Benson M. Hoffman

Aerobic Exercise and Neurocognitive Performance: A Meta-analytic Review of Randomized Controlled Trials

Objectives: To assess the effects of aerobic exercise training on neurocognitive performance. Although the effects of exercise on neurocognition have been the subject of several previous reviews and meta-analyses, they have been hampered by methodological shortcomings and are now outdated as a result of the recent publication of several large-scale, randomized, controlled trials (RCTs). Methods: We conducted a systematic literature review of RCTs examining the association between aerobic exercise training on neurocognitive performance between January 1966 and July 2009. Suitable studies were selected for inclusion according to the following criteria: randomized treatment allocation; mean age ≥18 years of age; duration of treatment >1 month; incorporated aerobic exercise components; supervised exercise training; the presence of a nonaerobic-exercise control group; and sufficient information to derive effect size data. Results: Twenty-nine studies met inclusion criteria and were included in our analyses, representing data from 2049 participants and 234 effect sizes. Individuals randomly assigned to receive aerobic exercise training demonstrated modest improvements in attention and processing speed (g = 0.158; 95% confidence interval [CI]; 0.055–0.260; p = .003), executive function (g = 0.123; 95% CI, 0.021–0.225; p = .018), and memory (g = 0.128; 95% CI, 0.015–0.241; p = .026). Conclusions: Aerobic exercise training is associated with modest improvements in attention and processing speed, executive function, and memory, although the effects of exercise on working memory are less consistent. Rigorous RCTs are needed with larger samples, appropriate controls, and longer follow-up periods. ITT = intention-to-treat; RCT = randomized controlled trial.

Exercise and Pharmacotherapy in the Treatment of Major Depressive Disorder

Objective: To assess whether patients receiving aerobic exercise training performed either at home or in a supervised group setting achieve reductions in depression comparable to standard antidepressant medication (sertraline) and greater reductions in depression compared to placebo controls. Methods: Between October 2000 and November 2005, we performed a prospective, randomized controlled trial (SMILE study) with allocation concealment and blinded outcome assessment in a tertiary care teaching hospital. A total of 202 adults (153 women; 49 men) diagnosed with major depression were assigned randomly to one of four conditions: supervised exercise in a group setting; home-based exercise; antidepressant medication (sertraline, 50–200 mg daily); or placebo pill for 16 weeks. Patients underwent the structured clinical interview for depression and completed the Hamilton Depression Rating Scale (HAM-D). Results: After 4 months of treatment, 41% of the participants achieved remission, defined as no longer meeting the criteria for major depressive disorder (MDD) and a HAM-D score of <8. Patients receiving active treatments tended to have higher remission rates than the placebo controls: supervised exercise = 45%; home-based exercise = 40%; medication = 47%; placebo = 31% (p = .057). All treatment groups had lower HAM-D scores after treatment; scores for the active treatment groups were not significantly different from the placebo group (p = .23). Conclusions: The efficacy of exercise in patients seems generally comparable with patients receiving antidepressant medication and both tend to be better than the placebo in patients with MDD. Placebo response rates were high, suggesting that a considerable portion of the therapeutic response is determined by patient expectations, ongoing symptom monitoring, attention, and other nonspecific factors. BDI = Beck Depression Inventory; CI = confidence interval; HAM-D = Hamilton Depression Rating Scale; ITT = intention-to-treat; MDD = major depressive disorder; SD = standard deviation; SSRIs = selective serotonin reuptake inhibitors; TSH = thyroid stimulating hormone.

