From Basic to Applied ScienceThe Case of the Differential Outcomes Procedure
- Luis J. Fuentes 1
- Victoria Plaza 2
- Ana B. Vivas 3
- Ángeles F. Estévez 4
-
1
Universidad de Murcia
info
-
2
Universidad Autónoma de Madrid
info
- 3 University of York Europe Campus
-
4
Universidad de Almería
info
ISSN: 1576-8597
Année de publication: 2023
Volumen: 44
Número: 2
Type: Article
D'autres publications dans: Psicológica: Revista de metodología y psicología experimental
Résumé
A major health and societal challenge nowadays is how to ameliorate and/or delay the onset of cognitive decline in humans suffering from diverse pathologies. Often, solutions can be found in basic science conducted in the laboratory through the use of very well-known experimental procedures. In the present review article, we set out to present the main findings from a research line that uses an experimental procedure originally discovered in animal studies investigating associative learning, the differential outcomes procedure (hereafter the DOP). Here we review the main findings of the DOP that relate to the different processes involved in associative learning and memory from a neurophysiological perspective. We take a step forward to illustrate how the DOP can be applied to real life settings to address important issues such as treatment adherence. Briefly, we first show how the DOP can be adapted to enhance discriminative learning and memory retention in children of different ages, younger adults, and healthy as well as pathological aging. Next, we illustrate how the DOP can be a cost-effective approach to tackle health challenges such as adherence to medical prescriptions in older people suffering from multiple morbidities. Finally, we discuss digital, mobile-based applications using the DOP to promote autonomy in older adults. Future directions in the DOP applications to health issues are also presented.
Références bibliographiques
- Acevedo, A., & Loewenstein, D. A. (2007). Nonpharmacological cognitive interventions in aging and dementia. Journal of Geriatric Psychiatry and Neurology, 20(4), 239–249. https://doi.org/10.1177/0891988707308808
- Arnáiz, E., & Almkvist, O. (2003). Neuropsychological features of mild cognitive impairment and preclinical Alzheimer’s disease: Neuropsychological features of MCI and AD. Acta Neurologica Scandinavica, 107, 34–41. https://doi.org/10.1034/j.1600-0404.107.s179.7.x
- Bosworth, H. B., Granger, B. B., Mendys, P., Brindis, R., Burkholder, R., Czajkowski, S. M., Daniel, J. G., Ekman, I., Ho, M., Johnson, M., Kimmel, S. E., Liu, L. Z., Musaus, J., Shrank, W. H., Buono, E. W., Weiss, K., & Granger, C. B. (2011). Medication adherence: A call for action. American Heart Journal, 162(3), 412–424. https://doi.org/10.1016/j.ahj.2011.06.007
- Brown, M. T., & Bussell, J. K. (2011). Medication Adherence: WHO Cares? Mayo Clinic Proceedings, 86(4), 304–314. https://doi.org/10.4065/mcp.2010.0575
- Carmona, I., Marí-Beffa, P., & Estévez, A. F. (2019a). Does the implicit outcomes expectancies shape learning and memory processes? Cognition, 189, 181–187. https://doi.org/10.1016/j.cognition.2019.04.007
- Carmona, I., Vivas, A. B., & Estévez, A. F. (2019b). Differential Outcomes Training Ameliorates Visual Memory Impairments in Patients With Alzheimer’s Disease: A Pilot Study. Frontiers in Psychology, 9, 2671. https://doi.org/10.3389/fpsyg.2018.02671
- Cavanaugh, J. C., & Blanchard-Fields, F. (2006). Adult development and aging (5th ed.). Wadsworth/Thomson Learning.
- Clapp, W. C., & Gazzaley, A. (2012). Distinct mechanisms for the impact of distraction and interruption on working memory in aging. Neurobiology of Aging, 33(1), 134–148. https://doi.org/10.1016/j.neurobiolaging.2010.01.012
- Costa, E., Pecorelli, S., Giardini, A., Savin, M., Menditto, E., Lehane, E., Laosa, O., Monaco, A., & Marengoni, A. (2015). Interventional tools to improve medication adherence: Review of literature. Patient Preference and Adherence, 1303. https://doi.org/10.2147/PPA.S87551
- De Wit, S., & Dickinson, A (2009). Associative theories of goal-directed behaviour: a case for animal– human translational models. Psychological Research 73, 463–476. https://doi.org/10.1007/s00426- 009-0230-6
- Delshad, A., Salari, H., & Hashemian, H. (2005). The Estimate of Drug Intake Level in Adults Using Cockrefot-Gault. Ofogh-e-Danesh, 10(4), 53–58.
