Aerobic exercise to improve cognitive function in older people without known cognitive impairment
Abstract
Background
There is increasing evidence that physical activity supports healthy ageing. Exercise is helpful for cardiovascular, respiratory and musculoskeletal systems, among others. Aerobic activity, in particular, improves cardiovascular fitness and, based on recently reported findings, may also have beneficial effects on cognition among older people.
Objectives
To assess the effect of aerobic physical activity, aimed at improving cardiorespiratory fitness, on cognitive function in older people without known cognitive impairment.
Search methods
We searched ALOIS ‐ the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, the Cochrane Controlled Trials Register (CENTRAL) (all years to Issue 2 of 4, 2013), MEDLINE (Ovid SP 1946 to August 2013), EMBASE (Ovid SP 1974 to August 2013), PEDro, SPORTDiscus, Web of Science, PsycINFO (Ovid SP 1806 to August 2013), CINAHL (all dates to August 2013), LILACS (all dates to August 2013), World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (http://apps.who.int/trialsearch), ClinicalTrials.gov (https://clinicaltrials.gov) and Dissertation Abstracts International (DAI) up to 24 August 2013, with no language restrictions.
Selection criteria
We included all published randomised controlled trials (RCTs) comparing the effect on cognitive function of aerobic physical activity programmes with any other active intervention, or no intervention, in cognitively healthy participants aged over 55 years.
Data collection and analysis
Two review authors independently extracted the data from included trials. We grouped cognitive outcome measures into eleven categories covering attention, memory, perception, executive functions, cognitive inhibition, cognitive speed and motor function. We used the mean difference (or standardised mean difference) between groups as the measure of the treatment effect and synthesised data using a random‐effects model. We conducted separate analyses to compare aerobic exercise interventions with no intervention and with other exercise, social or cognitive interventions. Also, we performed analyses including only trials in which an increase in the cardiovascular fitness of participants had been demonstrated.
Main results
Twelve trials including 754 participants met our inclusion criteria. Trials were from eight to 26 weeks in duration.
We judged all trials to be at moderate or high risk of bias in at least some domains. Reporting of some risk of bias domains was poor.
Our analyses comparing aerobic exercise to any active intervention showed no evidence of benefit from aerobic exercise in any cognitive domain. This was also true of our analyses comparing aerobic exercise to no intervention. Analysing only the subgroup of trials in which cardiorespiratory fitness improved in the aerobic exercise group showed that this improvement did not coincide with improvements in any cognitive domains assessed. Our subgroup analyses of aerobic exercise versus flexibility or balance interventions also showed no benefit of aerobic exercise in any cognitive domain.
Dropout rates did not differ between aerobic exercise and control groups. No trial reported on adverse effects.
Overall none of our analyses showed a cognitive benefit from aerobic exercise even when the intervention was shown to lead to improved cardiorespiratory fitness.
Authors' conclusions
We found no evidence in the available data from RCTs that aerobic physical activities, including those which successfully improve cardiorespiratory fitness, have any cognitive benefit in cognitively healthy older adults. Larger studies examining possible moderators are needed to confirm whether or not aerobic training improves cognition.
PICOs
Plain language summary
Aerobic exercise to improve cognitive function in older people without known cognitive impairment
Aerobic exercise is beneficial for healthy ageing. It has been suggested that the increased fitness brought about by aerobic exercise may help to maintain good cognitive function in older age. We looked for randomised controlled trials of aerobic exercise programmes for people over the age of 55 years, without pre‐existing cognitive problems, which measured effects on both fitness and cognition. The aerobic exercise programmes could be compared with no intervention (e.g. being on a waiting list for the exercise group) or with other kinds of activity (including non‐aerobic exercises such as strength or balance exercises, or social activities).
In this Cochrane Review, 12 trials including 754 participants met our inclusion criteria. Eight of the 12 trials reported that the aerobic exercise interventions resulted in increased fitness of the trained group. However, when we combined results across the trials, we did not find any significant benefits of aerobic exercise or increased fitness on any aspect of cognition. Many included trials had problems with their methods or reporting which reduced our confidence in the findings.
We did not find evidence that aerobic exercise or increased fitness improves cognitive function in older people. However, it remains possible that it may be helpful for particular subgroups of people, or that more intense exercise programmes could be beneficial. Therefore further research in this area is necessary.
Authors' conclusions
Background
Description of the condition
In 2005, there were over 925 million people worldwide aged 55 years or older according to the population database of the United Nations (WPP 2006). It is predicted that in 10 years this will increase to over 1.4 billion people. Subjective complaints about cognitive capacities increase with (older) age (Martin 2003; Newson 2006) and an objective decline in cognitive performance accelerates around the age of 50 (Salthouse 2003; Verhaeghen 1997), with the exception of cognitive skills with a large crystallised intelligence component. Research has shown that a regular exercise programme can slow down or prevent functional decline associated with ageing and improve health in this age group. The physical health benefits for older people who regularly participate in endurance, balance and resistance training programmes are well established. Such health benefits include improved muscle mass, arterial compliance, energy metabolism, cardiovascular fitness, muscle strength and overall functional capacity (Lemura 2000). It is suspected that physical activity may also enhance cognitive function (Colcombe 2003).
Description of the intervention
In this Cochrane Review we included the interventions of exercise programmes for older people which aimed to improve cardiorespiratory fitness, the ability of the circulatory and respiratory to supply oxygen to muscles during sustained physical activity, through for example walking, running or cycling. We compared their effects with a variety of control interventions: either no intervention or exercise interventions which would not be expected to enhance cardiorespiratory fitness, such as strength or balance programmes, or social or mental activities. Cardiorespiratory fitness may be assessed in a variety of ways. A common method is to measure VO2 max, which is the maximal oxygen uptake measured during exercise on a treadmill or cycle, although other physiological measures or walk times may also be used.
How the intervention might work
Research using animal models has provided insight into the possible cellular and molecular mechanisms that could underlie an effect of physical activity on cognitive function. Increased aerobic fitness increases oxygen extraction, glucose utilisation and cerebral blood flow (Churchill 2002). Cerebral blood flow meets metabolic needs of the brain and removes waste (Lojovich 2010). Increased aerobic fitness also increases Brain‐Derived Neurotrophic Factor (BDNF) and other growth factors which mediate structural changes (Cotman 2002; Cotman 2007). For example, BDNF is implicated in neurogenesis, synaptogenesis, dendritic branching and neuroprotection (Lojovich 2010). A preliminary survey of the literature on human research points towards the same possible physiological mechanisms that could explain the association between physical activity and cognitive vitality (Aleman 2000; Brown 2008; Colcombe 2006; Davenport 2012; Erickson 2009; McAuley 2004; Prins 2002). Hence it is hypothesised that improvements in cardiovascular (aerobic) fitness mediate the benefits of physical activity on cognitive capacity (Etnier 2007; McAuley 2004). Therefore this cardiovascular fitness hypothesis implies that changes in cognitive function are preceded by changes in aerobic fitness. The evidence for this hypothetical link between physical activity, cardiovascular fitness and cognitive function in older people comes from several longitudinal studies (Abbott 2004; Barnes 2003; Etgen 2010; Laurin 2001; Middleton 2011; Richards 2003; Sturman 2005; van Gelder 2004). However, results from training studies by Hill 1993 and Blumenthal 1991 failed to correlate changes in aerobic power (VO2 max) with changes in cognitive measures. At the same time, trials seldom report combinations of activity, fitness and cognition in a single trial.
Why it is important to do this review
Previous meta‐analyses have reported a robust effect of physical activity on cognitive function in older adults (Colcombe 2003; Etnier 1997b; Heyn 2004;Smith 2010), but it remains unclear whether improvement in cardiovascular fitness (as reflected by cardiovascular parameters such as VO2 max) accounts for the effects of physical activity on cognitive capacity. Physiological or psychological mechanisms other than aerobic fitness might still account for the effects found in these meta‐analyses. This Cochrane Review intends to investigate a hypothesised link between physical activity specifically aimed at the improvement of cardiorespiratory fitness and cognitive function. Such information will be useful in the quest to identify interventions that may be helpful for healthy ageing and protective against the development of neurodegenerative disorders such as Alzheimer's disease.
Objectives
To assess the effectiveness of physical activity, aimed at improving cardiorespiratory fitness, on cognitive function in older people without known cognitive impairment.
Methods
Criteria for considering studies for this review
Types of studies
We only included randomised controlled clinical trials (RCTs). Blinding of outcome assessors was not required for inclusion in this review. We did not apply any language restrictions but trials must have been published in peer‐reviewed journals.
Types of participants
Participants were aged 55 or older and not objectively cognitively impaired in any way greater than that expected from age alone. Hence, we excluded patients with mild cognitive impairment (MCI) or any form of dementia and patients with other conditions likely to be associated with cognitive impairment, such as stroke and depression. However, we included trials of participants with age‐related illnesses (e.g. osteoporosis, arthrosis) or specific disorders (e.g. chronic obstructive pulmonary disease (COPD), heart failure).