Meta-analysis of psychological interventions for chronic low back pain

The purpose of this meta-analysis of randomized controlled trials was to evaluate the efficacy of psychological interventions for adults with noncancerous chronic low back pain (CLBP). The authors updated and expanded upon prior meta-analyses by using broad definitions of CLBP and psychological intervention, a broad data search strategy, and state-of-the-art data analysis techniques. All relevant controlled clinical trials meeting the inclusion criteria were identified primarily through a computer-aided literature search. Two independent reviewers screened abstracts and articles for inclusion criteria and extracted relevant data. Cohens d effect sizes were calculated by using a random effects model. Outcomes included pain intensity, emotional functioning, physical functioning (pain interference or pain-specific disability, health-related quality of life), participant ratings of global improvement, health care utilization, health care provider visits, pain medications, and employment/disability compensation status. A total of 205 effect sizes from 22 studies were pooled in 34 analyses. Positive effects of psychological interventions, contrasted with various control groups, were noted for pain intensity, pain-related interference, health-related quality of life, and depression. Cognitive-behavioral and self-regulatory treatments were specifically found to be efficacious. Multidisciplinary approaches that included a psychological component, when compared with active control conditions, were also noted to have positive short-term effects on pain interference and positive long-term effects on return to work. The results demonstrated positive effects of psychological interventions for CLBP. The rigor of the methods used, as well as the results that reflect mild to moderate heterogeneity and minimal publication bias, suggest confidence in the conclusions of this review.

Exercise and Pharmacological Treatment of Depressive Symptoms in Patients With Coronary Heart Disease: Results From the UPBEAT (Understanding the Prognostic Benefits of Exercise and Antidepressant Therapy) Study

OBJECTIVES The aim of this study was to assess the efficacy of exercise and antidepressant medication in reducing depressive symptoms and improving cardiovascular biomarkers in depressed patients with coronary heart disease. BACKGROUND Although there is good evidence that clinical depression is associated with poor prognosis, optimal therapeutic strategies are currently not well defined. METHODS One hundred one outpatients with coronary heart disease and elevated depressive symptoms underwent assessment of depression, including a psychiatric interview and the Hamilton Rating Scale for Depression. Participants were randomized to 4 months of aerobic exercise (3 times/week), sertraline (50-200 mg/day), or placebo. Additional assessments of cardiovascular biomarkers included measures of heart rate variability, endothelial function, baroreflex sensitivity, inflammation, and platelet function. RESULTS After 16 weeks, all groups showed improvement on Hamilton Rating Scale for Depression scores. Participants in both the aerobic exercise (mean -7.5; 95% confidence interval: -9.8 to -5.0) and sertraline (mean -6.1; 95% confidence interval: -8.4 to -3.9) groups achieved larger reductions in depressive symptoms compared with those receiving placebo (mean -4.5; 95% confidence interval: -7.6 to -1.5; p = 0.034); exercise and sertraline were equally effective at reducing depressive symptoms (p = 0.607). Exercise and medication tended to result in greater improvements in heart rate variability compared with placebo (p = 0.052); exercise tended to result in greater improvements in heart rate variability compared with sertraline (p = 0.093). CONCLUSIONS Both exercise and sertraline resulted in greater reductions in depressive symptoms compared to placebo in patients with coronary heart disease. Evidence that active treatments may also improve cardiovascular biomarkers suggests that they may have a beneficial effect on clinical outcomes as well as on quality of life. (Exercise to Treat Depression in Individuals With Coronary Heart Disease; NCT00302068).

Exercise and pharmacotherapy in patients with major depression: one-year follow-up of the SMILE study.

Objective: To examine a 1-year follow-up of a 4-month, controlled clinical trial of exercise and antidepressant medication in patients with major depressive disorder (MDD). Methods: In the original study, 202 sedentary adults with MDD were randomized to: a) supervised exercise; b) home-based exercise; c) sertraline; or d) placebo pill. We examined two outcomes measured at 1-year follow-up (i.e., 16 months post randomization): 1) continuous Hamilton Depression Rating Scale score; and 2) MDD status (depressed; partial remission; full remission) in 172 available participants (85% of the original cohort). Regression analyses were performed to examine the effects of treatment group assignment, as well as follow-up antidepressant medication use and self-reported exercise (Godin Leisure-Time Exercise Questionnaire), on the two outcomes. Results: In the original study, patients receiving exercise achieved similar benefits compared with those receiving sertraline. At the time of the 1-year follow-up, rates of MDD remission increased from 46% at post treatment to 66% for participants available for follow-up. Neither initial treatment group assignment nor antidepressant medication use during the follow-up period were significant predictors of MDD remission at 1 year. However, regular exercise during the follow-up period predicted both Hamilton Depression Rating Scale scores and MDD diagnosis at 1 year. This relationship was curvilinear, with the association concentrated between 0 minute and 180 minutes of weekly exercise. Conclusion: The effects of aerobic exercise on MDD remission seem to be similar to sertraline after 4 months of treatment; exercise during the follow-up period seems to extend the short-term benefits of exercise and may augment the benefits of antidepressant use. Trial Registration: clinicaltrials.gov Identifier: NCT00331305. MDD = major depressive disorder; HAM-D = Hamilton Depression Rating Scale; SCID = Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders; PSSS = Perceived Social Support Scale.