- Divo, M. J., Martinez, C. H., & Mannino, D. M. (2014). Ageing and the epidemiology of multimorbidity. European Respiratory Journal, 44(4), 1055–1068. https://doi.org/10.1183/09031936.00059814
- Esteban, L., Plaza, V., López-Crespo, G., Vivas, A. B., & Estévez, A. F. (2014). Differential outcomes training improves face recognition memory in children and in adults with Down syndrome. Research in Developmental Disabilities, 35(6), 1384–1392. https://doi.org/10.1016/j.ridd.2014.03.031
- Esteban, L., Vivas, A. B., Fuentes, L. J., & Estévez, A. F. (2015). Spatial working memory is enhanced in children by differential outcomes. Scientific Reports, 5(1), 17112. https://doi.org/10.1038/srep17112 Estévez, A. F., & Fuentes, L. J. (2003). Differential outcomes effect in four-year-old children. Psicológica, 24(2), 159–167.
- Estévez, A. F., Fuentes, L. J., Marı ́-Beffa, P., González, C., & Alvarez, D. (2001). The Differential Outcome Effect as a Useful Tool to Improve Conditional Discrimination Learning in Children. Learning and Motivation, 32(1), 48–64. https://doi.org/10.1006/lmot.2000.1060
- Estévez, A. F., Fuentes, L. J., Overmier, J. B., & González, C. (2003). Differential outcomes effect in children and adults with Down Syndrome. American Journal on Mental Retardation, 108(2), 108. https://doi.org/10.1352/0895-8017(2003)108<0108:DOEICA>2.0.CO;2
- Estévez, A. F., Vivas, A. B., Alonso, D., Marí-Beffa, P., Fuentes, L. J., & Overmier, J. B. (2007). Enhancing challenged students’ recognition of mathematical relations through differential outcomes training. Quarterly Journal of Experimental Psychology, 60(4), 571–580. https://doi.org/10.1080/17470210600820039
- Feigin, V. L., Vos, T., Nichols, E., Owolabi, M. O., Carroll, W. M., Dichgans, M., Deuschl, G., Parmar, P., Brainin, M., & Murray, C. (2020). The global burden of neurological disorders: Translating evidence into policy. The Lancet Neurology, 19(3), 255–265. https://doi.org/10.1016/S1474-4422(19)30411-9
- Fernandez-Lazaro, C. I., García-González, J. M., Adams, D. P., Fernandez-Lazaro, D., Mielgo-Ayuso, J., Caballero-Garcia, A., Moreno Racionero, F., Córdova, A., & Miron-Canelo, J. A. (2019). Adherence to treatment and related factors among patients with chronic conditions in primary care: A cross-sectional study. BMC Family Practice, 20(1), 132. https://doi.org/10.1186/s12875-019-1019-3
- Fuentes, L. J., Molina, M., Plaza, V., García-Pérez, A., & Estévez, A. F. (2020). Discriminative learning and associative memory under the differential outcomes procedure is modulated by cognitive load. Acta Psychologica, 208, 103103. https://doi.org/10.1016/j.actpsy.2020.103103
- Goeters, S., Blakely, E., & Poling, A. (1992). The Differential Outcomes Effect. The Psychological Record, 42(3), 389–411. https://doi.org/10.1007/BF03399609
- González-Rodríguez, A., Godoy-Giménez, M., Cañadas, F., Sayans-Jiménez, P., & Estévez, A. F. (2020). Differential outcomes, schizotypy, and improvement of the recognition of emotional facial expressions: A preliminary study. Psicológica Journal, 41(2), 162–182. https://doi.org/10.2478/psicolj-2020-0008
- Hertzog, C., Pearman, A., Lustig, E., & Hughes, M. (2021). Fostering Self-Management of Everyday Memory in Older Adults: A New Intervention Approach. Frontiers in Psychology, 11, 560056. https://doi.org/10.3389/fpsyg.2020.560056
- Hochhalter, A. K., Sweeney, W. A., Bakke, B. L., Holub, R. J., & Overmier, J. B. (2001). Improving Face Recognition in Alcohol Dementia. Clinical Gerontologist, 22(2), 3–18. https://doi.org/10.1300/J018v22n02_02
- Iachini, T., Iavarone, A., Senese, V., Ruotolo, F., & Ruggiero, G. (2009). Visuospatial memory in healthy elderly, AD and MCI: A Review. Current Aging Science, 2(1), 43–59. https://doi.org/10.2174/1874609810902010043
- Jose, J., & Bond, C. (2021). Medication Adherence: Still a problem. International Journal of Pharmacy Practice, 29(2), 93–95. https://doi.org/10.1093/ijpp/riaa019
- Joseph, B., Overmier, J. B., & Thompson, T. (1997). Food- and nonfood-related differential outcomes in equivalence learning by adults with Prader-Willi syndrome. American Journal on Mental Retardation, 101(4), 374–386.