Types of interventions
We included the physical activity interventions of any programme of exercise of any intensity, duration or frequency which was aimed at improving cardiorespiratory fitness. Therefore, trials must have reported at least one objective measure of cardiorespiratory fitness. Acceptable comparator interventions were: no treatment; a strength or balance programme; or a programme of social activities or mental activities. Trials which had both an active comparator group and a no treatment group could contribute data to the 'aerobic exercise vs. any active intervention' meta‐analyses and to the 'aerobic exercise vs. no intervention' meta‐analyses.
Types of outcome measures
Trials had to report an objective measure of cardiorespiratory fitness. Acceptable measures included, but were not limited to: VO2 max, Graded Exercise Test (GXT) rate‐pressure product, heart rate and blood pressure during modified step test, the Six‐Minute Walk Test (6MWT), 400‐metre walk time, and ¼ mile walk time. Where trials measured more than one fitness parameter, we preferred the measure that we considered to be the purest measure of cardiorespiratory fitness, or was previously show to be correlated with VO2 max, or both.
Primary outcomes
The primary outcome measurement was cognitive function, tested with a neuropsychological test (sensitive to changes in cognitive function in adults) or test battery (a combination of several neuropsychological tests).
Secondary outcomes
Other outcome measures were drop‐out, as a measure of acceptability, and adverse events.
Search methods for identification of studies
Electronic searches
We searched ALOIS ‐ the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1946 to August 2013), EMBASE (Ovid SP 1974 to August 2013), PEDro, SPORTDiscus, Web of Science (Web of Science platform), PsycINFO (Ovid SP 1806 to August 2013), CINAHL (EBSCOhost), LILACS (BIREME), World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (http://apps.who.int/trialsearch), ClinicalTrials.gov (https://clinicaltrials.gov) and Dissertation Abstracts International (DAI) up to 24 August 2013 with no language restrictions.
We used a combination of MeSH and free text terms to find records of physical activity, including: exercise*, motor activit*, leisure activit*, physical fitness, physical endurance, exercise tolerance, exercise test, aerobic, aerobic capacity, physical activity, physical capacity, physical performance, training. We have listed the search strategy details in Appendix 1.
We performed a further search update up to November 2014. We have inserted the search results into the Studies awaiting classification section and will fully incorporate these trials in the next review update.
Searching other resources
We checked reference lists of the included trials and in reviews of the literature screened for relevant trials. Also we contacted experts in this area and relevant associations.
Data collection and analysis
Selection of studies
The Cochrane Trials Search Coordinator (ANS) assessed the titles and available abstracts of all trials identified by the initial search and excluded irrelevant trials. Two review authors (JY and NT; or MA and GA previously) independently assessed full paper copies of reports of potentially relevant trials. We resolved any disagreements on inclusion by discussion and through arbitration by a third review author (JR). Details of the study selection process can be found in Figure 1.
Study flow diagram for the August 2013 update search
Data extraction and management
Two review authors (JY and NT) independently extracted data from the published reports and JY entered them into RevMan 2014, with full agreement of the second review author. The summary statistics required for each trial and each outcome for continuous data were the mean (or mean change from baseline), the standard deviation (SD) and the number of participants for each treatment group at each assessment. For cognitive data in which a higher score denotes worse performance (e.g. reaction times, digit vigilance, trail making part A, trail making part B, Stroop interference data and error rates), we entered the mean as a negative variable. If only the standard error of the mean was reported, we calculated the SD using SD = SE x sqrt(N). For dichotomous data, we extracted the number of participants with each outcome in each group.
The included articles measured cognitive function using various rating scales. We grouped neuropsychological tests measuring approximately the same construct in a total of eleven categories (see Table 1; Kessels 2000; Lezak 2004). For each trial, only a single test was admitted to each category. Where a trial used more than one test within a category, then first we chose the one which was used most frequently in the included trials; if not, then the one that had been found to load onto the category in previous factor analysis (Salthouse 1996) or which we considered closer to the core construct of the category. We chose all included tests prior to extraction of results.
| Cognitive function | Cognitive tests | Trial |
| Cognitive speed | Simple RT | |
| Choice RT | ||
| Trailmaking part A | ||
| Digit symbol substitution | ||
| Verbal memory functions (immediate) | Randt memory test story recall | |
| 16 words immediate recall | ||
| Ross Information Processing Assessment memory immediate recall | ||
| Wechsler Adult Intelligence Scales logical memory immediate recall | ||
| Rey auditory verbal learning test trail I‐V | ||
| Hopkins Verbal Learning Test | ||
| Visual memory functions (immediate) | Benton visual retention | |
| Wechsler Memory Scales visual reproduction immediate recall | ||
| Working memory | Digit span backward | |
| 2‐Back | ||
| Memory function (delayed) | 16 words delayed recall | |
| Rey auditory verbal learning test delayed recall trail | ||
| 10 words delayed recall | ||
| Hopkins Verbal Learning Test ‐ 12 words | ||
| Executive functions | Trailmaking part B | |
| Ross Information Processing Assessment problem solving and abstract reasoning | ||
| Wechsler Memory Scales mental control | ||
| Task switching paradigm | ||
| Verbal fluency | ||
| Letter number sequencing | ||
| Perception | Face recognition | |
| Ross Information Processing Assessment auditory processing | ||
| Wechsler Adult Intelligence Scales visual reproduction | ||
| Cognitive inhibition | Stroop colour word test | |
| Stopping task | ||
| Flanker Task | ||
| Visual attention | Digit vigilance | |
| Tracking | ||
| 2&7 test | ||
| Visual search | ||
| Covert orienting of visuospatial attention | ||
| Auditory attention | Digit span forward | Blumenthal 1989, Emery 1990a, Fabre 2002, Hassmén 1997, Kramer 2001 |
| Motor function | Finger tapping | |
| Pursuit rotor task |
One trial (Blumenthal 1989) reported results for men and women separately in the same paper. In this case, we calculated pooled means and SDs by combining results for both genders.
Assessment of risk of bias in included studies
Two review authors (JY, NT) independently evaluated the methodological quality of the selected articles using two different methods. We used the criteria list for quality assessment of non‐pharmaceutical trials (CLEAR NPT) developed using consensus (Boutron 2005). This checklist includes information on sampling method, measurement, intervention and reporting of biases and limitations (see Table 2). We performed a small pilot exercise to clarify the method with some articles that we already excluded from the review process. We calculated Cohen's kappa (K) as a measure of inter‐observer agreement, and we relied on Landis 1977's benchmarks for assessing the relative strength of agreement. We resolved any discordance in assessment through a single round of discussion and arbitration by a third review author (JR).
We also used the recommended approach for assessing risk of bias in trials included in Cochrane Reviews, which is based on the evaluation of six specific methodological domains (namely, sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting and other issues). For each trial the six domains are analysed, described as reported in the trial and a final judgment on the likelihood of bias is provided. This is achieved by answering a pre‐specified question about the adequacy of the trial in relation to each domain, such that a judgement of "yes" indicates low risk of bias, "no" indicates high risk of bias, and "unclear" indicates unclear or unknown risk of bias. To make these judgments we used the criteria indicated by the Cochrane Handbook for Systematic Reviews of Interventions (see Higgins 2011 for a detailed description) and their applicability on the addiction field. We assessed the included trials using the criteria and the method indicated in Higgins 2011.
Measures of treatment effect
For continuous outcome data, we used the weighted mean difference (WMD) if trials used the same cognitive tests and if the outcome measurements were on the same scale. We calculated the standardised mean difference (SMD) in all other cases. For dichotomous data, such as drop‐out, we used the odds ratio (OR).
Dealing with missing data
To allow an intention‐to‐treat (ITT) analysis, we sought data on every participant randomised irrespective of compliance, whether or not the participant was subsequently deemed ineligible, or otherwise excluded from treatment or follow‐up. If ITT data were unavailable in the publications, we sought "on‐treatment" data or the data of those who completed the trial, where indicated.
Data synthesis
For each cognitive outcome category, we synthesised the data using a random‐effects model. We analysed the possible effects of aerobic exercise versus any active comparator (strength programme, flexibility or balance programme, social or mental programme) and versus no intervention (usual care or waiting list).
Subgroup analysis and investigation of heterogeneity
Heterogeneity was low across all domains in all meta‐analyses, therefore we did not subgroup analyses to explore heterogeneity.
In order to explore further the potential effects the different forms of exercise, we conducted subgroup analyses which compared aerobic exercise with (a) flexibility or balance interventions and (b) strength training. We further explored our hypothesis by performing analyses of only those trials in which an increase in fitness was demonstrated.
