Abstract
Background: Obesity impairs cognition and health-related quality of life (HRQOL) in older adults; however, the appropriate treatment of obese older adults remains controversial.
Objective: The objective was to determine the independent and combined effects of weight loss and exercise on cognition, mood, and HRQOL in obese older adults.
Design: One hundred seven frail, obese older adults were randomly assigned to a control, weight-management (diet), exercise, or weight-management-plus-exercise (diet-exercise) group for 1 y. In this secondary analysis, main outcomes were Modified Mini-Mental State Examination (3MS) and total Impact of Weight on Quality of Life-Lite (IWQOL) scores. Other outcomes included Word Fluency Test, Trail Making Test Parts A and B, and Geriatric Depression Scale (GDS) scores.
Results: Scores on the 3MS improved more in the diet (mean ± SE: 1.7 ± 0.4), exercise (2.8 ± 0.4), and diet-exercise (2.9 ± 0.4) groups than in the control group (0.1 ± 0.4) (between-group P = 0.0001–0.04); scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group. Scores on the Word Fluency Test improved more in the exercise (4.1 ± 0.8) and diet-exercise (4.2 ± 0.7) groups than in the control group (−0.8 ± 0.8; both P = 0.001). For the Trail Making Test Part A, scores in the diet-exercise group (−11.8 ± 1.9) improved more than in the control group (−0.8 ± 1.9) (P = 0.001); a similar finding was observed for the Trail Making Test Part B. Scores on the IWQOL improved more in the diet (7.6 ± 1.6), exercise (10.1 ± 1.6), and diet-exercise (14.0 ± 1.4) groups than in the control group (0.3 ± 1.6) (P = 0.0001–0.03); scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group. In the diet-exercise group, peak oxygen consumption and strength changes were independent predictors of 3MS changes; weight and strength changes were independent predictors of IWQOL changes. GDS scores did not change.
Conclusions: Weight loss and exercise each improve cognition and HRQOL, but their combination may provide benefits similar to exercise alone. These findings could inform practice guidelines with regard to optimal treatment strategies for obese older adults. This trial was registered atclinicaltrials.govas NCT00146107.
INTRODUCTION
Obesity in the older population is an urgent public health problem, with more than one-third of adults aged ≥65 y in the United States now classified as obese (1). This increasing population is at risk of adverse outcomes because obesity in older adults is associated with physical and metabolic complications that impair health-related quality of life (HRQOL)5 (2). Moreover, obese older adults may be at increased risk of dementia, given convergent metabolic mechanisms such as insulin resistance and chronic inflammation (3). Indeed, midlife obesity has been consistently associated with dementia risk (4–6); however, obesity in older adults has been associated with both increased (7, 8) and decreased (9, 10) dementia risk. Possible explanations for the paradoxical findings include confounding because of birth cohort effects (11) and weight loss preceding dementia diagnosis (12). Conversely, limited data from small, mostly short-term clinical trials suggest that weight loss and/or exercise may improve cognition, although other studies showed no effects (13–17). Importantly, most previous intervention studies included participants with wide ranges in age and BMI and thus did not focus on the vulnerable population of obese older adults (2, 16, 17). Furthermore, the potential mediators of the effects of weight loss and/or exercise on cognition and HRQOL still need to be elucidated (16, 18).
Lifestyle intervention (weight loss and exercise) is recommended as the cornerstone of obesity treatment at all ages (19, 20). However, this recommendation remains controversial in obese older adults because of the reduction in relative health risks with increasing BMI in this group and the concerns around the difficulty of behavioral change with advancing age, exacerbation of age-related lean tissue losses, and feasibility of long-term weight loss and other related health consequences (1). Thus, although weight loss and exercise are recommended as standard care for obese patients in general, this recommendation is not universally accepted by geriatricians for older adults. It is the common perception that extra weight may be protective against health risks in older adults (21, 22). Nevertheless, we recently reported that the combination of weight loss and exercise provides greater improvement in physical function and cardiometabolic health than either intervention alone (23, 24). Accordingly, we now report the results of the effects of weight loss alone, exercise alone, or combined weight loss and exercise on cognition, mood, and HRQOL in this population of frail, obese older adults.
SUBJECTS AND METHODS
The parent randomized controlled trial (RCT) evaluated the independent and combined effects of weight loss and exercise on physical function in obese older adults. The principal results showed that a combination of weight loss and exercise provides greater improvement in physical function than either intervention alone (23). The present study reports secondary analyses of the RCT examining changes in cognition, mood, and HRQOL as prespecified in the protocol.
Study population
This study was conducted at Washington University School of Medicine (WUSM) and approved by the university's institutional review board. Study oversight was provided by a data and safety monitoring board. Volunteers were recruited through advertisements, and informed consent was obtained from each participant. Details of the inclusion and exclusion criteria have been described (23). Briefly, eligible participants had to be older (aged ≥65 y), obese [BMI (in kg/m2) ≥30], sedentary (regular exercise <1 h/wk), and with stable body weight (±2 kg in the preceding year) and on stable medications (≥6 mo) before enrollment. Participants were required to meet 2 of the following 3 operational criteria for mild-moderate frailty: physical performance test score of 18–32, peak oxygen consumption (VO2peak) of 11–18 mL · kg−1 · min−1, and difficulty in 2 instrumental activities of daily living or 1 basic activity of daily living (23, 25). Exclusion criteria included severe cardiopulmonary disease, musculoskeletal or neuromuscular impairments that precluded exercise training (ET), known diagnosis of dementia or positive screening with the Mini-Mental State Examination (score <24) (26), history of malignant neoplasm, and current smoking.