Exercise Fails to Improve Neurocognition in Depressed Middle-Aged and Older Adults.

PURPOSE Although cross-sectional studies have demonstrated an association between higher levels of aerobic fitness and improved neurocognitive function, there have been relatively few interventional studies investigating this relationship, and results have been inconsistent. We assessed the effects of aerobic exercise on neurocognitive function in a randomized controlled trial of patients with major depressive disorder (MDD). METHODS Two-hundred and two sedentary men (n = 49) and women (n = 153), aged 40 yr and over and who met diagnostic criteria for MDD, were randomly assigned to the following: a) supervised exercise, b) home-based exercise, c) sertraline, or d) placebo pill. Before and after 4 months of treatment, participants completed measures of: Executive Function (Trail Making Test B-A difference score, Stroop Color-Word, Ruff 2 & 7 Test, Digit Symbol), Verbal Memory (Logical Memory, Verbal Paired Associates), and Verbal Fluency/Working Memory (Animal Naming, Controlled Oral Word Association Test, Digit Span). Multivariate analyses of covariance were performed to test the effects of treatment on posttreatment neuropsychological test scores, with baseline neuropsychological test scores, age, education, and change in depression scores entered as covariates. RESULTS The performance of exercise participants was no better than participants receiving placebo across all neuropsychological tests. Exercise participants performed better than participants receiving sertraline on tests of executive function but not on tests of verbal memory or verbal fluency/working memory. CONCLUSIONS We found little evidence to support the benefits of an aerobic exercise intervention on neurocognitive performance in patients with MDD.

Exercise as Treatment for Anxiety: Systematic Review and Analysis

BackgroundExercise has been shown to reduce symptoms of anxiety, but few studies have studied exercise in individuals preselected because of their high anxiety.PurposeThe objective of this study is to review and critically evaluate studies of exercise training in adults with either high levels of anxiety or an anxiety disorder.MethodsWe conducted a systematic review of randomized clinical trials (RCTs) in which anxious adults were randomized to an exercise or nonexercise control condition. Data were extracted concerning anxiety outcomes and study design. Existing meta-analyses were also reviewed.ResultsEvidence from 12 RCTs suggested benefits of exercise, for select groups, similar to established treatments and greater than placebo. However, most studies had significant methodological limitations, including small sample sizes, concurrent therapies, and inadequate assessment of adherence and fitness levels.ConclusionsExercise may be a useful treatment for anxiety, but lack of data from rigorous, methodologically sound RCTs precludes any definitive conclusions about its effectiveness.

Cerebrovascular risk factors, vascular disease, and neuropsychological outcomes in adults with major depression

Objective: To investigate the relationship of cerebrovascular risk factors (CVRFs), endothelial function, carotid artery intima medial thickness (IMT), and neuropsychological performance in a sample of 198 middle-aged and older individuals with major depressive disorder (MDD). Neuropsychological deficits are common among adults with MDD, particularly among those with CVRFs and potentially persons with subclinical vascular disease. Methods: CVRFs were indexed by the Framingham Stroke Risk Profile (FSRP) and serum cholesterol levels obtained by medical history and physical examination. Patients completed a neuropsychological test battery including measures of executive functioning, working memory, and verbal recall. Vascular function was indexed by carotid artery IMT and brachial artery flow mediated dilation (FMD). Hierarchical multiple regression analyses were used to investigate the association between CVRFs, vascular disease, and neurocognitive performance. Results: Greater FSRP scores were associated with poorer executive functioning (b = −0.86; p = .041) and working memory (b = −0.90; p = .024). Lower high-density lipoprotein levels also were associated with poorer executive functioning (b = 1.03; p = .035). Higher IMT (b = −0.83; p = .028) and lower FMD (b = 1.29; p = .032) were associated with poorer executive functioning after controlling for CVRFs. Lower FMD was also associated with poorer working memory (b = 1.58; p = .015). Conclusions: Greater CVRFs were associated with poorer neuropsychological performance. Vascular dysfunction also was associated with neuropsychological decrements independent of traditional CVRFs. CVRF = cerebrovascular risk factor; FSRP = Framingham Stroke Risk Profile; MDD = major depressive disorder; IMT = intima medial thickness; GTN = glyceryl trinitrate; GTN-D = glyceryl trinitrate dilation; FMD = flow mediated dilation; HDL = high-density lipoprotein; LDL = low-density lipoprotein; Ham-D = Hamilton Rating Scale for Depression; DSST = digit symbol substitution test; COWAT = controlled oral word association test; DST = digit span test; CHD = coronary heart disease.

