Aging with Multiple Sclerosis

Aging With Multiple Sclerosis

An Agenda for Examining the Effects of Physical Acitivty Behavior

Rachel E. Bollaert, PhD; Robert W. Motl, PhD

Topics in Geriatric Rehabilitation

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Abstract

This review discusses research on physical and cognitive function, physical activity behavior, and physical activity interventions in older adults with multiple sclerosis (MS). Research indicates that older adults with MS demonstrate reduced physical and cognitive function as well as physical activity compared with healthy older adults. Preliminary evidence suggests that levels and patterns of physical activity are associated with physical function and possibly cognition, and physical activity interventions can improve physical function in older adults with MS. Additional research is warranted that further clarifies the value and role of physical activity in managing the functional consequences of aging with MS.

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Multiple sclerosis (MS) is a chronic, often progressive, neurologic disease of the central nervous system,1 with an estimated prevalence of 1 per 1000 people in the United States.2 This disease has typically been described as occurring most often in young and middle-aged adults, but there is evidence of a demographic shift in the prevalence such that it is now common among older adults.3 For example, the peak prevalence of MS in Manitoba, Canada, occurred at 35 to 39 years of age, with no documented cases beyond an age of 64 years, in 1984.4 By 2004, the peak prevalence was at 55 to 59 years of age, with cases of MS documented beyond 80 years of age.4 This coincides with increased survival of those with MS, as 90% of adults with MS may live to be 70 years and older.5

Older adults with MS, operationally defined as those 60 years and older, undergo the effects of aging over and beyond the preexisting effects of MS itself6,7: this represents a state of aging with disability. There is consistent evidence that aging and MS separately are associated with declines in physical and cognitive function,8,9 and older adults with MS likely have even worse function than young and middle-aged adults with MS.10,11 This situation requires focal attention regarding approaches for managing the compounding effects of MS and aging among older adults living with this disease from an early age.

Unfortunately, there are few pharmacological options for managing worsening function in older adults with MS. The 15 Food and Drug Administration-approved disease-modifying therapies (DMTs) have primarily been tested in younger and middle-aged adults with relapsing-remitting MS, and may have no association with disability progression or effect on functional outcomes in older adults with MS.7 Accordingly, this requires a focus on alternative approaches, such as physical activity behavior, for managing the consequences of aging with MS. The focus on alternative approaches is warranted based on evidence for the benefits of physical activity participation among young and middle-aged adults with MS12,13 and older adults from the general population.14,15 We define physical activity as any bodily movement produced by contraction of skeletal muscles that results in a substantial increase in energy expenditure above resting levels, and exercise is a subset of physical activity that is planned, structured, and repetitive with the objective of improving or maintaining fitness.16

This review discusses existing research involving older adults with MS regarding (1) physical and cognitive function; (2) levels and rates of physical activity and sedentary behavior; (3) associations among physical activity, sedentary behavior, and physical and cognitive function; and (4) physical activity and exercise interventions for the promotion of healthy aging in MS. Such an endeavor will support our call for action involving focal research examining exercise and physical activity effects on functional outcomes in older adults with MS.

 

Physical and Cognitive Function in Older Adults with MS

The first section of this article focuses on declines in physical and cognitive function among older adults with MS. We do so because these 2 functions are among those valued most by people living with MS17 with direct relevance for independence and quality of life (QOL). We further note that declines in these functions commonly occur with normal aging in the absence of neurological disease and with the onset and worsening of MS in young and middle-aged adults. We discuss research examining these functions in older adults with MS as an indication of the effects of aging with MS on physical and cognitive status.

