Effects of Aerobic Exercise in Parkinson's Disease
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Study type: Interventional

Summary: 
      Motivated by reported improvements in aerobic fitness and executive functions after a 6-month
      aerobic walking intervention in normal sedentary elderly, we conducted a Phase I/II study to
      investigate effects of aerobic exercise on motor function, cognition, and quality of life in
      mild-moderate patients with Parkinson's disease (PD). To identify the best method to deliver
      fitness training, we also aimed to compare safety, tolerability, and fitness benefits between
      different training methods (continuous/moderate intensity vs. interval/alternating between
      low and vigorous intensity) and exercise settings (individual vs. group). Interval training
      reportedly facilitates higher fitness gains than continuous training. Group training may
      promote success through social interaction, whereas individual training offers greater
      flexibility.

      Details of the study can be found in the publication below:

      Phase I/II randomized trial of aerobic exercise in Parkinson disease in a community setting.

      Uc EY, Doerschug KC, Magnotta V, Dawson JD, Thomsen TR, Kline JN, Rizzo M, Newman SR, Mehta
      S, Grabowski TJ, Bruss J, Blanchette DR, Anderson SW, Voss MW, Kramer AF, Darling WG.

      Neurology. 2014 Jul 29;83(5):413-25. doi: 10.1212/WNL.0000000000000644. Epub 2014 Jul 2.

      PMID: 24991037
    

Detailed description: 
      Participants:

      The participants were recruited in Spring 2009, 2010, and 2011 through regional newspaper
      advertisements and solicitations in the Movement Disorders Clinic at the University of Iowa
      and the Veterans Affairs Medical Center of Iowa City. We phone screened respondents and
      evaluated eligible candidates in-person using clinical examination, MMSE, 12-lead ECG, blood
      count and biochemistry, followed by graded exercise test using cycle ergometry within one
      week of starting the intervention. At each visit, we obtained body weight and height, heart
      rate and blood pressure after 5 minutes of supine rest [Goldberg et al. 1988] and after 3
      minutes of standing. Throughout the study, the medications of participants continued to be
      managed by their treating neurologists.

      Inclusion criteria: Idiopathic PD; Hoehn and Yahr Scale I-III; men or women aged 50-80;
      stable dopaminergic treatment regimen for at least 4 weeks prior to baseline not requiring
      adjustment.

      Exclusion criteria: Current participation in an aerobic exercise program; Mini Mental Status
      Exam score <24; confounding medical, orthopedic or psychiatric disorders; cardiac
      abnormalities during cycle ergometry.

      Design:

      Initial design was a 2x2 randomized trial of different training methods (continuous vs.
      interval) and settings (individual vs. group). Sample size was estimated using 80% power to
      detect an effect size of 0.66 SD in VO2max (estimated improvement=10% /estimated SD of
      change=15%) within each arm at alpha=0.05 and an attrition rate of 25%.

      During the first two years, the participants were randomized in blocks of four to continuous
      or interval training. Logistical factors (e.g., rural residence) precluded randomization to
      group setting, leading to convenience-based assignments in the first year, and dropping of
      the group setting afterwards. In the third year, all participants were assigned to the
      continuous arm after preliminary analyses of prior data raised safety concerns about interval
      training.

      Intervention:

      The maximal heart rate (HRmax) in the exercise prescription was based on age [Goldberg,
      Elliot, and Kuehl1988] and reduced by 20% in participants who used beta-blockers [Wonisch et
      al. 2003]. The duration of exercise sessions (3x/week) was advanced from 15 to 45 minutes
      over the first 6 weeks. The goal for continuous training was to remain within 70-80% of HRmax
      throughout the session. Interval trainees alternated every 3 minutes between slower (60-70%
      of HRmax) and faster (80-90% of HRmax) walking[Wisloff et al. 2007]. We emphasized that these
      parameters were for guidance only and that the participants should give their best effort
      without feeling uncomfortable or unsafe.

      Participants were asked to wear electronic heart rate and walking speed monitors (Polar
      RS400, Kempele, Finland) and fill out diaries for each session. A trainer facilitated group
      training at a track and collected monitor data and exercise diaries. Trainers conducted home
      visits for the individual arm participants to choose walking routes (a primary outdoor route
      and an alternative indoor route) and orient the participant about safe exercise procedures,
      followed by biweekly home visits to monitor safety and compliance.

      Efficacy Measures:

      The participants were tested while on their usual antiparkinsonian regimen, always with
      adequate symptom control to allow comfortable participation in the protocol, at baseline and
      at the end of the intervention by evaluators blinded to the treatment arm, but not to
      pre-post training status.

      Aerobic fitness: Oxygen uptake (VO2) was measured from expired air samples on a
      breath-by-breath basis during cycle ergometry. We verified maximal effort when 2 of 3
      criteria were met [Balady et al. 2010]: 1) a plateau in VO2 between two or more workloads, 2)
      respiratory exchange ratio ≥1.10, and 3) HR > 85% of the age predicted HRmax.

