{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T18:08:55Z","timestamp":1787681335152,"version":"build-2784847793"},"reference-count":92,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013263","name":"Norwegian Health Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013263","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Parkinson\u2019s disease (PD) and frailty frequently co-occur and may interact bidirectionally through shared mechanisms of aging biology, mitochondrial dysfunction, inflammation, and reduced physiological reserve. Objective: We aimed to synthesize current evidence on prevalence, directionality, clinical overlap, adverse outcomes, and management implications of the PD\u2013frailty nexus. Methods: A narrative review of epidemiologic, cohort, and interventional studies was performed, examining frailty in PD and PD risk in prefrail\/frail populations, plus trials of multimodal interventions. Results: Frailty is common in PD, affecting approximately one-third of patients overall and becoming more prevalent as the disease advances. It independently predicts falls, cognitive decline, hospitalization, institutionalization, and mortality. Large cohorts suggest prefrailty\/frailty is associated with incident PD risk, supporting a potential bidirectional association rather than direct causation. Diagnostic complexity arises because PD motor and non-motor features overlap with frailty constructs, risking misclassification. Management based on Comprehensive Geriatric Assessment (CGA) enhances personalized, multidisciplinary care. Exercise, particularly combined aerobic and resistance training reduces frailty and improves mobility, postural control, and quality of life. Complementary nutritional strategies, including muscle-targeted supplementation, can further strengthen rehabilitation outcomes, while careful attention to social determinants and polypharmacy remains essential to optimizing overall health and functional independence. Conclusions: Frailty is best understood as a clinical marker of vulnerability within PD and a correlate of more adverse trajectories rather than a proven causal determinant. Systematic frailty assessment integrated into PD care may help refine prognosis, individualize treatment, and support efforts to preserve independence. Priorities include PD-adapted frailty tools, CGA implementation, and rigorous trials of combined exercise\u2013nutrition programs.<\/jats:p>","DOI":"10.3390\/jcm15010063","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T12:22:27Z","timestamp":1766578947000},"page":"63","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Parkinson\u2019s Disease and Frailty: A Two-Way Link Across Aging"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0425-4991","authenticated-orcid":false,"given":"Daniel","family":"Hern\u00e1ndez-Triana","sequence":"first","affiliation":[{"name":"Semillero de Neurociencias y Envejecimiento, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9488-8868","authenticated-orcid":false,"given":"Salom\u00f3n","family":"P\u00e1ez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Semillero de Neurociencias y Envejecimiento, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7456-2430","authenticated-orcid":false,"given":"Alexandre","family":"Mena","sequence":"additional","affiliation":[{"name":"Semillero de Neurociencias y Envejecimiento, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2799-3245","authenticated-orcid":false,"given":"Mar","family":"Gimeno","sequence":"additional","affiliation":[{"name":"Department of Neurology, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8165-1185","authenticated-orcid":false,"given":"Alejandra","family":"Soto-Leal","sequence":"additional","affiliation":[{"name":"Semillero de Neurociencias y Envejecimiento, Pontificia Universidad Javeriana, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5962-772X","authenticated-orcid":false,"given":"Maria Cruz","family":"Rodriguez-Oroz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5832-0603","authenticated-orcid":false,"given":"Miguel Germ\u00e1n","family":"Borda","sequence":"additional","affiliation":[{"name":"Department of Neurology, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Helse Stavanger HF, P.O. Box 8100, 4068 Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e464","DOI":"10.1016\/S2666-7568(24)00094-1","article-title":"Temporal trends in the prevalence of Parkinson\u2019s disease from 1980 to 2023: A systematic review and meta-analysis","volume":"5","author":"Zhu","year":"2024","journal-title":"Lancet Healthy Longev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","article-title":"Parkinson\u2019s disease","volume":"397","author":"Bloem","year":"2021","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Saramowicz, K., Siwecka, N., Galita, G., Kucharska-Lusina, A., Rozp\u0119dek-Kami\u0144ska, W., and Majsterek, I. (2023). Alpha-Synuclein Contribution to Neuronal and Glial Damage in Parkinson\u2019s Disease. Int. J. Mol. 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