Study design
In this 52-wk RCT, participants were randomly assigned to 1 of the following 4 groups stratified by sex: 1) control group, 2) group who participated in a weight-management program (diet group), 3) group who received ET (exercise group), and 4) group who received both weight-management and ET (diet-exercise group). The randomization algorithm was generated by the WUSM Biostatistics Division and maintained by a research team member who did not interact with the participants.
As previously described (23), participants in the control group received general information about a healthy diet at regular visits with the staff and were prohibited from participating in any weight-loss or exercise program.
Participants in the diet group were prescribed a diet that provided an energy deficit of 500–750 kcal/d from daily requirements (2). Groups met with dietitians for food diary review, caloric intake adjustments, and behavioral therapy. They were instructed to set weekly behavioral goals and to attend weekly weigh-in sessions. The goal was to achieve ∼10% weight loss for 6 mo and to maintain this weight for the remaining 6 mo of the study. Participants in the exercise group were counseled on maintaining a weight-stable diet. They participated in a supervised progressive multicomponent ET program. Exercise sessions were ∼90 min (∼15 min flexibility, 30 min aerobic, 30 min resistance training, and 15 min balance exercises) 3 times weekly at a WUSM exercise facility. The participants exercised so that their heart rate was ∼65% of their peak heart rate and gradually increased the intensity of exercise so that their heart rate was between 70% and 85% of their peak heart rate. The progressive resistance training included 9 upper-extremity and lower-extremity exercises with the use of weight-lifting machines. Participants performed 1–2 sets at a resistance of ∼65% of their one-repetition maximum (1-RM), with 8–12 repetitions of each exercise; they gradually increased the intensity to 2–3 sets at a resistance of ∼80% of their 1-RM, with 6–8 repetitions of each exercise (23). Participants who were randomly assigned to the diet-exercise group participated in both weight-management and ET programs described above, conducted separately from the other groups.
Outcome assessments
Main outcomes for this report were changes in the Modified Mini-Mental State Examination (3MS) and the total Impact of Weight on Quality of Life–Lite (IWQOL) at 12 mo. Other outcomes included the Word List Fluency Test, Trail Making Tests Parts A and B, and Geriatric Depression Scale (GDS)–Short Form. Outcomes were assessed at baseline, 6 mo, and 12 mo. Trained personnel who were blinded to group assignments conducted the assessments.
Cognitive measures
The 3MS is a test of global cognition with components for orientation, registration, attention, language, praxis, and immediate and delayed memory (27). Scores range from 0 to 100, with higher scores indicating better performance. The 3MS is more sensitive for mild cognitive impairment than the traditional 30-point Mini-Mental State Examination (27).
The Word List Fluency Test measures verbal production, semantic memory, and language. Participants were asked to name as many animals as possible in a 1-min period (28). Higher scores indicate better performance.
The Trail Making Test Parts A and B (Trails A and B) provides information on visuospatial scanning, speed of processing, mental flexibility, and executive function (29, 30). The tasks involve connecting 25 consecutively numbered circles (Trail A, greater focus on attention) or an alternating sequence of numbered and lettered circles (Trail B, greater focus on executive function). Shorter times to completion indicate better performance.
Mood
The GDS is a 15-item version of the 30-item form that assesses depressive symptoms during the past week (31). The scores range from 0 to 15, with higher scores indicating greater depression.
IWQOL
The IWQOL is a validated 31-item self-report measure of obesity-specific quality of life (32, 33). In addition to a total score, there are scores on 5 domains: physical function, self-esteem, sexual life, public distress, and work. Scores are transformed to a 0–100 scale, with 100 representing the best HRQOL.
Potential mediators or confounders of weight loss and exercise on outcomes grouped in blocks
Body weight and visceral fat
Body weight was measured in the morning after a 12-h fast. Visceral abdominal tissue volume was measured by MRI (Siemens), as previously described (34, 35). Briefly, 10 serial 10-mm axial images were acquired, beginning at L1 (identified by the origin of the psoas muscle) and moving downward (35). Baseline and 1-y images were batch-analyzed with the use of Hippo software (36).
Insulin sensitivity, inflammation, and insulin-like growth factor I
A standard 75-g oral-glucose-tolerance test was performed after an overnight fast and the insulin sensitivity index (ISI) was calculated by using the formula ISI = 10,000/square root of [(fasting glucose × fasting insulin) × (mean glucose × mean insulin)], as previously described (24, 37). As a marker of chronic inflammation, high-sensitivity C-reactive protein (hs-CRP) was measured by immunoturbidimetric assay (Hitachi 917; Roche). Insulin-like growth factor I (IGF-I) was measured by radioimmunoassay (Diagnostic Products).
Muscle strength and VO2peak
The 1-RM (maximal weight a person can lift at one repetition) for biceps curl, bench press, and seated row was summed to calculate upper extremity 1-RM strength; the 1-RM for knee extension, knee flexion, and leg press was summed to calculate lower extremity (LE) 1-RM strength (23, 38). VO2peak was assessed during graded treadmill walking by indirect calorimetry (True Max 2400; ParvoMedics), as previously described (25, 39). Briefly, the incremental test started at a speed determined during a warm-period to elicit ∼70% of age-predicted maximum heart rate and remained constant throughout the test, and grade was increased by 2% every 2 min. The test continued until the subject could no longer exercise because of exhaustion or until other conditions, such as electrocardiogram changes or development of symptoms, made it unsafe to continue (25, 39).