- Litt, M. D., & Schreibman, L. (1981). Stimulus-specific reinforcement in the acquisition of receptive labels by autistic children. Analysis and Intervention in Developmental Disabilities, 1(2), 171–186. https://doi.org/10.1016/0270-4684(81)90030-6
- López-Crespo, G., Plaza, V., Fuentes, L. J., & Estévez, A. F. (2009). Improvement of age-related memory deficits by differential outcomes. International Psychogeriatrics, 21(3), 503–510. https://doi.org/10.1017/S1041610209008576
- Lowe, R. (2020). Habit-Based and Goal-Directed Systems: Knowledge Transfer in Individual and Social Learning. In R. Giovagnoli & R. Lowe (Eds.), The Logic of Social Practices (Vol. 52, pp. 153–167). Springer International Publishing. https://doi.org/10.1007/978-3-030-37305-4_10
- Maki, P., Overmier, J. B., Delos, S., & Gutmann, A. J. (1995). Expectancies as factors influencing conditional discrimination performance of children. The Psychological Record, 45(1), 45–71.
- Malanga, P., & Poling, A. (1992). Letter recognition by adults with mental handicaps: Improving performance through differential outcomes. Developmental Disabilities Bulletin, 20(2), 39–48.
- Martella, D., Plaza, V., Estévez, A. F., Castillo, A., & Fuentes, L. J. (2012). Minimizing sleep deprivation effects in healthy adults by differential outcomes. Acta Psychologica, 139(3), 391–396. https://doi.org/10.1016/j.actpsy.2011.12.013
- Martínez, L., Estévez, A. F., Fuentes, L. J., & Overmier, J. B. (2009). Improving conditional discrimination learning and memory in five-year-old children: Differential outcomes effect using different types of reinforcement. Quarterly Journal of Experimental Psychology, 62(8), 1617–1630. https://doi.org/10.1080/17470210802557827
- Martínez, L., Flores, P., González-Salinas, C., Fuentes, L. J., & Estévez, A. F. (2013). The effects of differential outcomes and different types of consequential stimuli on 7-year-old children’s discriminative learning and memory. Learning & Behavior, 41(3), 298–308. https://doi.org/10.3758/s13420-013-0105-y
- Martínez, L., Marí-Beffa, P., Roldán-Tapia, D., Ramos-Lizana, J., Fuentes, L. J., & Estévez, A. F. (2012). Training with differential outcomes enhances discriminative learning and visuospatial recognition memory in children born prematurely. Research in Developmental Disabilities, 33(1), 76–84. https://doi.org/10.1016/j.ridd.2011.08.022
- Martínez-Pérez, V., Fuentes, L. J., & Campoy, G. (2021). The role of differential outcomes-based feedback on procedural memory. Psychological Research, 85(1), 238–245. https://doi.org/10.1007/s00426-019-01231-0
- Martyr, A., & Clare, L. (2012). Executive function and activities of daily living in Alzheimer’s Disease: A correlational meta-analysis. Dementia and Geriatric Cognitive Disorders, 33(2–3), 189–203. https://doi.org/10.1159/000338233
- Mateos, L. R., & Flores, C. J. (2016). El efecto de consecuencias diferenciales: Un caso de investigación traslacional. Universitas Psychologica, 15(2), 51. https://doi.org/10.11144/Javeriana.upsy15-2.ecdc
- McCormack, J. C., Elliffe, D., & Virués‐Ortega, J. (2019). Quantifying the effects of the differential outcomes procedure in humans: A systematic review and a meta‐analysis. Journal of Applied Behavior Analysis, 52(3), 870–892. https://doi.org/10.1002/jaba.578
- McNab, F., Zeidman, P., Rutledge, R. B., Smittenaar, P., Brown, H. R., Adams, R. A., & Dolan, R. J. (2015). Age-related changes in working memory and the ability to ignore distraction. Proceedings of the National Academy of Sciences, 112(20), 6515–6518. https://doi.org/10.1073/pnas.1504162112
