|
|
社会孤立对阿尔茨海默病影响的研究进展
|
Abstract:
阿尔茨海默病(Alzheimer disease, AD)是一种不可逆的神经退行性疾病。其病程长，目前没有药物能够有效治疗AD。目前有证据指出，孤独是AD和其他相关失智症发展的可变危险因素，与社会隔绝的人患失智症的风险往往比远离社会孤立的人患失智症风险高。感知到的社会孤立或孤独会促进并加剧大脑中的β-淀粉样蛋白斑块(amyloid-protein, Aβ)的沉积和tau蛋白过度磷酸化，而社会孤立和AD的不同阶段大脑区域都会受到影响表现出功能障碍，例如前额叶皮层、杏仁核或海马体。同时，社会孤立和感知孤独感会促进早期AD患者大脑中Aβ的产生和tau蛋白过度磷酸化，来自社会隔离和孤独的压力也会影响Aβ的积累和tau蛋白的过度磷酸化。此外，应激引起的糖皮质激素水平升高会导致Aβ和tau蛋白病变的加剧，从而加速神经纤维缠结的发展。社交孤立也可能通过增加氧化应激加重AD病理。感觉到被孤立和拥有孤独的经历都会对心理和身体健康产生不利影响。随着我国人口老龄化，再加上新型冠状病毒COVID-19的出现以及由此产生的隔离阻碍了社交，疫情隔离使人们减少了社交，会出现社会孤立这一现象，同时也会加剧AD病情发展。有研究指出，晚年远离社会隔离会降低患失智症风险4%，对此早期积极预防社会孤立尤其重要，远离社会孤立，应多出门走动与同伴交流，提高认知储备(Cognitive reserve, CR)水平及多认识新事物是积极预防AD的重要方法。
Alzheimer’s disease (AD) is an irreversible neurodegenerative disease. The course of disease is long, and no drugs can effectively treat AD. Evidence now points to loneliness as a modifiable risk factor for the development of AD and other related dementia. People who are socially isolated tend to have a higher risk of developing dementia than people who are socially isolated. Perceived social isolation or loneliness promotes and intensifies Aβ deposition and tau hyperphosphorylation in the brain. Both social isolation and different stages of AD affect brain regions that show dysfunction, such as the prefrontal cortex, amygdala, or hippocampus. At the same time, social isolation and perceived loneliness promote Aβ production and tau hyperphosphorylation in the brain of early AD patients. Stress from social isolation and loneliness also affects Aβ accumulation and tau hyperphosphorylation. The increase in glucocorticoid levels caused by stress leads to the exacerbation of Aβ and tau protein lesions, thereby accelerating the development of neurofibrillary tangles. Social isolation may also exacerbate AD pathology by increasing oxidative stress. Feeling isolated and having experiences of loneliness can both have adverse effects on mental and physical health. With the aging population in our country, the emergence of COVID-19 and the resulting isolation has hindered social interaction, which makes people reduce social interaction, resulting in social isolation and aggravating the development of Alzheimer’s disease. Studies have pointed out that staying away from social isolation in later life can reduce the risk of dementia by 4%. Therefore, it is particularly important to actively prevent social isolation in the early stage. To stay away from social isolation, we should go out and communicate with peers more, improve cognitive reserve (CR) level and learn more about new things
| [1] | Chen, X.Q. and Mobley, W.C. (2019) Alzheimer Disease Pathogenesis: Insights from Molecular and Cellular Biology Studies of Oligomeric Aβ and Tau Species. Frontiers in Neuroscience, 13, Article No. 659.
