Ryul Kim1, Sangmin Park1, Dallah Yoo1, Jin-Sun Jun2, Beomseok Jeon1. 1. From the Department of Neurology (R.K.), Inha University Hospital, Incheon; Department of Neurology (S.P.), School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu; Department of Neurology (D.Y.), Kyung Hee University Hospital; Department of Neurology (J.-S.J.), Kangnam Sacred Heart Hospital, Hallym University College of Medicine; and Department of Neurology (B.J.), College of Medicine, Seoul National University Hospital, Korea. 2. From the Department of Neurology (R.K.), Inha University Hospital, Incheon; Department of Neurology (S.P.), School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu; Department of Neurology (D.Y.), Kyung Hee University Hospital; Department of Neurology (J.-S.J.), Kangnam Sacred Heart Hospital, Hallym University College of Medicine; and Department of Neurology (B.J.), College of Medicine, Seoul National University Hospital, Korea. junjs@hallym.or.kr.
Abstract
OBJECTIVE: To determine whether greater physical activity could modify the negative association of APOE ε4 with longitudinal cognitive changes in early Parkinson disease (PD) and to uncover the disease-specific mechanism for explaining such benefits of physical activity. METHODS: We used data from the Parkinson's Progression Markers Initiative cohort. Because self-reported physical activity, measured by the Physical Activity Scale of the Elderly, was initiated at 2 years after enrollment, this longitudinal analysis was based on assessments performed at years 2, 3, and 4. Cognitive function was measured annually with the Montreal Cognitive Assessment (MoCA). Dopamine transporter (DAT) imaging was performed at years 2 and 4. We assessed the interactive associations between physical activity and the APOE ε4 allele on the longitudinal changes in MoCA scores and striatal DAT activities. RESULTS: A total of 173 patients with early PD (age 63.3 ± 10.0 years, 27% APOE ε4 carriers) were included. The APOE ε4 allele showed a steeper rate of cognitive decline than the non-APOE ε4 allele (estimate -1.33, 95% confidence interval [CI] -2.12 to -0.47, p = 0.002). However, there was a significant interaction between physical activity and APOE ε4 such that higher physical activity was related to slower APOE ε4-related cognitive decline (estimate 0.007, 95% CI 0.003-0.011, p = 0.001). No significant interaction was found between physical activity and the APOE ε4 allele regarding the change in striatal DAT activities. CONCLUSION: Increased physical activity attenuated APOE ε4-related vulnerability to early cognitive decline in patients with PD. This protective effect did not appear to be mediated by striatal dopaminergic function. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT01141023. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that increased physical activity was associated with decreased APOE ε4-related early cognitive decline in patients with PD.
OBJECTIVE: To determine whether greater physical activity could modify the negative association of APOE ε4 with longitudinal cognitive changes in early Parkinson disease (PD) and to uncover the disease-specific mechanism for explaining such benefits of physical activity. METHODS: We used data from the Parkinson's Progression Markers Initiative cohort. Because self-reported physical activity, measured by the Physical Activity Scale of the Elderly, was initiated at 2 years after enrollment, this longitudinal analysis was based on assessments performed at years 2, 3, and 4. Cognitive function was measured annually with the Montreal Cognitive Assessment (MoCA). Dopamine transporter (DAT) imaging was performed at years 2 and 4. We assessed the interactive associations between physical activity and the APOE ε4 allele on the longitudinal changes in MoCA scores and striatal DAT activities. RESULTS: A total of 173 patients with early PD (age 63.3 ± 10.0 years, 27% APOE ε4 carriers) were included. The APOE ε4 allele showed a steeper rate of cognitive decline than the non-APOE ε4 allele (estimate -1.33, 95% confidence interval [CI] -2.12 to -0.47, p = 0.002). However, there was a significant interaction between physical activity and APOE ε4 such that higher physical activity was related to slower APOE ε4-related cognitive decline (estimate 0.007, 95% CI 0.003-0.011, p = 0.001). No significant interaction was found between physical activity and the APOE ε4 allele regarding the change in striatal DAT activities. CONCLUSION: Increased physical activity attenuated APOE ε4-related vulnerability to early cognitive decline in patients with PD. This protective effect did not appear to be mediated by striatal dopaminergic function. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT01141023. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that increased physical activity was associated with decreased APOE ε4-related early cognitive decline in patients with PD.
Authors: Junchao Shen; Noor Amari; Rebecca Zack; R Tyler Skrinak; Travis L Unger; Marijan Posavi; Thomas F Tropea; Sharon X Xie; Vivianna M Van Deerlin; Richard B Dewey; Daniel Weintraub; John Q Trojanowski; Alice S Chen-Plotkin Journal: Ann Neurol Date: 2022-06-07 Impact factor: 11.274
Authors: Charity G Patterson; Elizabeth Joslin; Alexandra B Gil; Wendy Spigle; Todd Nemet; Lana Chahine; Cory L Christiansen; Ed Melanson; Wendy M Kohrt; Martina Mancini; Deborah Josbeno; Katherine Balfany; Garett Griffith; Mac Kenzie Dunlap; Guillaume Lamotte; Erin Suttman; Danielle Larson; Chantale Branson; Kathleen E McKee; Li Goelz; Cynthia Poon; Barbara Tilley; Un Jung Kang; Malú Gámez Tansey; Nijee Luthra; Caroline M Tanner; Jacob M Haus; Giamila Fantuzzi; Nikolaus R McFarland; Paulina Gonzalez-Latapi; Tatiana Foroud; Robert Motl; Michael A Schwarzschild; Tanya Simuni; Kenneth Marek; Anna Naito; Codrin Lungu; Daniel M Corcos Journal: Trials Date: 2022-10-06 Impact factor: 2.728