Constipation Predicts Cognitive Decline in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-up and Comparison with a Control Group

Article type: Research Article

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

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

Abstract: Background:Constipation has been linked to cognitive impairment development in Parkinson’s disease (PD). Objective:Our aim was to analyze cognitive changes observed in PD patients and controls from a Spanish cohort with regards to the presence or not of constipation. Methods:PD patients and controls recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were followed-up during 2 years. The change in cognitive status from baseline (V0) to 2-year follow-up was assessed with the PD-CRS (Parkinson’s Disease Cognitive Rating Scale). Subjects with a score ≥1 on item 21 of the NMSS (Non-Motor Symptoms Scale) at baseline (V0) were considered as “with constipation”. Regression analyses were applied for determining the contribution of constipation in cognitive changes. Results:At V0, 39.7% (198/499) of PD patients presented constipation compared to 11.4% of controls (14/123) (p < 0.0001). No change was observed in cognitive status (PD-CRS total score) neither in controls without constipation (from 100.24±13.72 to 100.27±13.68; p = 0.971) and with constipation (from 94.71±10.96 to 93.93±13.03; p = 0.615). The PD-CRS total score decreased significantly in PD patients with constipation (from 89.14±15.36 to 85.97±18.09; p < 0.0001; Coehn’s effect = –0.35) compared to patients without constipation (from 93.92±15.58 to 93.14±17.52; p = 0.250) (p = 0.018). In PD patients, to suffer from constipation at V0 was associated with a decrease in the PD-CRS total score from V0 to V2 (β= –0.1; 95% CI, –4.36 – –0.27; p = 0.026) and having cognitive impairment at V2 (OR = 1.79; 95% CI, 1.01 – 3.17; p = 0.045). Conclusion:Constipation is associated with cognitive decline in PD patients but not in controls.

Keywords: Cognition, constipation, impairment, non-motor symptoms, Parkinson’s disease

DOI: 10.3233/JPD-212868

Journal: Journal of Parkinson's Disease, vol. 12, no. 1, pp. 315-331, 2022