Physical function in older adults with MS

There is evidence from epidemiological18–20 and qualitative21–24 studies indicating that older age is associated with the loss of mobility in people with MS. This has informed more recent and focal efforts examining the effect of aging with MS on objectively measured physical function based on the Short Physical Performance Battery (SPPB).25 The SPPB is a widely applied, objective measure for quantifying lower extremity function in older adults that was originally developed for the purpose of determining risk of disablement and likelihood of assisted living placement.26 This measure includes standardized assessments of balance, gait speed, and repeated chair stands that can be quickly and easily administered by researchers and clinicians. The scores for each assessment range between 0 and 4 and can be summed into a total score that ranges between 0 and 12; higher SPPB scores reflect better lower extremity function. Previous research in healthy older adults has demonstrated a 1-point change in the total SPPB score aligned with meaningful differences in the risk for future mortality and nursing home admission.25

One initial study examined the validity of the SPPB as an objective measure of physical function in older adults with MS.27 Of note, this study reported that a sample of 48 older adults with MS (median age = 60 years; median Expanded Disability Status Scale (EDSS) score = 4.5) had a median SPPB score of 9.0, and this approached the expected SPPB score for nondisabled, healthy adults 71 years and older (mean SPPB score = 9.2).28 This suggests that older adults with MS might demonstrate a reduction in physical performance nearly 11 years soon than peers without MS. We further note that the lower extremity strength component (ie, repeated chair stands) of the SPPB demonstrated larger decrements in physical function (median = 1.0; interquartile range [IQR] = 1.0) than the measurements of gait speed (median = 4.0; IQR = 1.0) and balance (median = 4.0; IQR = 1.0).27 This implies that lower extremity strength, as measured by repeated chair stands, might explain the reduction of physical function among older adults with MS.

Another study compared levels of physical function, using the SPPB, in a community-dwelling sample of 20 older adults with MS (age ≥60 years; median EDSS = 4.5) and 20 healthy controls matched on sex and age.29 The median SPPB scores for older adults with MS and healthy controls were 10.0 and 11.5, respectively. There were statistically significant differences (P < .05) between groups for the overall SPPB score and the balance and gait speed component scores. The effect sizes, measured using Cliff's d (a nonparametric version of effect size that is comparable with Cohen's d), demonstrated that the differences were small to moderate in magnitude (d = 0.30-0.46). The difference between groups in the repeated chair stands component approached significance (d = 0.34). Of note, only 2 controls had SPPB scores below 10 (ie, 10%), whereas 8 older adults with MS had SPPB scores below 10 (ie, 40%); this represented a significant, 4-fold increase in the risk for future disability (P = .028) among the older adults with MS.29

We are aware of one study that examined differences between persons with MS (n = 698; 29-71 years of age) and healthy controls (n = 226; 18-72 years of age) on Timed 25-Foot Walk (T25FW) performance across the lifespan.9 The T25FW is a measure of walking speed over a short distance and is considered one of the best measures of ambulatory functioning for persons with MS.30 The linear regression models demonstrated an overall impact of aging on the T25FW with a linear decline in performance with increasing age in both groups. Notably, there was an age by MS diagnosis interaction for the T25FW, such that the age-related decline in T25FW performance was steeper in MS than controls. This suggests that the progression of physical dysfunction may be amplified by aging in MS compared with healthy controls.

One recent study included a comprehensive battery of physical function tests and compared the outcomes in 40 older adults with MS (age ≥60 years; median EDSS = 4.0) and 40 healthy older adults matched for age and sex.31 The measures of physical function included the SPPB and T25FW as well as the 6-minute walk (6MW), Timed Up-and-Go (TUG), and Six-Spot Step Test; these other measures provided a more comprehensive picture of walking endurance and mobility in older adults with MS. The older adults with MS demonstrated significantly worse performance (P < .05) on all outcomes than controls. Importantly, the measures of physical function demonstrated either moderate or large differences between older adults with MS and age- and sex-matched healthy controls based on effect size estimates (Cohen's d). Regarding the T25FW, older adults with MS completed the assessment in 7.3 (standard deviation [SD] = 3.7) seconds compared with 4.3 (SD = 0.6) seconds for healthy controls. Previous research demonstrated that a T25FW time between 6.0 and 7.99 seconds was associated with occupational disability and needing “some help” with instrumental activities of daily living in middle-aged adults with MS.32 The mean total SPPB score of 9.1 was comparable with values previously reported in older adults with MS27,29 and was further below the cut-off value of 10.0, thereby indicating elevated risk for developing future disability.28

