Objective cognitive performance and subjective complaints in patients with chronic Q fever or Q fever fatigue syndrome.

BACKGROUND: Primary aim of this study was to compare cognitive performance of patients with chronic Q fever or Q fever fatigue syndrome (QFS) to matched controls from the general population, while taking performance validity into account. Second, we investigated whether objective cognitive performance was related to subjective cognitive complaints or psychological wellbeing. METHODS: Cognitive functioning was assessed with a neuropsychological test battery measuring the domains of processing speed, episodic memory, working memory and executive functioning. Tests for performance validity and premorbid intelligence were also included. Validated questionnaires were administered to assess self-reported fatigue, depressive symptoms and cognitive complaints. RESULTS: In total, 30 patients with chronic Q fever, 32 with QFS and 35 controls were included. A high percentage of chronic Q fever patients showed poor performance validity (38%) compared to controls (14%, p = 0.066). After exclusion of participants showing poor performance validity, no significant differences between patients and controls were found in the cognitive domains. QFS patients reported a high level of cognitive complaints compared to controls (41.2 vs 30.4, p = 0.023). Cognitive complaints were not significantly related to cognitive performance in any of the domains for this patient group. CONCLUSIONS: The high level of self-reported cognitive complaints in QFS patients does not indicate cognitive impairment. A large proportion of the chronic Q fever patients showed suboptimal mental effort during neuropsychological assessment. More research into the underlying explanations is needed. Our findings stress the importance of assessing cognitive functioning by neuropsychological examination including performance validity, rather than only measuring subjective cognitive complaints.

Individual Differences in the Effects of Physical Activity on Cognitive Function in People with Mild to Moderate Dementia.

The aim of this study was to investigate whether the effect of physical activity on cognitive function in persons with dementia is moderated by patient characteristics as Apolipoprotein E and dementia type. We included 101 individuals with dementia and calculated the reliable change index to determine the change in global cognition, executive function, episodic memory, working memory, and processing speed before and after a 12-week exercise training. We found a higher treatment-related benefit in episodic memory in persons with non-Alzheimer's disease compared to persons with Alzheimer's disease, and in executive function in individuals with better baseline cognitive function.

NeuroExercise: The Effect of a 12-Month Exercise Intervention on Cognition in Mild Cognitive Impairment-A Multicenter Randomized Controlled Trial.

Exercise intervention studies in mild cognitive impairment (MCI), a prodromal stage of Alzheimer's disease (AD), have demonstrated inconsistent yet promising results. Addressing the limitations of previous studies, this trial investigated the effects of a 12-month structured exercise program on the progression of MCI. The NeuroExercise study is a multicenter randomized controlled trial across three European countries (Ireland, Netherlands, Germany). Hundred and eighty-three individuals with amnestic MCI were included and were randomized to a 12-month exercise intervention (3 units of 45 min) of either aerobic exercise (AE; n = 60), stretching and toning exercise (ST; n = 65) or to a non-exercise control group (CG; n = 58). The primary outcome, cognitive performance, was determined by an extensive neuropsychological test battery. For the primary complete case (CC) analyses, between-group differences were analyzed with analysis of covariance under two conditions: (1) the exercise group (EG = combined AE and ST groups) compared to the CG and (2) AE compared to ST. Primary analysis of the full cohort (n = 166, 71.5 years; 51.8% females) revealed no between-group differences in composite cognitive score [mean difference (95% CI)], 0.12 [(-0.03, 0.27), p = 0.13] or in any cognitive domain or quality of life. VO2 peak was significantly higher in the EG compared to the CG after 12 months [-1.76 (-3.39, -0.10), p = 0.04]. Comparing the two intervention groups revealed a higher VO2peak level in the aerobic exercise compared to the stretching and toning group, but no differences for the other outcomes. A 12-month exercise intervention did not change cognitive performance in individuals with amnestic MCI in comparison to a non-exercise CG. An intervention effect on physical fitness was found, which may be an important moderator for long term disease progression and warrants long-term follow-up investigations. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02913053, identifier: NCT02913053.

