Recent studies suggest that exercise-training interventions

Langlois, F., Vu, T.T.M., Chassé, K., Dupuis, G., Kergoat, M.J., & Bherer, L., (2012). Benefits of physical exercise training on cognition and quality of life in frail older adults. Journals of Gerontology Series B: Psychological Sciences and Social Sciences, doi:10.1093/geronb/gbs069 Benefits of Physical Exercise Training on Cognition and Quality of Life in Frail Older Adults Francis Langlois, 1,2 Thien Tuong Minh Vu, 2,3 Kathleen Chassé, 2 Gilles Dupuis, 1,4 Marie-Jeanne Kergoat, 2 and Louis Bherer 1,2 1 Département de psychologie, Université du Québec à Montréal (UQAM), Montréal, Canada. 2 Institut universitaire de gériatrie de Montréal (IUGM), Montréal, Canada. 3 Centre hospitalier de l université de Montréal (CHUM), Montréal, Canada. 4 Institut de Cardiologie de Montréal, Montréal, Canada. Objectives. Frailty is a state of vulnerability associated with increased risks of fall, hospitalization, cognitive deficits, and psychological distress. Studies with healthy senior suggest that physical exercise can help improve cognition and quality of life. Whether frail older adults can show such benefits remains to be documented. Method. A total of 83 participants aged 61 89 years were assigned to an exercise-training group (3 times a week for 12 weeks) or a control group (waiting list). Frailty was determined by a complete geriatric examination using specific criteria. Pre- and post-test measures assessed physical capacity, cognitive performance, and quality of life. Results. Compared with controls, the intervention group showed significant improvement in physical capacity (functional capacities and physical endurance), cognitive performance (executive functions, processing speed, and working memory), and quality of life (global quality of life, leisure activities, physical capacity, social/family relationships, and physical health). Benefits were overall equivalent between frail and nonfrail participants. Discussion. Physical exercise training leads to improved cognitive functioning and psychological well-being in frail older adults. Key Words: Aging Frailty Physical exercise Cognitive impairment Quality of life. Recent studies suggest that exercise-training interventions can lead to significant improvement in cognitive performances (Angevaren, Aufdemkampe, Verhaar, Aleman, & Vanhees, 2008) and enhanced quality of life (Elavsky et al., 2005). However, most studies published so far involved healthy community dwellers with few medical conditions and no limiting factors for exercise. Whether exercise interventions can lead to cognitive and psychological benefits in patients with chronic diseases and complex geriatric syndromes remains to be documented. Frailty is an emerging geriatric syndrome that can severely limit physical activity and exercise. Frailty refers to a complex health state of increased vulnerability to stressors due to impairments in multiple systems, and increased risks of adverse outcomes such as disability, falls, hospitalization, and death (Fried et al., 2001). Although conception and operationalization of frailty might differ (Bergman et al., 2007), it has gained increased attention among health professionals as being a frame of reference for risk quantification and prognosis in elderly populations (Lekan, 2009). The prevalence of frailty increases significantly with aging (Rockwood, Song, & Mitnitski, 2011). In addition to reduced physical capacity, frail older adults show specific cognitive deficits in executive functions and processing speed as well as reduced quality of life (Langlois et al., 2012). There is urgent need to find intervention approaches that would reduce the negative impacts of frailty and thereby lessen its social and economical impacts. This study assessed the effects of physical exercise training on cognition and quality of life in frail and nonfrail older adults. Based on findings that exercise training help enhance physical capacity and endurance in frail older adults (Barreto, 2009; Chin, van Uffelen, Riphagen, & van Mechelen, 2008), we hypothesized that both frail and nonfrail older adults would show significant gain on cognition and quality of life. Method Participants Eighty-three participants aged 61 89 participated in this study. They underwent a complete geriatric assessment to ensure that they could perform a physical exercise program at low risk. Participants were excluded if they showed limitations to undertake a physical exercise program, or signs of dementia (<25 at the mini-mental state examination [MMSE]; Folstein, 1975), or depression (>10 at the Geriatric depression scale; Yesavage et al., 1982). Participants were categorized as frail if they met at least two of the three following diagnostic criteria: (a) three of the five symptoms of frailty, as defined by Fried et al. (2001) The Author 2012. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Received October 27, 2011; Accepted June 26, 2012 Decision Editor: Bob G. Knight, PhD Page 1 of 5