https://doi.org/10.3389/fnins.2019.00659 |
| [2] | Keogh-Brown, M.R., Jensen, H.T., Arrighi, H.M. and Smith, R.D. (2016) The Impact of Alzheimer’s Disease on the Chinese Economy. eBioMedicine, 4, 184-190. https://doi.org/10.1016/j.ebiom.2015.12.019 |
| [3] | GBD 2019 Dementia Forecasting Collaborators (2022) Estimation of the Global Prevalence of Dementia in 2019 and Forecasted Prevalence in 2050: An Analysis for the Global Burden of Disease Study 2019. The Lancet Public Health, 7, E105-E125. https://doi.org/10.1016/S2468-2667(21)00249-8 |
| [4] | Nicholson, N.R. (2012) A Review of Social Isolation: An Important But Underassessed Condition in Older Adults. Journal of Prevention, 33, 137-152. https://doi.org/10.1007/s10935-012-0271-2 |
| [5] | Valtorta, N.K., Kanaan, M., Gilbody, S., Ronzi, S. and Hanratty, B. (2016) Loneliness and Social Isolation as Risk Factors for Coronary Heart Disease and Stroke: Systematic Review and Meta-Analysis of Longitudinal Observational Studies. Heart, 102, 1009-1016. https://doi.org/10.1136/heartjnl-2015-308790 |
| [6] | Holt-Lunstad, J. and Smith, T.B. (2016) Loneliness and Social Isolation as Risk Factors for CVD: Implications for Evidence-Based Patient Care and Scientific Inquiry. Heart, 102, 987-989.
https://doi.org/10.1136/heartjnl-2015-309242 |
| [7] | Tomaka, J., Thompson, S. and Palacios, R. (2006) The Relation of Social Isolation, Loneliness, and Social Support to Disease Outcomes among the Elderly. Journal of Aging and Health, 18, 359-384.
https://doi.org/10.1177/0898264305280993 |
| [8] | Cacioppo, J.T., Hawkley, L.C., Norman, G.J. and Berntson, G.G. (2011) Social Isolation. Annals of the New York Academy of Sciences, 1231, 17-22. https://doi.org/10.1111/j.1749-6632.2011.06028.x |
| [9] | Berkman, L.F., Glass, T., Brissette, I. and Seeman, T.E. (2000) From Social Integration to Health: Durkheim in the New Millennium. Social Science & Medicine, 51, 843-857. https://doi.org/10.1016/S0277-9536(00)00065-4 |
| [10] | Muntsant, A. and Gimenez-Llort, L. (2020) Impact of Social Isolation on the Behavioral, Functional Profiles, and Hippocampal Atrophy Asymmetry in Dementia in Times of Coronavirus Pandemic (COVID-19): A Translational Neuroscience Approach. Frontiers in Psychiatry, 11, Article ID: 572583. https://doi.org/10.3389/fpsyt.2020.572583 |
| [11] | Sutin, A.R., Stephan, Y., Luchetti, M. and Terracciano, A. (2020) Loneliness and Risk of Dementia. Journal of Gerontology, Series B, Psychological Sciences and Social Sciences, 75, 1414-1422. https://doi.org/10.1093/geronb/gby112 |
| [12] | Pino, L., Gonzalez-Velez, A.E., Prieto-Flores, M.E., Ayala, A., Fernandez-Mayoralas, G., Rojo-Perez, F., Martinez-Martin, P. and Forjaz, M.J. (2014) Self-Perceived Health and Quality of Life by Activity Status in Community-Dwelling Older Adults. Geriatrics & Gerontology International, 14, 464-473. https://doi.org/10.1111/ggi.12119 |
| [13] | Wilson, R.S., Krueger, K.R., Arnold, S.E., Schneider, J.A., Kelly, J.F., Barnes, L.L., Tang, Y. and Bennett, D.A. (2007) Loneliness and Risk of Alzheimer Disease. Archives of General Psychiatry, 64, 234-240.
