Physical Activity and Cognitive Function in Multiple Sclerosis

Transcription

1 RESEARCH NOTE Journal of Sport & Exercise Psychology, 2011, 33, Human Kinetics, Inc. Physical Activity and Cognitive Function in Multiple Sclerosis Robert W. Motl, 1 Eduard Gappmaier, 2 Kathryn Nelson, 2 and Ralph H.B. Benedict 3 1 University of Illinois; 2 University of Utah; 3 SUNY Buffalo Cognitive impairment is prevalent, disabling, and poorly managed in persons with multiple sclerosis (MS). This cross-sectional study examined the associations among physical activity, cognitive processing speed, and learning and memory in 33 persons with MS who underwent neuropsychological assessments and wore a physical activity monitor for 7 days. Cognitive impairment was greatest in cognitive processing speed. Physical activity was significantly correlated with cognitive processing speed (pr =.35), but not learning and memory (pr =.20), after controlling for sex, age, and education. Researchers should examine exercise training and physical activity effects on cognitive performance, particularly processing speed, in MS. Keywords: multiple sclerosis, exercise, cognitive impairment There is extensive evidence that cognition, particularly cognitive processing speed and episodic memory, is impaired, even in the absence of physical disability, among a large number of persons with multiple sclerosis (MS; Rao, Leo, Bermadin, & Unverzagt, 1991). Such cognitive impairment is largely associated with wholebrain atrophy (Benedict et al., 2006a) and topographically specific atrophy within the frontal and temporal cortices (Benedict et al., 2005; Calabrese et al., 2010) as similarly seen in aging (Colcombe et al., 2003). We note that cognitive impairment negatively impacts a range of activities (e.g., work, driving, social interaction, and medication adherence) and quality of life in this population (Benedict, 2005), and there are no approved medical therapies for cognitive impairment in MS (Benedict & Zivadinov, 2011). Collectively, the prevalence, burden, and poor management of cognition impairment underscore the importance of considering other approaches for its mitigation in persons with MS. There is evidence indicating that exercise training is associated with beneficial outcomes other than cognition in MS. Exercise training has been associated with Robert W. Motl is with the Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL. Eduard Gappmaier and Kathryn Nelson are with the Department of Physical Therapy, University of Utah, Salt Lake City, UT. Ralph H.B. Benedict is with the Department of Neurology, SUNY Buffalo School of Medicine, Buffalo, NY. 734

2 Physical Activity and Cognitive Function in MS 735 improvements in aerobic capacity and muscle strength, symptoms of fatigue and mood, walking mobility, and quality of life in persons with MS (Garrett & Coote, 2009; Motl & Gosney, 2008; Snook & Motl, 2009). We further note that similar beneficial outcomes of exercise training have been reported in older adults (e.g., Gu & Conn, 2008; Netz, Wu, Becker, & Tenenbaum, 2005). This is important for supporting the possibility that the positive effects of aerobic fitness and exercise training on both cognition and brain structure (i.e., whole brain and regional gray and white matter volumes) in healthy and impaired older adults (Colcombe & Kramer, 2003; Kramer & Erickson, 2007) might be applicable in persons with MS. Research examining aerobic fitness and exercise training in association with cognition among persons with MS is nascent yet critical given the prevalence, impact, and poor management of this impairment. To date, researchers have reported that aerobic capacity (i.e., peak oxygen consumption) was associated with better cognition as measured by Paced Auditory Serial Addition Test (PASAT) and Symbol Digit Modalities Test (SDMT) in persons with MS; there were no associations with measures of learning and memory provided by the Selective Reminding Test (SRT) and Spatial Recall Test (Prakash et al., 2007; Prakash, Snook, Motl, & Kramer, 2010). One limitation of that previous research (Prakash et al., 2007, 2010) was the focus on aerobic capacity because this fitness characteristic is a physiological surrogate of physical activity that does not adequately address the nature of association between physical activity as a modifiable behavior and outcomes such as cognition (cf., Williams, 2001). This cross-sectional study examined the association between free-living physical activity and neuropsychological measures of cognitive processing speed and learning and memory in persons with MS, after controlling for sex, education, and age. The cross-sectional design is consistent with previous research on physical activity and cognition (Gapin & Etnier, 2010) and appropriate for providing preliminary proof-of-principle data for designing and conducting a randomized controlled trial (RCT) of physical activity and cognition in MS. Based on previous research of healthy and impaired older adults (Colcombe & Kramer, 2003; Kramer & Erickson, 2007), we expected that those with MS who were more physically active would perform better on neuropsychological tests of cognitive processing speed and learning and memory given similarities in brain pathobiology of cognitive impairment and beneficial outcomes of exercise training in MS and aging populations. Participants Method The sample included 33 (22 female) participants who underwent neuropsychological and physical activity assessment as part of entry into the University of Utah Multiple Sclerosis Rehabilitation and Wellness Program. The data were collected as part of a routine clinical intake assessment, rather than for eligibility or inclusion criteria, for the program and were not part of a RCT. Participants were ambulatory and had a diagnosis of definite MS. Participants ranged in age between 39 and 79 years with a mean of 59.0 years (SD = 10.0 years). Of the 33 participants, 5 were high-school graduates, 14 had some college education, and 14 were college graduates. The average time since diagnosis was 17.6 years (SD = 10.0 years) and ranged