- Midão, L., Giardini, A., Menditto, E., Kardas, P., & Costa, E. (2018). Polypharmacy prevalence among older adults based on the survey of health, ageing and retirement in Europe. Archives of Gerontology and Geriatrics, 78, 213–220. https://doi.org/10.1016/j.archger.2018.06.018
- Mok, L. W. (2012). Short-term retrospective versus prospective memory processing as emergent properties of the mind and brain: Human fMRI evidence. Neuroscience, 226, 236–252. https://doi.org/10.1016/j.neuroscience.2012.09.005
- Mok, L. W., Thomas, K. M., Lungu, O. V., & Overmier, J. B. (2009). Neural correlates of cue-unique outcome expectations under differential outcomes training: An fMRI study. Brain Research, 1265, 111– 127. https://doi.org/10.1016/j.brainres.2008.12.072
- Molina, M., Carmona, I., Fuentes, L. J., Plaza, V., & Estévez, A. F. (2020). Enhanced learning and retention of medical information in Alzheimer’s disease after differential outcomes training. PLOS ONE, 15(4), e0231578. https://doi.org/10.1371/journal.pone.0231578
- Molina, M., Plaza, V., Fuentes, L. J., & Estévez, A. F. (2015). The Differential Outcomes Procedure Enhances Adherence to Treatment: A Simulated Study with Healthy Adults. Frontiers in Psychology, 6. https://doi.org/10.3389/fpsyg.2015.01780
- Nyberg, L. (2017). Functional brain imaging of episodic memory decline in ageing. Journal of Internal Medicine, 281(1), 65–74. https://doi.org/10.1111/joim.12533
- Onder, G., Bonassi, S., Abbatecola, A. M., Folino-Gallo, P., Lapi, F., Marchionni, N., Pani, L., Pecorelli, S., Sancarlo, D., Scuteri, A., Trifirò, G., Vitale, C., Zuccaro, S. M., Bernabei, R., & Fini, M. (2014). High Prevalence of Poor Quality Drug Prescribing in Older Individuals: A Nationwide Report From the Italian Medicines Agency (AIFA). The Journals of Gerontology: Series A, 69(4), 430–437. https://doi.org/10.1093/gerona/glt118
- Overmier, J. B., & Lawry, J. A. (1979). Pavlovian conditioning and the mediation of behavior. In G.H. Bower (Ed), The psychology of learning and motivation (pp. 1-56). Academic Press.
- Overmier, J. B., Savage, L. M., & Sweeney, W. A. (1999). Behavioral and pharmacological analyses of memory: New behavioral options for remediation. In M. Haug & R. E. Whalen (Eds.), Animal models of human emotion and cognition. (pp. 231–245). American Psychological Association. https://doi.org/10.1037/10335-014
- Pavlov, I. P. (1927). Conditioned reflexes: An investigation of the physiological activity of the cerebral cortex. Oxford University Press.
- Pérez-Jover, V., Mira, J., Carratala-Munuera, C., Gil-Guillen, V., Basora, J., López-Pineda, A., & Orozco- Beltrán, D. (2018). Inappropriate Use of Medication by Elderly, Polymedicated, or Multipathological Patients with Chronic Diseases. International Journal of Environmental Research and Public Health, 15(2), 310. https://doi.org/10.3390/ijerph15020310
- Petersen, R. C. (2016). Mild Cognitive Impairment: CONTINUUM: Lifelong Learning in Neurology, 22(2, Dementia), 404–418. https://doi.org/10.1212/CON.0000000000000313
- Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., & Kokmen, E. (1999). Mild Cognitive Impairment: Clinical characterization and outcome. Archives of Neurology, 56(3), 303. https://doi.org/10.1001/archneur.56.3.303
- Plaza, V., Esteban, L., Estévez, A. F., & Fuentes, L. J. (2013). El procedimiento de consecuencias diferenciales mejora el reconocimiento de rostros con independencia de su valencia emocional [The differential outcomes procedure improves face recognition irrespective of their emotional valence]. Psicológica, 34(1), 79–95.
