Multimorbidity Clusters in the Oldest Old: Results from the EpiChron Cohort
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Demographic and Clinical Characteristics of the Study Population
3.2. Multimorbidity Clusters in Octogenarians
3.3. Multimorbidity Clusters in Nonagenarians
3.4. Multimorbidity Clusters in Centenarians
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Palladino, R.; Tayu Lee, J.; Ashworth, M.; Triassi, M.; Millett, C. Associations between multimorbidity, healthcare utilisation and health status: Evidence from 16 European countries. Age Ageing 2016, 45, 431–435. [Google Scholar] [CrossRef] [PubMed]
- Barnett, K.; Mercer, S.W.; Norbury, M.; Watt, G.; Wyke, S.; Guthrie, B. Epidemiology of multimorbidity and implications for health care, research, and medical education: A cross-sectional study. Lancet 2012, 380, 37–43. [Google Scholar] [CrossRef]
- Makovski, T.T.; Schmitz, S.; Zeegers, M.P.; Stranges, S.; van den Akker, M. Multimorbidity and quality of life: Systematic literature review and meta-analysis. Ageing Res Rev. 2019, 53, 100903. [Google Scholar] [CrossRef] [PubMed]
- Del Cura-González, I.; López-Rodríguez, J.A.; Leiva-Fernández, F.; Gimeno-Feliu, L.A.; Pico-Soler, V.; Bujalance-Zafra, M.J.; Domínguez-Santaella, M.; Polentinos-Castro, E.; Poblador-Plou, B.; Ara-Bardají, P.; et al. Effectiveness of the MULTIPAP Plus intervention in youngest-old patients with multimorbidity and polypharmacy aimed at improving prescribing practices in primary care: Study protocol of a cluster randomized trial. Trials 2022, 23, 479. [Google Scholar] [CrossRef] [PubMed]
- Muth, C.; Uhlmann, L.; Haefeli, W.E.; Rochon, J.; van den Akker, M.; Perera, R.; Güthlin, C.; Beyer, M.; Oswald, F.; Valderas, J.M.; et al. Effectiveness of a complex intervention on Prioritising Multimedication in Multimorbidity (PRIMUM) in primary care: Results of a pragmatic cluster randomised controlled trial. BMJ Open 2018, 8, e017740. [Google Scholar] [CrossRef]
- Salisbury, C.; Man, M.S.; Bower, P.; Guthrie, B.; Chaplin, K.; Gaunt, D.M.; Brookes, S.; Fitzpatrick, B.; Gardner, C.; Hollinghurst, S.; et al. Management of multimorbidity using a patient-centred care model: A pragmatic cluster-randomised trial of the 3D approach. Lancet 2018, 392, 41–50. [Google Scholar] [CrossRef]
- Palmer, K.; Marengoni, A.; Forjaz, M.J.; Jureviciene, E.; Laatikainen, T.; Mammarella, F.; Muth, C.; Navickas, R.; Prados-Torres, A.; Rijken, M.; et al. Multimorbidity care model: Recommendations from the consensus meeting of the Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS). Health Policy 2018, 122, 4–11. [Google Scholar] [CrossRef]
- Palmer, K.; Carfì, A.; Angioletti, C.; Di Paola, A.; Navickas, R.; Dambrauskas, L.; Jureviciene, E.; João Forjaz, M.; Rodriguez-Blazquez, C.; Prados-Torres, A.; et al. A Methodological Approach for Implementing an Integrated Multimorbidity Care Model: Results from the Pre-Implementation Stage of Joint Action CHRODIS-PLUS. Int. J. Environ. Res. Public Health 2019, 16, 5044. [Google Scholar] [CrossRef]
- Smith, S.M.; Wallace, E.; O’Dowd, T.; Fortin, M. Interventions for improving outcomes in patients with multimorbidity in primary care and community settings. Cochrane Database Syst. Rev. 2021, 1, CD006560. [Google Scholar] [CrossRef]
- National Institute for Health and Care Excellence. NICE Guideline [NG56]. Multimorbidity: Clinical assessment and management. 2016. Available online: https://www.nice.org.uk/guidance/ng56 (accessed on 10 July 2022).
- National Institute for Health and Care Excellence. Quality Standard [QS153]. Multimorbidity. 2017. Available online: https://www.nice.org.uk/guidance/qs153 (accessed on 10 July 2022).
- The Academy of Medical Sciences. Multimorbidity: A Priority for Global Health Research. 2018. Available online: https://acmedsci.ac.uk/file-download/82222577 (accessed on 10 July 2022).
- The Academy of Medical Sciences. Advancing Research to Tackle Multimorbidity: The UK and LMIC Perspectives. 2018. Available online: https://acmedsci.ac.uk/file-download/11182404 (accessed on 10 July 2022).