Statistical analyses
The same statistical methodologies used in the parent RCT were applied (23). Briefly, intention-to-treat analyses were performed by including all available observations (3 visits) in the analysis. Baseline characteristics were compared by using ANOVAs or Fisher's exact test. Longitudinal changes between groups were tested by using mixed-model repeated-measures ANOVA. Change from baseline was used as the dependent variable with group, visit, and group × visit as independent effects and baseline values and education (for cognition) as covariates. The primary focus of the analyses for the main outcomes (3MS and total IWQOL) was the contrast emphasizing the 12-mo change in outcome in the 4 groups. In the mixed model, when the group × visit P value was <0.05, prespecified contrast statements were used to test the following 4 hypotheses: changes in the diet group were different from those in the control group, changes in the exercise group were different from those in the control group, changes in the diet-exercise group were different from those in the control group, and changes in the diet-exercise group were different from those in the diet group and exercise group. Analyses for within-group changes were performed by using mixed-model repeated-measures ANOVA. Pearson's correlation was used to examine relations among changes in variables, and 3MS and total IWQOL followed by stepwise multiple linear regression were used to identify which variables were independent contributors to the changes in the 3MS and total IWQOL in each intervention group. Baseline characteristics are presented as means ±SDs and changes in outcome variables are presented as least-squares adjusted means ± SEs unless otherwise indicated. Statistical tests were 2-tailed, and P < 0.05 was considered significant. Data analysis was generated by using SAS version 9.3 (SAS Institute).
RESULTS
The CONSORT (Consolidated Standards of Reporting Trials) diagram summarizing recruitment, randomization, and follow-up has been reported (23). Briefly, 107 participants were randomly assigned and 93 (87%) completed the study. Fourteen participants (4 in the control, 3 in the diet, 4 in the exercise, and 3 in the diet-exercise group) discontinued the intervention but were included in the intention-to-treat analyses. Baseline characteristics were not different between the groups (Table 1). Diet compliance was 83% (IQR: 79–89%) in the diet group and 82% (IQR: 76–89%) in the diet-exercise group. Exercise compliance was 88% (IQR: 85–92%) in the exercise group and 83% (IQR: 80–88%) in the diet-exercise group.
TABLE 1.
Baseline characteristics of participants1
| Group |
|||||
| Control (n = 27) | Diet (n = 26) | Exercise (n = 26) | Diet-exercise (n = 28) | P2 | |
| Age (y) | 69 ± 43 | 70 ± 4 | 70 ± 4 | 70 ± 4 | 0.85 |
| Female [n (%)] | 18 (67) | 17 (65) | 16 (61) | 16 (57) | 0.89 |
| White [n (%)] | 22 (81) | 23 (88) | 21 (81) | 25 (89) | 0.78 |
| Height (cm) | 165.8 ± 9.7 | 169.2 ± 9.5 | 168.1 ± 10.1 | 165.4 ± 8.7 | 0.38 |
| Weight (kg) | 101.0 ± 16.3 | 104.1 ± 15.3 | 99.2 ± 17.4 | 99.1 ± 16.8 | 0.66 |
| BMI (kg/m2) | 37.3 ± 4.7 | 37.2 ± 4.5 | 36.9 ± 5.4 | 37.2 ± 5.4 | 0.93 |
| Visceral fat (cm3) | 2591 ± 1539 | 2175 ± 1082 | 2231 ± 1183 | 2086 ± 1337 | 0.58 |
| Years of education | 16.9 ± 3.0 | 15.3 ± 3.7 | 16.7 ± 4.2 | 16.3 ± 3.8 | 0.53 |
| Physical performance test score | 26.8 ± 4.5 | 28.6 ± 1.9 | 27.1 ± 3.1 | 28.0 ± 2.9 | 0.17 |
| VO2peak (L/min) | 1.69 ± 0.49 | 1.84 ± 0.41 | 1.76 ± 0.51 | 1.73 ± 0.38 | 0.66 |
| UE 1-RM strength (kg) | 83.8 ± 34.4 | 106.5 ± 45.3 | 90.5 ± 45.5 | 90.1 ± 41.7 | 0.24 |
| LE 1-RM strength (kg) | 145.5 ± 42.9 | 169.5 ± 54.7 | 144.6 ± 45.6 | 154.6 ± 61.7 | 0.30 |
| History of cardiovascular disease [n (%)] | 8 (30) | 8 (31) | 7 (27) | 9 (31) | 0.98 |
| Previous cigarette use [n (%)] | 9 (33) | 7 (26) | 9 (34) | 1 (39) | 0.82 |
| Use of CNS-affecting drugs [n (%)] | |||||
| Antidepressant | 3 (1) | 2 1) | 2 (1) | 3 (1) | 0.95 |
| Anticholinergic | 0 (0) | 2 (1) | 1 (0) | 1 (0) | 0.54 |
| Sedative-hypnotic | 1 (0) | 1 (0) | 1 (0) | 1 (0) | 1.00 |
CNS, central nervous system; LE, lower extremity; UE, upper extremity; VO2peak, peak oxygen consumption; 1-RM, 1-repetition maximum.
P values were calculated with the use of ANOVA for quantitative data and Fisher's exact test for counts.
Mean ± SD (all such values).