3 736 Motl et al. between 3 and 42 years. The sample had a range of Expanded Disability Status Scale scores between 3.5 and 7.0 with an interquartile range of 2.25 and median of 6.0. Procedure The procedure was approved by a university institutional review board, and all participants provided appropriately obtained written informed consent and then demographic and clinical information. Participants completed a neuropsychological test battery based on consensus opinion of gold standard approaches in MS (e.g., Benedict et al., 2002; Rao et al., 1991), and cognitive processing speed and episodic memory were emphasized, as these domains are most commonly affected in MS (Chiaravalloti & DeLuca, 2008; Rao et al., 1991). The neuropsychological testing included the 3-s PASAT (Gronwall, 1977), SDMT (Smith, 1982), SRT (Buschke & Fuld, 1974), and Brief Visuospatial Memory Test Revised (BVMT-R; Benedict, 1997). The participants further wore a StepWatch (Cymatech, Seattle, WA) Step Activity Monitor (SAM) during the waking hours of a 7-day period as a measure of free-living physical activity (Busse, Pearson, Van Deursen, & Wiles, 2004). The SAM is a small ( mm), lightweight (1.3 oz), and waterproof, dual-axis, microprocessor-driven accelerometer that is attached around the ankle with a Velcro strap. The unit is calibrated per participant and will not record leg movements while lying in bed. The SAM is 98% accurate in recording steps in a variety of clinical populations with slow or shuffling gait, including persons with MS (Busse et al., 2004). The SAM recorded steps in 1-min intervals, synchronized on a 24-hr clock (midnight to midnight), and resulted in a temporal series of 1,440 observations per day. Participants documented wear times on a log and we only included days with a minimum wear time of 8 hr when generating the outcome of average steps per day over a 7-day period. The SAM does provide other metrics on the intensity of physical activity that are based on the rate of steps per minute, but such metrics have not been validated in persons with MS. This would question the integrity and interpretation of those metrics if included in the current study. All participants had three or more days of valid data and this is satisfactory for a reliable measure of physical activity in MS (Motl et al., 2007). Statistical Analysis All analyses were completed using PASW version 18.0 (SPSS Inc, Chicago, IL) and significance was noted at p <.05 with a one-tailed test given our directional hypotheses. We examined the extent of cognitive impairment by comparing the scores on the neuropsychological assessments with normative data from a control sample (Strober et al., 2009) and creating z scores. The control sample in that study included 46 healthy volunteers (39 women and 7 men) with a mean age of 45.2 (SD = 9.9) years and mean education of 15.0 (SD = 1.8) years who were group matched with the MS sample (Strober et al.). The control and MS samples further did not differ in gender or ethnic distribution (Strober et al.). Subsequent values for cognitive function were presented as mean ± standard deviation for the z-scores. We then created composite scores for cognitive processing speed (mean of z score