Page 2 of 5 LANGLOIS ET AL. Table 1. Baseline Characteristics of Participants Control group (n = 36) Training group (n = 36) Frail vs. nonfrail Control vs. training Characteristics Nonfrail (n = 19) Frail (n = 17) Nonfrail (n = 19) Frail (n = 17) p Value p Value Age, M ± SD 70.95 ± 5.38 75.41 ± 4.91 68.74 ± 5.52 74.47 ± 6.99 <.001.25 Female, n (%) 17 (89.47) 13 (76.47) 14 (73.68) 12 (70.59).41.26 Education, M ± SD 13.00 ± 2.71 12.68 ± 4.33 15.47 ± 3.12 13.35 ± 4.92.19.09 Cardiovascular diseases, total M ± SD 0.79 ± 0.92 1.53 ± 1.23 1.11 ± 1.29 2.12 ± 1.27.003.11 Hypertension, n (%) 7 (36.84) 10 (58.82) 8 (42.11) 14 (82.35).009.24 Diabetes mellitus, n (%) 1 (5.26) 4 (23.53) 2 (10.53) 2 (11.76).21.72 Dyslipidemia, n (%) 6 (31.58) 7 (41.18) 7 (36.84) 13 (76.47).04.10 Heart failure, n (%) 0 (0) 0 (0) 0 (0) 1 (5.88).29.32 Arrhythmia, n (%) 1 (5.26) 1 (5.88) 1 (5.26) 2 (11.76).55.64 Valvular disease, n (%) 0 (0) 3 (17.65) 1 (5.26) 1 (5.88).13.64 Musculoskeletal disorders, total M ± SD 2.58 ± 1.61 4.59 ± 3.06 3.05 ± 2.97 6.35 ± 4.86.001.15 Head and neck problems, n (%) 4 (21.05) 4 (23.53) 6 (31.58) 6 (35.29).77.29 Arthritis, n (%) 11 (57.89) 11 (64.71) 13 (68.42) 13 (76.47).50.32 Osteoporosis, n (%) 5 (26.32) 6 (35.29) 0 (0) 3 (17.65).15.02 History of fractures, n (%) 3 (15.79) 6 (35.29) 4 (21.05) 5 (29.41).17 1.00 Poor standing posture, n (%) 0 (0) 3 (17.65) 0 (0) 4 (23.53).003.69 Irregular gait pattern, n (%) 2 (10.53) 4 (23.53) 1 (5.26) 7 (41.18).01.55 Gastrointestinal, total M ± SD 0.63 ± 1.01 0.94 ± 1.25 0.68 ± 1.42 1.59 ± 1.73.07.28 Swallowing difficulty, n (%) 1 (5.26) 1 (5.88) 1 (5.26) 7 (41.18).03.04 Pyrosis or reflux, n (%) 2 (10.53) 3 (17.65) 6 (31.58) 5 (29.41).80.09 Digestive problems, n (%) 5 (26.32) 6 (35.29) 2 (10.53) 7 (41.18).06.60 Pulmonary disease, total M ± SD 0.47 (0.96) 0.59 (0.94) 0.32 (0.48) 0.65 (1.00).27.81 Asthma, n (%) 1 (5.26) 3 (17.65) 1 (5.26) 1 (5.88).32.39 COPD, n (%) 2 (10.53) 3 (17.65) 1 (5.26) 1 (5.88).58.23 History of depression, n (%) 2 (10.53) 2 (11.76) 5 (26.32) 7 (41.18).41.02 Mobility aids, n (%) 1 (5.26) 4 (23.53) 1 (5.26) 4 (23.53).03 1.00 At least one ADL or IADL disability, n (%) 1 (5.26) 6 (35.29) 2 (10.53) 10 (58.82) <.001.18 Number of daily medications, M ± SD 3.74 ± 2.71 6.12 ± 3.82 3.79 ± 2.96 6.71 ± 2.69 <.001.66 Notes. ADL = activity of daily living; COPD = chronic obstructive pulmonary disease; IADL = instrumental activity of daily living. Chi-square tests were used for categorical variables, and ANOVAs were used for continuous variables. (muscular weakness, slow walking speed, fatigability, sedentarity, and unintentional weight lost); (b) a score of 28/36 on the modified Physical Performance Test (PPT; Binder et al., 2004); and (c) identified as frail according to the geriatrician s judgment (mildly frail or worse on the clinical frailty scale) after assessing the 70 possible deficits of the frailty index (Rockwood et al., 2005). To be classified as nonfrail, participants could not meet any of these three frailty criteria. This was a matched-control group design in which participants were randomly assigned to the control or the training conditions to form subgroups of three to five participants, while ensuring that the female-to-male ratio was equivalent in each group of frail and nonfrail participants. The physical exercise-training program consisted of 12 weeks of 1-h exercise session 3 days a week. Training was conducted in subgroups of three to five participants to ensure adequate supervision. Each session included 10 min of warm up exercises (stretching and balancing), 10 30 min of aerobic workout (using treadmills, recumbent bikes, and elliptical), and 10 min of strength training, followed by 10 min of cool down exercises. The intensity and duration of the aerobic exercises were increased individually, using the modified Borg Rating of Perceived Exertion scale (0 10) to reach moderate to hard intensity. Participants in the control group were instructed to maintain their current level of activity during the entire study period. After participating in the study, they were offered the opportunity to join a physical training program. Table 1 presents baseline demographic and medical characteristics of participants. There was no significant