Scores on the 3MS improved more in the diet group (1.7 ± 0.4), exercise group (2.8 ± 0.4), and diet-exercise group (2.9 ± 0.4) than in the control group (0.1 ± 0.4). Scores improved more in the diet-exercise group than in the diet group but not more than in the exercise group (Table 2). Scores on the Word Fluency Test improved more in the exercise group (4.1 ± 0.8) and diet-exercise group (4.2 ± 0.7) than in the control group (−0.8 ± 0.8). The Word Fluency Test score tended to improve more in the diet-exercise group than in the diet group. In both the Trails A and B tests, the scores in the diet-exercise group (−11.8 ± 1.9 and −21.8 ± 5.1, respectively) but not the diet group or exercise group improved more than in the control group (−0.8 ± 1.9 and −1.8 ± 4.9, respectively). GDS scores did not change in any group.
TABLE 2.
Effects of diet, exercise, or a combination of both on cognition and mood in obese older adults1
| Baseline2 | Change at 6 mo3 | Change at 12 mo3 | Difference in change from baseline to 12 mo (95% CI) | P4 | |
| Main outcome | |||||
| 3MS | |||||
| Control group | 96.3 ± 0.8 | 0.1 ± 0.4 | 0.1 ± 0.4 | — | — |
| Diet group | 96.0 ± 0.6 | 1.1 ± 0.45 | 1.7 ± 0.45 | — | — |
| Exercise group | 94.9 ± 0.9 | 1.9 ± 0.45 | 2.8 ± 0.45 | — | — |
| Diet-exercise group | 95.6 ± 0.8 | 1.8 ± 0.45 | 2.9 ± 0.45 | — | — |
| Intergroup comparisons | |||||
| Diet vs control | — | — | — | 1.5 (0.1, 3.0) | 0.04 |
| Exercise vs control | — | — | — | 3.0 (1.5, 4.5) | 0.0001 |
| Diet-exercise vs control | — | — | — | 3.0 (1.5, 4.4) | 0.0001 |
| Diet-exercise vs diet | — | — | — | 1.4 (0.0, 2.8) | 0.04 |
| Diet-exercise vs exercise | — | — | — | 0.0 (−1.5, 1.4) | 0.99 |
| Other outcomes | |||||
| Word List Fluency | |||||
| Control group | 17.9 ± 1.1 | −0.4 ± 0.7 | −0.8 ± 0.8 | — | — |
| Diet group | 17.3 ± 0.7 | 1.3 ± 0.7 | 1.4 ± 0.7 | — | — |
| Exercise group | 17.9 ± 0.8 | 2.3 ± 0.75 | 4.1 ± 0.85 | — | — |
| Diet-exercise group | 19.5 ± 0.8 | 2.2 ± 0.75 | 4.2 ± 0.75 | — | — |
| Intergroup comparisons | |||||
| Diet vs control | — | — | — | 2.3 (−0.5, 5.0) | 0.11 |
| Exercise vs control | — | — | — | 4.9 (2.1, 7.7) | 0.001 |
| Diet-exercise vs control | — | — | — | 4.5 (1.8, 7.2) | 0.001 |
| Diet-exercise vs diet | — | — | — | 2.3 (−0.3, 4.9) | 0.08 |
| Diet-exercise vs exercise | — | — | — | −0.3 (−3.0, 2.3) | 0.80 |
| Trail A | |||||
| Control group | 42.9 ± 3.0 | −1.6 ± 2.0 | −0.8 ± 1.9 | — | — |
| Diet group | 41.8 ± 2.4 | −6.1 ± 2.05 | −7.1 ± 2.05 | — | — |
| Exercise group | 40.3 ± 2.3 | −5.1 ± 2.0 | −8.4 ± 2.15 | — | — |
| Diet-exercise group | 47.7 ± 5.6 | −7.4 ± 1.95 | −11.8 ± 1.95 | — | — |
| Intergroup comparisons | |||||
| Diet vs control | — | — | — | −5.8 (−13.2, 1.5) | 0.12 |
| Exercise vs control | — | — | — | −6.6 (−14.1, 0.8) | 0.08 |
| Diet-exercise vs control | — | — | — | −12.9 (−20.1, −5.8) | 0.001 |
| Diet-exercise vs diet | — | — | — | −7.1 (−14.3, 0.2) | 0.06 |
| Diet-exercise vs exercise | — | — | — | −6.3 (−13.6, 1.1) | 0.09 |
| Trail B | |||||
| Control group | 106.9 ± 7.8 | −0.9 ± 4.8 | −1.8 ± 4.9 | — | — |
| Diet group | 106.9 ± 9.3 | −15.4 ± 5.05 | −20.7 ± 5.25 | — | — |
| Exercise group | 102.5 ± 7.3 | −8.9 ± 5.15 | −16.1 ± 5.55 | — | — |
| Diet-exercise group | 102.2 ± 8.3 | −14.7 ± 4.85 | −21.8 ± 5.15 | — | — |
| Intergroup comparisons | |||||
| Diet vs control | — | — | — | −17.9 (−35.8, 0.3) | 0.05 |
| Exercise vs control | — | — | — | −12.6 (−31.2, 5.9) | 0.18 |
| Diet-exercise vs control | — | — | — | −18.1 (−36.1, 0.1) | 0.049 |
| Diet-exercise vs diet | — | — | — | −0.4 (−18.6, 18.3) | 0.98 |
| Diet-exercise vs exercise | — | — | — | −5.5 (−24.2, 13.3) | 0.56 |
| GDS | |||||
| Control group | 1.9 ± 0.6 | −0.7 ± 0.3 | −0.1 ± 0.4 | — | — |
| Diet group | 1.4 ± 0.5 | −0.6 ± 0.3 | −0.2 ± 0.3 | — | — |
| Exercise group | 1.5 ± 0.4 | −0.3 ± 0.3 | −0.3 ± 0.3 | — | — |
| Diet-exercise group | 1.0 ± 0.2 | 0.1 ± 0.2 | −0.4 ± 0.3 | — | — |
| Intergroup comparisons | |||||
| Diet vs control | — | — | — | 0.2 (−1.0, 1.3) | 0.78 |
| Exercise vs control | — | — | — | −0.1 (−1.2, 1.1) | 0.92 |
| Diet-exercise vs control | — | — | — | 0.1 (−1.1, 1.2) | 0.89 |
| Diet-exercise vs diet | — | — | — | −0.1 (−1.0, 0.9) | 0.87 |
| Diet-exercise vs exercise | — | — | — | 0.1 (−0.9, 1.2) | 0.77 |
The samples for analysis were n = 27 for the control group, n = 26 for the diet group, n = 26 for the exercise group, and n = 28 for the diet-exercise group. GDS, Geriatric Depression Scale; 3MS, Modified Mini-Mental State Examination; —, not applicable.