https://doi.org/10.1001/archpsyc.64.2.234 |
| [14] | Sundstrom, A., Adolfsson, A.N., Nordin, M. and Adolfsson, R. (2020) Loneliness Increases the Risk of All-Cause Dementia and Alzheimer’s Disease. Journal of Gerontology, Series B, Psychological Sciences and Social Sciences, 75, 919-926. https://doi.org/10.1093/geronb/gbz139 |
| [15] | Akhter-Khan, S.C., Tao, Q., Ang, T., Itchapurapu, I.S., Alosco, M.L., Mez, J., Piers, R.J., Steffens, D.C., Au, R. and Qiu, W.Q. (2021) Associations of Loneliness with Risk of Alzheimer’s Disease Dementia in the Framingham Heart Study. Alzheimer’s & Dementia, 17, 1619-1627. https://doi.org/10.1002/alz.12327 |
| [16] | Livingston, G., J Huntley., Sommerlad, A., Ames, D., Ballard, C., Banerjee, S., Brayne, C., Burns, A., Cohen-Mansfield, J., Cooper, C., Costafreda, S.G., Dias, A., Fox, N., Gitlin, L.N., Howard, R., Kales, H.C., Kivimaki, M., Larson, E.B., Ogunniyi, A., Orgeta, V., Ritchie, K., Rockwood, K., Sampson, E.L., Samus, Q., Schneider, L.S., Selbaek, G., Teri, L. and Mukadam, N. (2020) Dementia Prevention, Intervention, and Care: 2020 Report of the Lancet Commission. Lancet, 396, 413-446. https://doi.org/10.1016/S0140-6736(20)30367-6 |
| [17] | Hsiao, Y.H., Kuo, J.R., Chen, S.H. and Gean, P.W. (2012) Amelioration of Social Isolation-Triggered Onset of Early Alzheimer’s Disease-Related Cognitive Deficit by N-Acetylcysteine in a Transgenic Mouse Model. Neurobiology of Disease, 45, 1111-1120. https://doi.org/10.1016/j.nbd.2011.12.031 |
| [18] | Huang, H., Wang, L., Cao, M., Marshall, C., Gao, J., Xiao, N., Hu, G. and Xiao, M. (2015) Isolation Housing Exacerbates Alzheimer’s Disease-Like Pathophysiology in Aged APP/PS1 Mice. International Journal of Neuropsychopharmacology, 18, Article No. u116. https://doi.org/10.1093/ijnp/pyu116 |
| [19] | De Jong, G.J. and Van Tilburg, T. (2010) The De Jong Gierveld Short Scales for Emotional and Social Loneliness: Tested on, Data from 7 Countries in the UN Generations and Gender Surveys. European Journal of Ageing, 7, 121-130.
https://doi.org/10.1007/s10433-010-0144-6 |
| [20] | Minou Weijs-Perrée, P.V.D.B. (2015) Factors Influencing Social Satisfaction and Loneliness: A Path Analysis. Journal of Transport Geography, 45, 24-31. https://doi.org/10.1016/j.jtrangeo.2015.04.004 |
| [21] | Kemperman, A., Van Den Berg, P., Weijs-Perree, M. and Uijtdewillegen, K. (2019) Loneliness of Older Adults: Social Network and the Living Environment. International Journal of Environmental Research and Public Health, 16, 406.
https://doi.org/10.3390/ijerph16030406 |
| [22] | O’Leary, T.P., Mantolino, H.M., Stover, K.R. and Brown, R.E. (2020) Age-Related Deterioration of Motor Function in Male and Female 5xFAD Mice from 3, to 16 Months of Age. Genes, Brain and Behavior, 19, e12538.
https://doi.org/10.1111/gbb.12538 |
| [23] | Boutoleau-Bretonniere, C., Pouclet-Courtemanche, H., Gillet, A., Bernard, A., Deruet, A.L., Gouraud, I., Mazoue, A., Lamy, E., Rocher, L. and El Kapogiannis, D., H.M. (2020) The Effects of Confinement on Neuropsychiatric Symptoms in Alzheimer’s Disease During the COVID-19 Crisis. Journal of Alzheimer’s Disease, 76, 41-47.
https://doi.org/10.3233/JAD-200604 |
| [24] | Wang, H., Li, T., Barbarino, P., Gauthier, S., Brodaty, H., Molinuevo, J.L., Xie, H., Sun, Y., Yu, E., Tang, Y., Weidner, W. and Yu, X. (2020) Dementia Care during COVID-19. Lancet, 395, 1190-1191.
