5-46-54</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Avila J, Perry G. A Multilevel View of the Development of Alzheimer's Disease. Neuroscience. 2021;457:283–293. doi: 10.1016/j.neuroscience.2020.11.015</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Bell KFS, Bennett DA, Cuello AC. Paradoxical upregulation of glutamatergic presynaptic boutons during mild cognitive impairment. J. Neurosci. 2007;27(40):10810–10817. doi: 10.1523/JNEUROSCI.3269-07.2007</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Bodranghien F, Bastian A, Casali C, еt al. Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome. Cerebellum. 2016;15(3):369–391. doi: 10.1007/s12311-015-0687-3</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Myakotnykh VS, Sidenkova AP, Kravchenko ES, et al. [Somatic pathology in elderly and senile persons suffering from Alzheimer's disease and Alzheimer's type dementia]. Adv Gerontol. 2023;36(2):256–264. Russian.</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Lloret A, Esteve D, Lloret MA, et al. When Does Alzheimer's Disease Really Start? The Role of Biomarkers. Int J Mol Sci 2019;20(22):5536. doi: 10.3390/ijms20225536</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Sidenkova A, Litvinenko V. Gender Features of the Cognitive Reserve. Psychiatr Danub. 2021;33(Suppl 4):745–748.</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Nelson ME, Andel R, Hort J. Cognitive reserve, neuropathology, and progression towards Alzheimer's disease. Aging. 2023;15(13):5963–5965. doi: 10.18632/aging.204909</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Stern Y. What is cognitive reserve? Theory and research application of the reserve concept. J Int Neuropsychol Soc. 2002;8(3);448–460.</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Soldan A, Pettigrew C, Cai Q, et al. Cognitive reserve and long-term change in cognition in aging and preclinical Alzheimer's disease. Neurobiol Aging. 2017;60:164–172. doi: 10.1016/j.neurobiolaging.2017.09.002</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Stern Y, Barnes CA, Grady C, et al. Brain reserve, cognitive reserve, compensation, and maintenance: operationalization, validity, and mechanisms of cognitive resilience. Neurobiol Aging. 2019;83:124–129. doi: 10.1016/j.neurobiolaging.2019.03.022</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Soldan A, Pettigrew C, Zhu Y, et al. Cognitive reserve and midlife vascular risk: Cognitive and clinical outcomes. Ann Clin Transl Neurol. 2020;7(8):1307–1317. doi: 10.1002/acn3.51120</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Stern Y, Albert M, Barnes CA, et al. A framework for concepts of reserve and resilience in aging. Neurobiol Aging. 2022;124:100–103. doi: 10.1016/j.neurobiolaging.2022.10.015</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Jack CR Jr, Knopman DS, Jagust WJ, et al. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 2010;9(1):119–128. doi: 10.1016/S1474-4422(09)70299-6</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):280–292. doi: 10.1016/j.jalz.2011.03.003</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535–562. doi: 10.1016/j.jalz.2018.02.018</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Lodder C, Scheyltjens I, Stancu IC, et al. CSF1R inhibition rescues tau pathology and neurodegeneration in an A/T/N model with combined AD pathologies, while preserving plaque associated microglia. Acta Neuropathol Commun. 2021;9(1):108. doi: 10.1186/s40478-021-01204-8</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Colangeli S, Boccia M, Verde P, et al. Cognitive Reserve in Healthy Aging and Alzheimer's Disease: A Meta-Analysis of fMRI Studies. Am J Alzheimers Dis Other Demen. 2016;31(5):443–449. doi: 10.1177/1533317516653826</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020;396(10248):413–446. doi: 10.1016/S0140-6736(20)30367-6</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Lemstra AW, de Beer MH, Teunissen CE, et al. Concomitant AD pathology affects clinical manifestation and survival in dementia with Lewy bodies. J Neurol Neurosurg Psychiatry. 2017;88(2):113–118. doi: 10.1136/jnnp-2016-313775</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>de Rooij SR. Are Brain and Cognitive Reserve Shaped by Early Life Circumstances? Front Neurosci. 