Values are observed means ± SEs.
Values are least-squares adjusted means ± SEs from the repeated-measures analysis.
P values for comparisons between groups for changes from baseline to 12 mo were calculated with the use of mixed-model repeated-measures ANOVA contrasts (with baseline values and education as covariates in analyses of cognitive tests and with baseline values as covariates in analyses of mood). The P value for the group × visit interaction for the main outcome of 3MS was 0.001. P values for the group × visit interaction for the other outcomes were 0.01 for Word Fluency, 0.04 for Trail A, 0.38 for Trail B, and 0.36 for the GDS.
P < 0.05 for the comparison of the value at the follow-up time with the within-group baseline value, as calculated with the use of mixed-model repeated-measures ANOVA.
The total IWQOL scores improved more in the diet group (7.6 ± 1.6), exercise group (10.1 ± 1.6), and diet-exercise group (14.0 ± 1.4) than in the control group (0.3 ± 1.6). Scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group (Table 3). All domains of the IWQOL (physical function, self-esteem, sexual life, public distress, work) followed the same pattern of improvement as the total IWQOL score, with the most consistent improvement occurring in physical function across the intervention groups.
TABLE 3.
Effects of diet, exercise, or a combination of both on the IWQOL in obese older adults1
| Baseline2 | Change at 6 mo3 | Change at 12 mo3 | Difference in change from baseline to 12 mo (95% CI) | P4 | |
| Main outcome | |||||
| Total IWQOL | |||||
| Control group | 75.4 ± 3.7 | −2.4 ± 1.4 | 0.3 ± 1.6 | — | — |
| Diet group | 82.8 ± 1.8 | 8.5 ± 1.55 | 7.6 ± 1.65 | — | — |
| Exercise group | 77.2 ± 3.5 | 7.1 ± 1.65 | 10.1 ± 1.65 | — | — |
| Diet-exercise group | 76.5 ± 3.0 | 10.2 ± 1.45 | 14.0 ± 1.45 | — | — |
| Intergroup comparisons | |||||
| Diet vs control | — | — | — | 6.1 (0.6, 11.7) | 0.03 |
| Exercise vs control | — | — | — | 9.5 (3.9, 15.1) | 0.001 |
| Diet-exercise vs control | — | — | — | 13.6 (8.2, 18.9) | 0.0001 |
| Diet-exercise vs diet | — | — | — | 7.4 (2.1, 12.8) | 0.007 |
| Diet-exercise vs exercise | — | — | — | 4.1 (−1.4, 9.5) | 0.15 |
| Other outcomes | |||||
| Physical function | |||||
| Control group | 62.5 ± 4.1 | −0.6 ± 1.9 | −0.3 ± 2.1 | — | — |
| Diet group | 73.4 ± 2.1 | 11.5 ± 1.95 | 9.9 ± 2.05 | — | — |
| Exercise group | 67.4 ± 4.2 | 8.7 ± 2.05 | 10.4 ± 2.15 | — | — |
| Diet-exercise group | 67.7 ± 4.0 | 15.7 ± 1.85 | 16.3 ± 1.95 | — | — |
| Intergroup comparisons | |||||
| Diet vs control | — | — | — | 8.3 (0.9, 15.7) | 0.03 |
| Exercise vs control | — | — | — | 9.8 (2.3, 17.3) | 0.001 |
| Diet-exercise vs control | — | — | — | 15.7 (8.4, 23.0) | 0.0001 |
| Diet-exercise vs diet | — | — | — | 7.4 (0.2, 14.6) | 0.007 |
| Diet-exercise vs exercise | — | — | — | 5.9 (−1.4, 13.2) | 0.14 |
| Self-esteem | |||||
| Control group | 71.3 ± 4.3 | −3.5 ± 2.5 | 2.2 ± 2.8 | — | — |
| Diet group | 74.7 ± 3.6 | 14.7 ± 2.65 | 9.7 ± 2.65 | — | — |
| Exercise group | 71.7 ± 4.8 | 5.0 ± 2.7 | 10.3 ± 2.85 | — | — |
| Diet-exercise group | 71.7 ± 4.1 | 9.7 ± 2.55 | 14.7 ± 2.65 | — | — |
| Intergroup comparisons | |||||
| Diet vs. control | — | — | — | 6.7 (−3.3, 16.7) | 0.19 |
| Exercise vs. control | — | — | — | 8.0 (−2.2, 18.1) | 0.12 |
| Diet-exercise vs control | — | — | — | 12.5 (2.6, 22.3) | 0.01 |
| Diet-exercise vs diet | — | — | — | 5.7 (−4.0, 15.4) | 0.24 |
| Diet-exercise vs exercise | — | — | — | 4.5 (−5.4, 14.4) | 0.37 |
| Sexual life | |||||
| Control group | 77.0 ± 7.1 | −3.3 ± 3.0 | 1.6 ± 3.3 | — | — |
| Diet group | 86.2 ± 3.8 | 1.0 ± 3.2 | 4.0 ± 3.4 | — | — |
| Exercise group | 74.4 ± 5.3 | 9.1 ± 3.45 | 14.4 ± 3.35 | — | — |
| Diet-exercise group | 74.7 ± 5.0 | 13.4 ± 3.05 | 17.3 ± 3.05 | — | — |
| Intergroup comparisons | |||||
| Diet vs control | — | — | — | 0.2 (−12.3, 12.7) | 0.97 |