https://doi.org/10.1016/S0140-6736(20)30755-8 |
| [25] | Lara, B., Carnes, A., Dakterzada, F., Benitez, I. and Pinol-Ripoll, G. (2020) Neuropsychiatric Symptoms and Quality of Life in Spanish Patients with Alzheimer’s Disease During the COVID-19 Lockdown. European Journal of Neurology, 27, 1744-1747. https://doi.org/10.1111/ene.14339 |
| [26] | Brown, E.E., Kumar, S., Rajji, T.K., Pollock, B.G. and Mulsant, B.H. (2020) Anticipating and Mitigating the Impact of the COVID-19 Pandemic on Alzheimer’s Disease and Related Dementias. American Journal of Geriatric Psychiatry, 28, 712-721. https://doi.org/10.1016/j.jagp.2020.04.010 |
| [27] | Soares, W.B., Silvestre, I.T., Lima, A. and De Almondes, K.M. (2020) The Influence of Telemedicine Care on the Management of Behavioral and Psychological Symptoms in Dementia (BPSD) Risk Factors Induced or Exacerbated During the COVID-19 Pandemic. Frontiers in Psychiatry, 11, Article ID: 577629.
https://doi.org/10.3389/fpsyt.2020.577629 |
| [28] | Serrano-Pozo, A., Frosch, M.P., Masliah, E. and Hyman, B.T. (2011) Neuropathological Alterations in Alzheimer Disease. Cold Spring Harbor Perspectives in Medicine, 1, a6189. https://doi.org/10.1101/cshperspect.a006189 |
| [29] | Heneka, M.T., Carson, M.J., El Khoury, J., Landreth, G.E., Brosseron, F., Feinstein, D.L., Jacobs, A.H., Wyss-Coray, T., Vitorica, J., Ransohoff, R.M., Herrup, K., Frautschy, S.A., Finsen, B., Brown, G.C., Verkhratsky, A., Yamanaka, K., Koistinaho, J., Latz, E., Halle, A., Petzold, G.C., Town, T., Morgan, D., Shinohara, M.L., Perry, V.H., Holmes, C., Bazan, N.G., Brooks, D.J., Hunot, S., Joseph, B., Deigendesch, N., Garaschuk, O., Boddeke, E., Dinarello, C.A., Breitner, J.C., Cole, G.M., Golenbock, D.T. and Kummer, M.P. (2015) Neuroinflammation in Alzheimer’s Disease. The Lancet Neurology, 14, 388-405. https://doi.org/10.1016/S1474-4422(15)70016-5 |
| [30] | Karch, C.M. and Goate, A.M. (2015) Alzheimer’s Disease Risk Genes and Mechanisms of Disease Pathogenesis. Biological Psychiatry, 77, 43-51. https://doi.org/10.1016/j.biopsych.2014.05.006 |
| [31] | Avila, J. and Perry, G. (2021) A Multilevel View of the Development of Alzheimer’s Disease. Neuroscience, 457, 283-293. https://doi.org/10.1016/j.neuroscience.2020.11.015 |
| [32] | Cacioppo, S., Capitanio, J.P. and Cacioppo, J.T. (2014) Toward a Neurology of Loneliness. Psychological Bulletin, 140, 1464-1504. https://doi.org/10.1037/a0037618 |
| [33] | Moreno-Jimenez, E.P., Flor-Garcia, M., Terreros-Roncal, J., Rabano, A., Cafini, F., Pallas-Bazarra, N., Avila, J. and Llorens-Martin, M. (2019) Adult Hippocampal Neurogenesis Is Abundant in Neurologically Healthy Subjects and Drops Sharply in Patients with Alzheimer’s Disease. Nature Medicine, 25, 554-560.