Physical Exercise Training Improves Quality of Life in Healthy Older Adults: A Meta-Analysis.

The current meta-analysis first aimed to quantify the overall effect of physical exercise training on the quality of life (QoL) in healthy older adults. Second, the effects on the social, physical, and psychological QoL were assessed. In total, 16 randomized controlled trials were included. The primary analysis showed a medium effect of physical exercise training on QoL in healthy older adults (standard mean difference [SMD] = 0.38, confidence interval, CI, [0.18, 0.59], p < .05). The secondary analyses showed a positive medium effect of physical exercise training on the physical component of QoL (SMD = 0.39, CI [0.17, 0.60], p < .05), and a positive medium effect of physical exercise training on the psychological component of QoL (SMD = 0.348, CI [0.125, 0.570], p < .05), and no significant effect of physical exercise training on the social component of QoL was observed (SMD = 0.16, CI [-0.07, 0.38], p = .17). These findings warrant implementation efforts pertaining to exercise training for older adults to improve the QoL in our aging societies.

Exergaming as a Physical Exercise Strategy Reduces Frailty in People With Dementia: A Randomized Controlled Trial.

OBJECTIVES: People with dementia are known to be physically frailer, more sedentary, and participate less in regular physical exercise compared to their healthy peers. Physical activity interventions have the potential to reduce the level of frailty in community-dwelling older adults. Exergaming combines physical exercise with cognitive stimulation in a virtual environment. It is an innovative and fun way of exercising, which may aid people with dementia to be more physically active. The primary aim of this study was to investigate the efficacy of a 12-week exergame training and equally long aerobic training, both compared to an active control group, on frailty in people with dementia. DESIGN: A 3-armed randomized controlled trial compared exergame training, aerobic training, and an active control intervention. PARTICIPANTS: 115 people with dementia [mean (standard deviation [SD]) age = 79.2 (6.9) years; mean (SD) Mini-Mental State Examination score = 22.9 (3.4)]. METHODS: Participants were randomized and individually trained 3 times a week during 12 weeks. The Evaluative Frailty Index for Physical activity (EFIP) was used to assess the level of frailty at baseline and after the 12-week intervention period. Between-group differences were analyzed with analysis of covariance. RESULTS: The exergame group showed a trend toward higher adherence compared to the aerobic group (87.3% vs 81.1%, P = .05). A significant reduction on the EFIP was found in the exergame group (EG) compared to the active control group (CG) [mean difference (95% confidence interval) between EG and CG: -0.034 [-0.062, -0.007], P = .012], with a small-to-moderate effect size (partial η2 = 0.055). CONCLUSIONS AND IMPLICATIONS: This is the first study to show that a 12-week exergame intervention reduces the level of frailty in people with dementia. This is an important and promising result, because frailty is a powerful predictor for adverse health outcomes, and its reduction may have positive effects on health status. Moreover, exergaming resulted in high adherence rates of physical exercise, which makes it an effective strategy to engage people with dementia in physical activity.

The quest for synergy between physical exercise and cognitive stimulation via exergaming in people with dementia: a randomized controlled trial.