| Exercise vs control | — | — | — | 13.4 (1.2, 25.7) | 0.03 |
| Diet-exercise vs control | — | — | — | 16.3 (4.6, 28.0) | 0.007 |
| Diet-exercise vs diet | — | — | — | 16.1 (4.0, 28.2) | 0.009 |
| Diet-exercise vs exercise | — | — | — | 2.9 (−8.9, 14.7) | 0.63 |
| Public distress | |||||
| Control group | 83.9 ± 3.9 | −1.3 ± 1.7 | −3.9 ± 1.9 | — | — |
| Diet group | 91.0 ± 2.4 | 5.5 ± 1.85 | 5.0.2 ± 1.95 | — | — |
| Exercise group | 89.2 ± 3.4 | 3.9 ± 1.95 | 4.1 ± 2.05 | — | — |
| Diet-exercise group | 86.1 ± 3.6 | 5.2 ± 1.75 | 9.2 ± 1.75 | — | — |
| Intergroup comparisons | |||||
| Diet vs control | — | — | — | 7.5 (0.4, 14.7) | 0.04 |
| Exercise vs control | — | — | — | 6.9 (−0.4, 14.1) | 0.06 |
| Diet-exercise vs control | — | — | — | 12.6 (5.8, 19.5) | 0.0004 |
| Diet-exercise vs diet | — | — | — | 5.1 (−1.8, 12.0) | 0.15 |
| Diet-exercise vs exercise | — | — | — | 5.8 (−1.2, 12.8) | 0.11 |
| Work | |||||
| Control group | 85.0 ± 3.3 | −5.0 ± 2.2 | −4.0 ± 2.4 | — | — |
| Diet group | 89.0 ± 2.1 | 4.1 ± 2.25 | 3.3 ± 2.35 | — | — |
| Exercise group | 84.0 ± 4.1 | 5.1 ± 2.5 | 8.0 ± 2.65 | — | — |
| Diet-exercise group | 85.5 ± 3.2 | 5.9 ± 2.25 | 9.3 ± 2.25 | — | — |
| Intergroup comparisons | |||||
| Diet vs control | — | — | — | 6.5 (−2.0, 15.0) | 0.13 |
| Exercise vs control | — | — | — | 12.2 (3.4, 20.9) | 0.006 |
| Diet-exercise vs control | — | — | — | 13.2 (4.9, 21.4) | 0.002 |
| Diet-exercise vs diet | — | — | — | 6.7 (−1.6, 14.9) | 0.11 |
| Diet-exercise vs exercise | — | — | — | 1.0 (−7.5, 9.5) | 0.82 |
The samples for analysis were n = 27 for the control group, n = 26 for the diet group, n = 26 for the exercise group, and n = 28 for the diet-exercise group. IWQOL, Impact of Weight on Quality of Life–Lite; —, not applicable.
Values are observed means ± SEs.
Values are least-squares adjusted means ± SEs from the repeated-measures analysis.
P values for comparison between groups for changes from baseline to 12 mo were calculated with the use of mixed-model repeated-measures ANOVA contrasts (with baseline values as covariates). The P value for the group × visit interaction for the main outcome of total IWQOL was 0.0001. The P value for the group × visit interaction for the other outcomes were 0.0001 for physical function, 0.001 for self-esteem, 0.04 for public distress, 0.01 for sexual life, 0.02 for work, and 0.04 for public distress.
P < 0.05 for the comparison of the value at the follow-up time with the within-group baseline value, as calculated with the use of mixed-model repeated-measures ANOVA.
As reported (23), body weight decreased similarly in the diet-exercise and diet groups (−8.6 ± 3.8 and −9.7 ± 5.4 kg, respectively), whereas weight was constant in the exercise and control groups. Visceral fat decreased similarly in the diet-exercise and diet group (−787 ± 896 and −561 ± 454 cm3, respectively), whereas it decreased modestly (−115 ± 244 cm3) in the exercise group (24). The ISI increased more in the diet-exercise group (2.4 ± 2.3) than in the diet group (1.2 ± 1.6) but not more than in the exercise or control group (24). hs-CRP concentrations decreased similarly in the diet-exercise group and diet group (−1.8 ± 3.4 and 1.1 ± 1.4 mg/L) but not in the exercise or control group (24). IGF-I concentrations did not significantly change in any group (40). Upper extremity 1-RM strength increased similarly in the diet-exercise and exercise groups (18.5 ± 23.5 and 22.9 ± 25.4 kg) but not in the diet or control group (−5.6 ± 24.5 and −0.5 ± 13.1 kg) (between-group P = 0.0001). Likewise, LE 1-RM strength increased similarly in the diet-exercise and exercise groups (55.7 ± 37.3 and 64.0 ± 54.2 kg) but not in the diet or control group (6.1 ± 25.0 and −1.4 ± 41.5 kg) (between-group P = 0.0001). VO2peak improved similarly in the diet-exercise group and exercise group (0.15 ± 0.12 and 0.14 ± 0.15 L/min) and did not change in the diet or control group (24).