As an extension to subgroup analyses, a meta‐regression would allow the effect of cardiovascular fitness (VO2 max or any other measure of the degree of aerobic fitness) on cognitive outcomes to be investigated. However, we did not consider meta‐regression in this Cochrane Review due to the small number of included trials (< eight trials) in all meta‐analyses.
Results
Description of studies
Results of the search
The August 2013 search identified 352 promising abstracts (see PRIMSA flow diagram). We identified seven potentially relevant theses but these had no associated peer‐reviewed publications. We asked the authors of the theses to provide information on published data, but none were provided. We examined the full texts of 82 articles. We identified 2 new trials for inclusion bringing the total number of trials included to 12 trials involving 754 participants.
Included studies
We have listed the details of the methods, participants, interventions and outcomes for each included trial in the Characteristics of included studies table. Also, we have summarized the intervention types in each trial in Table 2.
| Trial | Aerobic exercise | Strength | Flexibility/balance | Social | Cognitive | Education | Miscellaneous | No intervention |
| x | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | x | |
| x | ‐ | x | ‐ | ‐ | ‐ | ‐ | x | |
| x | ‐ | ‐ | x | ‐ | ‐ | ‐ | x | |
| x | ‐ | ‐ | x | x | ‐ | ‐ | ‐ | |
| x | ‐ | x | ‐ | ‐ | ‐ | ‐ | ‐ | |
| x | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | x | |
| x | ‐ | ‐ | ‐ | x | x | ‐ | ‐ | |
| x | ‐ | x | ‐ | ‐ | ‐ | ‐ | x | |
| x | x | x | ‐ | ‐ | ‐ | ‐ | ‐ | |
| x | ‐ | x | ‐ | ‐ | ‐ | ‐ | x | |
| x | x | ‐ | ‐ | ‐ | ‐ | ‐ | x | |
| x | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | x |
Bakken 2001 conducted a small RCT (N = 15) comparing an aerobic exercise group to a waiting list control group for eight weeks. Both groups showed slight improvement in a measure of aerobic fitness over the course of the trial. The only cognitive outcome parameter was the accuracy index ‐ a test of visual attention.
Blumenthal 1989 randomised 101 participants to aerobic exercise training, a yoga/flexibility programme or a waiting list control group over 16 weeks. Participants in the aerobic training group only experienced a significant increase in their VO2 max. Outcomes included tests of cognitive speed, verbal, visual and working memory, executive functions, cognitive inhibition, visual and auditory attention and motor function.
Madden 1989 reported different cognitive outcomes for a subset of the participants from Blumenthal 1989. We did not included any of the data from this paper in the analyses because Blumenthal 1989 reported data for the same outcome categories.
Emery 1990a assigned 48 participants to an exercise programme, a social activity group or a waiting list control group for 12 weeks. No effect of the exercise programme on cardiovascular function was demonstrated. As attrition from the social group was comparable to that of the control group, and attendance for the social group was poor overall (ranged from 10% to 94%), the trial authors pooled data from the social activity and waiting list control groups (we included this pooled group in the 'exercise versus any intervention' analyses). This trial included tests for cognitive speed and auditory attention.
Fabre 2002 presented data from 32 participants randomly assigned to an aerobic exercise programme, a mental training programme, a combined aerobic/mental programme or a social activity group. We did not use data from the combined aerobic exercise/mental training group in this review. There was a significant increase in VO2 max in the aerobic training group but no change in the other two groups. The trial included tests for verbal and visual memory, perception and executive functions.
Kramer 2001 recruited a total of 174 participants and randomly assigned participants to an aerobic walking group or a stretching and toning group. The aerobic walking group improved their VO2 max measures while the stretching and toning group decreased their VO2 max measures. The trial authors assessed cognitive speed, verbal and visual memory, perception, executive and motor functions as well as cognitive inhibition, visual and auditory attention with various cognitive tests. Mean results of the subtests of the pursuit rotor task, Rey's auditory verbal learning test, spatial attention and visual search task were summed and divided by the number of tasks. SD values of these subtests were pooled.
Langlois 2012 randomly assigned 83 participants, ensuring gender ratio equivalence, to a 12‐week exercise training group or a control group that maintained their previous activity levels. Participants in the exercise training group improved in physical fitness, as measured by the 6MWT, significantly more than controls. Outcomes included tests of cognitive speed, verbal and working memory, executive functions and inhibition.
Legault 2011 published a pilot RCT of 73 participants randomly assigned to a physical activity training group, a cognitive training group, a combined intervention group or a 'healthy aging' control group, which we considered an active intervention. We did not use data from the combined intervention group in this review. The physical activity training group improved in a fitness measure while the cognitive training and control group did not. Cognitive speed, verbal memory, working memory, executive function and cognitive inhibition were tested in the participants.
Moul 1995 recruited 30 participants and randomly assigned them to a walking condition, weight training or control condition, which we considered to be a flexibility intervention, for 16 weeks. VO2 max significantly increased in the walking group but not in the weight training or control conditions. The Ross Information Processing Assessment was used to evaluate changes in cognitive function.
Oken 2006 randomised 135 participants into an aerobic group, a yoga group or a waiting list control group for six months. There were no significant differences between the groups in their fitness measure. Cognitive speed, delayed memory functions, executive functions, visual attention and cognitive inhibition were assessed in order to test for effects on cognition.
Panton 1990 included data on 49 participants randomly assigned to a walk/jog group, a strength group or a no intervention control condition for 26 weeks. VO2 max significantly improved for the walk/jog group while there was no significant change for strength as well as the control groups. Tests for cognitive speed were performed to analyse cognitive function.
Whitehurst 1991 recruited 14 participants and randomly assigned them to an exercise programme or a no intervention control condition for eight weeks. Participants in the exercise group significantly increased their VO2 max scores, whereas participants in the control group did not. Choice reaction times were tested for evaluation of cognitive function.
Excluded studies
We have listed details of excluded trials in the Characteristics of excluded studies table. We excluded trials because they were not RCTs (19), did not use a cognitively normal older population (11), did not meet other inclusion criteria (1: Kharti 2001 included depressed participants), did not have objective aerobic fitness parameters (16), did not have objective cognitive outcomes (5), assessed cognition during exercise (3), did not have pre‐ to post‐ intervention data (4), did not have a non‐aerobic control group (2), had not been published (7), the data was published in an already included trial (2), or for other reasons: objective cognitive measures were not analysed by group (Emery 1990b) or the control group was exercising but not given a formal program (Etnier 2001).
Risk of bias in included studies
We have presented the results of the quality assessment of non‐pharmaceutical trials (CLEAR NPT) (Boutron 2005) in Table 3. The overall methodological quality score of the included trials ranged from 24 to 39 (minimum possible score of 14 points, maximum possible score of 48 points; lower scores denote a better methodological quality). For most trials, the blinding treatment providers and participants was scored "no, because blinding is not feasible". Two review authors (JY, NT) calculated Cohen's kappa (K) as a measure of inter‐observer reliability after the initial screening and reached 0.84, almost perfect according to Landis 1977.
| Study ID | Number | |||||||||
| 1 / 2 | 3 | 4 | 5 | 6 / 6.1.1 / 6.1.2 | 7 / 7.1.1 / 7.1.2 | 8 / 8.1.1 | 9 | 10 | Total | |
| 3 / 3 | 1 | 3 | 1 | 2 / 3 / 2 | 2 / 3 / 2 | 1 / 0 | 1 | 2 | 28 | |
| 3 / 3 | 1 | 3 | 1 | 2 / 2 / 2 | 2 / 2 / 2 | 4 / 3 | 1 | 3 | 34 | |
| 3 / 3 | 1 | 3 | 1 | 2 / 2 / 2 | 2 / 2 / 2 | 4 / 3 | 1 | 2 | 33 | |
| 3 / 3 | 1 | 3 | 2 | 2 / 1 / 1 | 2 / 1 / 1 | 4 / 3 | 1 | 1 | 29 | |
| 3 / 3 | 1 | 3 | 1 | 2 / 3 / 1 | 2 / 3 / 1 | 4 / 3 | 1 | 2 | 33 | |
| 3 / 3 | 1 | 3 | 3 | 2 / 3 / 2 | 2 / 3 / 2 | 4 / 3 | 1 | 2 | 37 | |
| 3 / 3 | 1 | 3 | 1 | 2 / 3 / 1 | 2 / 3 / 1 | 4 / 3 | 1 | 1 | 31 | |
| 3 / 3 | 1 | 3 | 1 | 2 / 3 / 2 | 2 / 3 / 2 | 4 / 3 | 1 | 2 | 34 | |
| 3 / 3 | 1 | 3 | 3 | 2 / 3 / 1 | 2 / 3 / 1 | 4 / 3 | 1 | 1 | 34 | |
| 1 / 1 | 1 | 3 | 1 | 2 / 2 /1 | 2 / 2 / 1 | 1 / 3 | 1 | 2 | 24 | |
| 3 / 3 | 1 | 3 | 2 | 2 / 3 / 3 | 2 / 3 / 3 | 4 / 3 | 1 | 2 | 38 | |
| 3 / 3 | 1 | 3 | 2 | 2 / 3 / 3 | 2 / 3 / 3 | 4 / 3 | 1 | 3 | 39 | |
See Table 4 for CLEAR NPT items.