- Aiello, A.; Accardi, G.; Aprile, S.; Caldarella, R.; Carru, C.; Ciaccio, M.; De Vivo, I.; Gambino, C.M.; Ligotti, M.E.; Vasto, S.; et al. Age and Gender-related Variations of Molecular and Phenotypic Parameters in A Cohort of Sicilian Population: From Young to Centenarians. Aging Dis. 2021, 12, 1773–1793. [Google Scholar] [CrossRef]
- Caruso, C. (Ed.) Centenarians. An Example of Positive Biology, 1st ed.; Springer Nature Switzerland AG: Cham, Switzerland, 2019. [Google Scholar]
- Santoro, A.; Bientinesi, E.; Monti, D. Immunosenescence and inflammaging in the aging process: Age-related diseases or longevity? Ageing Res. Rev. 2021, 71, 101422. [Google Scholar] [CrossRef] [PubMed]
- Aiello, A.; Farzaneh, F.; Candore, G.; Caruso, C.; Davinelli, S.; Gambino, C.M.; Ligotti, M.E.; Zareian, N.; Accardi, G. Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention. Front. Immunol. 2019, 10, 2247. [Google Scholar] [CrossRef] [PubMed]
- Vasto, S.; Buscemi, S.; Barera, A.; Di Carlo, M.; Accardi, G.; Caruso, C. Mediterranean diet and healthy ageing: A Sicilian perspective. Gerontology 2014, 60, 508–518. [Google Scholar] [CrossRef]
- Caruso, C.; Passarino, G.; Puca, A.; Scapagnini, G. “Positive biology”: The centenarian lesson. Immun. Ageing 2012, 9, 5. [Google Scholar] [CrossRef] [PubMed]
- Harvard Medical School. Fighting Inflammation. Special Health Report; Harvard Health Publishing: Boston, MA, USA, 2020. [Google Scholar]
- Hitt, R.; Young-Xu, Y.; Silver, M.; Perls, T. Centenarians: The older you get, the healthier you have been. Lancet 1999, 354, 652. [Google Scholar] [CrossRef]
- Evert, J.; Lawler, E.; Bogan, H.; Perls, T. Morbidity profiles of centenarians: Survivors, delayers, and escapers. J. Gerontol. A Biol. Sci. Med. Sci. 2003, 58, 232–237. [Google Scholar] [CrossRef]
- Fortin, M.; Soubhi, H.; Hudon, C.; Bayliss, E.A.; van den Akker, M. Multimorbidity’s many challenges. BMJ 2007, 334, 1016–1017. [Google Scholar] [CrossRef]
- Fortin, M.; Bravo, G.; Hudon, C.; Vanasse, A.; Lapointe, L. Prevalence of multimorbidity among adults seen in family practice. Ann. Fam. Med. 2005, 3, 223–228. [Google Scholar] [CrossRef]
- Prados-Torres, A.; Poblador-Plou, B.; Gimeno-Miguel, A.; Calderón-Larrañaga, A.; Poncel-Falcó, A.; Gimeno-Feliú, L.A.; González-Rubio, F.; Laguna-Berna, C.; Marta-Moreno, J.; Clerencia-Sierra, M.; et al. Cohort Profile: The Epidemiology of Chronic Diseases and Multimorbidity. The EpiChron Cohort Study. Int. J. Epidemiol. 2018, 47, 382–384f. [Google Scholar] [CrossRef]
- Gimeno-Miguel, A.; Clerencia-Sierra, M.; Ioakeim, I.; Poblador-Plou, B.; Aza-Pascual-Salcedo, M.; González-Rubio, F.; Rodríguez Herrero, R.; Prados-Torres, A. Health of Spanish centenarians: A cross-sectional study based on electronic health records. BMC Geriatr. 2019, 19, 226. [Google Scholar] [CrossRef]
- Whitty, C.J.M.; Watt, F.M. Map clusters of diseases to tackle multimorbidity. Nature 2020, 579, 494–496. [Google Scholar] [CrossRef] [PubMed]
- Marengoni, A.; Rizzuto, D.; Wang, H.X.; Winblad, B.; Fratiglioni, L. Patterns of chronic multimorbidity in the elderly population. J Am. Geriatr. Soc. 2009, 57, 225–230. [Google Scholar] [CrossRef] [PubMed]
- Ofori-Asenso, R.; Chin, K.L.; Curtis, A.J.; Zomer, E.; Zoungas, S.; Liew, D. Recent Patterns of Multimorbidity Among Older Adults in High-Income Countries. Popul. Health Manag. 2019, 22, 127–137. [Google Scholar] [CrossRef] [PubMed]