Bivariate analyses showed that changes in several variables correlated with changes in 3MS and total IWQOL (Supplemental Table 1 under “Supplemental data” in the online issue). In addition, stepwise multiple regression showed that the following variables were independent predictors of changes in the 3MS: 1) diet group: changes in ISI and hs-CRP (explaining 25% of the variance in changes in the 3MS); 2) exercise group: changes in VO2peak and LE 1-RM (explaining 24% of the variance in changes in the 3MS); and 3) diet-exercise group: changes in LE 1-RM and VO2peak (explaining 19% of the variance in changes in the 3MS) (Table 4). Moreover, stepwise multiple regression showed that the following variables were independent predictors of changes in the total IWQOL: 1) diet group: changes in body weight (explaining 15% of the variance in changes in the IWQOL); 2) exercise group: changes in LE 1-RM (explaining 17% of the variance in changes in the IWQOL); and 3) diet-exercise group: changes in body weight and LE 1-RM (explaining 32% of the variance in changes in the IWQOL) (Table 4).
TABLE 4.
Final models in the stepwise multiple regression analyses identifying predictors of changes in the 3MS and total IWQOL among the intervention groups1
| β | P | |
| Final model of variables affecting change in 3MS | ||
| Diet group (multiple R = 0.503, P = 0.0003) | ||
| Change in ISI | 0.468 ± 0.119 | 0.0001 |
| Change in hs-CRP | −0.309 ± 0.119 | 0.01 |
| Exercise group (multiple R = 0.489, P = 0.001) | ||
| Change in VO2peak | 0.319 ± 0.121 | 0.01 |
| Change in LE 1-RM strength | 0.314 ± 0.131 | 0.01 |
| Diet-exercise group (multiple R = 0.436, P = 0.002) | ||
| Change in LE 1-RM strength | 0.272 ± 0.136 | 0.03 |
| Change in VO2peak | 0.257 ± 0.124 | 0.04 |
| Final model of variables affecting change in total IWQOL | ||
| Diet group (R = 0.383, P = 0.002) | ||
| Change in body weight | −0.383 ± 0.123 | 0.002 |
| Exercise group strength (R = 0.406, P = 0.002) | ||
| Change in LE 1-RM | 0.406 ± 0.149 | 0.002 |
| Diet-exercise group (multiple R = 0.564, P = 0.0001) | ||
| Change in body weight | −0.365 ± 0.128 | 0.004 |
| Change in LE 1-RM strength | 0.293 ± 0.116 | 0.01 |
Values are βs ± SEs. The samples for analysis were n = 23 for the control group, n = 23 for the diet group, n = 22 for the exercise group, and n = 25 for the diet-exercise group. Stepwise multiple linear regression analysis was used to identify which variables were independent contributors to the changes in the 3MS and total IWQOL in each intervention group. Variables entered into the model were as follows: change in body weight, change in visceral fat, change in ISI, change in hs-CRP, change in insulin-like growth factor I, change in VO2peak, change in upper extremity 1-RM strength, change in LE 1-RM strength, and years of education (for 3MS only). hs-CRP, high-sensitivity C-reactive protein; ISI, insulin sensitivity index; IWQOL, Impact of Weight on Quality of Life–Lite; LE, lower extremity; VO2peak, peak oxygen consumption; 1-RM, one-repetition maximum; 3MS, Modified Mini-Mental State Examination.
Supplementary analyses that evaluated the independent and interaction effects of weight-loss and exercise factors showed a significant interaction effect on our 2 main outcomes of 3MS and total IWQOL (Supplemental Table 2 under “Supplemental data” in the online issue), consistent with the main results.
DISCUSSION
In this 1-y RCT in frail, obese older adults, weight loss plus exercise and exercise alone equally improved scores in the global 3MS test and to a greater extent than weight loss alone. Similar positive results were observed on the Word Fluency and Trails A and B tests that assess cognitive domains such as language and attention/executive function. Moreover, weight loss plus exercise and exercise alone equally improved scores in the IWQOL and to a greater extent than weight loss alone.
To our knowledge, the current study is the first RCT to directly compare the independent and combined effects of weight loss and exercise on cognition in obese older adults. Although weight loss is the primary treatment of obesity, whether weight-loss therapy is net beneficial or harmful in older adults is unclear (1). For example, in contrast to the consistent association between midlife obesity and dementia risk (4–6), observational studies have shown a paradoxical relation between BMI and cognition in older adults (9, 41, 42). A few interventional studies examined the effect of weight loss on cognition and reported positive and negative results, but these lacked a rigorous RCT design and focused on middle-aged, not older, adults (16). The current RCT, therefore, clearly shows for the first time that weight loss improves cognition in frail, obese older adults. However, we also found that the positive effects of weight loss on cognition were not additive to ET.