| Number | Checklist item |
| 1 | Was the generation of allocation sequences adequate? |
| 2 | Was the treatment allocation concealed? |
| 3 | Were the details of the intervention administered to each group made available?a |
| 4 | Were care providers' experience or skillb in each arm appropriate?c |
| 5 | Was participant (i.e. patients) adherence assessed quantitatively?d |
| 6 | Were participants adequately blinded? |
| 6.1.1 | If participants were not adequately blinded, were all other treatments and care (cointerventions) the same in each randomised group? |
| 6.1.2 | If participants were not adequately blinded, were withdrawals and lost to follow‐up the same in each randomised group? |
| 7 | Were care providers or persons caring for the participants adequately blinded? |
| 7.1.1 | If care providers were not adequately blinded, were all other treatments and care (cointerventions) the same in each randomised group? |
| 7.1.2 | If care providers were not adequately blinded, were withdrawals and losses to follow‐up the same in each randomised group? |
| 8 | Were outcome assessors adequately blinded to assess the primary outcomes? |
| 8.1.1 | If outcome assessors were not adequately blinded, were specific methods used to avoid ascertainment bias?e |
| 9 | Was the follow‐up schedule the same in each group?f |
| 10 | Were the main outcomes analysed according to the ITT principle? |
| a | The answer should be "Yes" if these data are either described in the report or made available for each arm (reference to preliminary report, online addendum, etc.). |
| b | Care provider experience or skill will be assessed only for therapist‐dependent interventions (where the success of the intervention is directly linked to the providers' technical skill. For other treatment this item is not relevant and should be answered "Unclear". |
| c | Appropriate experience or skill should be determined according to published data, preliminary studies, guidelines, run‐in period, or a group of experts and should be specified in the protocol for each study arm before the beginning of the survey. |
| d | Treatment adherence will be assessed only for the treatments necessitating iterative interventions (physiotherapy that supposes several sessions, in contrast to a one‐shot treatment such as surgery). For one‐shot treatments, this item is not relevant and should be answered "Unclear". |
| e | The answer is "0" if the answer to 8 is "Yes". The answer should be "Yes" if the main outcome is objective or hard, or if outcomes were assessed by a blinded or at least an independent endpoint review committee, or if outcomes were assessed by an independent outcome assessor trained to perform the measurements in a standardised manner, or if the outcome assessor was blinded to the study purpose and hypothesis. |
| f | This item is not relevant if follow‐up is part of the question. For example, this item is not relevant for a trial assessing frequent versus less frequent follow‐up for cancer recurrence. In these situations, this item should be answered "Unclear". |
| For items 6, 7 and 8 a score of 1 was given for a "Yes", a score of 2 for "No, because blinding is not feasible", a score of 3 for "No, although blinding is feasible" and a score of 4 for "Unclear". The other items of the checklist (1 to 5, 6.1.1, 6.1.2, 7.1.1, 7.1.2, 8.1.1, 9 and 10) were given a score of 1 for "Yes", 2 for "No" and 3 for "Unclear". | |
We have presented the results of our 'Risk of bias' assessment in the Characteristics of included studies tables and in Figure 2. We only considered one trial to be at low risk of bias for sequence generation (Oken 2006). We judged the remaining 11 trials to be at unclear risk of bias for sequence generation. Procedures to ensure allocation concealment were not described in the included papers; all 12 papers were judged to be at unclear risk of bias in this domain. In all 12 included trials blinding of participants and trainers was not feasible. This was unlikely to introduce bias in trainers, so we considered all 12 trials to be at low risk of bias for blinding trainers. This may have introduced bias in participants, so all 12 trials were judged to be at high risk of blinding of the participants. We judged five trials (Bakken 2001; Legault 2011; Oken 2006; Panton 1990; Whitehurst 1991) to be at low risk of bias for blinding of the assessors for the cognitive outcomes because assessment of cognition was by means of computerised tests. We considered the other seven trials to be at unclear risk of bias for this item. Four trials (Fabre 2002; Legault 2011; Moul 1995; Whitehurst 1991) were judged to be at low risk of bias for addressing incomplete data. Besides Legault 2011, in all cases this was due to the fact that there were no drop‐outs from these trials. Legault 2011 reported drop‐outs per group and analysed using ITT principles. All other eight trials were judged being at high risk of bias for this item since they reported drop‐outs but either lacked information on the group assignment of these drop‐outs (Panton 1990) or lacked ITT analysis, or both. We judged all trials, except Blumenthal 1989, to be at unclear risk of bias for selective reporting since there was insufficient information to permit a judgment. Blumenthal 1989 was judged being at high risk for this item since data on one pre‐specified primary cognitive outcome was missing. We considered all trials to be at low risk of bias for other potential threats to validity. However, we could not rule out risk of contamination bias, where the control group, on finding out the purpose of a trial, could have increased their levels of aerobic exercise as well.
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Effects of interventions
Aerobic exercise versus any active intervention
Eight trials including 506 participants contributed data on at least one cognitive domain. Duration of the intervention in these trials ranged from eight weeks to 26.07 weeks. In six trials, trial authors showed an increase in aerobic fitness in the active intervention but not the comparison group. We were able to conduct meta‐analyses for all 11 of our pre‐specified cognitive domains (Analysis 1.1 to Analysis 1.11; Figure 3; Figure 4; Figure 5; Figure 6; Figure 7; Figure 8; Figure 9; Figure 10; Figure 11; Figure 12; Figure 13). There was no evidence of benefit of the aerobic exercise intervention in any cognitive domain.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.1 Cognitive speed.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.2 Verbal memory functions (immediate).
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.3 Visual memory functions (immediate).
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.4 Working memory.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.5 Memory functions (delayed).
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.6 Executive functions.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.7 Perception.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.8 Cognitive inhibition.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.9 Visual attention.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.10 Auditory attention.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.11 Motor function.
There was no difference in dropout rates between the aerobic exercise intervention and comparison groups (OR 0.96, 95% CI 0.44 to 2.10; seven trials, 469 participants; Analysis 1.12; Figure 14).
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.12 Drop‐out.
Aerobic exercise versus no intervention
Six trials including 296 participants contributed data on at least one cognitive domain. The duration of the intervention in these trials ranged from eight to 26.07 weeks. In four trials, trial authors showed an increase in aerobic fitness in the active intervention but not the comparison group. We were able to conduct meta‐analyses for 10 of our 11 pre‐specified cognitive domains, besides perception (Analysis 2.1 to Analysis 2.10; Figure 15; Figure 16; Figure 17; Figure 18; Figure 19; Figure 20; Figure 21; Figure 22; Figure 23; Figure 24). There was no evidence of benefit of the aerobic exercise intervention in any cognitive domain.
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.1 Cognitive speed.
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.2 Verbal memory functions (immediate).
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.3 Visual memory functions (immediate).
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.4 Working memory.
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.5 Memory functions (delayed).
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.6 Executive functions.
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.7 Cognitive inhibition.
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.8 Visual attention.
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.9 Auditory attention.
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.10 Motor function.
There was no difference in dropout rates between the aerobic exercise intervention and comparison groups (OR 1.84, 95% CI 0.79 to 4.29; five trials, 267 participants; Analysis 2.11; Figure 25).
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.11 Drop‐out.
Aerobic exercise versus flexibility/balance intervention
Analysing only the subgroup of trials in which the aerobic exercise intervention was compared to flexibility or balance control groups, four trials (351 participants) contributed data on at least one cognitive domain (Blumenthal 1989; Kramer 2001; Moul 1995; Oken 2006). Intervention duration in these trials ranged from 16 to 26.07 weeks. We were able to conduct meta‐analyses on all 11 of our pre‐specified cognitive domains (Analysis 3.1 to Analysis 3.11). There was no evidence of benefit of the aerobic exercise intervention in any cognitive domain.
There was no difference in dropout rates between the aerobic exercise intervention and comparison groups (OR 0.99, 95% CI 0.58 to 1.72; four trials, 351 participants; Analysis 3.12).
Aerobic exercise versus strength training intervention
Subgroup analyses of aerobic exercise intervention compared to strength training controls was not possible since we could only include one trial in these analyses.