https://doi.org/10.1038/s41591-019-0375-9 |
| [34] | D’Oleire, U.F., Jacobs, H., Biddle, K.D., Properzi, M., Hanseeuw, B., Schultz, A.P., Rentz, D.M., Johnson, K.A., Sperling, R.A. and Donovan, N.J. (2018) Regional Tau Pathology and Loneliness in Cognitively Normal Older Adults. Translational Psychiatry, 8, Article No. 282. https://doi.org/10.1038/s41398-018-0345-x |
| [35] | Terry, R.D., Masliah, E., Salmon, D.P., Butters, N., Deteresa, R., Hill, R., Hansen, L.A. and Katzman, R. (1991) Physical Basis of Cognitive Alterations in Alzheimer’s Disease: Synapse Loss Is the Major Correlate of Cognitive Impairment. Annals of Neurology, 30, 572-580. https://doi.org/10.1002/ana.410300410 |
| [36] | Hsiao, Y.H., Chen, P.S., Chen, S.H. and Gean, P.W. (2011) The Involvement of Cdk5 Activator P35 in Social Isolation-Triggered Onset of Early Alzheimer’s Disease-Related Cognitive Deficit in the Transgenic Mice. Neuropsychopharmacology, 36, 1848-1858. https://doi.org/10.1038/npp.2011.69 |
| [37] | Lin, Y.S., Lin, Y.F., Chen, K.C., Yang, Y.K. and Hsiao, Y.H. (2019) Collapsin Response Mediator Protein 5 (CRMP5) Causes Social Deficits and Accelerates Memory Loss in an Animal Model of Alzheimer’s Disease. Neuropsychopharmacology, 157, Article ID: 107673. https://doi.org/10.1016/j.neuropharm.2019.107673 |
| [38] | Dong, Z., Han, H., Li, H., Bai, Y., Wang, W., Tu, M., Peng, Y., Zhou, L., He, W., Wu, X., Tan, T., Liu, M., Wu, X., Zhou, W., Jin, W., Zhang, S., Sacktor, T.C., Li, T., Song, W. and Wang, Y.T. (2015) Long-Term Potentiation Decay and Memory Loss Are Mediated by AMPAR Endocytosis. Journal of Clinical Investigation, 125, 234-247.
https://doi.org/10.1172/JCI77888 |
| [39] | Pereda-Perez, I., Popovic, N., Otalora, B.B., Popovic, M., Madrid, J.A., Rol, M.A. and Venero, C. (2013) Long-Term Social Isolation in the Adulthood Results in CA1 Shrinkage and Cognitive Impairment. Neurobiology of Learning and Memory, 106, 31-39. https://doi.org/10.1016/j.nlm.2013.07.004 |
| [40] | Schiavone, S., Sorce, S., Dubois-Dauphin, M., Jaquet, V., Colaianna, M., Zotti, M., Cuomo, V., Trabace, L. and Krause, K.H. (2009) Involvement of NOX2 in the Development of Behavioral and Pathologic Alterations in Isolated Rats. Biological Psychiatry, 66, 384-392. https://doi.org/10.1016/j.biopsych.2009.04.033 |
| [41] | Liu, Z., Zhou, T., Ziegler, A.C., Dimitrion, P. and Zuo, L. (2017) Oxidative Stress in Neurodegenerative Diseases: From Molecular Mechanisms to Clinical Applications. Oxidative Medicine and Cellular Longevity, 2017, Article ID: 2525967. https://doi.org/10.1155/2017/2525967 |
| [42] | Huang, W.J., Zhang, X. and Chen, W.W. (2016) Role of Oxidative Stress in Alzheimer’s Disease. Biomedical Reports, 4, 519-522. https://doi.org/10.3892/br.2016.630 |
| [43] | Leigh-Hunt, N., Bagguley, D., Bash, K., Turner, V., Turnbull, S., Valtorta, N. and Caan, W. (2017) An Overview of Systematic Reviews on the Public Health Consequences of Social Isolation and Loneliness. Public Health, 152, 157-171. https://doi.org/10.1016/j.puhe.2017.07.035 |
| [44] | Donovan, N.J., Okereke, O.I., Vannini, P., Amariglio, R.E., Rentz, D.M., Marshall, G.A., Johnson, K.A. and Sperling, R.A. (2016) Association of Higher Cortical Amyloid Burden with Loneliness in Cognitively Normal Older Adults. JAMA Psychiatry, 73, 1230-1237. https://doi.org/10.1001/jamapsychiatry.2016.2657 |
| [45] | Huang, H.J., Liang, K.C., Ke, H.C., Chang, Y.Y. and Hsieh-Li, H.M. (2011) Long-Term Social Isolation Exacerbates the Impairment of Spatial Working Memory in APP/PS1 Transgenic Mice. Brain Research, 1371, 150-160.