Neurobehavioral Functioning and Survival Following Lung Transplantation

BACKGROUND Neurobehavioral functioning is widely recognized as being an important consideration in lung transplant candidates, but little is known about whether these factors are related to clinical outcomes. The present study examined the relationship of neurobehavioral functioning, including measures of executive function and memory, depression, and anxiety, to long-term survival among lung transplant recipients. METHODS The sample was drawn from 201 patients who underwent transplantation at Duke University and Washington University who participated in a dual-site clinical trial investigating medical and psychosocial outcomes in transplant candidates with end-stage lung disease. All patients completed the Beck Depression Inventory-II (BDI-II) and Spielberger State-Trait Anxiety Inventory at baseline and again after 12 weeks, while a subset of 86 patients from Duke University also completed neurocognitive testing. Patients were followed for survival up to 12 years after completing baseline assessments. RESULTS One hundred eleven patients died over a mean follow-up of 10.8 years (SD=0.8). Baseline depression, anxiety, and neurocognitive function were examined as predictors of posttransplant survival, controlling for age, 6-min walk distance, FEV, and native disease; education and cardiovascular risk factors were also included in the model for neurocognition. Lower executive function (hazard ratio [HR]=1.09, P=.012) and memory performance (HR=1.11, P=.030) were independently associated with greater mortality following lung transplant. Although pretransplant depression and anxiety were not predictive of mortality, patients who scored>13 on the BDI-II at baseline and after 3 months pretransplant had greater mortality (HR=1.85 [95% CI, 1.04, 3.28], P=.036). CONCLUSIONS Neurobehavioral functioning, including persistently elevated depressive symptoms and lower neurocognitive performance, was associated with reduced survival after lung transplantation. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00113139; URL: www.clinicaltrials.gov.

Intima-media thickness and age of first depressive episode

BACKGROUND Late life depression, including patients with vascular depression, has been associated with higher levels of intima-media thickness (IMT). Although individuals with vascular depression tend to report a later onset of depression, the relationship of IMT and age of first depressive episode is uncertain in younger adults. We therefore investigated the relationship between IMT and age of first depressive episode in a sample of 202 adults (age range 40-81 years) with major depression (MDD). METHODS Depression status was assessed using the Structured Clinical Interview Schedule and the Hamilton Depression Rating Scale. Patients underwent a physical examination in which a medical history was obtained. IMT was measured from the left and right common carotid arteries. Simple regression analyses were used to investigate the association between IMT and self-reported age of first depressive episode. RESULTS IMT was associated with a later onset of first major depressive episode (b=.225, P=.0005) and this association remained significant after controlling for age, Framingham Stroke Risk Profile, smoking pack years, physical activity, high- and low-density lipoprotein, body mass index, triglyceride levels, and history of chronic medical conditions (b=.142, P=.028). Each .10mm increase in IMT was associated with a 2.6-year later reported occurrence of first major depressive episode (MDE). Similarly, higher levels of IMT were associated with fewer previous MDEs (b=-.149, P=.020) and this effect remained significant in our multivariate model (b=-.140, P=.030). In contrast, IMT was not associated with current depressive severity (b=-.024, P=.720). CONCLUSIONS Greater levels of IMT are associated with a later onset of depression and fewer previous depressive episodes among middle-aged and older adults, independent of cardiovascular co-morbidities. These findings provide preliminary evidence that increased vascular burden may be associated with a later onset of depression.