Fitness improved: aerobic exercise versus any active intervention
Analysing only the subgroup of trials in which the aerobic exercise intervention was shown to enhance fitness relative to any active intervention control groups, six trials including 367 participants contributed data on at least one cognitive domain (Blumenthal 1989; Fabre 2002; Kramer 2001; Legault 2011; Moul 1995; Panton 1990). The duration of the intervention in these trials ranged from eight to 26.07 weeks. We were able to conduct meta‐analyses for all 11 of our pre‐specified cognitive domains (Analysis 5.1 to Analysis 5.11). There was no evidence of benefit of the aerobic exercise intervention in any cognitive domain.
There was no difference in dropout rates between the aerobic exercise intervention and comparison groups (OR 1.22, 95% CI 0.66 to 2.25; five trials, 330 participants; Analysis 5.12).
Fitness improved: aerobic exercise versus no intervention
Analysing only the subgroup of trials in which the aerobic exercise intervention was shown to significantly improve fitness relative to no intervention control groups, four trials involving 183 participants contributed data on at least one cognitive domain. Intervention duration in these trials ranged from eight to 26 weeks (Blumenthal 1989; Langlois 2012; Panton 1990; Whitehurst 1991). We were able to conduct meta‐analyses for 10 of our 11 pre‐specified cognitive domains, besides perception (Analysis 6.1 to Analysis 6.10). There was no evidence of benefit of the aerobic exercise intervention in any cognitive domain.
There was no difference in dropout rates between the aerobic exercise intervention and comparison groups (OR 1.50, 95% CI 0.50 to 4.50; three trials, Analysis 6.11).
All analyses showed no difference on cognitive test scores between aerobic exercise groups and either active comparator or no treatment groups (controls or waiting list groups). In terms of dropout (without Panton 1990, which did not include dropouts by group), there were no differences between aerobic exercise and any of our other intervention groups. Also, no trial included adverse events as an outcome and none of the trial reports made any mention of adverse events.
Discussion
Summary of main results
This Cochrane Review examined the effect of physical activity aimed at improving cardiorespiratory fitness on cognitive function in healthy older people without known cognitive impairment. The hypothesis being tested is that physical activity brings about improvements in cognition which are mediated by increased cardiovascular (aerobic) fitness (Colcombe 2004; Kramer 1999; McAuley 2004). If true, this would imply that a physically active lifestyle resulting in enhanced fitness could positively affect people's cognitive abilities as they age and may even prevent, or at least delay, the onset of neurodegenerative disorders such as Alzheimer's disease.
Nine of the 12 included trials reported that aerobic exercise interventions resulted in increased cardiorespiratory fitness of the intervention group. This is not unexpected as significant evidence already points to exercise having a beneficial effect on cardiorespiratory fitness. However, this was not accompanied by any impact on cognitive function. Several issues need further consideration. Firstly, the quality of the included trials could have also affected our results. Reporting of methods in the included papers was generally quite poor. For all but one trial, the randomisation methods were unclear. It was not feasible to blind participants and trainers, but for most trials it was also unclear if outcome assessors were blinded, raising the risk of detection bias. Attrition was poorly reported. No trials had published protocols so it was not possible to tell if there was selective reporting of results. Of note, no included trials assessed for contamination bias which could have worked against finding group differences. Secondly, with healthy older populations, it is possible that "ceiling effects" prevented detection of cognitive improvement. The risk of this will depend on the task used and what is being measured. In the included papers, no trial author discussed any potential impact of a ceiling effect on the variables measured. However, there was much variation in each measure included in our analyses which makes ceiling effects unlikely.
Agreements and disagreements with other studies or reviews
Five meta‐analytic studies and one systematic review published data based on very similar hypotheses yet failed to find comparable results:
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Etnier 1997b included 134 articles in their review. Their aim was to give a comprehensive overview of all literature available with sufficient information to calculate effect sizes. Therefore, apart from RCTs, the review included several cross‐sectional studies. It reported data on the acute effects of exercise and data on strength and flexibility regimens as well as results for younger age groups and cognitively impaired individuals. The authors concluded that exercise has a small positive effect on cognition and with the effect size depending on the exercise paradigm, the quality of the trial, the participants and the cognitive tests used as outcome measures.
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van Uffelen 2008 set out to systematically review the effect of exercise on cognitive performance in older adults with and without dementia. They found 23 papers that met their inclusion criteria. They included strength exercise interventions, trials which did not assess any fitness parameters and a trial where both groups received aerobic training, while this review did not. Their review observed exercise programmes in healthy older adults improved memory, information processing abilities and executive function.
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Smith 2010 meta‐analytic review assessed the effects of aerobic exercise on cognitive performance. Their criteria differed from this Cochrane Review in including participants with MCI, younger participants and trials which did not assess cardiorespiratory fitness. They also included some unpublished trials. The authors concluded that aerobic exercise is significantly and positively related to modest improvements in attention and processing speed, executive function and memory.
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The meta‐analysis presented by Colcombe 2003 included 18 studies. Their aim ("to examine the hypothesis that aerobic fitness training enhances the cognitive vitality of healthy but sedentary older adults") and exclusion criteria (cross‐sectional design, no random assignment, unsupervised exercise programme, training lacking in fitness component and an average age below 55) were similar to ours. The reviews differed in that we excluded trials in which allocation was clearly quasi‐randomised or did not present any fitness parameter. We also excluded interventions that were not purely exercise and which included participants who were cognitively impaired or suffered from depression. Colcombe 2003 concluded that physical activity is beneficial for all analysed cognitive functions.
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Etnier 2006 published a meta‐analytic review on the relationship between aerobic fitness and cognitive performance. Their primary goal was "to provide a statistically powerful test of the viability of the cardiovascular fitness hypothesis by examining the dose‐response relationship between aerobic fitness and cognition". Their search identified 30 studies which reported data on cross‐sectional comparisons, pre‐post comparisons and RCTs. Etnier 2006 included only those studies which assessed aerobic fitness by maximal, submaximal or a composite measure of fitness which included VO2 max, whereas we included all measures of aerobic fitness. We imposed a lower age limit and did not include trials on depressed participants whereas Etnier 2006 included all ages and at least one trial on depressed subjects. Etnier 2006 included unpublished master theses and doctoral dissertations, whereas we only included data published in peer reviewed journals. Post‐test comparisons showed no significant relationships between aerobic fitness and cognitive performance. For the exercise groups, increased fitness was associated with worse cognitive function. Age interacted with fitness and was a significant negative predictor of cognitive performance for older adults.
Although we did not identify any relationship between physical activity or cardiorespiratory fitness and cognitive function, it is possible that certain subgroups of the population, such as those starting from a lower baseline of fitness, could react differently to aerobic training. Other factors which might influence the relationship include: age, frequency of cognitive activities (Christensen 1993; Hultsch 1993; Hultsch 1999; Lachman 2010; Marquine 2012; Wilson 1999; Wilson 2005), social network (Crooks 2008; Seeman 2001), and adherence to a Mediterranean diet (Panagiotakos 2007; Tangney 2011). The search for possible subgroups has provided some promising results (examples in Etnier 2007; Podewils 2005; Schuit 2001).
It is possible that the intensity of physical activities is important (Angevaren 2007; Brown 2012; Tierney 2010; van Gelder 2004) which may have implications for the effectiveness of some of the training programmes in the included RCTs. However, Smith 2010 did not find any relationship between intensity of physical activity and change in cognitive function.
Study flow diagram for the August 2013 update search
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.1 Cognitive speed.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.2 Verbal memory functions (immediate).
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.3 Visual memory functions (immediate).
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.4 Working memory.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.5 Memory functions (delayed).
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.6 Executive functions.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.7 Perception.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.8 Cognitive inhibition.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.9 Visual attention.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.10 Auditory attention.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.11 Motor function.
Forest plot of comparison: 1 Aerobic exercise versus any active intervention, outcome: 1.12 Drop‐out.
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.1 Cognitive speed.
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.2 Verbal memory functions (immediate).
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.3 Visual memory functions (immediate).
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.4 Working memory.
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.5 Memory functions (delayed).
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.6 Executive functions.
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.7 Cognitive inhibition.
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.8 Visual attention.
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.9 Auditory attention.
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.10 Motor function.
Forest plot of comparison: 2 Aerobic exercise versus no intervention, outcome: 2.11 Drop‐out.
Comparison 1 Aerobic exercise versus any active intervention, Outcome 1 Cognitive speed.
Comparison 1 Aerobic exercise versus any active intervention, Outcome 2 Verbal memory functions (immediate).
Comparison 1 Aerobic exercise versus any active intervention, Outcome 3 Visual memory functions (immediate).
Comparison 1 Aerobic exercise versus any active intervention, Outcome 4 Working memory.
Comparison 1 Aerobic exercise versus any active intervention, Outcome 5 Memory functions (delayed).
Comparison 1 Aerobic exercise versus any active intervention, Outcome 6 Executive functions.
Comparison 1 Aerobic exercise versus any active intervention, Outcome 7 Perception.
Comparison 1 Aerobic exercise versus any active intervention, Outcome 8 Cognitive inhibition.