Our results, which showed positive effects of ET on cognition in obese older adults, are in general agreement with most previous RCTs of exercise training in nonobese middle-aged and older adults (17, 18). However, an important addition is the use of combined aerobic and resistance ET in obese older adults, whereas most previous studies in other populations used aerobic training alone. Although aerobic training studies usually showed positive effects on cognition (17), the few resistance training studies yielded equivocal results (43–45). Characteristics of studies showing cognitive benefits from resistance training were of longer duration using high-intensity protocols (46, 47). In the current 1-y RCT, we used moderate- to high-intensity aerobic and resistance training to improve VO2peak and 1-RM strength in obese older adults. Therefore, the current RCT provides novel data on the effects of combined aerobic and resistance training on cognition in this high-risk older population.
The stepwise multiple regression supported our findings that weight loss and exercise had independent effects on cognition. In final models, changes in ISI and hs-CRP predicted changes in the 3MS in the diet group, whereas changes in VO2peak and LE 1-RM strength predicted changes in the 3MS in the exercise group. Thus, the positive effects of weight loss on cognition may be mediated through weight-loss–induced improvement in insulin sensitivity and decreased inflammation (14). Our findings are consistent with animal models that suggest that improved insulin signaling and reduced inflammation induce higher brain synaptic plasticity and stimulation of neurofacilatory pathways in the brain, resulting in improved cognition (48, 49). In addition, the positive effects of exercise may be mediated through training-induced improvement in aerobic fitness and muscle strength (18). Our findings are also consistent with animal models that suggest that ET results in neurogenesis and angiogenesis, which are linked to improved memory and learning (50, 51). IGF-I has been shown to be an upregulated neurotrophic factor in both aerobic and resistance exercise (18). We found that IGF-I concentrations did not change in response to ET, possibly because of diminished growth hormone/IGF-I axis response with aging (52). Interestingly, changes in VO2peak and LE 1-RM were the independent predictors of change in the 3MS in both the exercise group and diet-exercise group. These findings are consistent with a ceiling effect of ET on cognition vis-à-vis weight loss, such that we observed no further effect of diet when added to exercise in the diet-exercise group.
HRQOL reflects an individual's subjective evaluation of and reaction to health. Indeed, obesity impairs important aspects of HRQOL (19) and by using an obesity-specific quality of life instrument, IWQOL (32), we found that weight loss improved HRQOL specifically in obese older adults. This finding was further supported in our stepwise multiple regression, where change in body weight was the lone predictor of change in total IWQOL in the diet group. Interestingly, although exercise was not associated with weight loss, exercise also improved HRQOL as assessed by the IWQOL. In fact, change in LE 1-RM was the lone predictor of change in IWQOL score in the exercise group, suggesting the importance of better physical function in improving a sense of well-being (53). Accordingly, among the 5 IWQOL domains, physical function showed the most consistent improvement across all groups. Importantly, change in body weight and change in LE 1-RM were both independent predictors of change in total IWQOL in the diet-exercise group, suggesting that weight loss and exercise might have additive effects on HRQOL. Indeed, the score in the total IWQOL increased more in the diet-exercise group than in the diet group, although it did not increase more than in the exercise group.
The strengths of our study include the RCT design, comprehensive lifestyle programs, and the degree of adherence to the 1-y intervention, which allowed for assessment of the distinct effects of weight loss, exercise, or a combination of both on cognition and HRQOL. A limitation is that we were unable to include neuroimaging studies to examine brain structure and function because of the participant burden from the other tests as part of the parent RCT (23). We were unable to detect an effect of our interventions on mood, probably because of the low baseline GDS scores. Participants who volunteered may be different from the general population so our results may not necessarily generalize to the obese older population. Another potential limitation is that many statistical tests were performed without rigorous correction for the multiplicity of tests. Our approach to minimize type 1 error for our main outcomes (3MS and total IWQOL) included the following: 1) the use of prespecified contrast statements to test 4 specific hypothesis and 2) performing these focused tests only after achieving a significant overall F test (P < 0.05).
Obesity in older adults challenges our health care professionals and health delivery systems (54–56). We previously showed that weight loss and exercise each ameliorate frailty and decrease cardiometabolic risk factors, but the combination of both provides the greatest benefits. Optimal treatment strategies in obese older adults should consider the relative positive effects and risks of weight loss, exercise, or both in improving multiple health outcomes in this growing segment of the older population (1, 2, 23, 24).
Supplementary Material
Acknowledgments
The authors’ responsibilities were as follows—DTV: had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis; DRS and DTV: conceived of and designed the study and obtained funding; NN, KS, DRS, and DTV: acquired the data; NN, KS, DLW, DRS, CQ, and DTV: analyzed and interpreted the data, drafted the manuscript, and critically revised the manuscript for important intellectual content; CQ: performed statistical analysis; and NN, KS, and DTV: supervised the study. The sponsors of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The authors did not declare any conflicts of interest.
Footnotes
Abbreviations used: ET, exercise training; GDS, Geriatric Depression Scale; HRQOL, health-related quality of life; hs-CRP, high-sensitivity C-reactive protein; IGF-I, insulin-like growth factor I; ISI, insulin sensitivity index; IWQOL, Impact of Weight on Quality of Life–Lite; LE, lower extremity; RCT, randomized controlled trial; VO2peak, peak oxygen consumption; WUSM, Washington University School of Medicine; 1-RM, one-repetition maximum; 3MS, Modified Mini-Mental State Examination.
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