{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T03:29:14Z","timestamp":1785641354533,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Advanced Parkinson\u2019s disease (APD) has been recently defined as a stage in which certain symptoms and complications are present, with a detrimental influence on the overall patient\u2019s health conditions and with a poor response to conventional treatments. However, historically, the term APD has been controversial, thus consequently, APD prevalence has not been previously studied. Objectives: The main objective was to determine the prevalence of APD in patients diagnosed with idiopathic PD in hospitals of the Spanish National Healthcare System. Secondary objectives were the prevalence and incidence of PD and the clinical and sociodemographic characteristics and quality of life of patients with APD or non-APD. Methods: This was a non-interventional, cross-sectional, multicenter, national study in the hospital setting. Results: The study population included 929 patients with PD (mean age 71.8 \u00b1 10.1 years; 53.8% male) and a mean time since diagnosis of 6.6 \u00b1 5.4 years. At the time of diagnosis, 613 patients (66.06%) reported having had premotor symptoms. The Hoehn and Yahr stage was 1 in 15.7% of the patients, 2 in 42.8%, 3 in 30.1%, 4 in 9.9%, and 5 in 1.4%; 46.9% of the patients had comorbidities (mean age-adjusted Charlson comorbidity index 3.5 \u00b1 1.7; median 10-year survival 77%) and the mean 8-item Parkinson\u2019s Disease Quality of Life Questionnaire was 27.8 \u00b1 20.5. We found an APD prevalence of 38.21% (95%CI: 35.08\u201341.42%), a PD prevalence of 118.4 (95%CI: 117.3\u2013119.6), and a PD incidence of 9.4 (95%CI: 5.42\u201313.4) all per 100,000 population. Among the APD population, a 15.2% were receiving some form of therapy for advanced stages of the disease (deep brain stimulation, levodopa\/carbidopa intestinal gel, or apomorphine subcutaneous infusion). Conclusions: The percentage of patients with APD in the hospitals of the Spanish National Healthcare System was 38.2%.<\/jats:p>","DOI":"10.3390\/brainsci11121557","type":"journal-article","created":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T04:01:28Z","timestamp":1637812888000},"page":"1557","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Prevalence of Advanced Parkinson\u2019s Disease in Patients Treated in the Hospitals of the Spanish National Healthcare System: The PARADISE Study"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7744-6850","authenticated-orcid":false,"given":"Juan Carlos","family":"Mart\u00ednez-Castrillo","sequence":"first","affiliation":[{"name":"Departamento de Neurolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal, Ctra. de Colmenar Viejo, km. 9100, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Mart\u00ednez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III (ISCIII), Calle Valderrebollo, 5, 28031 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel","family":"Burgos","sequence":"additional","affiliation":[{"name":"Pivotal, S.L.U. Calle Gobelas, 19, 28023 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Arroyo","sequence":"additional","affiliation":[{"name":"AbbVie Spain S.L.U. Avenida De Burgos 91, 28050 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"AbbVie Spain S.L.U. Avenida De Burgos 91, 28050 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Rosario","family":"Luqu\u00edn","sequence":"additional","affiliation":[{"name":"Servicio de Neurolog\u00eda, IdiSNA, Cl\u00ednica Universidad de Navarra (CUN), Av. de P\u00edo XII, 36, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Mat\u00edas","family":"Arbelo","sequence":"additional","affiliation":[{"name":"Servicio de Neurolog\u00eda, Hospital Universitario San Roque Las Palmas, Calle Dolores de la Rocha 5, 35001 Las Palmas de Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,24]]},"reference":[{"key":"ref_1","unstructured":"Aarli, J.A., Tarun, D., Janca, A., and Muscetta, A. (2006). Neurological Disorders: Public Health Challenges, World Health Organization."},{"key":"ref_2","unstructured":"GBD 2016 Parkinson\u2019s Disease Collaborators (2018). Global, regional, and national burden of Parkinson\u2019s disease, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol., 17, 939\u2013953."