- Clerencia-Sierra, M.; Calderón-Larrañaga, A.; Martínez-Velilla, N.; Vergara-Mitxeltorena, I.; Aldaz-Herce, P.; Poblador-Plou, B.; Machón-Sobrado, M.; Egüés-Olazabal, N.; Abellán-van Kan, G.; Prados-Torres, A. Multimorbidity Patterns in Hospitalized Older Patients: Associations among Chronic Diseases and Geriatric Syndromes. PLoS ONE 2015, 10, e0132909. [Google Scholar] [CrossRef]
- Schäfer, I.; von Leitner, E.C.; Schön, G.; Koller, D.; Hansen, H.; Kolonko, T.; Kaduszkiewicz, H.; Wegscheider, K.; Glaeske, G.; van den Bussche, H. Multimorbidity patterns in the elderly: A new approach of disease clustering identifies complex interrelations between chronic conditions. PLoS ONE 2010, 5, e15941. [Google Scholar] [CrossRef]
- Ioakeim-Skoufa, I.; Poblador-Plou, B.; Carmona-Pírez, J.; Díez-Manglano, J.; Navickas, R.; Gimeno-Feliu, L.A.; González-Rubio, F.; Jureviciene, E.; Dambrauskas, L.; Prados-Torres, A.; et al. Multimorbidity Patterns in the General Population: Results from the EpiChron Cohort Study. Int. J. Environ. Res. Public Health 2020, 17, 4242. [Google Scholar] [CrossRef]
- Violán, C.; Fernández-Bertolín, S.; Guisado-Clavero, M.; Foguet-Boreu, Q.; Valderas, J.M.; Vidal Manzano, J.; Roso-Llorach, A.; Cabrera-Bean, M. Five-year trajectories of multimorbidity patterns in an elderly Mediterranean population using Hidden Markov Models. Sci. Rep. 2020, 10, 16879. [Google Scholar] [CrossRef]
- Gellert, P.; von Berenberg, P.; Oedekoven, M.; Klemt, M.; Zwillich, C.; Hörter, S.; Kuhlmey, A.; Dräger, D. Centenarians Differ in Their Comorbidity Trends During The 6 Years Before Death Compared to Individuals Who Died in Their 80s or 90s. J. Gerontol. A Biol. Sci. Med. Sci. 2018, 73, 1357–1362. [Google Scholar] [CrossRef]
- Clerencia-Sierra, M.; Ioakeim-Skoufa, I.; Poblador-Plou, B.; González-Rubio, F.; Aza-Pascual-Salcedo, M.; Machón, M.; Gimeno-Miguel, A.; Prados-Torres, A. Do Centenarians Die Healthier Than Younger Elders? A Comparative Epidemiological Study in Spain. J. Clin. Med. 2020, 9, 1563. [Google Scholar] [CrossRef]
- Carnahan, R.M.; Lund, B.C.; Perry, P.J.; Pollock, B.G.; Culp, K.R. The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: Associations with serum anticholinergic activity. J. Clin. Pharmacol. 2006, 46, 1481–1486. [Google Scholar] [CrossRef]
- Eum, S.; Hill, S.K.; Rubin, L.H.; Carnahan, R.M.; Reilly, J.L.; Ivleva, E.I.; Keedy, S.K.; Tamminga, C.A.; Pearlson, G.D.; Clementz, B.A.; et al. Cognitive burden of anticholinergic medications in psychotic disorders. Schizophr. Res. 2017, 190, 129–135. [Google Scholar] [CrossRef] [PubMed]
- Poblador-Plou, B.; Carmona-Pírez, J.; Ioakeim-Skoufa, I.; Poncel-Falcó, A.; Bliek-Bueno, K.; Cano-Del Pozo, M.; Gimeno-Feliú, L.A.; González-Rubio, F.; Aza-Pascual-Salcedo, M.; Bandrés-Liso, A.C.; et al. Baseline Chronic Comorbidity and Mortality in Laboratory-Confirmed COVID-19 Cases: Results from the PRECOVID Study in Spain. Int. J. Environ. Res. Public Health 2020, 17, 5171. [Google Scholar] [CrossRef] [PubMed]
- Ancín Ducay, J.M.; Erce López, S.; Extramiana Cameno, E.; Izcue Argandoña, A. Correlación de Códigos CIE-9-MC (8a Edic.)—CIAP-2 Para la Gestión de Incapacidad Temporal, 8th ed.; Instituto de Salud Públicay Laboral de Navarra: Pamplona, Spain, 2014. Available online: http://www.navarra.es/NR/rdonlyres/E520399C-0612-4C75-A912-B16295014FC3/281429/codigosCIE_9_MC1.pdf (accessed on 10 July 2022).
- Elixhauser, A.; Steiner, C.; Palmer, L. Clinical Classifications Software (CCS), 2009. Agency for Healthcare Research and Quality. Available online: http://www.hcup-us.ahrq.gov/toolssoftware/ccs/ccs.jsp (accessed on 10 July 2022).
- Chronic Condition Indicator (CCI) for ICD-9-CM. Available online: https://www.hcup-us.ahrq.gov/toolssoftware/chronic/chronic.jsp (accessed on 10 July 2022).
- WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC Classification and DDD Assignment 2022; WHO Collaborating Centre for Drug Statistics Methodology: Oslo, Norway, 2021. [Google Scholar]
- Newcomer, S.R.; Steiner, J.F.; Bayliss, E.A. Identifying subgroups of complex patients with cluster analysis. Am. J. Manag. Care 2011, 17, e324–e332. [Google Scholar] [PubMed]
- Carmona-Pírez, J.; Poblador-Plou, B.; Ioakeim-Skoufa, I.; González-Rubio, F.; Gimeno-Feliú, L.A.; Díez-Manglano, J.; Laguna-Berna, C.; Marin, J.M.; Gimeno-Miguel, A.; Prados-Torres, A. Multimorbidity clusters in patients with chronic obstructive airway diseases in the EpiChron Cohort. Sci. Rep. 2021, 11, 4784. [Google Scholar] [CrossRef]
- Calinski, T.; Harabasz, J. A dendrite method foe cluster analysis. Commun. Stat. 1974, 3, 1–27. [Google Scholar]
- Martin, P.; Gondo, Y.; Arai, Y.; Ishioka, Y.; Johnson, M.A.; Miller, L.S.; Woodard, J.L.; Poon, L.W.; Hirose, N. Cardiovascular health and cognitive functioning among centenarians: A comparison between the Tokyo and Georgia centenarian studies. Int. Psychogeriatr. 2019, 31, 455–465. [Google Scholar] [CrossRef]
- Tettamanti, M.; Marcon, G. Cohort profile: ‘Centenari a Trieste’ (CaT), a study of the health status of centenarians in a small defined area of Italy. BMJ Open 2018, 8, e019250. [Google Scholar] [CrossRef]
- von Berenberg, P.; Dräger, D.; Zahn, T.; Neuwirth, J.; Kuhlmey, A.; Gellert, P. Chronic conditions and use of health care service among German centenarians. Age Ageing 2017, 46, 939–945. [Google Scholar] [CrossRef]
- Hazra, N.C.; Dregan, A.; Jackson, S.; Gulliford, M.C. Differences in Health at Age 100 According to Sex: Population-Based Cohort Study of Centenarians Using Electronic Health Records. J. Am. Geriatr. Soc. 2015, 63, 1331–1337. [Google Scholar] [CrossRef]
- Gessert, C.E.; Elliott, B.A.; Haller, I.V. Dying of old age: An examination of death certificates of Minnesota centenarians. J. Am. Geriatr. Soc. 2002, 50, 1561–1565. [Google Scholar] [CrossRef]
- Vestergaard, S.; Andersen-Ranberg, K.; Skytthe, A.; Christensen, K.; Robine, J.M.; Jeune, B. Health and function assessments in two adjacent Danish birth cohorts of centenarians: Impact of design and methodology. Eur. J. Ageing 2015, 13, 15–23. [Google Scholar] [CrossRef] [PubMed]
- Vetrano, D.L.; Grande, G.; Marengoni, A.; Calderón-Larrañaga, A.; Rizzuto, D. Health Trajectories in Swedish Centenarians. J. Gerontol. A Biol. Sci. Med. Sci. 2021, 76, 157–163. [Google Scholar] [CrossRef] [PubMed]
- Andersen-Ranberg, K.; Schroll, M.; Jeune, B. Healthy centenarians do not exist, but autonomous centenarians do: A population-based study of morbidity among Danish centenarians. J. Am. Geriatr. Soc. 2001, 49, 900–908. [Google Scholar] [CrossRef] [PubMed]
- Alvarez, J.A.; Medford, A.; Strozza, C.; Thinggaard, M.; Christensen, K. Stratification in health and survival after age 100: Evidence from Danish centenarians. BMC Geriatr. 2021, 21, 406. [Google Scholar] [CrossRef]
- Arai, Y.; Hirose, N.; Yamamura, K.; Shimizu, K.; Takayama, M.; Ebihara, Y.; Osono, Y. Serum insulin-like growth factor-1 in centenarians: Implications of IGF-1 as a rapid turnover protein. J. Gerontol. A Biol. Sci. Med. Sci. 2001, 56, M79–M82. [Google Scholar] [CrossRef]