2022;16:825811. doi: 10.3389/fnins.2022.825811</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Barnes CA, McNaughton BL. Physiological compensation for loss of afferent synapses in rat hippocampal granule cells during senescence. J Physiol. 1980;309:473–485. doi: 10.1113/jphysiol.1980.sp01352</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Norris CM, Korol DL, Foster TC. Increased susceptibility to induction of long-term depression and long-term potentiation reversal during aging. J Neurosci. 1996;16(17):5382–5392. doi: 10.1523/JNEUROSCI.16-17-05382.1996</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Kunkle BW, Grenier-Boley B, Sims R, et al. Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat Genet. 2019;51(3):414–430. doi: 10.1038/s41588-019-0358-2</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Soldan A, Pettigrew C, Albert M. Cognitive Reserve from the Perspective of Preclinical Alzheimer Disease: 2020 Update. Clin Geriatr Med. 2020;36(2):247–263. doi: 10.1016/j.cger.2019.11.006</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Jessen F, Spottke A, Boecker H, et al. Design and first baseline data of the DZNE multicenter observational study on predementia Alzheimer's disease (DELCODE). Alzheimers Res Ther. 2018;10(1):15. doi: 10.1186/s13195-017-0314-2</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Yildirim Z, Delen F, Berron D, et al. Brain reserve contributes to distinguishing preclinical Alzheimer's stages 1 and 2. Alzheimers Res Ther. 2023;15(1):43. doi: 10.1186/s13195-023-01187-9</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Slobodin TN, Goreva AV. [Cognitive reserve: causes of decline and protective mechanisms]. Mezhdunarodnyj nevrologicheskij zhurnal. 2012;(3):161–165. Russian.</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Seblova D, Berggren R, Lövdén M. Education and age-related decline in cognitive performance: Systematic review and meta-analysis of longitudinal cohort studies. Ageing Res Rev. 2020;58:101005. doi: 10.1016/j.arr.2019.101005.</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>Chen YR, Liang CS, Chu H, et al. Diagnostic accuracy of blood biomarkers for Alzheimer's disease and amnestic mild cognitive impairment: A meta-analysis. Ageing Res Rev. 2021;71:101446. doi: 10.1016/j.arr.2021.101446</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>Irvine K, Laws KR, Gale TM, et al. Greater cognitive deterioration in women than men with Alzheimer's disease: a meta-analysis. J Clin Exp Neuropsychol. 2012;34(9):989–998. doi: 10.1080/13803395.2012.712676</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>Harrison SL, Sajjad A, Bramer WM, et al. Exploring strategies to operationalize cognitive reserve: A systematic review of reviews. J Clin Exp Neuropsychol. 2015;37(3):253–264. doi: 10.1080/13803395.2014.1002759</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>Strizhickaja OJu. [Cognitive reserve, gerotranscendences and psychological well-being in the aging period: theoretical and empirical models]. Problemy sovremennogo pedagogicheskogo obrazovanija. 2017;57(13):198–208. Russian.</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>Anderson JAE, Hawrylewicz K, Grundy J. Does bilingualism protect against dementia? A meta-analysis. Psychon Bull Rev. 2020;27(5):952–965. doi: 10.3758/s13423-020-01736-5</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>Meng X, D'Arcy C. Education and dementia in the context of the cognitive reserve hypothesis: a systematic review with meta-analyses and qualitative analyses. PLoS One. 2012;7(6):e38268. doi: 10.1371/journal.pone.0038268</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>Paulavicius AM, Mizzaci CC, Tavares DRB, et al. Bilingualism for delaying the onset of Alzheimer's disease: a systematic review and meta-analysis. Eur Geriatr Med. 2020;11(4):651–658. doi: 10.1007/s41999-020-00326-x</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>Nelson ME, Jester DJ, Petkus AJ, et al. Cognitive Reserve, Alzheimer's Neuropathology, and Risk of Dementia: A Systematic Review and Meta-Analysis. Neuropsychol Rev. 2021;31(2):233–250. doi: 10.1007/s11065-021-09478-4</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Minkova L, Habich A, Peter J, et al. Gray matter asymmetries in aging and neurodegeneration: A review and meta-analysis. Hum Brain Mapp. 2017;38(12):5890–5904. doi:10.1002/hbm.23772</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>van Loenhoud AC, Groot C, Vogel JW, et al. Is intracranial volume a suitable proxy for brain reserve? Alzheimers Res Ther. 2018;10(1):91. doi: 10.1186/s13195-018-0408-5</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>Kang M, Ang TF, Devine SA, et al. A genome-wide search for pleiotropy in more than 100,000 harmonized longitudinal cognitive domain scores. Mol Neurodegener. 