Cognitive function in older adults with MS

There are data from a qualitative study in adults with MS and associated caregivers regarding the perceptions of cognitive function.33 The sample consisted of 279 dyads of persons with MS (mean age = 62.8 years; mean disease duration = 18.3 years) and caregivers. Cognition was measured using an interview question that addressed poor concentration and forgetfulness with response options of “not a problem,” “interferes a little bit,” or “interferes a great deal” with daily activities. The responses were used to identify those experiencing cognitive symptoms. Approximately 61% of persons with MS reported cognitive symptoms that interfered with engagement in everyday activities. Approximately 62.7% of caregivers reported that care recipients experienced cognitive symptoms. This provides convergent qualitative evidence (ie, agreement between dyads) for the presence of cognitive decline with age in adults with MS that can be supplemented and documented more fully by neuropsychological testing.

To that end, one study examined performance on neuropsychological measures of information processing speed and interference (i.e., Stroop Color and Word Naming Tests) between groups of adults with MS (n = 245) and healthy age- and sex-matched controls (n = 188) across 5 age cohorts (ie, 18-29, 30-39, 40-49, 50-58, and 59-74 years of age).8 Overall, there were significant main effects for group and age cohort, whereby adults with MS performed worse than controls and older adults performed worse than younger adults on all cognitive measures. However, there was no group by age cohort interaction, such that persons with MS and healthy controls demonstrated similar trajectories of cognitive decline across the 5 age cohorts (ie, parallel declines across age cohorts). Another recent study examined differences between persons with MS (n = 698; 29-71 years of age) and healthy controls (n = 226; 18-72 years of age) in cognitive function (ie, Paced Auditory Serial Addition Test [PASAT] and the Brief International Cognitive Assessment for MS [BICAMS]) across the lifespan. The PASAT is a measure of information processing speed and the BICAMS includes measures of information processing speed (ie, Symbol Digit Modalities Test [SDMT]), verbal memory (ie, California Verbal Learning Test-II [CVLT-II]), and visual memory (ie, Brief Visuospatial Memory Test-Revised [BVMT-R]).9 Adults with MS performed worse on all measures of cognitive function than controls based on effect sizes (d = 0.53-1.19). The impact of age was significant across all cognitive measures, such that both adults with MS and controls demonstrated declines in cognitive function with increasing age. However, the age × MS diagnosis interactions were not significant for any cognitive assessment; this indicated no differential effect of MS on cognitive function across the lifespan. Such results suggest that age-related declines in cognitive functioning occur similarly among adults with MS and healthy older adults, and that adults with MS generally have worse cognitive performance compared with healthy controls, regardless of age.

Another cross-sectional study examined age-related cognitive declines in persons with MS.11 The sample included 257 adults with MS who underwent the BICAMS, including measures of information processing speed (ie, SDMT), verbal memory CVLT-II), and visual memory (BVMT-R). Participants were divided into 4 age cohorts (ie, 30-39, 40-49, 50-59, and 60-79 years of age), and the primary statistical model involved analysis of variance with a priori linear contrasts. There were statistically significant, linear declines for all cognitive domains assessed by the BICAMS across age cohorts. This confirms the presence of age-related declines in cognitive functioning among adults with MS, such that older adults with MS have worse cognitive performance than younger adults with MS.

One preliminary study of 20 older adults with MS and 20 older adults without MS (aged ≥60 years) demonstrated that older adults with MS had significantly decreased cognitive performance in the domain of information processing speed (ie, Trail Making Test A; d = 0.73) and memory and executive functioning (Repeated Battery for the Assessment of Neuropsychological Status; d = 0.72) that exceeded ½ SD compared with older adults without MS.10 Those findings were replicated in a recent study of older adults with MS (n = 40) and healthy older adults (n = 40) that demonstrated older adults with MS only performed worse in one measure of cognitive function (ie, information processing speed; SDMT) compared with healthy controls (mean = 48.4, SD = 11.3, and mean = 55.0, SD = 7.8, respectively).31 There were no statistically significant differences in the other measures of cognitive function, including verbal (ie, CVLT-II) and visual memory (ie, BVMT-R), and information processing speed (ie, PASAT). Such results confirm that older adults with MS have worse cognitive performance than age- and sex-matched controls, particularly in the domain of cognitive processing speed.