- Ostan, R.; Monti, D.; Gueresi, P.; Bussolotto, M.; Franceschi, C.; Baggio, G. Gender, aging and longevity in humans: An update of an intriguing/neglected scenario paving the way to a gender-specific medicine. Clin. Sci. 2016, 130, 1711–1725. [Google Scholar] [CrossRef]
- Vaupel, J.W. Biodemography of human ageing. Nature 2010, 464, 536–542. [Google Scholar] [CrossRef]
- Oksuzyan, A.; Juel, K.; Vaupel, J.W.; Christensen, K. Men: Good health and high mortality. Sex differences in health and aging. Aging Clin. Exp. Res. 2008, 20, 91–102. [Google Scholar] [CrossRef]
- Bonduriansky, R.; Maklakov, A.; Zajitschek, F.; Brooks, R. Sexual selection, sexual conflict and the evolution of ageing and life span. Funct. Ecol. 2008, 22, 443–453. [Google Scholar] [CrossRef]
- Perls, T. Genetic and phenotypic markers among centenarians. J. Gerontol. A Biol. Sci. Med. Sci. 2001, 56, M67–M70. [Google Scholar] [CrossRef]
- Caruso, C.; Accardi, G.; Virruso, C.; Candore, G. Sex, gender and immunosenescence: A key to understand the different lifespan between men and women? Immun. Ageing 2013, 10, 20. [Google Scholar] [CrossRef]
- Ailshire, J.A.; Beltrán-Sánchez, H.; Crimmins, E.M. Becoming centenarians: Disease and functioning trajectories of older US Adults as they survive to 100. J. Gerontol. A Biol. Sci. Med. Sci. 2015, 70, 193–201. [Google Scholar] [CrossRef] [PubMed]
- Doblhammer, G.; Barth, A. Prevalence of Morbidity at Extreme Old Age in Germany: An Observational Study Using Health Claims Data. J. Am. Geriatr. Soc. 2018, 66, 1262–1268. [Google Scholar] [CrossRef] [PubMed]
- Ng, S.K.; Holden, L.; Sun, J. Identifying comorbidity patterns of health conditions via cluster analysis of pairwise concordance statistics. Stat. Med. 2012, 31, 3393–3405. [Google Scholar] [CrossRef] [PubMed]
- Prados-Torres, A.; Calderón-Larrañaga, A.; Hancco-Saavedra, J.; Poblador-Plou, B.; van den Akker, M. Multimorbidity patterns: A systematic review. J. Clin. Epidemiol. 2014, 67, 254–266. [Google Scholar] [CrossRef]
- Carmona-Pírez, J.; Ioakeim-Skoufa, I.; Gimeno-Miguel, A.; Poblador-Plou, B.; González-Rubio, F.; Muñoyerro-Muñiz, D.; Rodríguez-Herrera, J.; Goicoechea-Salazar, J.A.; Prados-Torres, A.; Villegas-Portero, R. Multimorbidity Profiles and Infection Severity in COVID-19 Population Using Network Analysis in the Andalusian Health Population Database. Int. J. Environ. Res. Public Health 2022, 19, 3808. [Google Scholar] [CrossRef]
- Ng, S.K.; Tawiah, R.; Sawyer, M.; Scuffham, P. Patterns of multimorbid health conditions: A systematic review of analytical methods and comparison analysis. Int. J. Epidemiol. 2018, 47, 1687–1704. [Google Scholar] [CrossRef]
- Mucherino, S.; Gimeno-Miguel, A.; Carmona-Pirez, J.; Gonzalez-Rubio, F.; Ioakeim-Skoufa, I.; Moreno-Juste, A.; Orlando, V.; Aza-Pascual-Salcedo, M.; Poblador-Plou, B.; Menditto, E.; et al. Changes in Multimorbidity and Polypharmacy Patterns in Young and Adult Population over a 4-Year Period: A 2011-2015 Comparison Using Real-World Data. Int. J. Environ. Res. Public Health 2021, 18, 4422. [Google Scholar] [CrossRef]
- Menditto, E.; Gimeno Miguel, A.; Moreno Juste, A.; Poblador Plou, B.; Aza Pascual-Salcedo, M.; Orlando, V.; González Rubio, F.; Prados Torres, A. Patterns of multimorbidity and polypharmacy in young and adult population: Systematic associations among chronic diseases and drugs using factor analysis. PLoS ONE 2019, 14, e0210701. [Google Scholar] [CrossRef]