2023;18(1):40. doi: 10.1186/s13024-023-00633-4</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>Ligthart S, Vaez A, Võsa U, et al. Genome Analyses of &gt;200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders. Am J Hum Genet. 2018;103(5):691–706. doi: 10.1016/j.ajhg.2018.09.009</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>Bentley AR, Sung YJ, Brown MR, et al. Multi-ancestry genomewide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids. Nat Genet. 2019;51(4):636–648. doi: 10.1038/s41588-019-0378-y</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>Fleck JI, Kuti J, Mercurio J, et al. The Impact of Age and Cognitive Reserve on Resting-State Brain Connectivity. Front Aging Neurosci. 2017;9:392. doi: 10.3389/fnagi.2017.00392</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>Rao G, Gao H, Wang X, et al. MRI measurements of brain hippocampus volume in relation to mild cognitive impairment and Alzheimer disease: A systematic review and metaanalysis. Medicine (Baltimore). 2023;102(36):e34997. doi: 10.1097/MD.0000000000034997</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>van Loenhoud AC, van der Flier WM, Wink AM, et al. Cognitive reserve and clinical progression in Alzheimer disease: A paradoxical relationship. Neurology. 2019;93(4):e334–e346. doi: 10.1212/WNL.0000000000007821</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>Yang X, Wu H, Song Y, et al. Functional MRI-specific alterations in frontoparietal network in mild cognitive impairment: an ALE meta-analysis. Front Aging Neurosci. 2023;15:1165908. doi: 10.3389/fnagi.2023.1165908</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>de Las Fuentes L, Sung YJ, Noordam R, et al. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci. Mol Psychiatry. 2021;26(6):2111–2125. doi: 10.1038/s41380-020-0719-3</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>Li X, Zhang Y, Zhang C, et al. Education counteracts the genetic risk of Alzheimer's disease without an interaction effect. Front Public Health. 2023;11:1178017. doi: 10.3389/fpubh.2023.1178017</mixed-citation></ref><ref id="B59"><label>59.</label><mixed-citation>Davydovskij IV. [The problem of causality in medicine]. Moscow: Medgiz; 1962. Russian.</mixed-citation></ref><ref id="B60"><label>60.</label><mixed-citation>Mirza SS, Portegies ML, Wolters FJ, et al. Higher Education Is Associated with a Lower Risk of Dementia after a Stroke or TIA. The Rotterdam Study. Neuroepidemiology. 2016;46(2):120–127. doi: 10.1159/000443649</mixed-citation></ref><ref id="B61"><label>61.</label><mixed-citation>Gatz M, Svedberg P, Pedersen NL, et al. Education and the risk of Alzheimer's disease: findings from the study of dementia in Swedish twins. J Gerontol B Psychol Sci Soc Sci. 2001;56(5):292–300. doi: 10.1093/geronb/56.5.p292</mixed-citation></ref><ref id="B62"><label>62.</label><mixed-citation>Sharp ES, Gatz M. Relationship between education and dementia: an updated systematic review. Alzheimer Dis Assoc Disord. 2011;25(4):289–304. doi: 10.1097/WAD.0b013e318211c83c</mixed-citation></ref><ref id="B63"><label>63.</label><mixed-citation>Jellinger KA. Basic mechanisms of neurodegeneration: a critical update. J Cell Mol Med. 2010;14(3):457–487. doi: 10.1111/j.1582-4934.2010.01010.x</mixed-citation></ref><ref id="B64"><label>64.</label><mixed-citation>Billman GE. Homeostasis: The Underappreciated and Far Too Often Ignored Central Organizing Principle of Physiology. Front Physiol. 2020;11:200. doi: 10.3389/fphys.2020.00200</mixed-citation></ref><ref id="B65"><label>65.</label><mixed-citation>Perneczky R, Kempermann G, Korczyn AD, et al. Translational research on reserve against neurodegenerative disease: consensus report of the International Conference on Cognitive Reserve in the Dementias and the Alzheimer’s Association Reserve, Resilience and Protective Factors Professional Interest Area working groups. BMC Med. 2019;17(1):47. doi: 10.1186/s12916-019-1283-z</mixed-citation></ref><ref id="B66"><label>66.