Objectively-Measured Physical and Cognitive Fatigue Across the - PDF document

5/30/2019 Objectively-Measured Physical and Cognitive Fatigue Across the Lifespan in Adults with Multiple Sclerosis C. Danielle Jones, Katie L. Cederberg, E. Morghen Sikes, Robert W. Motl, Brian M. Sandroff University of Alabama at Birmingham Department of Physical Therapy AGING WITH MS • Emerging public health and clinical crisis • As of 2017, approximately 25% of persons with MS are over age 65 1 • Coincides with shifting demographics of general population • Many persons with MS experience consequences of neurological disease plus effects of aging • Fatigue 1 Wallin et al., 2019 1

5/30/2019 FATIGUE AS A COMPLEX PHENOMENON • Subjective, general state of recurrent and profound exhaustion that is not alleviated by sleep or rest 2-4 • One of most prevalent and debilitating MS symptoms • Despite some efficacious treatments, mechanisms are poorly- understood 5,6 • Inability to sustain performance during objective physical and cognitive tasks undertaken over time (i.e., objectively-measured fatigue) 7-9 • Specific consequence of several neurological disorders, including MS 7,9 • No correlation with generalized measures of subjective fatigue in MS 10,11 2 Krupp et al., 2003; 3 Andreasen et al., 2018; 4 Kluger et al., 2013; 5 Vucic et al., 2010; 6 MacAllister et al., 2005; 7 Chaudhuri et al., 2004; 8 Holtzer et al., 2010; 9 Chaudhuri & Behan, 2000; 10 DeLuca, 2005; 11 Bailey et al., 2007 OBJECTIVELY-MEASURED FATIGUE IN MS • May occur in both physical and cognitive domains among persons with MS • Based on the inability of persons with MS to sustain performance over the duration of physical and cognitive tasks 12-16 • Associated with physiological deconditioning and suboptimal brain activation in persons with MS 17-19 • Objectively-measured physical and cognitive fatigue not exclusive to MS; also common and debilitating in older adults 20-22 12 Leone et al., 2016; 13 Calay et al., 2012; 14 Walker et al., 2012; 15 Morrow et al., 2015; 16 Holtzer et al., 2013; 17 Ramari et al., 2018; 18 DeLuca et al. ,2008; 19 Dobryakova et al., 2018; 20 Simonsick et al., 2014; 21 Moreh et al., 2010; 22 Egerton et al., 2016; 2

5/30/2019 COGNITIVE-MOTOR COUPLING IN MS • Do objectively-measured physical and cognitive fatigue worsen together with age in MS? • Objectively-measured physical and cognitive dysfunction co-occur among adults with MS (i.e., cognitive-motor coupling) 23,24 • Physical and cognitive dysfunction worsen together with increasing age in MS 24, 25 • It is unknown if that pattern of associations extends to objectively-measured physical and cognitive fatigue 23 Benedict et al., 2011; 24 Bollaert et al., 2019; 25 Roy et al., 2016; OBJECTIVE AND HYPOTHESIS • Study Objective: • Characterize objectively-measured physical and cognitive fatigue across the lifespan in adults with MS based on inability to sustain performance on physical/cognitive tests over time • Six-minute walk (6MW) • Symbol Digit Modalities Test (SDMT) • Study Hypothesis: • Older adults with MS would demonstrate worse objectively-measured physical and cognitive fatigue than younger and middle-aged adults with MS 3

5/30/2019 PARTICIPANTS • 125 adults with definite MS diagnosis • Age between 20-79 years • Ambulatory with or without assistance • Relapse-free for ≥ 30 days • Willing and able to complete study procedures • A priori study aim: enroll similar number of MS participants into separate age groups • Y ounger adults: 20 – 39 years (n = 40) • Middle-aged adults: 40 – 59 years (n = 44) • Older adults: 60 – 79 years (n = 41) OBJECTIVELY-MEASURED PHYSICAL FATIGUE • 6MW was administered using standardized instructions 27 • Recorded the distance walked (feet) each minute; primary outcome was total distance walked over 6-minutes (i.e., actual 6MW performance) • Operationalized based on inability to sustain performance over the duration of the 6MW 12,13,17, 26 26 Dalgas et al., 2014; 27 Goldman et al., 2008; 4

5/30/2019 OBJECTIVELY-MEASURED PHYSICAL FATIGUE Step 1 Step 2 • Calculated ‘predicted sustained 6MW performance’ • Calculated the % difference between actual 6MW performance and the ‘predicted sustained • Recorded performance from 0:00-1:00 and 6MW performance’ value as a function of extrapolated that value across the duration of ‘predicted sustained 6MW performance’ the 6MW (i.e., 6-minutes) • T otal distance walked over the first minute of the test, multiplied times 6 OBJECTIVELY-MEASURED COGNITIVE FATIGUE • SDMT was administered using standardized instructions 28 • Raw score was recorded every 30-seconds; primary outcome was raw score over 90-seconds (i.e., actual SDMT performance) • Operationalized based on inability to sustain performance over the duration of the SDMT 16 28 Smith, 1982; 5