BACKGROUND: Exercise is often proposed as a non-pharmacological intervention to delay cognitive decline in people with dementia, but evidence remains inconclusive. Previous studies suggest that combining physical exercise with cognitive stimulation may be more successful in this respect. Exergaming is a promising intervention in which physical exercise is combined with cognitively challenging tasks in a single session. The aim of this study was to investigate the effect of exergame training and aerobic training on cognitive functioning in older adults with dementia. METHODS: A three-armed randomized controlled trial (RCT) compared exergame training, aerobic training and an active control intervention consisting of relaxation and flexibility exercises. Individuals with dementia were randomized and individually trained three times a week during 12 weeks. Cognitive functioning was measured at baseline, after the 12-week intervention period and at 24-week follow-up by neuropsychological assessment. The domains of executive function, episodic memory, working memory and psychomotor speed were evaluated. Test scores were converted into standardized z-scores that were averaged per domain. Between-group differences were analysed with analysis of covariance. RESULTS: Data from 115 people with dementia (mean (SD) age = 79.2 (6.9) years; mean (SD) MMSE score = 22.9 (3.4)) were analysed. There was a significant improvement in psychomotor speed in the aerobic and exergame groups compared to the active control group (mean difference domain score (95% CI) aerobic versus control 0.370 (0.103-0.637), p = 0.007; exergame versus control 0.326 (0.081-0.571), p = 0.009). The effect size was moderate (partial η2 = 0.102). No significant differences between the intervention and control groups were found for executive functioning, episodic memory and working memory. CONCLUSIONS: To our knowledge, this is the first RCT evaluating the effects of exergame training and aerobic training on cognitive functioning in people with dementia. We found that both exergame training and aerobic training improve psychomotor speed, compared to an active control group. This finding may be clinically relevant as psychomotor speed is an important predictor for functional decline. No effects were found on executive function, episodic memory and working memory. TRIAL REGISTRATION: Netherlands Trial Register, NTR5581 . Registered on 7 October 2015.

The influence of computer-based cognitive flexibility training on subjective cognitive well-being after stroke: A multi-center randomized controlled trial.

BACKGROUND: Stroke can result in cognitive complaints that can have a large impact on quality of life long after its occurrence. A number of computer-based training programs have been developed with the aim to improve cognitive functioning. Most studies investigating their efficacy used only objective outcome measures, whereas a reduction of subjective cognitive complaints may be equally important for improving quality of life. A few studies used subjective outcome measures but were inconclusive, partly due to methodological shortcomings such as lack of proper active and passive control groups. OBJECTIVE: The aim of the current study was to investigate whether computer-based cognitive flexibility training can improve subjective cognitive functioning and quality of life after stroke. METHODS: We performed a randomized controlled double blind trial (RCT). Adults (30-80 years old) who had a stroke 3 months to 5 years ago, were randomly assigned to either an intervention group (n = 38), an active control group (i.e., mock training; n = 35), or a waiting list control group (n = 24). The intervention and mock training consisted of 58 half-hour sessions within 12 weeks. The primary subjective outcome measures were cognitive functioning (Cognitive Failure Questionnaire), executive functioning (Dysexecutive Functioning Questionnaire), quality of life (Short Form Health Survey), instrumental activities of daily living (IADL; Lawton & Brody IADL scale), and participation in society (Utrecht Scale for Evaluation of Rehabilitation-Participation). Secondary subjective outcome measures were recovery after stroke, depressive symptoms (Hospital Anxiety Depression Scale-depression subscale), fatigue (Checklist Individual Strength-Fatigue subscale), and subjective cognitive improvement (exit list). Finally, a proxy of the participant rated the training effects in subjective cognitive functioning, subjective executive functioning, and IADL. RESULTS AND CONCLUSIONS: All groups improved on the two measures of subjective cognitive functioning and subjective executive functioning, but not on the other measures. These cognitive and executive improvements remained stable 4 weeks after training completion. However, the intervention group did not improve more than the two control groups. This suggests that improvement was due to training-unspecific effects. The proxies did not report any improvements. We, therefore, conclude that the computer-based cognitive flexibility training did not improve subjective cognitive functioning or quality of life after stroke.

Positive effects of combined cognitive and physical exercise training on cognitive function in older adults with mild cognitive impairment or dementia: A meta-analysis.