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1002\/mds.25945","article-title":"The prevalence of Parkinson\u2019s disease: A systematic review and meta-analysis","volume":"29","author":"Pringsheim","year":"2014","journal-title":"Mov. Disord."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1016\/j.parkreldis.2007.06.005","article-title":"The rationale for continuous dopaminergic stimulation in advanced Parkinson\u2019s disease","volume":"13","author":"Nyholm","year":"2007","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ejma, M., Madetko, N., Brzecka, A., Guranski, K., Alster, P., Misiuk-Hoj\u0142o, M., Somasundaram, S.G., Kirkland, C.E., and Aliev, G. (2020). The Links between Parkinson\u2019s Disease and Cancer. Biomedicines, 8.","DOI":"10.3390\/biomedicines8100416"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1016\/S0140-6736(09)60492-X","article-title":"Parkinson\u2019s disease","volume":"373","author":"Lees","year":"2009","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/mds.10362","article-title":"Prevalence of PD and other types of parkinsonism in three elderly populations of central Spain","volume":"18","author":"Molina","year":"2003","journal-title":"Mov. Disord."},{"key":"ref_8","unstructured":"(2021, November 16). Ministerio de Sanidad, Consumo y Bienestar Social, Cat\u00e1logo Nacional de Hospitales (National Hospitals Catalog). Available online: https:\/\/www.mscbs.gob.es\/ciudadanos\/prestaciones\/centrosServiciosSNS\/hospitales\/home.htm."},{"key":"ref_9","unstructured":"Balding, D.J., Cressie, N.A.C., Fitzmaurice, G.M., Goldstein, H., Molenberghs, G., Scott, D.W., Smith, A.F.M., Tsay, R.S., and Weisberg, S. (2013). Stratification and Stratified Random Sampling. Sampling of Populations: Methods and Applications, John Wiley & Sons Inc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41531-018-0056-2","article-title":"Validation of a simple screening tool for early diagnosis of advanced Parkinson\u2019s disease in daily practice: The CDEPA questionnaire","volume":"4","author":"Kulisevsky","year":"2018","journal-title":"NPJ Parkinson\u2019s Dis."},{"key":"ref_11","first-page":"4047392","article-title":"Consensus on the Definition of Advanced Parkinson\u2019s Disease: A Neurologists-Based Delphi Study (CEPA Study)","volume":"2017","author":"Luquin","year":"2017","journal-title":"Parkinson\u2019s Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation","volume":"40","author":"MCharlson","year":"1987","journal-title":"J. Chronic Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1080\/08870449708406741","article-title":"The PDQ-8: Development and validation of a short-form parkinson\u2019s disease questionnaire","volume":"12","author":"Jenkinson","year":"1997","journal-title":"Psychol. Health"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1212\/WNL.17.5.427","article-title":"Parkinsonism: Onset, progression and mortality","volume":"17","author":"Hoehn","year":"1967","journal-title":"Neurology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Fasano, A., Fung, V.S.C., Lopiano, L., Elibol, B., Smolentseva, I.G., Seppi, K., Tak\u00e1ts, A., Onul, K., Parra, J.C., and Bergmann, L. (2019). Characterizing advanced Parkinson\u2019s disease: OBSERVE-PD observational study results of 2615 patients. BMC Neurol., 19.","DOI":"10.1186\/s12883-019-1276-8"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S1474-4422(13)70293-X","article-title":"Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson\u2019s disease: A randomised, controlled, double-blind, double-dummy study","volume":"13","author":"Olanow","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/S1474-4422(18)30239-4","article-title":"Apomorphine subcutaneous infusion in patients with Parkinson\u2019s disease with persistent motor fluctuations (TOLEDO): A multicentre, double-blind, randomised, placebo-controlled trial","volume":"17","author":"Katzenschlager","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1056\/NEJMoa060281","article-title":"A randomized trial of deep-brain stimulation for Parkinson\u2019s disease","volume":"355","author":"Deuschl","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.neurol.2015.09.012","article-title":"Epidemiology of Parkinson\u2019s disease","volume":"172","author":"Elbaz","year":"2016","journal-title":"Rev. Neurol."