- Payne, R.A. The epidemiology of polypharmacy. Clin. Med. 2016, 16, 465–469. [Google Scholar] [CrossRef]
- Weng, M.C.; Tsai, C.F.; Sheu, K.L.; Lee, Y.T.; Lee, H.C.; Tzeng, S.L.; Ueng, K.C.; Chen, C.C.; Chen, S.C. The impact of number of drugs prescribed on the risk of potentially inappropriate medication among outpatient older adults with chronic diseases. QJM Int. J. Med. 2013, 106, 1009–1015. [Google Scholar] [CrossRef] [PubMed]
- Hernández-Rodríguez, M.Á.; Sempere-Verdú, E.; Vicens-Caldentey, C.; González-Rubio, F.; Miguel-García, F.; Palop-Larrea, V.; Orueta-Sánchez, R.; Esteban-Jiménez, Ó.; Sempere-Manuel, M.; Arroyo-Aniés, M.P.; et al. Drug Prescription Profiles in Patients with Polypharmacy in Spain: A Large-Scale Pharmacoepidemiologic Study Using Real-World Data. Int. J. Environ. Res. Public Health 2021, 18, 4754. [Google Scholar] [CrossRef] [PubMed]
- Zheng, Y.B.; Shi, L.; Zhu, X.M.; Bao, Y.P.; Bai, L.J.; Li, J.Q.; Liu, J.J.; Han, Y.; Shi, J.; Lu, L. Anticholinergic drugs and the risk of dementia: A systematic review and meta-analysis. Neurosci. Biobehav. Rev. 2021, 127, 296–306. [Google Scholar] [CrossRef] [PubMed]
- Sargent, L.; Nalls, M.; Amella, E.J.; Mueller, M.; Lageman, S.K.; Bandinelli, S.; Colpo, M.; Slattum, P.W.; Singleton, A.; Ferrucci, L. Anticholinergic Drug Induced Cognitive and Physical Impairment: Results from the InCHIANTI Study. J. Gerontol. A Biol. Sci. Med. Sci. 2020, 75, 995–1002. [Google Scholar] [CrossRef]
- American Society of Consultant Pharmacists. Don’t Use Anticholinergic Medications Concomitantly with Cholinesterase Inhibitors in Patients with Dementia. 2021. Available online: https://www.choosingwisely.org/clinician-lists/ascp4-dont-use-anticholinergic-medications-concomitantly-with-cholinesterase-inhibitors-in-patients-with-dementia/ (accessed on 10 July 2022).
- Alberti, G.; Zimmet, P.; Shaw, J.; Grundy, S. The IDF Consensus Worldwide Definition of the Metabolic Syndrome; International Diabetes Federation: Brussel, Belgium, 2006. [Google Scholar]
- Leonardi, G.C.; Accardi, G.; Monastero, R.; Nicoletti, F.; Libra, M. Ageing: From inflammation to cancer. Immun. Ageing 2018, 15, 1. [Google Scholar] [CrossRef]
- Franceschi, C.; Bonafè, M.; Valensin, S.; Olivieri, F.; De Luca, M.; Ottaviani, E.; De Benedictis, G. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann. N. Y. Acad. Sci. 2000, 908, 244–254. [Google Scholar] [CrossRef]
- Franceschi, C. Inflammaging as a major characteristic of old people: Can it be prevented or cured? Nutr. Rev. 2007, 65, S173–S176. [Google Scholar] [CrossRef]
- Franceschi, C.; Capri, M.; Monti, D.; Giunta, S.; Olivieri, F.; Sevini, F.; Panourgia, M.P.; Invidia, L.; Celani, L.; Scurti, M.; et al. Inflammaging and anti-inflammaging: A systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev. 2007, 128, 92–105. [Google Scholar] [CrossRef]
- Accardi, G.; Caruso, C. Immune-inflammatory responses in the elderly: An update. Immun. Ageing 2018, 15, 11. [Google Scholar] [CrossRef]
- Arai, Y.; Martin-Ruiz, C.M.; Takayama, M.; Abe, Y.; Takebayashi, T.; Koyasu, S.; Suematsu, M.; Hirose, N.; von Zglinicki, T. Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians. EBioMedicine 2015, 2, 1549–1558. [Google Scholar] [CrossRef]
Demographic and Clinical Information a | Octogenarians | Nonagenarians | Centenarians | pmen b | pwomen b | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