Combined cognitive and physical exercise interventions have potential to elicit cognitive benefits in older adults with mild cognitive impairment (MCI) or dementia. This meta-analysis aims to quantify the overall effect of these interventions on global cognitive functioning in older adults with MCI or dementia. Ten randomized controlled trials that applied a combined cognitive-physical intervention with cognitive function as an outcome measure were included. For each study effect sizes were computed (i.e., post-intervention standardized mean difference (SMD) scores) and pooled, using a random-effects meta-analysis. The primary analysis showed a small-to-medium positive effect of combined cognitive-physical interventions on global cognitive function in older adults with MCI or dementia (SMD[95% confidence interval]=0.32[0.17;0.47], p<0.00). A combined intervention was equally beneficial in patients with dementia (SMD=0.36[0.12;0.60], p<0.00) and MCI (SMD=0.39[0.15;0.63], p<0.05). In addition, the analysis showed a moderate-to-large positive effect after combined cognitive-physical interventions for activities of daily living (ADL) (SMD=0.65[0.09;1.21], p<0.01)and a small-to-medium positive effect for mood (SMD=0.27[0.04;0.50], p<0.01). These functional benefits emphasize the clinical relevance of combined cognitive and physical training strategies.

Brain training improves recovery after stroke but waiting list improves equally: A multicenter randomized controlled trial of a computer-based cognitive flexibility training.

BACKGROUND: Brain training is currently widely used in an attempt to improve cognitive functioning. Computer-based training can be performed at home and could therefore be an effective add-on to available rehabilitation programs aimed at improving cognitive functioning. Several studies have reported cognitive improvements after computer training, but most lacked proper active and passive control conditions. OBJECTIVE: Our aim was to investigate whether computer-based cognitive flexibility training improves executive functioning after stroke. We also conducted within-group analyses similar to those used in previous studies, to assess inferences about transfer effects when comparisons to proper control groups are missing. METHODS: We conducted a randomized controlled, double blind trial. Adults (30-80 years old) who had suffered a stroke within the last 5 years were assigned to either an intervention group (n = 38), active control group (i.e., mock training; n = 35), or waiting list control group (n = 24). The intervention and mock training consisted of 58 half-hour sessions within a 12-week period. Cognitive functioning was assessed using several paper-and-pencil and computerized neuropsychological tasks before the training, immediately after training, and 4 weeks after training completion. RESULTS AND CONCLUSIONS: Both training groups improved on training tasks, and all groups improved on several transfer tasks (three executive functioning tasks, attention, reasoning, and psychomotor speed). Improvements remained 4 weeks after training completion. However, the amount of improvement in executive and general cognitive functioning in the intervention group was similar to that of both control groups (active control and waiting list). Therefore, this improvement was likely due to training-unspecific effects. Our results stress the importance to include both active and passive control conditions in the study design and analyses. Results from studies without proper control conditions should be interpreted with care.

Effects of Continuous Positive Airway Pressure on Cognitive and Functional Outcome of Stroke Patients with Obstructive Sleep Apnea: A Randomized Controlled Trial.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) in stroke patients is associated with worse functional and cognitive status during inpatient rehabilitation. We hypothesized that a four-week period of continuous positive airway pressure (CPAP) treatment would improve cognitive and functional outcomes. METHODS: We performed a randomized controlled trial in stroke patients admitted to a neurorehabilitation unit. Patients were assigned to rehabilitation treatment as usual (control group) or to CPAP treatment (CPAP group). Primary outcomes were cognitive status measured by neuropsychological examination, and functional status measured by two neurological scales and a measure of activities of daily living (ADL). Secondary measures included sleepiness, sleep quality, fatigue, and mood. Tests were performed at baseline and after the four-week intervention period. RESULTS: We randomly assigned 20 patients to the CPAP group and 16 patients to the control group. The average CPAP compliance was 2.5 hours per night. Patients in the CPAP group showed significantly greater improvement in the cognitive domains of attention and executive functioning than the control group. CPAP compliance was associated with greater improvement in cognitive functioning. CPAP did not result in measurable improvement on measures of neurological status or ADL, or on any of the secondary measures. CONCLUSIONS: CPAP treatment improves cognitive functioning of stroke patients with OSA. COMMENTARY: A commentary on this article appears in this issue on page 467.