Summary

Collectively, the existing data suggest that older adults with MS demonstrate a robust reduction of physical function compared with healthy older adults, and the degree of age-related decline in physical function is larger in MS than controls. By comparison, there is no current evidence for a greater reduction in cognitive function among adults aging with MS than health controls. The primary findings are that cognitive function declines with age in older adults with MS, as it does with adults without MS, and that the decline may be specific to certain domains of cognitive function (ie, information processing speed and memory); there is no evidence of an age by cohort interaction on cognitive function, but older adults with MS do performing worse on measures of cognition than age- and sex-matched controls. Clearly, future research might better characterize physical and cognitive functions across the lifespan in MS compared with matched controls. Of note, this research might move past standard neuropsychological assessments of cognition in MS and include other domain-specific assessments, including those commonly adopted in aging research (e.g., flanker task as a measure of executive function; Trail Making Task as a measure of information processing speed; and spatial recognition task as a measure of relational memory).34,35 This might permit a more nuanced assessment of the effects of aging with MS on cognitive function.

 

Physical Activity and Sedentary Behavior in Older Adults with MS

Older adults with MS are not engaging in sufficient amounts of physical activity for accruing the health benefits and are further engaging in high amounts of sedentary behavior36,37; the levels of physical activity and sedentary behavior might be concomitantly associated with the aforementioned reductions in physical and cognitive function in older adults with MS. One previous study demonstrated that older adults with MS (ie, ≥60 years of age) spent 7 and 12 fewer minutes per day in moderate-to-vigorous physical activity (MVPA) compared with middle-aged (ie, ages 40-59 years) and young adults (ie, ages 20-39 years), respectively.36 Only 14% of older adults with MS meet public health guidelines for MVPA (ie, ≥30 minutes/day of MVPA), and this was significantly lower when compared with approximately 21% and 28% in middle-aged and young adults with MS. The study further demonstrated that older adults with MS spent significantly more time in sedentary behavior per day (554 minutes) compared with young adults (510 minutes).36

Another recent study examined objectively measured physical activity and sedentary behavior (ie, accelerometry) in a sample of 40 older adults with MS (aged ≥55 years).37 The results of this study demonstrated that the median score for MVPA was 4.6 minutes/day, and this was lower than previously reported for healthy older adults (ie, 13.8 minutes/day).38 Older adults with MS further spent 221.4 minutes/day in light physical activity (LPA), and this too was lower than reported for healthy older adults (ie, 314.2 minutes/day).38 Older adults with MS engaged in 542.6 minutes/day, or approximately 9 hours/day, of sedentary behavior, and this was comparable with the estimate of 9.4 hours/day for healthy older adults.39

One study has examined levels of physical activity and sedentary behavior (ie, minutes/day), and patterns of physical activity and sedentary behavior (ie, number and average duration [minutes] of sedentary bouts; long sedentary bouts [>30 minutes]; and activity bouts) in 40 older adults with MS (aged ≥60 years) and 40 healthy older adults matched on age and sex.31 The results indicated that older adults with MS engaged in less MVPA (minutes/day), more sedentary behavior (minutes/day), and longer duration of long (≥30 minutes) sedentary bouts compared with healthy controls (means (SD) = 12.6 (14.1) vs 35.7 (23.0); 539.7 (84.7) vs 534.4 (81.8); and 51.4 (8.2) vs 47.8 (6.0), respectively). There were no statistically significant differences in LPA (minutes/day) or other pattern metrics of physical activity and sedentary behavior between older adults with MS and matched controls.31

Summary

Overall, research indicates that the majority of older adults with MS are not engaging in sufficient amounts of physical activity for accruing the associated health benefits, and the low rates of physical activity might be increasing the risks of many secondary, preventable comorbidities (eg, diabetes and hypertension) that can exacerbate MS disease progression and mortality.40 The rate and decline of participation in physical activity might be explained by older adults with MS perceiving significant barriers for engaging in this behavior, particularly the accessibility and acceptability of supervised, center-based programs and environments.41 Additional research from a lifespan perspective for describing rates of physical activity and sedentary behavior, including both levels and patterns, is warranted as well as is a potential focus on measurement. For example, MS-specific accelerometry cut points for physical activity have been developed for young and middle-aged adults with MS,42 but these have not been specifically examined and validated in older adults with MS.