Comparison 1 Aerobic exercise versus any active intervention, Outcome 9 Visual attention.
Comparison 1 Aerobic exercise versus any active intervention, Outcome 10 Auditory attention.
Comparison 1 Aerobic exercise versus any active intervention, Outcome 11 Motor function.
Comparison 1 Aerobic exercise versus any active intervention, Outcome 12 Drop‐out.
Comparison 2 Aerobic exercise versus no intervention, Outcome 1 Cognitive speed.
Comparison 2 Aerobic exercise versus no intervention, Outcome 2 Verbal memory functions (immediate).
Comparison 2 Aerobic exercise versus no intervention, Outcome 3 Visual memory functions (immediate).
Comparison 2 Aerobic exercise versus no intervention, Outcome 4 Working memory.
Comparison 2 Aerobic exercise versus no intervention, Outcome 5 Memory functions (delayed).
Comparison 2 Aerobic exercise versus no intervention, Outcome 6 Executive functions.
Comparison 2 Aerobic exercise versus no intervention, Outcome 7 Cognitive inhibition.
Comparison 2 Aerobic exercise versus no intervention, Outcome 8 Visual attention.
Comparison 2 Aerobic exercise versus no intervention, Outcome 9 Auditory attention.
Comparison 2 Aerobic exercise versus no intervention, Outcome 10 Motor function.
Comparison 2 Aerobic exercise versus no intervention, Outcome 11 Drop‐out.
Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 1 Cognitive speed.
Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 2 Verbal memory functions (immediate).
Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 3 Visual memory functions (immediate).
Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 4 Working memory.
Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 5 Memory functions (delayed).
Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 6 Executive functions.
Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 7 Perception.
Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 8 Cognitive inhibition.
Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 9 Visual attention.
Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 10 Auditory attention.
Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 11 Motor function.
Comparison 3 Aerobic exercise versus flexibility/balance programme, Outcome 12 Drop‐out.
Comparison 4 Aerobic exercise versus strength programme, Outcome 1 Verbal memory functions (immediate).
Comparison 4 Aerobic exercise versus strength programme, Outcome 2 Executive functions.
Comparison 4 Aerobic exercise versus strength programme, Outcome 3 Perception.
Comparison 4 Aerobic exercise versus strength programme, Outcome 4 Cognitive speed.
Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 1 Cognitive speed.
Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 2 Verbal memory functions (immediate).
Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 3 Visual memory functions (immediate).
Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 4 Working memory.
Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 5 Memory functions (delayed).
Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 6 Executive functions.
Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 7 Perception.
Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 8 Cognitive inhibition.
Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 9 Visual attention.
Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 10 Auditory attention.
Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 11 Motor function.
Comparison 5 Fitness Improved: aerobic exercise versus any active intervention, Outcome 12 Drop‐out.
Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 1 Cognitive speed.
Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 2 Verbal memory functions (immediate).
Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 3 Visual memory functions (immediate).
Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 4 Working memory.
Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 5 Memory functions (delayed).
Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 6 Executive functions.
Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 7 Cognitive inhibition.
Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 8 Visual attention.
Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 9 Auditory attention.
Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 10 Motor function.
Comparison 6 Fitness improved: aerobic exercise versus no intervention, Outcome 11 Drop‐out.
| Cognitive function | Cognitive tests | Trial |
| Cognitive speed | Simple RT | |
| Choice RT | ||
| Trailmaking part A | ||
| Digit symbol substitution | ||
| Verbal memory functions (immediate) | Randt memory test story recall | |
| 16 words immediate recall | ||
| Ross Information Processing Assessment memory immediate recall | ||
| Wechsler Adult Intelligence Scales logical memory immediate recall | ||
| Rey auditory verbal learning test trail I‐V | ||
| Hopkins Verbal Learning Test | ||
| Visual memory functions (immediate) | Benton visual retention | |
| Wechsler Memory Scales visual reproduction immediate recall | ||
| Working memory | Digit span backward | |
| 2‐Back | ||
| Memory function (delayed) | 16 words delayed recall | |
| Rey auditory verbal learning test delayed recall trail | ||
| 10 words delayed recall | ||
| Hopkins Verbal Learning Test ‐ 12 words | ||
| Executive functions | Trailmaking part B | |
| Ross Information Processing Assessment problem solving and abstract reasoning | ||
| Wechsler Memory Scales mental control | ||
| Task switching paradigm | ||
| Verbal fluency | ||
| Letter number sequencing | ||
| Perception | Face recognition | |
| Ross Information Processing Assessment auditory processing | ||
| Wechsler Adult Intelligence Scales visual reproduction | ||
| Cognitive inhibition | Stroop colour word test | |
| Stopping task | ||
| Flanker Task | ||
| Visual attention | Digit vigilance | |
| Tracking | ||
| 2&7 test | ||
| Visual search | ||
| Covert orienting of visuospatial attention | ||
| Auditory attention | Digit span forward | Blumenthal 1989, Emery 1990a, Fabre 2002, Hassmén 1997, Kramer 2001 |
| Motor function | Finger tapping | |
| Pursuit rotor task |
| Trial | Aerobic exercise | Strength | Flexibility/balance | Social | Cognitive | Education | Miscellaneous | No intervention |
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| x | ‐ | ‐ | x | x | ‐ | ‐ | ‐ | |
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| x | ‐ | ‐ | ‐ | x | x | ‐ | ‐ | |
| x | ‐ | x | ‐ | ‐ | ‐ | ‐ | x | |
| x | x | x | ‐ | ‐ | ‐ | ‐ | ‐ | |
| x | ‐ | x | ‐ | ‐ | ‐ | ‐ | x | |
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| x | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | x |
| Study ID | Number | |||||||||
| 1 / 2 | 3 | 4 | 5 | 6 / 6.1.1 / 6.1.2 | 7 / 7.1.1 / 7.1.2 | 8 / 8.1.1 | 9 | 10 | Total | |
| 3 / 3 | 1 | 3 | 1 | 2 / 3 / 2 | 2 / 3 / 2 | 1 / 0 | 1 | 2 | 28 | |
| 3 / 3 | 1 | 3 | 1 | 2 / 2 / 2 | 2 / 2 / 2 | 4 / 3 | 1 | 3 | 34 | |
| 3 / 3 | 1 | 3 | 1 | 2 / 2 / 2 | 2 / 2 / 2 | 4 / 3 | 1 | 2 | 33 | |
| 3 / 3 | 1 | 3 | 2 | 2 / 1 / 1 | 2 / 1 / 1 | 4 / 3 | 1 | 1 | 29 | |
| 3 / 3 | 1 | 3 | 1 | 2 / 3 / 1 | 2 / 3 / 1 | 4 / 3 | 1 | 2 | 33 | |
| 3 / 3 | 1 | 3 | 3 | 2 / 3 / 2 | 2 / 3 / 2 | 4 / 3 | 1 | 2 | 37 | |
| 3 / 3 | 1 | 3 | 1 | 2 / 3 / 1 | 2 / 3 / 1 | 4 / 3 | 1 | 1 | 31 | |
| 3 / 3 | 1 | 3 | 1 | 2 / 3 / 2 | 2 / 3 / 2 | 4 / 3 | 1 | 2 | 34 | |
| 3 / 3 | 1 | 3 | 3 | 2 / 3 / 1 | 2 / 3 / 1 | 4 / 3 | 1 | 1 | 34 | |
| 1 / 1 | 1 | 3 | 1 | 2 / 2 /1 | 2 / 2 / 1 | 1 / 3 | 1 | 2 | 24 | |
| 3 / 3 | 1 | 3 | 2 | 2 / 3 / 3 | 2 / 3 / 3 | 4 / 3 | 1 | 2 | 38 | |
| 3 / 3 | 1 | 3 | 2 | 2 / 3 / 3 | 2 / 3 / 3 | 4 / 3 | 1 | 3 | 39 | |
| See Table 4 for CLEAR NPT items. | ||||||||||
| Number | Checklist item |
| 1 | Was the generation of allocation sequences adequate? |
| 2 | Was the treatment allocation concealed? |
| 3 | Were the details of the intervention administered to each group made available?a |
| 4 | Were care providers' experience or skillb in each arm appropriate?c |
| 5 | Was participant (i.e. patients) adherence assessed quantitatively?d |
| 6 | Were participants adequately blinded? |
| 6.1.1 | If participants were not adequately blinded, were all other treatments and care (cointerventions) the same in each randomised group? |
| 6.1.2 | If participants were not adequately blinded, were withdrawals and lost to follow‐up the same in each randomised group? |
| 7 | Were care providers or persons caring for the participants adequately blinded? |
| 7.1.1 | If care providers were not adequately blinded, were all other treatments and care (cointerventions) the same in each randomised group? |
| 7.1.2 | If care providers were not adequately blinded, were withdrawals and losses to follow‐up the same in each randomised group? |