M | W | p | M | W | p | M | W | p | pocto-nona | pnona-cent | pocto-cent | pocto-nona | pnona-cent | pocto-cent | |
Total Population (n) | 26,758 | 26,563 | 12,929 | 22,896 | 466 | 1 830 | |||||||||
Age (mean) | 84.70 | 85.25 | 0.000 | 92.81 | 93.35 | 0.000 | 101.62 | 101.62 | 0.956 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
Number of Chronic Diseases (mean) | 5.84 | 6.23 | 0.000 | 5.57 | 5.70 | 0.000 | 4.36 | 4.51 | 0.229 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
Number of Drugs (mean) | 5.03 | 5.09 | 0.167 | 4.95 | 4.77 | <0.001 | 3.47 | 3.58 | 0.563 | 0.270 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
Polypharmacy c (%) | 52.71 | 52.91 | 0.640 | 53.72 | 52.31 | 0.01 | 36.48 | 38.20 | 0.495 | ns | <0.001 | <0.001 | <0.001 | <0.001 | ns |
Excessive Polypharmacy d (%) | 18.94 | 20.07 | 0.001 | 15.66 | 14.29 | 0.000 | 6.87 | 6.50 | 0.777 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 |
ADS e (mean) | 1.21 | 1.25 | 0.002 | 1.19 | 1.21 | 0.517 | 1.04 | 0.95 | 0.320 | 1.000 | 0.161 | 0.119 | 0.017 | 0.000 | 0.000 |
ADS e score (%) | 0.001 | 0.026 | 0.331 | 0.015 | 0.015 | 0.015 | 0.000 | 0.000 | 0.000 | ||||||
0 | 54.57 | 52.65 | 53.72 | 52.43 | 60.52 | 59.95 | ns | <0.001 | ns | ns | <0.001 | ns | |||
1 | 15.37 | 15.96 | 15.89 | 16.66 | 13.73 | 15.74 | ns | ns | ns | ns | ns | <0.001 | |||
2 | 10.43 | 10.96 | 10.56 | 11.48 | 8.15 | 9.62 | ns | ns | ns | ns | <0.001 | <0.001 | |||
3 | 7.92 | 8.34 | 8.59 | 8.35 | 7.51 | 6.39 | <0.001 | ns | <0.001 | ns | <0.001 | ns | |||
4 | 4.94 | 5.22 | 5.13 | 5.03 | 4.29 | 4.43 | ns | ns | ns | ns | ns | ns | |||
≥5 | 6.78 | 6.87 | 6.10 | 6.05 | 5.79 | 3.88 | <0.001 | ns | <0.001 | <0.001 | <0.001 | <0.001 |
Cluster | Prev a (%) | Number of Conditions (Mean) | Conditions b | Number of Drugs (Mean) | PP c (%) | EPP d (%) | ADS e Mean Score | ADS Score f (%) | |||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
0 | 1 | 2 | 3 | 4 | ≥5 | ||||||||
Octogenarians | |||||||||||||
MO1 | 57.92 | 6.1 | HT, dyslipidaemia, DM, cardiac arrhythmias, endocrine–metabolic disorders, coagulation/haemorrhagic disorders, CHF, KD. | 5.5 | 57.1 | 22.2 | 1.2 | 53.4 | 17.2 | 10.1 | 7.9 | 5.0 | 6.6 |
MO2 | 31.97 | 5.6 | Genitourinary symptoms, delirium and dementia, ictus, chronic ulcer of skin. | 4.8 | 51.2 | 16.3 | 1.3 | 54.0 | 13.1 | 11.9 | 8.6 | 5.1 | 7.4 |
MO3 | 10.11 | 3.1 | COPD, neoplasms. | 3.1 | 32.1 | 8.3 | 1.0 | 63.2 | 12.5 | 8.0 | 6.1 | 4.1 | 6.1 |
Nonagenarians | |||||||||||||
MN1 | 43.81 | 5.5 | HT, dyslipidaemia, DM. | 5.2 | 56.6 | 16.5 | 1.2 | 53.2 | 16.8 | 10.0 | 9.0 | 5.3 | 5.8 |
MN2 | 30.20 | 6.7 | Cardiac arrhythmias, coagulation/haemorrhagic disorders, CHF, KD. | 5.9 | 64.3 | 21.2 | 1.4 | 48.0 | 18.1 | 11.9 | 8.7 | 5.9 | 7.4 |
MN3 | 18.09 | 4.1 | Genitourinary symptoms, delirium and dementia, ictus, chronic ulcer of skin. | 3.7 | 39.5 | 8.7 | 1.1 | 58.7 | 12.1 | 11.0 | 8.3 | 4.3 | 5.6 |
MN4 | 7.90 | 2.5 | COPD, neoplasms, visual deficits, prostate hyperplasia. | 2.8 | 30.0 | 5.9 | 0.8 | 67.2 | 11.3 | 7.4 | 6.7 | 3.2 | 4.2 |
Centenarians | |||||||||||||
MC1 | 51.29 | 4.6 | Genitourinary symptoms, chronic ulcer of skin. | 3.7 | 38.5 | 7.5 | 1.1 | 55.2 | 16.3 | 9.6 | 7.5 | 5.4 | 5.9 |
MC2 | 35.84 | 3.9 | HT, visual deficits, ictus, osteoarthritis, anaemias. | 3.1 | 33.5 | 4.8 | 0.9 | 69.5 | 9.0 | 4.8 | 8.4 | 2.4 | 6.0 |