 

Associations of Physical Activity, Sedentary Behavior, and Physical and Cognitive Function in Older Adults with MS

There is evidence for both reduced function and physical activity among older adults with MS. To that end, the reduction in physical activity participation may be associated with the decline in physical and cognitive functions among older adults with MS.41 This is based on the substantial evidence for benefits of physical activity behavior in young and middle-aged adults with MS.16 Other existing research has indicated that increasing physical activity and/or reducing sedentary behavior improves physical function in healthy older adults in the general population.14,15,43 However, there have only been 2 studies examining the associations of physical activity, sedentary behavior, and physical and cognitive function in older adults with MS.31,37

One cross-sectional study examined the associations between objectively measured levels (ie, minutes/day) of MVPA, LPA, and sedentary behavior with performance measures of physical function, including the SPPB, T25FW, and 6MW, in a sample of 40 older adults with MS (aged ≥55 years).37 Pearson correlations (r) demonstrated that minutes/day of LPA and MVPA, but not sedentary behavior, were significantly associated with the measures of physical function, and the associations were stronger for LPA (r = 0.55-0.66) than MVPA (r = 0.31-0.53). The regression analyses further indicated that LPA, but not MVPA, was significantly associated with SPPB, 6MW, and T25FW scores with strong β-coefficients (|0.58| to |0.63|) and R2 values (0.31-0.42). These results suggest that LPA may be an important target for improving physical function in older adults with MS.37

Another study examined the associations of physical function (ie, T25FW, 6MW, TUG, 6-spot step test, and SPPB), cognitive function (SDMT, PASAT, CVLT-II, and BVMT-R), levels of physical activity and sedentary behavior (ie, minutes/day), and patterns of physical activity and sedentary behavior (ie, number and average duration [minutes] of sedentary bouts; long sedentary bouts [>30 minutes]; and activity bouts) in 40 older adults with MS (aged ≥60 years) and 40 healthy older adults matched for age and sex.31 Pearson correlations (r) indicated statistically significant, moderate-to-large associations between LPA and number of activity bouts/day with most measures of physical function. There were further moderate-to-large associations between MVPA and duration of activity bouts with physical function measures. There was a significant and moderate association between SDMT (ie, information processing speed) and number of activity bouts/day (r = 0.32). Pearson correlations further indicated statistically significant and moderate-to-large associations between sedentary behavior, duration of sedentary bouts, and number and duration of long (≥30 minutes) sedentary bouts and most physical function variables. There were no statistically significant associations between any of the sedentary behavior and cognitive function measures. The follow-up linear regression analyses demonstrated that both levels of MVPA and sedentary behavior and patterns of sedentary behavior (ie, duration of long sedentary bouts) partially explained the differences in physical and cognitive function between older adults with MS and healthy controls. Importantly, these results suggest the beneficial effects of physical activity on physical function may be dependent on intensity of activity (ie, LPA or MVPA). The study suggests that patterns of sedentary behavior were moderately associated with physical function and support the notion that transitions from sedentary behavior toward physical activity may be important for physical function.31

Summary

There is limited evidence for the associations among function, physical activity, and sedentary behavior in older adults with MS. The preliminary research suggests that physical activity and sedentary behavior might be targets of behavior change interventions for improving function in this MS demographic. The initial evidence suggests that physical activity and sedentary behavior are associated with physical function more so than cognitive function in older adults with MS. Perhaps this is due to the larger age-related impairments in physical function among older adults with MS than healthy older adults. Physical activity interventions might focus on LPA and MVPA, as both intensities seem be beneficial for function in older adults with MS.