4 Physical Activity and Cognitive Function in MS 737 for PASAT and SDMT) and learning and memory (mean of z score for SRT and BVMT-R) and examined the association with physical activity using Pearson product moment correlation coefficients (r) and partial correlation coefficients (pr) that controlled for sex, education, and age. We combine tests into a composite z score based on previous work (Prakash et al., 2007, 2010) for improving the reliability of the measures of cognitive processing speed and learning and memory. We further developed composite scores based on factor analytic results, separating cognitive processing speed and memory factors (Benedict et al., 2006b) as a method of reducing the data set and avoiding type-1 error. Results The mean scores (SD) for the SDMT, PASAT, SRT, and BVMT-R among those with MS in this study were 40.3 (10.1), 37.1 (10.6), 45.5 (11.8), and 21.2 (6.3), respectively. The present study did not have a control group or sample, and the corresponding normative values from a separate control sample (Strober et al., 2009) for creating z scores were 62.1 (10.7), 49.7 (9.8), 51.5 (7.3), and 26.2 (5.8), respectively. The mean z scores for neuropsychological tests indicated cognitive impairment was greatest in the SDMT ( 2.0 ± 0.9 SDs worse than normative controls) and PASAT ( 1.3 ± 1.1 SDs worse than normative controls). There was less cognitive impairment on the SRT ( 0.8 ± 1.6 SDs worse than normative controls) and BVMT-R ( 0.9 ± 1.1 SDs worse than normative controls). The mean z scores were 1.7 ± 0.9 and 0.8 ± 1.2 for the composites of cognitive processing speed and learning and memory, respectively. The mean score from the SAM was 2,396 steps per day (SD = 1,531 steps per day, median = 2,333 steps per day) with a range between 30 and 5,733 steps per day. The standardized skewness and kurtosis values were 0.90 and 0.66, respectively. The mean value from the SAM is consistent with other samples of persons with MS (Busse et al., 2004) who had a mean value of 2,985 steps per day (range = 689 5,340 steps per day). Physical activity was significantly associated with the composite of cognitive processing speed (r =.39, p =.023), and the association was still statistically significant when controlling for sex, education, and age (pr =.35, p =.047). The association was not altered when removing the person with 30 steps per day (r =.38, p =.029) or in a nonparametric analysis that included the entire sample (ρ =.36, p =.031). The partial regression scatter plot, along with the line of best fit and 95% confidence interval, is provided in the upper part of Figure 1. The association was nearly significant between physical activity and the composite of learning and memory (r =.28, p =.082), but not after controlling for sex, education, and age (pr =.20, p =.176). The association was slightly altered when removing the person with 30 steps per day (r =.34, p =.044), but in a nonparametric analysis that included the entire sample (ρ =.21, p =.147). The partial regression scatter plot, along with the line of best fit and 95% confidence interval, is provided in the lower part of Figure 1.

5 Figure 1 Partial regression plots, along with the line of best fit and 95% confidence interval, for the associations among physical activity and cognitive processing speed and learning and memory, controlling for sex, age, and education. 738

6 Physical Activity and Cognitive Function in MS 739 Discussion The primary, novel finding of this study was a positive association between objectively measured physical activity and cognitive processing speed in MS, after controlling for age, education, and sex; physical activity was not significantly associated with learning and memory. This complements and extends previous research demonstrating that aerobic capacity is associated with cognitive processing speed in persons with MS (Prakash et al., 2007, 2010). The findings of our current study and those of previous research (Prakash et al., 2007, 2010) provide the proofof-principle evidence for the design and implementation of a RCT examining the effects of either exercise training or physical activity on cognitive performance, particularly cognitive processing speed, in persons with MS. Such a RCT would seem imperative given that cognitive impairment is prevalent, life altering, and poorly managed in persons with MS (Benedict & Zivadinov, 2011). There are important similarities in the brain pathobiology of cognitive impairment between MS and aging populations. Indeed, cognition impairment in persons with MS is largely associated with whole-brain atrophy (Benedict et al., 2006a) and atrophy within the frontal and temporal cortices (Benedict et al., 2005; Calabrese et al., 2010) as seen in aging (Colcombe et al., 2003). This is important because the beneficial changes in cognition associated with aerobic fitness and exercise training have coincided with alterations in brain cortical structure based on magnetic resonance imaging (MRI) protocols in older adults (Kramer & Erickson, 2007). For example, one study (Colcombe et al., 2003) examined the association between aerobic fitness (estimated VO 2 max from the Rockport 1-mile walk protocol) and gray and white matter density maps using MRI and voxel-based morphometry in a sample of 55 older adults. Aerobic fitness was associated with the amelioration of age-related declines in brain gray and white matter density, with the greatest sparing of anterior white matter tracts and gray matter density in prefrontal and temporal cortices; those regions and tracts are critical in cognition and researchers have reported similar associations between cardiorespiratory fitness and brain gray and white matter density in MS (Prakash et al., 2007, 2010). This suggests that there might be similarity in the mechanisms for improvements in cognition after exercise training between MS and aging. Such an observation is important for isolating a potential common neural basis for exercise-training effects on cognition. Strengths of the current study include neuropsychological testing with gold standard methods; assessment of physical activity using an objective measure; and control for potential confounders, namely, sex, education, and age. There is a notable limitation: the cross-sectional design does not establish causality among variables, and cognitive function might be as important for being physically active as vice versa. Nevertheless, we are intrigued by the data and wonder about the implications of physical activity for improving cognitive impairment in MS a common, disabling, and poorly managed condition (Benedict & Zivadinov, 2011). To that end, a RCT of exercise training or lifestyle physical activity for improving cognitive performance in MS might be a worthwhile endeavor, particularly given the growing literature indicating that exercise training results in better cognitive functioning among older adults by improving brain cortical structure, function, and connectivity (Kramer & Erickson, 2007).

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