Obstructive Sleep Apnea is Related to Impaired Cognitive and Functional Status after Stroke.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a common sleep disorder in stroke patients and is associated with prolonged hospitalization, decreased functional outcome, and recurrent stroke. Research on the effect of OSA on cognitive functioning following stroke is scarce. The primary objective of this study was to compare stroke patients with and without OSA on cognitive and functional status upon admission to inpatient rehabilitation. DESIGN: Case-control study. SETTING AND PATIENTS: 147 stroke patients admitted to a neurorehabilitation unit. INTERVENTIONS: N/A. MEASUREMENTS: All patients underwent sleep examination for diagnosis of OSA. We assessed cognitive status by neuropsychological examination and functional status by two neurological scales and a measure of functional independence. RESULTS: We included 80 stroke patients with OSA and 67 stroke patients without OSA. OSA patients were older and had a higher body mass index than patients without OSA. OSA patients performed worse on tests of attention, executive functioning, visuoperception, psychomotor ability, and intelligence than those without OSA. No differences were found for vigilance, memory, and language. OSA patients had a worse neurological status, lower functional independence scores, and a longer period of hospitalization in the neurorehabilitation unit than the patients without OSA. OSA status was not associated with stroke type or classification. CONCLUSIONS: Obstructive sleep apnea (OSA) is associated with a lower cognitive and functional status in patients admitted for stroke rehabilitation. This underlines the importance of OSA as a probable prognostic factor, and calls for well-designed randomized controlled trials to study its treatability.

The effect of obstructive sleep apnea and treatment with continuous positive airway pressure on stroke rehabilitation: rationale, design and methods of the TOROS study.

BACKGROUND: Obstructive sleep apnea is a common sleep disorder in stroke patients. Obstructive sleep apnea is associated with stroke severity and poor functional outcome. Continuous positive airway pressure seems to improve functional recovery in stroke rehabilitation. To date, the effect of continuous positive airway pressure on cognitive functioning in stroke patients is not well established. The current study will investigate the effectiveness of continuous positive airway pressure on both cognitive and functional outcomes in stroke patients with obstructive sleep apnea. METHODS/DESIGN: A randomized controlled trial will be conducted on the neurorehabilitation unit of Heliomare, a rehabilitation center in the Netherlands. Seventy stroke patients with obstructive sleep apnea will be randomly allocated to an intervention or control group (n = 2×35). The intervention will consist of four weeks of continuous positive airway pressure treatment. Patients allocated to the control group will receive four weeks of treatment as usual. Outcomes will be assessed at baseline, immediately after the intervention and at two-month follow-up.In a supplementary study, these 70 patients with obstructive sleep apnea will be compared to 70 stroke patients without obstructive sleep apnea with respect to cognitive and functional status at rehabilitation admission. Additionally, the societal participation of both groups will be assessed at six months and one year after inclusion. DISCUSSION: This study will provide novel information on the effects of obstructive sleep apnea and its treatment with continuous positive airway pressure on rehabilitation outcomes after stroke. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR3412.

Can a prediction model combining self-reported symptoms, sociodemographic and clinical features serve as a reliable first screening method for sleep apnea syndrome in patients with stroke?