https://doi.org/10.1016/j.brainres.2010.11.043 |
| [46] | Ren, Q.G., Gong, W.G., Wang, Y.J., Zhou, Q.D. and Zhang, Z.J. (2015) Citalopram Attenuates Tau Hyperphosphorylation and Spatial Memory Deficit Induced by Social Isolation Rearing in Middle-Aged Rats. Journal of Molecular Neuroscience, 56, 145-153. https://doi.org/10.1007/s12031-014-0475-4 |
| [47] | Green, K.N., Billings, L.M., Roozendaal, B., Mcgaugh, J.L. and Laferla, F.M. (2006) Glucocorticoids Increase Amyloid-Beta and Tau Pathology in a Mouse Model of Alzheimer’s Disease. Journal of Neuroscience, 26, 9047-9056.
https://doi.org/10.1523/JNEUROSCI.2797-06.2006 |
| [48] | Popp, J., Wolfsgruber, S., Heuser, I., Peters, O., Hull, M., Schroder, J., Moller, H.J., Lewczuk, P., Schneider, A., Jahn, H., Luckhaus, C., Perneczky, R., Frolich, L., Wagner, M., Maier, W., Wiltfang, J., Kornhuber, J. and Jessen, F. (2015) Cerebrospinal Fluid Cortisol and Clinical Disease Progression in MCI and Dementia of Alzheimer’s Type. Neurobiology of Aging, 36, 601-607. https://doi.org/10.1016/j.neurobiolaging.2014.10.031 |
| [49] | Ouanes, S. and Popp, J. (2019) High Cortisol and the Risk of Dementia and Alzheimer’s Disease: A Review of the Literature. Frontiers in Aging Neuroscience, 11, Article No. 43. https://doi.org/10.3389/fnagi.2019.00043 |
| [50] | Gong, W.G., Wang, Y.J., Zhou, H., Li, X.L., Bai, F., Ren, Q.G. and Zhang, Z.J. (2017) Citalopram Ameliorates Synaptic Plasticity Deficits in Different Cognition-Associated Brain Regions Induced by Social Isolation in Middle-Aged Rats. Molecular Neurobiology, 54, 1927-1938. https://doi.org/10.1007/s12035-016-9781-x |
| [51] | Peterman, J.L., White, J.D., Calcagno, A., Hagen, C., Quiring, M., Paulhus, K., Gurney, T., Eimerbrink, M.J., Curtis, M., Boehm, G.W. and Chumley, M.J. (2020) Prolonged Isolation Stress Accelerates the Onset of Alzheimer’s Disease-Related Pathology in 5xFAD Mice Despite Running Wheels and Environmental Enrichment. Behavioural Brain Research, 379, Article ID: 112366. https://doi.org/10.1016/j.bbr.2019.112366 |
| [52] | Cheng, S.T. (2016) Cognitive Reserve and the Prevention of Dementia: The Role of Physical and Cognitive Activities. Current Psychiatry Reports, 18, Article No. 85. https://doi.org/10.1007/s11920-016-0721-2 |
| [53] | Cabeza, R., Albert, M., Belleville, S., Craik, F., Duarte, A., Grady, C.L., Lindenberger, U., Nyberg, L., Park, D.C., Reuter-Lorenz, P.A., Rugg, M.D., Steffener, J. and Rajah, M.N. (2018) Maintenance, Reserve and Compensation: The Cognitive Neuroscience of Healthy Ageing. Nature Reviews Neuroscience, 19, 701-710.