</label><mixed-citation>Stern Y. Cognitive reserve. Neuropsychologia. 2009;47(10):2015–2028. doi: 10.1016/j.neuropsychologia.2009.03.004</mixed-citation></ref><ref id="B67"><label>67.</label><mixed-citation>Mankhong S, Kim S, Lee S, et al. Development of Alzheimer's Disease Biomarkers: From CSF- to BloodBased Biomarkers. Biomedicines. 2022;10(4):850. doi: 10.3390/biomedicines10040850</mixed-citation></ref><ref id="B68"><label>68.</label><mixed-citation>Dubois B, Hampel H, Feldman HH, et al. Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria. Alzheimers Dement. 2016;12(3):292–323. doi: 10.1016/j.jalz.2016.02.002</mixed-citation></ref><ref id="B69"><label>69.</label><mixed-citation>Kim J, Kim MS. An Overview of Cognitive Reserve in Aging Based on Keyword Network Analysis. Inquiry. 2022;59:469580221139374. doi: 10.1177/00469580221139374</mixed-citation></ref><ref id="B70"><label>70.</label><mixed-citation>Koberskaja NN, Tabeeva GR. [The modern concept of cognitive reserve]. Nevrologija, nejropsihiatrija, psihosomatika. 2019;(11):96–102. Russian.</mixed-citation></ref><ref id="B71"><label>71.</label><mixed-citation>Sidenkova AP, Litvinenko VV, Serdjuk OV, et al. [Cognitive reserve and education in adulthood and old age (literature review)]. Sibirskij vestnik psihiatrii i narkologii. 2019;(4):52–59. Russian.</mixed-citation></ref><ref id="B72"><label>72.</label><mixed-citation>Robitaille A, van den Hout A, Machado RJM, et al. Transitions across cognitive states and death among older adults in relation to education: A multistate survival model using data from six longitudinal studies. Alzheimers Dement. 2018;(4):462–472. doi: 10.1016/j.jalz.2017.10.003</mixed-citation></ref><ref id="B73"><label>73.</label><mixed-citation>Liberati G, Raffone A, Olivetti Belardinelli M. Cognitive reserve and its implications for rehabilitation and Alzheimer's disease. Cogn Process. 2012;13(1):1–12. doi: 10.1007/s10339-011-0410-3</mixed-citation></ref><ref id="B74"><label>74.</label><mixed-citation>Valenzuela MJ, Sachdev P. Brain reserve and dementia: a systematic review. Psychol Med. 2006;36(4):441–454. doi: 10.1017/S0033291705006264</mixed-citation></ref><ref id="B75"><label>75.</label><mixed-citation>Kunkle BW, Schmidt M, Klein HU, et al. Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel: A Meta-analysis. JAMA Neurol. 2021;78(1):102–113. doi: 10.1001/jamaneurol.2020.3536</mixed-citation></ref><ref id="B76"><label>76.</label><mixed-citation>Joshi PK, Esko T, Mattsson H, et al. Directional dominance on stature and cognition in diverse human populations. Nature. 2015;523(7561):459–462. doi: 10.1038/nature14618</mixed-citation></ref><ref id="B77"><label>77.</label><mixed-citation>Kawagoe T. Overview of (f) MRI Studies of Cognitive Aging for Non-Experts: Looking through the Lens of Neuroimaging. Life (Basel). 2022;12(3):416. doi: 10.3390/life12030416</mixed-citation></ref><ref id="B78"><label>78.</label><mixed-citation>Santiago JA, Quinn JP, Potashkin JA. Physical Activity Rewires the Human Brain against Neurodegeneration. Int J Mol Sci. 2022;23(11):6223. doi: 10.3390/ijms23116223</mixed-citation></ref><ref id="B79"><label>79.</label><mixed-citation>Khodadadifar T, Soltaninejad Z, Ebneabbasi A, et al. In search of convergent regional brain abnormality in cognitive emotion regulation: A transdiagnostic neuroimaging meta-analysis. Hum Brain Mapp. 2022;43(4):1309–1325. doi: 10.1002/hbm.25722</mixed-citation></ref><ref id="B80"><label>80.</label><mixed-citation>Therriault J, Schindler SE, Salvadó G, et al. Biomarker-based staging of Alzheimer disease: rationale and clinical applications. Nat Rev Neurol. 2024;20(4):232–244. doi: 10.1038/s41582-024-00942-2</mixed-citation></ref><ref id="B81"><label>81.</label><mixed-citation>Novikova MS, Zaharov VV. [The role of cognitive reserve in the correction of cognitive impairment]. Povedencheskaja nevrologija. 2023;(1):40–48. Russian.</mixed-citation></ref><ref id="B82"><label>82.</label><mixed-citation>Dainikova EI, Pizova NV. [Cognitive reserve and cognitive impairments: drug and nondrug treatments]. Nevrologija, nejropsihiatrija, psihosomatika. 2014;(2S):62–68. Russian. doi: 10.14412/2074-2711-2014-2S-62-68</mixed-citation></ref></ref-list></back></article>