| 8 | Were outcome assessors adequately blinded to assess the primary outcomes? |
| 8.1.1 | If outcome assessors were not adequately blinded, were specific methods used to avoid ascertainment bias?e |
| 9 | Was the follow‐up schedule the same in each group?f |
| 10 | Were the main outcomes analysed according to the ITT principle? |
| a | The answer should be "Yes" if these data are either described in the report or made available for each arm (reference to preliminary report, online addendum, etc.). |
| b | Care provider experience or skill will be assessed only for therapist‐dependent interventions (where the success of the intervention is directly linked to the providers' technical skill. For other treatment this item is not relevant and should be answered "Unclear". |
| c | Appropriate experience or skill should be determined according to published data, preliminary studies, guidelines, run‐in period, or a group of experts and should be specified in the protocol for each study arm before the beginning of the survey. |
| d | Treatment adherence will be assessed only for the treatments necessitating iterative interventions (physiotherapy that supposes several sessions, in contrast to a one‐shot treatment such as surgery). For one‐shot treatments, this item is not relevant and should be answered "Unclear". |
| e | The answer is "0" if the answer to 8 is "Yes". The answer should be "Yes" if the main outcome is objective or hard, or if outcomes were assessed by a blinded or at least an independent endpoint review committee, or if outcomes were assessed by an independent outcome assessor trained to perform the measurements in a standardised manner, or if the outcome assessor was blinded to the study purpose and hypothesis. |
| f | This item is not relevant if follow‐up is part of the question. For example, this item is not relevant for a trial assessing frequent versus less frequent follow‐up for cancer recurrence. In these situations, this item should be answered "Unclear". |
| For items 6, 7 and 8 a score of 1 was given for a "Yes", a score of 2 for "No, because blinding is not feasible", a score of 3 for "No, although blinding is feasible" and a score of 4 for "Unclear". The other items of the checklist (1 to 5, 6.1.1, 6.1.2, 7.1.1, 7.1.2, 8.1.1, 9 and 10) were given a score of 1 for "Yes", 2 for "No" and 3 for "Unclear". | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Cognitive speed Show forest plot | 6 | 389 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.08, 0.33] |
| 1.1 Simple reaction time | 2 | 113 | Std. Mean Difference (IV, Random, 95% CI) | 0.09 [‐0.28, 0.46] |
| 1.2 Choice reaction time | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 1.3 Trailmaking part A | 1 | 49 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.36 [‐0.96, 0.24] |
| 1.4 Digit symbol substitution | 3 | 227 | Std. Mean Difference (IV, Random, 95% CI) | 0.24 [‐0.03, 0.50] |
| 2 Verbal memory functions (immediate) Show forest plot | 5 | 292 | Std. Mean Difference (IV, Random, 95% CI) | 0.08 [‐0.38, 0.55] |
| 2.1 16 words immediate recall | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 2.2 Randt Memory test story recall | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | 0.34 [‐0.15, 0.83] |
| 2.3 Ross Information Processing Assessment immediate memory | 1 | 30 | Std. Mean Difference (IV, Random, 95% CI) | 0.60 [‐0.18, 1.37] |
| 2.4 Wechsler Adult Intelligence Scales logical memory immediate recall | 1 | 24 | Std. Mean Difference (IV, Random, 95% CI) | ‐1.41 [‐2.36, ‐0.45] |
| 2.5 Rey auditory verbal learning trial I‐V | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.10 [‐0.25, 0.45] |
| 2.6 Hopkins Verbal Learning Test (immediate) | 1 | 49 | Std. Mean Difference (IV, Random, 95% CI) | 0.34 [‐0.27, 0.94] |
| 3 Visual memory functions (immediate) Show forest plot | 2 | 89 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.26 [‐0.97, 0.44] |
| 3.1 Benton visual retention (#error) | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | 0.02 [‐0.47, 0.50] |
| 3.2 Wechsler Memory Scales visual reproduction | 1 | 24 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.73 [‐1.61, 0.15] |
| 4 Working memory Show forest plot | 3 | 238 | Std. Mean Difference (IV, Random, 95% CI) | 0.10 [‐0.16, 0.36] |
| 4.1 Digit span backward | 2 | 189 | Std. Mean Difference (IV, Random, 95% CI) | 0.16 [‐0.13, 0.45] |
| 4.2 2‐Back (accuracy, Hits ‐ False Alarms) | 1 | 49 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.14 [‐0.74, 0.46] |
| 5 Memory functions (delayed) Show forest plot | 3 | 249 | Std. Mean Difference (IV, Random, 95% CI) | 0.10 [‐0.16, 0.35] |
| 5.1 16 words delayed recall | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 5.2 Rey auditory verbal learning delayed recall trial | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.19 [‐0.17, 0.54] |
| 5.3 10 words delayed recall | 1 | 76 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.10 [‐0.55, 0.35] |
| 5.4 Hopkins Verbal Learning Test ‐ 12 words (delayed) | 1 | 49 | Std. Mean Difference (IV, Random, 95% CI) | 0.18 [‐0.42, 0.78] |
| 6 Executive functions Show forest plot | 6 | 367 | Std. Mean Difference (IV, Random, 95% CI) | 0.38 [‐0.14, 0.90] |
| 6.1 Trailmaking part B | 2 | 113 | Std. Mean Difference (IV, Random, 95% CI) | 0.27 [‐0.11, 0.65] |
| 6.2 Ross Information Processing Assessment problem solving and abstract reasoning | 1 | 30 | Std. Mean Difference (IV, Random, 95% CI) | 2.75 [1.69, 3.82] |
| 6.3 Wechsler Memory Scales mental control | 1 | 24 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.31 [‐1.16, 0.55] |
| 6.4 Task switching paradigm (accuracy) | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.03 [‐0.32, 0.38] |
| 6.5 Verbal fluency | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 6.6 Letter number sequencing | 1 | 76 | Std. Mean Difference (IV, Random, 95% CI) | 0.07 [‐0.38, 0.52] |
| 7 Perception Show forest plot | 3 | 178 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.01 [‐0.50, 0.48] |
| 7.1 Face recognition (delayed recall) | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.17 [‐0.18, 0.53] |
| 7.2 Ross Information Processing Assessment auditory processing | 1 | 30 | Std. Mean Difference (IV, Random, 95% CI) | 0.21 [‐0.55, 0.97] |
| 7.3 Wechsler Adult Intelligence Scales visual reproduction | 1 | 24 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.73 [‐1.61, 0.15] |
| 8 Cognitive inhibition Show forest plot | 4 | 314 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.06 [‐0.28, 0.17] |
| 8.1 Stroop colour word (interference) | 2 | 141 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.13 [‐0.46, 0.20] |
| 8.2 Stopping task (accuracy choice RT) | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.01 [‐0.35, 0.36] |
| 8.3 Flanker Task (Incongruent RT) | 1 | 49 | Std. Mean Difference (IV, Random, 95% CI) | 0.00 [‐0.59, 0.60] |
| 9 Visual attention Show forest plot | 3 | 265 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.03, 0.46] |
| 9.1 Digit vigilance | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 9.2 Tracking (accuracy index) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 9.3 2&7 test | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | 0.30 [‐0.19, 0.79] |
| 9.4 Visual search (accuracy) | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.25 [‐0.10, 0.60] |
| 9.5 Covert orienting of visuospatial attention | 1 | 76 | Std. Mean Difference (IV, Random, 95% CI) | 0.09 [‐0.36, 0.54] |
| 10 Auditory attention Show forest plot | 4 | 251 | Mean Difference (IV, Random, 95% CI) | 0.15 [‐0.38, 0.69] |
| 10.1 Digit span forward | 4 | 251 | Mean Difference (IV, Random, 95% CI) | 0.15 [‐0.38, 0.69] |
| 11 Motor function Show forest plot | 2 | 189 | Std. Mean Difference (IV, Random, 95% CI) | 0.08 [‐0.20, 0.37] |
| 11.1 Finger tapping | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | 0.19 [‐0.30, 0.68] |
| 11.2 Pursuit rotor task (tracking error) | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.02 [‐0.33, 0.38] |
| 12 Drop‐out Show forest plot | 7 | 469 | Odds Ratio (M‐H, Random, 95% CI) | 0.96 [0.44, 2.10] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Cognitive speed Show forest plot | 5 | 260 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.16, 0.41] |
| 1.1 Simple reaction time | 2 | 109 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.09 [‐0.47, 0.29] |
| 1.2 Choice reaction time | 1 | 14 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.53 [‐1.60, 0.54] |
| 1.3 Trailmaking part A | 1 | 72 | Std. Mean Difference (IV, Random, 95% CI) | 0.31 [‐0.15, 0.78] |
| 1.4 Digit symbol substitution | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | 0.44 [‐0.05, 0.94] |