- Plaza, V., Estévez, A. F., López-Crespo, G., & Fuentes, L. J. (2011). Enhancing recognition memory in adults through differential outcomes. Acta Psychologica, 136(1), 129–136. https://doi.org/10.1016/j.actpsy.2010.11.001
- Plaza, V., López-Crespo, G., Antúnez, C., Fuentes, L. J., & Estévez, A. F. (2012). Improving delayed face recognition in Alzheimer’s disease by differential outcomes. Neuropsychology, 26(4), 483–489. https://doi.org/10.1037/a0028485
- Plaza, V., Molina, M., Fuentes, L. J., & Estévez, A. F. (2018). Learning and Recall of Medical Treatment- Related Information in Older Adults Using the Differential Outcomes Procedure. Frontiers in Psychology, 9, 157. https://doi.org/10.3389/fpsyg.2018.00157
- Reber, P. J. (2008). Cognitive Neuroscience of Declarative and Nondeclarative Memory. In Advances in Psychology (Vol. 139, pp. 113–123). Elsevier. https://doi.org/10.1016/S0166-4115(08)10010-3
- Rescorla, R. A., & Solomon, R. L. (1967). Two-process learning theory: Relationships between Pavlovian conditioning and instrumental learning. Psychological Review, 74, 151-182. https://doi.org/10.1037/h0024475
- Rittmo, J., Carlsson, R., Gander, P., & Lowe, R. (2020). Vicarious Value Learning: Knowledge transfer through affective processing on a social differential outcomes task. Acta Psychologica, 209, 103134. https://doi.org/10.1016/j.actpsy.2020.103134
- Royall, D. R., Lauterbach, E. C., Kaufer, D., Malloy, P., Coburn, K. L., & Black, K. J. (2007). The cognitive correlates of functional status: A review from the Committee on Research of the American Neuropsychiatric Association. The Journal of Neuropsychiatry and Clinical Neurosciences, 19(3), 249– 265. https://doi.org/10.1176/jnp.2007.19.3.249
- Sala, G., Aksayli, N. D., Tatlidil, K. S., Tatsumi, T., Gondo, Y., & Gobet, F. (2019). Near and far transfer in cognitive training: A second-order meta-analysis. Collabra: Psychology, 5(1), 18. https://doi.org/10.1525/collabra.203
- Salimi, S., Irish, M., Foxe, D., Hodges, J. R., Piguet, O., & Burrell, J. R. (2018). Can visuospatial measures improve the diagnosis of Alzheimer’s disease? Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 10(1), 66–74. https://doi.org/10.1016/j.dadm.2017.10.004
- Saunders, R. R., & Sailor, W. (1979). A Comparison of Three Strategies of Reinforcement on Two-Choice Learning Problems with Severely Retarded Children. AAESPH Review, 4(4), 323–333. https://doi.org/10.1177/154079697900400401
- Savage, L. M. (2001). In search of the neurobiological underpinnings of the differential outcomes effect. Integrative Physiological & Behavioral Science, 36(3), 182–195. https://doi.org/10.1007/BF02734092
- Savage, L. M., Buzzeti, R. A., & Ramirez, D. R. (2004). The effects of hippocampal lesions on learning, memory, and reward expectancies. Neurobiology of Learning and Memory, 82(2), 109–119. https://doi.org/10.1016/j.nlm.2004.05.002
- Savage, L. M., Koch, A. D., & Ramirez, D. R. (2007). Basolateral amygdala inactivation by muscimol, but not ERK/MAPK inhibition, impairs the use of reward expectancies during working memory: Amygdala inactivation and reward expectation. European Journal of Neuroscience, 26(12), 3645–3651. https://doi.org/10.1111/j.1460-9568.2007.05959.x
- Savage, L. M., & Langlais, P. J. (1995). Differential outcomes attenuate memory impairments on matching-to-position following pyrithiamine-induced thiamine deficiency in rats. Psychobiology, 23(2), 153–160. https://doi.org/10.3758/BF03327071