OBJECTIVE: To determine whether a prediction model combining self-reported symptoms, sociodemographic and clinical parameters could serve as a reliable first screening method in a step-by-step diagnostic approach to sleep apnea syndrome (SAS) in stroke rehabilitation. DESIGN: Retrospective study. SETTING: Rehabilitation center. PARTICIPANTS: Consecutive sample of patients with stroke (N=620) admitted between May 2007 and July 2012. Of these, 533 patients underwent SAS screening. In total, 438 patients met the inclusion and exclusion criteria. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We administered an SAS questionnaire consisting of self-reported symptoms and sociodemographic and clinical parameters. We performed nocturnal oximetry to determine the oxygen desaturation index (ODI). We classified patients with an ODI ≥15 as having a high likelihood of SAS. We built a prediction model using backward multivariate logistic regression and evaluated diagnostic accuracy using receiver operating characteristic analysis. We calculated sensitivity, specificity, and predictive values for different probability cutoffs. RESULTS: Thirty-one percent of patients had a high likelihood of SAS. The prediction model consisted of the following variables: sex, age, body mass index, and self-reported apneas and falling asleep during daytime. The diagnostic accuracy was .76. Using a low probability cutoff (0.1), the model was very sensitive (95%) but not specific (21%). At a high cutoff (0.6), the specificity increased to 97%, but the sensitivity dropped to 24%. A cutoff of 0.3 yielded almost equal sensitivity and specificity of 72% and 69%, respectively. Depending on the cutoff, positive predictive values ranged from 35% to 75%. CONCLUSIONS: The prediction model shows acceptable diagnostic accuracy for a high likelihood of SAS. Therefore, we conclude that the prediction model can serve as a reasonable first screening method in a stepped diagnostic approach to SAS in stroke rehabilitation.

Neuropsychological functioning after CPAP treatment in obstructive sleep apnea: a meta-analysis.

The generally held clinical view is that treatment with continuous positive airway pressure (CPAP) improves cognition in patients with obstructive sleep apnea (OSA). However, the cognitive domains in which recovery is found differ between studies. A meta-analysis was conducted to quantify the effect of CPAP treatment in OSA on neuropsychological functioning. A literature search of studies published from January 1990 to July 2012 was performed. The inclusion criteria were: randomized controlled trial, diagnosis of OSA by poly(somno)graphy, apnea/hypopnea index, duration and compliance of CPAP treatment reported, use of one or more standardized neuropsychological tests. Mean weighted effect sizes of CPAP treatment for seven cognitive domains were calculated, including processing speed, attention, vigilance, working memory, memory, verbal fluency and visuoconstruction. Thirteen studies encompassing 554 OSA patients were included. A small, significant effect on attention was observed in favor of CPAP (d = 0.19). For the other cognitive domains the effect sizes did not reach significance. Improvement on measures of sleepiness was modest (d = 0.30-0.53) and comparable to prior research. In conclusion, this meta-analysis indicates that the effect of CPAP on cognition is small and limited to attention. Contrary to the general assumption, only slight improvement of neuropsychological functioning after CPAP treatment can be expected.

Diagnostic accuracy of nocturnal oximetry for detection of sleep apnea syndrome in stroke rehabilitation.

BACKGROUND AND PURPOSE: Sleep apnea syndrome (SAS) is a common sleep disorder in stroke patients and is associated with decreased recovery and increased risk of recurrent stroke and mortality. The standard diagnostic test for SAS is poly(somno)graphy, but this is often not feasible in stroke rehabilitation settings. This study investigated the diagnostic value of nocturnal oximetry for screening SAS in stroke rehabilitation. METHODS: Fifty-six stroke patients underwent nocturnal polygraphy and oximetry. Sensitivity, specificity, and positive and negative predictive values for the oxygen desaturation index were calculated. Patient and sleep characteristics were used to develop a predictive model of apnea-hypopnea index. RESULTS: Forty-six percent of the stroke patients had SAS. The majority of SAS patients was male, older, and had a higher body mass index than patients without SAS. Sensitivity, specificity, and positive and negative predictive values for the oxygen desaturation index ≥15 were, respectively, 77%, 100%, 100%, and 83%. Oxygen desaturation index predicted 87% of the variance in the apnea-hypopnea index. Patient characteristics did not add significantly to the prediction model. CONCLUSIONS: Nocturnal oximetry is an accurate diagnostic screening instrument for the detection of SAS in stroke patients.