      Cognition: Due to sensitivity of the Eriksen's flanker task performance to changes in aerobic
      fitness status [Colcombe et al. 2004;Kluding et al. 2011], we chose change in Percent
      Increase Score (PIS) on flanker task as the primary cognitive outcome measure. Participants
      were asked to identify the orientation of a central arrow cue ('<' or '>'), which was flanked
      on both sides by two arrow cues that either pointed in the same direction (congruent: <<<<<)
      or a different direction (incongruent: >><>>). Using reaction times (RT) during congruent and
      incongruent trials, the PIS was calculated as =((RT_incongruent - RT_congruent) /
      RT_congruent) * 100.[Colcombe, Kramer, Erickson, Scalf, McAuley, Cohen, Webb, Jerome,
      Marquez, and Elavsky2004] The Stroop test was used as another measure of inhibition.

      We assessed set shifting using Wisconsin Card Sorting Test and Trail-Making Test (B-A),[Uc,
      Rizzo, Johnson, Dastrup, Anderson, and Dawson2009] visual perception using Judgment of Line
      Orientation and Complex Figure Test (CFT)-Copy, verbal memory using Rey Auditory Verbal
      Learning Test, visual memory using CFT-Recall, language using Controlled Oral Word
      Association Test,[Uc, Rizzo, Johnson, Dastrup, Anderson, and Dawson2009] and general
      cognition using Montreal Cognitive Assessment.[Chou et al. 2010] Parkinsonism: Unified
      Parkinson's Disease Rating Scale and timed motor tests (7m Walk and finger tapping),[Defer et
      al. 1999] Functional Reach test for balance,[Uc, Rizzo, Johnson, Dastrup, Anderson, and
      Dawson2009] total daily levodopa equivalents,[Tomlinson et al. 2010] and a patient diary
      [Hauser et al. 2004].

      Quality of life: Fatigue Severity Scale,[Friedman et al. 2011] Geriatric Depression
      Scale,[Uc, Rizzo, Johnson, Dastrup, Anderson, and Dawson2009] PD Quality of Life Scale
      (PDQUALIF) [Welsh et al. 2003].

      Statistical analysis Two-sample t-tests, Wilcoxon Rank-Sum, or Fisher's Exact tests were used
      to compare baseline features and exercise characteristics and outcomes between different
      treatment arms, and between the completers and dropouts, and to compare baseline cognitive
      performance of our PD participants with controls from our driving studies.[Uc, Rizzo,
      Johnson, Dastrup, Anderson, and Dawson2009] Regression methods were used to adjust these
      comparisons for age, education, and gender.

      As all treatment arms were designed to deliver a similar average aerobic intensity, we
      planned to pool a priori all completers throughout the study to analyze the effects of
      aerobic exercise with higher statistical power. We used Wilcoxon Signed Ranks tests or paired
      t-tests to compare final vs. baseline outcomes. When a significant change in outcomes was
      observed, we used regression models to assess and adjust for the effect of different settings
      and training methods, calendar year, and change in levodopa equivalent. We also used Pearson
      correlations and regression models to quantify associations of changes in outcomes with
      changes in aerobic fitness.

      The analyses of magnetic resonance imaging studies and other biomarkers is continuing and
      will be published in the future.

      Reference List

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      Chou KL, Amick MM, Brandt J et al. A recommended scale for cognitive screening in clinical
      trials of Parkinson's disease. Mov Disord 2010; 25: 2501-2507.

      Colcombe SJ, Kramer AF, Erickson KI et al. Cardiovascular fitness, cortical plasticity, and
      aging. Proc Natl Acad Sci U S A 2004; 101: 3316-3321.

      Defer GL, Widner H, Marie RM, Remy P, Levivier M. Core assessment program for surgical
      interventional therapies in Parkinson's disease (CAPSIT-PD). Mov Disord 1999; 14: 572-584.

      Friedman JH, Abrantes A, Sweet LH. Fatigue in Parkinson's disease. Expert Opin Pharmacother
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      Goldberg L, Elliot DL, Kuehl KS. Assessment of exercise intensity formulas by use of
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      Hauser RA, Deckers F, Lehert P. Parkinson's disease home diary: Further validation and
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      Kluding PM, Tseng BY, Billinger SA. Exercise and executive function in individuals with
      chronic stroke: a pilot study. J Neurol Phys Ther 2011; 35: 11-17.

      Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE. Systematic review of levodopa dose
      equivalency reporting in Parkinson's disease. Mov Disord 2010; 25: 2649-2653.

      Uc EY, Rizzo M, Johnson AM, Dastrup E, Anderson SW, Dawson JD. Road Safety in Drivers with
      Parkinson Disease. Neurology 2009; 73: 2112-2119.

      Welsh M, McDermott MP, Holloway RG, Plumb S, Pfeiffer R, Hubble J. Development and testing of
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      Wisloff U, Stoylen A, Loennechen JP et al. Superior cardiovascular effect of aerobic interval
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      Wonisch M, Hofmann P, Fruhwald FM et al. Influence of beta-blocker use on percentage of
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Intervention name(s): Continuous training; Interval training
Intervention type(s): Behavioral; Behavioral
Intervention description(s): The maximal heart rate (HRmax) in the exercise prescription was based on age[Goldberg, Elliot, and Kuehl1988] and reduced by 20% in participants who used beta-blockers.[Wonisch et al. 2003] The duration of exercise sessions (3x/week) was advanced from 15 to 45 minutes over the first 6 weeks. The goal for continuous training was to remain within 70-80% of HRmax throughout the session.; Interval trainees alternated every 3 minutes between slower (60-70% of HRmax) and faster (80-90% of HRmax) walking [Wisloff et al. 2007].
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Parkinson Disease; Exercise/*physiology; *Physical Fitness; Rehabilitation; Cognition