https://doi.org/10.1038/s41583-018-0068-2 |
| [54] | Stern, Y., Arenaza-Urquijo, E.M., Bartres-Faz, D., Belleville, S., Cantilon, M., Chetelat, G., Ewers, M., Franzmeier, N., Kempermann, G., Kremen, W.S., Okonkwo, O., Scarmeas, N., Soldan, A., Udeh-Momoh, C., Valenzuela, M., Vemuri, P. and Vuoksimaa, E. (2020) Whitepaper: Defining and Investigating Cognitive Reserve, Brain Reserve, and Brain Maintenance. Alzheimer’s & Dementia, 16, 1305-1311. https://doi.org/10.1016/j.jalz.2018.07.219 |
| [55] | Stern, Y. (2012) Cognitive Reserve in Ageing and Alzheimer’s Disease. The Lancet Neurology, 11, 1006-1012.
https://doi.org/10.1016/S1474-4422(12)70191-6 |
| [56] | Voss, M.W., Vivar, C., Kramer, A.F. and Van Praag, H. (2013) Bridging Animal and Human Models of Exercise-Induced Brain Plasticity. Trends in Cognitive Sciences, 17, 525-544. https://doi.org/10.1016/j.tics.2013.08.001 |
| [57] | Stern, C. and Munn, Z. (2009) Cognitive Leisure Activities and Their Role in Preventing Dementia: A Systematic Review. JBI Library of Systematic Reviews, 7, 1292-1332. https://doi.org/10.11124/01938924-200907290-00001 |
| [58] | Yates, L.A., Ziser, S., Spector, A. and Orrell, M. (2016) Cognitive Leisure Activities and Future Risk of Cognitive Impairment and Dementia: Systematic Review and Meta-Analysis. International Psychogeriatrics, 28, 1791-1806.
https://doi.org/10.1017/S1041610216001137 |
| [59] | Menardi, A., Pascual-Leone, A., Fried, P.J. and Santarnecchi, E. (2018) The Role of Cognitive Reserve in Alzheimer’s Disease and Aging: A Multi-Modal Imaging Review. Journal of Alzheimer’s Disease, 66, 1341-1362.
https://doi.org/10.3233/JAD-180549 |
| [60] | Arenaza-Urquijo, E.M. and Vemuri, P. (2020) Improving the Resistance and Resilience Framework for Aging and Dementia Studies. Alzheimer’s Research & Therapy, 12, Article No. 41. https://doi.org/10.1186/s13195-020-00609-2 |
| [61] | Brookmeyer, R., Gray, S. and Kawas, C. (1998) Projections of Alzheimer’s Disease in the United States and the Public Health Impact of Delaying Disease Onset. American Journal of Public Health, 88, 1337-1342.
https://doi.org/10.2105/AJPH.88.9.1337 |
| [62] | Dykstra, P.A., Van Tilburg, T.G. and Gierveld, J.D.J. (2005) Changes in Older Adult Loneliness: Results from a Seven-Year Longitudinal Study. Research on Aging, 27, 725-747. https://doi.org/10.1177/0164027505279712 |
| [63] | Bowling, A., Grundy, E. and Farquhar, M. (1995) Changes in Network Composition among the Very Old Living in Inner London. Journal of Cross-Cultural Gerontology, 10, 331-347. https://doi.org/10.1007/BF00972333 |
| [64] | Amieva, H., Stoykova, R., Matharan, F., Helmer, C., Antonucci, T.C. and Dartigues, J.F. (2010) What Aspects of Social Network Are Protective for Dementia? Not the Quantity but, The Quality of Social Interactions Is Protective up to 15 Years Later. Psychosomatic Medicine, 72, 905-911. https://doi.org/10.1097/PSY.0b013e3181f5e121 |
| [65] | Camozzato, A., Godinho, C., Varela, J., Kohler, C., Rinaldi, J. and Chaves, M.L. (2015) The Complex Role of Having Confidant on the Development of Alzheimer’s Disease in a Community-Based Cohort of Older People in Brazil. Neuroepidemiology, 44, 78-82. https://doi.org/10.1159/000371521 |
| [66] | Valtorta, N. and Hanratty, B. (2012) Loneliness, Isolation and the Health of Older Adults: Do We Need a New Research Agenda? Journal of the Royal Society of Medicine, 105, 518-522. https://doi.org/10.1258/jrsm.2012.120128. |
