Parkinson’s Disease Motor Subtypes Change with the Progression of the Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up

Article type: Research Article

Authors: Santos García, Diego^{a; *} | Canfield, Hector^a | de Deus Fonticoba, Teresa^b | Cores Bartolomé, Carlos^a | Naya Ríos, Lucía^a | García Roca, Lucía^a | Martínez Miró, Cristina^a | Jesús, Silvia^{c; d} | Aguilar, Miquel^e | Pastor, Pau^e | Cosgaya, Marina^f | García Caldentey, Juan^g | Caballol, Nuria^h | Legarda, Inésⁱ | Hernández Vara, Jorge^j | Cabo, Iria^k | López Manzanares, Lydia^l | González Aramburu, Isabel^{d; m} | Ávila Rivera, María A.ⁿ | Gómez Mayordomo, Víctor^o | Nogueira, Víctor^p | Puente, Víctor^q | Dotor, Julio^r | Borrué, Carmen^s | Solano Vila, Berta^t | Álvarez Sauco, María^u | Vela, Lydia^v | Escalante, Sonia^w | Cubo, Esther^x | Carrillo Padilla, Francisco^y | Martínez Castrillo, Juan C.^z | Sánchez Alonso, Pilar^aa | Alonso Losada, Maria G.^bb | López Ariztegui, Nuria^cc | Gastón, Itziar^dd | Kulisevsky, Jaime^{d; ee} | Blázquez Estrada, Marta^ff | Seijo, Manuel^k | Rúiz Martínez, Javier^gg | Valero, Caridad^hh | Kurtis, Mónicaⁱⁱ | de Fábregues, Oriol^j | González Ardura, Jessica^jj | Alonso Redondo, Ruben^kk | Ordás, Carlos^ll | López Díaz, Luis M.^mm | McAfee, Darrianⁿⁿ | Martinez-Martin, Pablo^d | Mir, Pablo^{c; d} | COPPADIS Study Group

Affiliations: [a] Complejo Hospitalario Universitario de A Coruña (CHUAC), A Coruña, Spain | [b] Complejo Hospitalario Universitario de Ferrol (CHUF), A Coruña, Spain | [c] Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain | [d] Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Spain | [e] Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain | [f] Hospital Clínic de Barcelona, Barcelona, Spain | [g] Centro Neurológico Oms 42, Palma de Mallorca, Spain | [h] Consorci Sanitari Integral, Hospital Moisés Broggi, Sant Joan Despí, Barcelona, Spain | [i] Hospital Universitario Son Espases, Palma de Mallorca, Spain | [j] Hospital Universitario Vall d'Hebron, Barcelona, Spain | [k] Complejo Hospitalario Universitario de Pontevedra (CHOP), Pontevedra, Spain | [l] Hospital Universitario La Princesa, Madrid, Spain | [m] Hospital Universitario Marqués de Valdecilla, Santander, Spain | [n] Consorci Sanitari Integral, Hospital General de L'Hospitalet, L'Hospitalet de Llobregat, Barcelona, Spain | [o] Hospital Universitario Clínico San Carlos, Madrid, Spain | [p] Hospital Da Costa, Burela, Lugo, Spain | [q] Hospital del Mar, Barcelona, Spain | [r] Hospital Universitario Virgen Macarena, Sevilla, Spain | [s] Hospital Infanta Sofía, Madrid, Spain | [t] Institut d’Assistència Sanitària (IAS) - Institut Català de la Salut, Girona, Spain | [u] Hospital General Universitario de Elche, Elche, Spain | [v] Fundación Hospital de Alcorcón, Madrid, Spain | [w] Fundación Hospital de Alcorcón, Madrid, Spain | [x] Complejo Asistencial Universitario de Burgos, Burgos, Spain | [y] Hospital Universitario de Canarias, San Cristóbal de la Laguna, Santa Cruz de Tenerife, Spain | [z] Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain | [aa] Hospital Universitario Puerta de Hierro, Madrid, Spain | [bb] Hospital Álvaro Cunqueiro, Complejo Hospitalario Universitario de Vigo (CHUVI), Vigo, Spain | [cc] Complejo Hospitalario de Toledo, Toledo, Spain | [dd] Complejo Hospitalario de Navarra, Pamplona, Spain | [ee] Hospital de Sant Pau, Barcelona, Spain | [ff] Hospital Universitario Central de Asturias, Oviedo, Spain | [gg] Hospital Universitario Donostia, San Sebastián, Spain | [hh] Hospital Arnau de Vilanova, Valencia, Spain | [ii] Hospital Ruber Internacional, Madrid, Spain | [jj] Hospital de Cabueñes, Gijón | [kk] Universitario Lucus Augusti (HULA), Lugo, Spain | [ll] Hospital Rey Juan Carlos, Madrid, Spain, Madrid, Spain | [mm] Complejo Hospitalario Universitario de Orense (CHUO), Orense, Spain | [nn] Univeristy of Maryland School of Medicine, Baltimore, MD, USA

Correspondence: [*] Correspondence to: Dr. Diego Santos García, Department of Neurology, Hospital Universitario de A Coruña (HUAC), Complejo Hospitalario Universitario de A Coruña (CHUAC), C/ As Xubias 84, 15006, A Coruña, Spain. Tel.: +34 646173341; E-mail: [email protected]; ORCID: 0000-0002-3126-5111.

Abstract: Background:Motor phenotype (MP) can be associated with a different prognosis in Parkinson’s disease (PD), but it is not fixed and can change over time. Objective:Our aim was to analyze how the MP changed over time and to identify factors associated with the changes in PD patients from a multicenter Spanish PD cohort. Methods:PD patients who were recruited from January-2016 to November-2017 (baseline visit; V0) and evaluated again at a 2-year±30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort, were included in this study.MP was calculated at both visits based on Jankovic classification in TD (tremor dominant), IND (indeterminate), or PIGD (postural instability and gait difficulty). Sociodemographic and clinical data were collected, including serum biomarkers. Results:Five hundred eleven patients (62.57±8.59 years old; 59.2%males) were included in the study. At V0, MP was: 47.4%(242/511) TD; 36.6%(187/511) PIGD; 16%(82/511) IND. Up to 38%(194/511) of the patients changed their phenotype from V0 to V2, being the most frequent from TD to IND (8.4%) and from TD to PIGD (6.7%). A worse cognitive status (OR = 0.966) and less autonomy for activities of daily living (OR  =  0.937) at V0 and a greater increase in the globalNMS burden (OR  =  1.011) from V0 to V2 were associated with changing from TD to another phenotype after 2-year follow-up. Conclusion:The MP in PD can change over time. With disease progression, the percentage of cases with non-tremoric MP increases. PD patients who changed from TD to postural instability and gait difficulty increased NMS burden significantly.

Keywords: Changes, motor, Parkinson’s disease, phenotype, postural instability, gait difficulty, tremor

DOI: 10.3233/JPD-213004

Journal: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 935-955, 2022