},{"key":"ref_20","first-page":"125","article-title":"Epidemiology of Parkinson\u2019s disease in Spain and its contextualisation in the world","volume":"66","year":"2018","journal-title":"Rev. De Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1007\/s00415-004-0333-3","article-title":"Prevalence of Parkinson\u2019s disease and other types of Parkinsonism. A door-to-door survey in Bidasoa, Spain","volume":"251","author":"Bergareche","year":"2004","journal-title":"J. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1002\/mds.10087","article-title":"Prevalence of Parkinson\u2019s disease in Cantalejo, Spain: A door-to-door survey","volume":"17","author":"Duarte","year":"2002","journal-title":"Mov. Disord."},{"key":"ref_23","first-page":"479","article-title":"The estimation of the prevalence of Parkinson\u2019s disease in Navarra. An epidemiological study on the consumption of antiparkinsonian drugs","volume":"69","author":"Sanz","year":"1995","journal-title":"Rev. Espa\u00f1ola De Salud P\u00fablica"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.semerg.2013.12.004","article-title":"Epidemiolog\u00eda del parkinsonismo en el \u00c1rea de Salud de Guadalajara","volume":"40","author":"Dragomir","year":"2014","journal-title":"Semerge"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1002\/1531-8257(199907)14:4<596::AID-MDS1008>3.0.CO;2-U","article-title":"Prevalence of Parkinson\u2019s disease in lower Aragon, Spain","volume":"14","author":"Errea","year":"1999","journal-title":"Mov. Disord."},{"key":"ref_26","first-page":"641","article-title":"The prevalence and pharmacological cost of Parkinson\u2019s disease in Spain","volume":"43","year":"2006","journal-title":"Rev. De Neurol."},{"key":"ref_27","first-page":"405","article-title":"Use of antiparkinsonian agents in Castilla-La Mancha. Estimate of prevalence of Parkinson disease","volume":"27","year":"1998","journal-title":"Rev. De Neurol."},{"key":"ref_28","first-page":"1001","article-title":"Estimation of the prevalence of Parkinson\u2019s disease in Asturia, Spain. A pharmacoepidemiological study of the consumption of antiparkinson drugs","volume":"31","year":"2000","journal-title":"Rev. De Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/mds.10305","article-title":"Systematic review of incidence studies of Parkinson\u2019s disease","volume":"18","author":"Twelves","year":"2003","journal-title":"Mov. Disord."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1002\/mds.22359","article-title":"Geographical difference in Parkinson\u2019s disease prevalence within West Scotland","volume":"24","author":"Newman","year":"2009","journal-title":"Mov. Disord."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3389\/fneur.2020.00180","article-title":"Progressive Supranuclear Palsy-Parkinsonism Predominant (PSP-P)-A Clinical Challenge at the Boundaries of PSP and Parkinson\u2019s Disease (PD)","volume":"11","author":"Alster","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_32","first-page":"3719578","article-title":"Diagnostic Validation for Participants in the Washington State Parkinson Disease Registry","volume":"2018","author":"Kim","year":"2018","journal-title":"Parkinson's Dis."},{"key":"ref_33","unstructured":"National Collaborating Centre for Chronic Conditions (UK) (2006). Parkinson\u2019s Disease: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care, Royal College of Physician."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1136\/jnnp.73.5.529","article-title":"How valid is the clinical diagnosis of Parkinson\u2019s disease in the community","volume":"73","author":"Schrag","year":"2002","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_35","unstructured":"(2021, November 16). Memoria 2014 MUGEJU, Mutualidad General Judicial. Available online: http:\/\/www.mugeju.es\/es\/includes\/documentos\/mugeju\/mugeju2014.pdf."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/11\/12\/1557\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:35:21Z","timestamp":1760168121000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/11\/12\/1557"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,24]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["brainsci11121557"],"URL":"https:\/\/doi.org\/10.3390\/brainsci11121557","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,24]]}}}