- Savage, L. M., Pitkin, S. R., & Careri, J. M. (1999). Memory enhancement in aged rats: The differential outcomes effect. Developmental Psychobiology, 35(4), 318–327. https://10.1002/(SICI)1098- 2302(199912)35:4<318::AID-DEV6>3.0.CO;2-8
- Savage, L. M., & Ramos, R. L. (2009). Reward expectation alters learning and memory: The impact of the amygdala on appetitive-driven behaviors. Behavioural Brain Research, 198(1), 1–12. https://doi.org/10.1016/j.bbr.2008.10.028
- Shepp, B. E. (1962). Some cue properties of anticipated rewards in discrimination learning of retardates. Journal of Comparative and Physiological Psychology, 55(5), 856–859. https://doi.org/10.1037/h0040940
- Sokol, M. C., McGuigan, K. A., Verbrugge, R. R., & Epstein, R. S. (2005). Impact of Medication Adherence on Hospitalization Risk and Healthcare Cost. Medical Care, 43(6), 521–530. https://doi.org/10.1097/01.mlr.0000163641.86870.af
- Thorndike, E. L. (1911). Animal intelligence; experimental studies. The Macmillan Company,. https://doi.org/10.5962/bhl.title.55072
- Trapold, M. A. (1970). Are expectancies based upon different positive reinforcing events discriminably different? Learning and Motivation, 1(2), 129–140. https://doi.org/10.1016/0023-9690(70)90079-2
- Trapold, M. A., & Overmier, J. B. (1972). The second learning process in instrumental learning. In Classical conditioning II: Current research and theory (In A H Black&W F Prokasy (Eds.), pp. 427–452). Urcuioli, P. J. (2005). Behavioral and associative effects of differential outcomes in discrimination learning. Animal Learning & Behavior, 33(1), 1–21. https://doi.org/10.3758/BF03196047
- Urcuioli, P. J. (2013). Stimulus control and stimulus class formation. In G. J. Madden, W. V. Dube, T. D. Hackenberg, G. P. Hanley, & K. A. Lattal (Eds.), APA handbook of behavior analysis, Vol. 1: Methods and principles. (pp. 361–386). American Psychological Association. https://doi.org/10.1037/13937-016
- Vivas, A. B., Ypsilanti, A., Ladas, A. I., Kounti, F., Tsolaki, M., & Estévez, A. F. (2018). Enhancement of Visuospatial Working Memory by the Differential Outcomes Procedure in Mild Cognitive Impairment and Alzheimer’s Disease. Frontiers in Aging Neuroscience, 10, 364. https://doi.org/10.3389/fnagi.2018.00364
- Walsh, C. A., Cahir, C., Tecklenborg, S., Byrne, C., Culbertson, M. A., & Bennett, K. E. (2019). The association between medication non‐adherence and adverse health outcomes in ageing populations: A systematic review and meta‐analysis. British Journal of Clinical Pharmacology, 85(11), 2464–2478. https://doi.org/10.1111/bcp.14075
- Werner-Seidler, A., Perry, Y., & Christensen, H. (2016). An Australian Example of Translating Psychological Research into Practice and Policy: Where We are and Where We Need to Go. Frontiers in Psychology, 7. https://doi.org/10.3389/fpsyg.2016.00200
- WHO. (2003). Adherence to long-term therapies: Evidence for Action. https://apps.who.int/iris/handle/10665/42682?locale-attribute=es&
- WHO. (2022a). Ageing and health. https://www.who.int/news-room/fact-sheets/detail/ageing-and- health
- WHO. (2022b). Noncommunicable Diseases. https://www.who.int/news-room/fact- sheets/detail/noncommunicable-diseases
- Yap, A. F., Thirumoorthy, T., & Kwan, Y. H. (2016). Medication adherence in the elderly. Journal of Clinical Gerontology and Geriatrics, 7(2), 64–67. https://doi.org/10.1016/j.jcgg.2015.05.001
- Yarnall, A. J., Sayer, A. A., Clegg, A., Rockwood, K., Parker, S., & Hindle, J. V. (2017). New horizons in multimorbidity in older adults. Age and Ageing, 46(6), 882–888. https://doi.org/10.1093/ageing/afx150