MC3 | 12.88 | 2.9 | CHF, delirium and dementia, cardiac arrhythmias, COPD, acute myocardial infarction, thyroid disorders. | 3.4 | 36.7 | 10.0 | 1.1 | 56.7 | 16.7 | 11.7 | 5.0 | 5.0 | 5.0 |
Cluster | Prev a (%) | Number of Conditions (Mean) | Conditions b | Number of Drugs (Mean) | PP c (%) | EPP d (%) | ADS e Mean Score | ADS Score f (%) | |||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
0 | 1 | 2 | 3 | 4 | ≥5 | ||||||||
Octogenarians | |||||||||||||
WO1 | 36.72 | 7.7 | Dyslipidaemia, DM, endocrine–metabolic disorders. | 6.3 | 64.3 | 27.3 | 1.5 | 45.0 | 18.6 | 12.7 | 9.5 | 6.1 | 8.0 |
WO2 | 22.75 | 4.6 | Cardiac arrhythmias, CHF, coagulation/haemorrhagic disorders. | 4.4 | 45.9 | 16.6 | 1.0 | 59.5 | 14.9 | 9.2 | 6.7 | 4.1 | 5.6 |
WO3 | 21.89 | 6.0 | Osteoarthritis. | 4.9 | 51.3 | 18.7 | 1.3 | 52.6 | 16.4 | 10.6 | 8.0 | 5.3 | 7.2 |
WO4 | 18.65 | 4.7 | Delirium and dementia, chronic ulcer of skin. | 3.8 | 40.9 | 11.7 | 1.1 | 59.3 | 11.6 | 10.2 | 8.5 | 4.7 | 5.7 |
Nonagenarians | |||||||||||||
WN1 | 34.09 | 6.2 | Delirium and dementia. | 4.7 | 52.1 | 13.0 | 1.3 | 49.5 | 14.7 | 13.9 | 10.0 | 5.1 | 6.8 |
WN2 | 32.17 | 5.1 | Hypertension. | 4.9 | 53.7 | 15.3 | 1.2 | 53.2 | 18.1 | 10.3 | 7.6 | 5.3 | 5.4 |
WN3 | 17.06 | 5.9 | Ictus. | 5.1 | 55.7 | 16.5 | 1.2 | 53.0 | 18.1 | 10.4 | 7.5 | 5.3 | 5.9 |
WN4 | 10.16 | 5.7 | Chronic ulcer of skin. | 4.9 | 53.3 | 15.8 | 1.3 | 51.3 | 17.9 | 10.4 | 8.5 | 4.9 | 7.1 |
WN5 | 6.52 | 3.1 | Genitourinary symptoms, CHF. | 3.3 | 35.8 | 8.0 | 0.9 | 64.1 | 14.0 | 9.4 | 5.5 | 3.1 | 3.9 |
Centenarians | |||||||||||||
WC1 | 41.04 | 4.3 | HT, osteoarthritis, visual deficits. | 4.0 | 42.9 | 7.2 | 1.0 | 56.3 | 17.3 | 11.9 | 5.9 | 5.2 | 3.5 |
WC2 | 26.61 | 4.9 | Chronic ulcer of skin. | 3.6 | 38.0 | 7.2 | 1.0 | 60.0 | 14.6 | 8.4 | 7.6 | 4.7 | 4.7 |
WC3 | 15.19 | 3.2 | Genitourinary symptoms, ictus. | 3.0 | 31.3 | 4.0 | 0.9 | 62.2 | 16.6 | 7.6 | 6.8 | 3.6 | 3.2 |
WC4 | 11.64 | 5.3 | Delirium and dementia, dyslipidaemia, endocrine–metabolic disorders. | 3.8 | 43.2 | 8.0 | 1.1 | 59.6 | 14.1 | 10.8 | 6.1 | 3.8 | 5.6 |
WC5 | 5.52 | 1.0 | CHF. | 1.3 | 12.9 | 2.0 | 0.4 | 81.2 | 10.9 | 2.0 | 4.0 | 1.0 | 1.0 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ioakeim-Skoufa, I.; Clerencia-Sierra, M.; Moreno-Juste, A.; Elías de Molins Peña, C.; Poblador-Plou, B.; Aza-Pascual-Salcedo, M.; González-Rubio, F.; Prados-Torres, A.; Gimeno-Miguel, A. Multimorbidity Clusters in the Oldest Old: Results from the EpiChron Cohort. Int. J. Environ. Res. Public Health 2022, 19, 10180. https://doi.org/10.3390/ijerph191610180
Ioakeim-Skoufa I, Clerencia-Sierra M, Moreno-Juste A, Elías de Molins Peña C, Poblador-Plou B, Aza-Pascual-Salcedo M, González-Rubio F, Prados-Torres A, Gimeno-Miguel A. Multimorbidity Clusters in the Oldest Old: Results from the EpiChron Cohort. International Journal of Environmental Research and Public Health. 2022; 19(16):10180. https://doi.org/10.3390/ijerph191610180
Chicago/Turabian StyleIoakeim-Skoufa, Ignatios, Mercedes Clerencia-Sierra, Aida Moreno-Juste, Carmen Elías de Molins Peña, Beatriz Poblador-Plou, Mercedes Aza-Pascual-Salcedo, Francisca González-Rubio, Alexandra Prados-Torres, and Antonio Gimeno-Miguel. 2022. "Multimorbidity Clusters in the Oldest Old: Results from the EpiChron Cohort" International Journal of Environmental Research and Public Health 19, no. 16: 10180. https://doi.org/10.3390/ijerph191610180