 

Physical Activity Interventions in Older Adults with MS

The co-occurrence of reduced function and physical activity combined with evidence of associations between such outcomes supports the focus on physical activity interventions for targeting dysfunction in older adults with MS. To date, there have been few exercise training or physical activity interventions designed for improving function among older adults with MS. We are aware of one randomized controlled trial (RCT) that examined the effects of a 12-week home-based exercise program targeting balance, walking, and lower limb/core muscle strength for reducing fall risk in a sample of 13 older adults with MS (50-75 years of age).44 The primary outcome of interest was the fall risk score, as determined by the short from of the Physiological Profile Assessment. This assessment is a standardized battery that includes measures of vision, lower limb proprioception, strength, postural sway, and cognitive function. Secondary outcomes included mobility and balance outcomes and self-reported falls. Overall, the intervention reduced the physiological fall risk score in the exercise group compared with control, and this reduction was large in magnitude, based on effect size estimates (η2 = 0.2). This reduced fall risk score was associated with improvements in balance (ie, postural control). This suggests that exercise-related improvements in balance might yield a reduction in physiological fall risk among older adults with MS.

Another more recent RCT examined the efficacy of a home-based physical activity intervention for improving physical function based on the SPPB among older adults with MS45; the approach was originally designed, developed, and tested for efficacy among the general population of older adults.14,15 The RCT included 48 older adults with MS (aged ≥50 years) who were randomly assigned into a 6-month DVD-delivered physical activity program or a healthy aging DVD attention control condition. The physical activity program targeted mobility, strength, and flexibility, and it was well received, based on formative assessment, with no documented adverse events. After the 6-month physical activity program, participants reported engaging in more minutes/day of MVPA compared with the DVD control condition (d = 0.73). The physical activity program yielded a small, clinically meaningful improvement in physical function, based on the SPPB, and a moderate improvement in QOL as a secondary end point. Importantly, the intervention delivery mechanism overcame accessibility and acceptability barriers, and could be scaled for broad reach among the growing population of older adults with MS. This would represent a novel, low-cost resource for managing the age-related declines in physical function, QOL, MVPA, and possibly cognitive function.

Summary

The very limited research supports the efficacy of physical activity interventions for improving metrics of physical function among older adults with MS. This clearly underscores the need for an expansion of efforts regarding the design and delivery of interventions for increasing physical activity, decreasing sedentary behavior, and possibly improving physical and cognitive function.

 

Overall Summary and Conclusion

There is a “graying” of the population of persons living with MS that coincides with increased life expectancy and the shifting demographic landscape worldwide. This growing cohort of older adults with MS undergoes the effects of a chronic, disabling, and oftentimes progressive neurological disease along with the consequences of normal aging. Older adults with MS undergo a faster rate of disability progression than younger adults with MS,46 and demonstrate reduced physical function compared with controls matched on age and sex. Older adults with MS further demonstrate reduced cognitive function, particularly in the domains of information processing speed and memory. The significant burden of aging with MS on physical and cognitive function, and ultimately QOL and independence, will require substantial management by health care providers. To date, very little is known about managing the consequences of MS among older adults. There are 15 DMTs approved by the FDA that represent the first line of treatment primarily for younger and middle-aged adults with relapsing-remitting MS. These DMTs have not been systematically examined for safety and efficacy in older adults with MS. This presents a major clinical problem for health care providers, particularly neurologists, who will spend increasing amounts of time and effort, with limited resources, managing the consequences of aging with MS. This will further present a major problem for payers who bear the bulk of the cost for drugs that may or may not be useful for managing MS in older adults. Accordingly, alternative approaches are sorely needed that have efficacy for improving physical and cognitive functioning, while minimizing health care burden, in older adults with MS. The premise of this article is that one such approach might involve participation in physical activity. There are initial data indicating that physical function is associated with levels and patterns of physical activity and sedentary behavior, and preliminary evidence from RCTs that physical activity interventions can improve physical function among older adults with MS. The evidence is less established regarding physical activity and cognitive function among older adults with MS. We hope that researchers might follow our clarion call in this article and engage in a variety of efforts that will clarify and establish the value and role of physical activity in managing the consequences of aging with MS.

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