Alison J Yarnall1, Antoneta Granic2, Samantha Waite3, Kieren G Hollingsworth4, Charlotte Warren5, Amy E Vincent5, Doug M Turnbull6, Robert W Taylor6, Richard M Dodds2, Avan A Sayer7. 1. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; NIHR Newcastle Biomedical Research Centre, Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. 2. NIHR Newcastle Biomedical Research Centre, Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; AGE Research Group, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne, United Kingdom. 3. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom. 4. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Newcastle Magnetic Resonance Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom. 5. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Wellcome Trust Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom. 6. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Wellcome Trust Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; Newcastle NHS Highly Specialised Mitochondrial Diagnostic Laboratory, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. 7. NIHR Newcastle Biomedical Research Centre, Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; AGE Research Group, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne, United Kingdom. Electronic address: avan.sayer@newcastle.ac.uk.
Abstract
INTRODUCTION: There has been little work on the relationship between sarcopenia, a progressive skeletal muscle disorder, and age-related neurodegenerative diseases such as Parkinson's disease (PD). OBJECTIVES: We aimed to determine: 1) the feasibility of characterizing skeletal muscle across a range of cognitive function in PD; 2) if muscle mitochondrial respiratory chain (MRC) function and content are preserved in older adults with PD. METHODS: Sarcopenia was defined using handgrip strength, chair rise and bioimpedance analysis. MRC function was assessed using phosphorous magnetic resonance spectroscopy (MRS) by estimating τ1/2 PCr (s) (phosphocreatine half-time recovery) in the calf muscles following a bout of aerobic exercise. Biopsy of the vastus lateralis muscle was performed, and MRC content assessed by fluorescent immunohistochemistry for porin and components of MRC Complexes I and IV. RESULTS: Nine participants (78% male; mean age 79.9; PD duration 3.3 years) were recruited. Four had cognitive impairment. Six participants had probable sarcopenia. Eight participants completed MRS and had mean (SD) τ1/2 PCr of 37.8 (7.6) seconds, suggesting preserved mitochondrial function. Muscle biopsies were obtained in all and the procedure was well tolerated. Porin Z-score, a proxy for mitochondrial mass, was lower than expected compared to controls (0-89% of fibres with low porin). There was a small amount of Complex I (0.16-4.59%) and Complex IV (0-3.79%) deficiency. CONCLUSIONS: Detailed phenotyping, muscle biopsy and imaging was feasible and acceptable across a spectrum of cognitive function in PD. Sarcopenia was relatively common and may be associated with lower mitochondrial mass and low levels of MRC deficiency.
INTRODUCTION: There has been little work on the relationship between sarcopenia, a progressive skeletal muscle disorder, and age-related neurodegenerative diseases such as Parkinson's disease (PD). OBJECTIVES: We aimed to determine: 1) the feasibility of characterizing skeletal muscle across a range of cognitive function in PD; 2) if muscle mitochondrial respiratory chain (MRC) function and content are preserved in older adults with PD. METHODS:Sarcopenia was defined using handgrip strength, chair rise and bioimpedance analysis. MRC function was assessed using phosphorous magnetic resonance spectroscopy (MRS) by estimating τ1/2 PCr (s) (phosphocreatine half-time recovery) in the calf muscles following a bout of aerobic exercise. Biopsy of the vastus lateralis muscle was performed, and MRC content assessed by fluorescent immunohistochemistry for porin and components of MRC Complexes I and IV. RESULTS: Nine participants (78% male; mean age 79.9; PD duration 3.3 years) were recruited. Four had cognitive impairment. Six participants had probable sarcopenia. Eight participants completed MRS and had mean (SD) τ1/2 PCr of 37.8 (7.6) seconds, suggesting preserved mitochondrial function. Muscle biopsies were obtained in all and the procedure was well tolerated. Porin Z-score, a proxy for mitochondrial mass, was lower than expected compared to controls (0-89% of fibres with low porin). There was a small amount of Complex I (0.16-4.59%) and Complex IV (0-3.79%) deficiency. CONCLUSIONS: Detailed phenotyping, muscle biopsy and imaging was feasible and acceptable across a spectrum of cognitive function in PD. Sarcopenia was relatively common and may be associated with lower mitochondrial mass and low levels of MRC deficiency.