5/30/2019 OBJECTIVELY-MEASURED COGNITIVE FATIGUE Step 1 Step 2 • Calculated ‘predicted sustained SDMT performance’ • Calculated the % difference betw een actual SDMT performance and the ‘predicted sustained • Recorded performance from 0:00 to 0:30 and SDMT performance’ value as a function of extrapolated that value across the duration of ‘predicted sustained SDMT performance’ the SDMT (i.e., 90-seconds) • Raw score over the first 30-seconds of the test, multiplied times 3 DISABILITY STATUS • Patient-Determined Disease Steps (PDDS) scale 29 • Valid and reliable self-report measure of disability status in MS 30 • Single item for measuring self- reported neurological impairment on an ordinal scale, ranging from 0 (normal) through 8 (bedridden) • Higher scores reflect worse MS- related disability 29 Hadjimichael et al., 2007; 30 Learmonth et al., 2013; 6

5/30/2019 PROCEDURE • Study was approved by a University IRB and all participants provided written informed consent • All participants initially provided demographic and clinical characteristics, followed by administration of the PDDS, SDMT , and 6MW during a single session • All participants remunerated $25 for study completion DATA ANALYSIS • All data analyzed in SPSS version 25 (SPSS Inc., Armonk, NY) Step 1 Step 2 Step 3 Examined differences among Performed bivariate Pearson Performed additional bivariate age-groups in objectively- correlations between Pearson correlations between measured physical and objectively-measured actual 6MW and SDMT cognitive fatigue using physical and cognitive fatigue performance separate 1-way A NOVA s � T o evaluate the extent of � Post-hoc Bonferroni follow- cognitive-motor ups to examine specific coupling 24,25 differences in objectively- measured fatigue based on age-groups 7

5/30/2019 RESULTS - SAMPLE CHARACTERISTICS Overall 20-39 40-59 60-79 Variable p -value (n = 125) (n = 40) (n = 44) (n = 41) Age 49.3 (14.1) 33.2 (5.0)* ‡ 48.5 (5.8) † 65.8 (4.4) <.01 Sex (n, % female) 94/125 (75.2%) 32/40 (80.0%) 32/44 (72.7%) 30/41 (73.2%) .70 Education (y ears) 16.2 (2.3) 16.1 (2.6) 16.3 (1.9) 16.0 (2.4) .83 17/40 (42.5%) * ‡ 29/44 (65.9%) Race (n, % Caucasian) 80/125 (64.0%) 34/41 (82.9%) <.01 MS ty pe (n, % RRMS) 107/125 (85.6%) 34/40 (85.0%) 39/44 (88.6%) 34/41 (82.9%) .82 Disease duration 13.0 (8.6) 6.5 (5.1) * ‡ 12.4 (5.8) † 19.9 (8.7) <.01 (y ears) PDDS (median, range) 1.0 (0.0 – 7.0) 1.0 (0.0-5.0) 1.0 (0.0-6.0) 2.0 (0.0-7.0) .56 Note: * denotes significant differences between younger and middle-aged; † denotes significant differences betwe en middle-aged and older; ‡ denotes differences between younger and older. OBJECTIVELY-MEASURED PHYSICAL FATIGUE Objectively -Measured Phy sical Fatigue 1800 4.8% 1600 1400 1200 Distance Walked (feet) 1000 Overall Actual 800 Overall Predicted S ustained 600 400 200 0 1:00 2:00 3:00 4:00 5:00 6:00 Time 8

5/30/2019 STEP 1A: 1-WAY ANOVA 20-39 40-59 60-79 Age Group (n = 40) (n = 44) (n = 41) Phy sical Fatigue (%) 4.5 (5.5) 5.1 (8.2) 4.7 (8.1) • No statistically significant age-group differences on objectively- measured physical fatigue • F (2, 122) = 0.07, p = .94, η p2 < .01 • Younger, middle-aged, and older adults with MS demonstrated similar objectively-measured physical fatigue during the 6MW OBJECTIVELY-MEASURED COGNITIVE FATIGUE Objectively-Measured Cognitive Fatigue 9.0% 60 50 40 Raw Score 30 Overall Actual Overall Predicted S ustained 20 10 0 30 -s ec ond s 60 -s ec ond s 90 -s ec ond s Time 9

5/30/2019 STEP 1B: 1-WA Y ANOVA 20-39 40-59 60-79 Age Group (n = 40) (n = 44) (n = 41) Cognitive Fatigue (%) 6.4 (10.0) 7.8 (9.1) 12.8 (10.3) * ‡ Note: * denotes significant differences between middle-aged and older; ‡ denotes differences betwee n younger and older. • Moderate-sized, statistically significant age-group difference on objectively-measured cognitive fatigue • F (2, 122) = 4.81, p = .01, η p2 = .07 • Older adults demonstrated significantly greater objectively- measured cognitive fatigue than younger adults and middle- aged adults with MS during the SDMT STEP 2: FATIGUE CORRELATIONS r p 95% CI Overall (n = 125) .09 .34 -.09 - .26 • Non-significant Pearson correlation between objectively-measured physical and cognitive fatigue in overall sample 10