difference between the training and control groups at baseline in physical capacity, cognitive, and quality of life. Measures Pre- and post-test assessments took place within 1 week before and after the 12-week study period. Physical capacity, cognition, and quality of life, were assessed in the same order in three different sessions, with 1 day of rest between each session. The physical capacity assessment included the modified PPT, grip strength (hand-held dynamometer), physical endurance (6-Minute Walk Test [MWT]), mobility (Timed Up and Go Test), and gait speed (mean score of comfortable and maximum gait speed). The cognitive evaluation involved six cognitive domains: (a) global cognitive functioning (MMSE), (b) abstract verbal reasoning (Similarities of the Wechsler Adult Intelligence Scale [WAIS-III]), (c) processing speed (composite score of the Digit-Symbol Coding subtest of the WAIS-III), the Trail

PHYSICAL EXERCISE FOR FRAIL OLDER ADULTS Page 3 of 5 Making Test (TMT) part A, and the naming and reading conditions of the modified Stroop Color-Word Test, (d) working memory (composite score of the Letter-Number Sequencing and the Digit Span backward subtests of the WAIS-III), (e) episodic memory (composite score of the Rey Auditory Verbal Learning Test), and (f) executive functions (composite score of the TMT part B minus part A, and the Interference and flexibility conditions of the modified Stroop Color-Word Test minus the naming and reading conditions). Composite scores (X) were created based on an equally unit-weighted approach using z scores: composite score (X) = mean (z score A, z score B, z score C,...). All measures used for each composite score were highly intercorrelated and were found to measure a specific cognitive function. The Quality of Life Systemic Inventory questionnaire (Duquette, Dupuis, & Perrault, 1994) assessed the capacity to achieve personal goals in 28 life domains (e.g., marital life, self-esteem, and sleep) and provide quality of life scores in nine dimensions depicted in Figure 1. Statistical Analyses Given that frail and nonfrail participants differed in baseline functioning and to allow scores comparison from different measurement scales on a common scale, z scores were computed on raw scores by subtracting individual scores to the group s mean (pre and post combined), divided by the group s standard deviation (pre and post combined). Intervention effects were assessed on z score change from pre-test to post-test. Z score change provides a reliable measure of the intervention effect size, which allows comparison of both experimental groups (control vs. intervention) and frailty condition (frail vs. nonfrail) using a standardized method. Three multivariate analyses of variance (MANOVAs) were performed on all dependent variables of each dimension: physical capacity, cognition, and quality of life. Dependent variables were z score change. Group (intervention vs. control) and frailty (frail vs. nonfrail) were fixed factors. Follow-up analyses were performed using univariate ANOVAs. Significance level was set at.05. Analyses were performed with SPSS statistical software, version 16.0 (SPSS Inc., Chicago, IL). Results In the intervention group, 36/43 participants completed the study (3 frail and 4 nonfrail participants dropped out before completion due to schedule conflict [3], medical [3], or personal [1] complications). In the control group, 36/40 seniors completed the study (2 frail and 2 nonfrail participants did not attend the post-test session). Participants who dropped out were comparable to those who completed the study on all physical, cognitive, and psychological measures. Intent-to-treat analyses performed with the data available for the 11 participants who did not complete the study did not modify any of the reported results. Figure 1 shows the z score change for each variable of the three dimensions: physical capacity, cognitive function, and quality of life. Physical Capacity Results from the MANOVA showed a significant main effect of group, F(5, 63) = 9.47, p <.001, due to a larger improvement in the training group compared with the control group in functional capacity (PPT), F(1, 68) = 24.03, p <.001, and physical endurance (6-MWT), F(1, 68) = 4.79, p =.03. No effect of training was found on gait speed (p =.58), mobility (p =.26), or grip strength (p =.08). The group frailty interaction was not significant, F(5, 63) = 1.58, n.s., although improvement in functional capacity (PPT) was larger in frail (z score change =.79) than in nonfrail participants (z score change =.36). Improvement at the 6-MWT was equivalent in frail (z score change of.33) and nonfrail individuals (z score change =.20). Cognition A significant main group effect, F(6, 63) = 3.27, p =.007, was observed, due to larger improvement in the training group in processing speed, F(1, 68) = 6.38, p =.014, working memory, F(1, 68) = 4.61, p =.035, and executive functions F(1, 68) = 4.45, p =.039. There was no group frailty interaction, F(6, 63) < 1. Respectively for frail and nonfrail individuals, z score changes were.24 and.35 in processing speed,.35 and.13 in working memory, and.36 and.24 in executive functions. Quality of Life A main group effect was observed in Quality of Life, F(11, 58) = 2.04, p =.04, due to larger gains in the training group compared with the control group in global quality of life, F(1, 68) = 3.97, p =.05, leisure activities, F(1, 68) = 9.13, p =.004, perception of physical capacity, F(1, 68) = 5.76, p =.019, social/family relationships, F(1, 68) = 4.41, p =.039, and physical health, F(1, 68) = 4.40, p =.040. No group frailty interaction was found, F(11, 58) < 1. Respectively for frail and nonfrail elders, z score changes were.09 and.30 in global quality of life,.35 and.52 in leisure activities,.44 and.34 in perception of physical capacity,.14 and.35 in social/family relationships, and.27 and.14 in self-perceived physical health. Discussion The effect of a 3-month physical exercise intervention was assessed in frail and nonfrail older adults on three dimensions: physical capacity, cognitive performance, and quality of life. Training-related improvement was observed in functional capacity, physical endurance,

Page 4 of 5 LANGLOIS ET AL. Figure 1. Z score change in the training and control groups for each measure of the three dimensions: physical capacity (top panel), cognition (middle panel), and quality of life (lower panel). *p.05. **p.01. ***p.001. executive functioning, processing speed, working memory, and self-reported quality of life in leisure activities, physical capacity, social/family relationships, and health. Benefits were overall equivalent in frail and nonfrail participants. Improvement in physical capacity replicates past findings with frails seniors (Chin et al., 2008), although some studies did not report such benefits (Faber, Bosscher, Chin, & van Wieringen, 2006). Positive results report here might be related to individualize adapted training, which might have maximized training effects. Although past studies reported exercise-induced improvement in cognition in healthy older adults (Colcombe & Kramer, 2003), this study is the first to report enhanced cognitive performances in frail older adults. Larger gains were observed in executive control, processing speed, and working memory, all playing a critical role in everyday activities, such as driving, cooking, or managing finances.

PHYSICAL EXERCISE FOR FRAIL OLDER ADULTS Page 5 of 5 It is noteworthy that frail older adults tolerated very well the physical training program designed by a kinesiologist and the dropout rate was very low (16.3%). This could be due to the fact that training was individualized and adapted to the strength and needs of the participant, based on the geriatric examination and a physical therapist s assessment. This might also very well explain the substantial benefits observed in this study. While the frailty condition improved significantly in all dimensions (i.e., physical capacity, cognition, and quality of life), it is unlikely that only a 3-month exercise program is sufficient to reverse frailty condition, and this was not formally assessed in this study. Future randomized clinical trials including larger sample sizes and active control groups are required to support the present findings. Future studies should also assess whether all executive control mechanisms improve to the same extent after physical training, as recent reports suggest that some executive mechanisms might be more age sensitive than others (Verhaeghen, 2011). Finally, subsequent studies need to assess whether training-induced cognitive improvements generalize to real life situation. Funding F.L. received salary support from the Canadian Institutes of Health Research (CIHR), and L.B. is supported by the Canadian Research Chair Program. Correspondence Correspondence should be addressed to Louis Bherer, Département de psychologie, Université du Québec à Montréal (UQAM), CRIUGM, 4545 Queen Mary, Montreal, Quebec, H3W 1W4, Canada. E-mail: bherer. louis@uqam.ca. References Angevaren, M., Aufdemkampe, G., Verhaar, H. J., Aleman, A., & Vanhees, L. (2008). Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment. 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