| 2 Verbal memory functions (immediate) Show forest plot | 2 | 137 | Std. Mean Difference (IV, Random, 95% CI) | 0.09 [‐0.24, 0.43] |
| 2.1 Randt Memory test story recall | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.04 [‐0.53, 0.45] |
| 2.2 16 words immediate recall | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 2.3 Ross Information Processing Assessment immediate memory | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 2.4 Wechsler Adult Intelligence Scales logical memory immediate recall | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 2.5 Rey auditory verbal learning trial I‐V | 1 | 72 | Std. Mean Difference (IV, Random, 95% CI) | 0.21 [‐0.25, 0.67] |
| 2.6 Hopkins Verbal Learning Test (immediate) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 3 Visual memory functions (immediate) Show forest plot | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.09 [‐0.57, 0.40] |
| 3.1 Benton visual retention (#error) | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.09 [‐0.57, 0.40] |
| 3.2 Wechsler Memory Scales visual reproduction | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 4 Working memory Show forest plot | 2 | 137 | Mean Difference (IV, Random, 95% CI) | 0.30 [‐0.54, 1.15] |
| 4.1 Digit span backward | 2 | 137 | Mean Difference (IV, Random, 95% CI) | 0.30 [‐0.54, 1.15] |
| 4.2 2‐Back (accuracy, Hits ‐ False Alarms) | 0 | 0 | Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 5 Memory functions (delayed) Show forest plot | 2 | 152 | Std. Mean Difference (IV, Fixed, 95% CI) | 0.09 [‐0.23, 0.41] |
| 5.1 16 words delayed recall | 0 | 0 | Std. Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| 5.2 Rey auditory verbal learning delayed recall trial | 1 | 72 | Std. Mean Difference (IV, Fixed, 95% CI) | 0.25 [‐0.21, 0.72] |
| 5.3 10 words delayed recall | 1 | 80 | Std. Mean Difference (IV, Fixed, 95% CI) | ‐0.05 [‐0.49, 0.38] |
| 5.4 Hopkins Verbal Learning Test ‐ 12 words (delayed) | 0 | 0 | Std. Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| 6 Executive functions Show forest plot | 3 | 217 | Std. Mean Difference (IV, Random, 95% CI) | 0.18 [‐0.16, 0.53] |
| 6.1 Trailmaking part B | 2 | 137 | Std. Mean Difference (IV, Random, 95% CI) | 0.30 [‐0.16, 0.76] |
| 6.2 Ross Information Processing Assessment problem solving and abstract reasoning | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 6.3 Wechsler Memory Scales mental control | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 6.4 Task switching paradigm (accuracy) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 6.5 Verbal fluency | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 6.6 Letter number sequencing | 1 | 80 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.03 [‐0.47, 0.41] |
| 7 Cognitive inhibition Show forest plot | 3 | 217 | Std. Mean Difference (IV, Random, 95% CI) | 0.20 [‐0.06, 0.47] |
| 7.1 Stroop colour word (interference) | 3 | 217 | Std. Mean Difference (IV, Random, 95% CI) | 0.20 [‐0.06, 0.47] |
| 7.2 Stopping task (accuracy choice RT) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 7.3 Flanker Task (Incongruent RT) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 8 Visual attention Show forest plot | 3 | 155 | Std. Mean Difference (IV, Random, 95% CI) | 0.05 [‐0.26, 0.37] |
| 8.1 Digit vigilance | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 8.2 Tracking (accuracy index) | 1 | 10 | Std. Mean Difference (IV, Random, 95% CI) | 0.76 [‐0.55, 2.07] |
| 8.3 2&7 test | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | 0.04 [‐0.44, 0.53] |
| 8.4 Visual search (accuracy) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 8.5 Covert orienting of visuospatial attention | 1 | 80 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.02 [‐0.45, 0.42] |
| 9 Auditory attention Show forest plot | 1 | 65 | Mean Difference (IV, Fixed, 95% CI) | 0.16 [‐1.01, 1.33] |
| 9.1 Digit span forward | 1 | 65 | Mean Difference (IV, Fixed, 95% CI) | 0.16 [‐1.01, 1.33] |
| 10 Motor function Show forest plot | 1 | 65 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐7.87, 8.08] |
| 10.1 Finger tapping | 1 | 65 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐7.87, 8.08] |
| 10.2 Pursuit rotor task (tracking error) | 0 | 0 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| 11 Drop‐out Show forest plot | 5 | 267 | Odds Ratio (IV, Random, 95% CI) | 1.84 [0.79, 4.29] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Cognitive speed Show forest plot | 3 | 265 | Std. Mean Difference (IV, Random, 95% CI) | 0.23 [‐0.01, 0.47] |
| 1.1 Simple reaction time | 1 | 76 | Std. Mean Difference (IV, Random, 95% CI) | 0.18 [‐0.27, 0.63] |
| 1.2 Choice reaction time | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 1.3 Trailmaking part A | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 1.4 Digit symbol substitution | 2 | 189 | Std. Mean Difference (IV, Random, 95% CI) | 0.25 [‐0.04, 0.54] |
| 2 Verbal memory functions (immediate) Show forest plot | 3 | 209 | Std. Mean Difference (IV, Random, 95% CI) | 0.36 [‐0.09, 0.80] |
| 2.1 Randt Memory test story recall | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | 0.34 [‐0.15, 0.83] |
| 2.2 16 words immediate recall | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 2.3 Ross Information Processing Assessment immediate memory | 1 | 20 | Std. Mean Difference (IV, Random, 95% CI) | 1.14 [0.18, 2.10] |
| 2.4 Wechsler Adult Intelligence Scales logical memory immediate recall | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 2.5 Rey auditory verbal learning trial I‐V | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.10 [‐0.25, 0.45] |
| 3 Visual memory functions (immediate) Show forest plot | 1 | 65 | Mean Difference (IV, Fixed, 95% CI) | 0.05 [‐1.65, 1.76] |
| 3.1 Benton visual retention (#error) | 1 | 65 | Mean Difference (IV, Fixed, 95% CI) | 0.05 [‐1.65, 1.76] |
| 3.2 Wechsler Memory Scales visual reproduction | 0 | 0 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| 4 Working memory Show forest plot | 2 | 189 | Mean Difference (IV, Random, 95% CI) | 0.36 [‐0.41, 1.12] |
| 4.1 Digit span backward | 2 | 189 | Mean Difference (IV, Random, 95% CI) | 0.36 [‐0.41, 1.12] |
| 5 Memory functions (delayed) Show forest plot | 2 | 200 | Std. Mean Difference (IV, Random, 95% CI) | 0.08 [‐0.20, 0.36] |
| 5.1 16 words delayed recall | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 5.2 Rey auditory verbal learning delayed recall trial | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.19 [‐0.17, 0.54] |
| 5.3 10 words delayed recall | 1 | 76 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.10 [‐0.55, 0.35] |
| 6 Executive functions Show forest plot | 4 | 285 | Std. Mean Difference (IV, Random, 95% CI) | 0.23 [‐0.09, 0.55] |
| 6.1 Trailmaking part B | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | 0.36 [‐0.13, 0.85] |
| 6.2 Ross Information Processing Assessment problem solving and abstract reasoning | 1 | 20 | Std. Mean Difference (IV, Random, 95% CI) | 1.08 [0.13, 2.03] |
| 6.3 Wechsler Memory Scales mental control | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 6.4 Task switching paradigm (accuracy) | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.03 [‐0.32, 0.38] |
| 6.5 Verbal fluency | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 6.6 Letter number sequencing | 1 | 76 | Std. Mean Difference (IV, Random, 95% CI) | 0.07 [‐0.38, 0.52] |
| 7 Perception Show forest plot | 2 | 144 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.11, 0.54] |
| 7.1 Face recognition (delayed recall) | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.17 [‐0.18, 0.53] |
| 7.2 Ross Information Processing Assessment auditory processing | 1 | 20 | Std. Mean Difference (IV, Random, 95% CI) | 0.48 [‐0.41, 1.38] |
| 7.3 Wechsler Adult Intelligence Scales visual reproduction | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 8 Cognitive inhibition Show forest plot | 3 | 265 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.06 [‐0.31, 0.18] |
| 8.1 Stroop colour word (interference) | 2 | 141 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.13 [‐0.46, 0.20] |
| 8.2 Stopping task (accuracy choice RT) | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.01 [‐0.35, 0.36] |
| 9 Visual attention Show forest plot | 3 | 265 | Std. Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.03, 0.46] |
| 9.1 Digit vigilance | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 9.2 Tracking (accuracy index) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 9.3 2&7 test | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | 0.30 [‐0.19, 0.79] |
| 9.4 Visual search (accuracy) | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.25 [‐0.10, 0.60] |
| 9.5 Covert orienting of visuospatial attention | 1 | 76 | Std. Mean Difference (IV, Random, 95% CI) | 0.09 [‐0.36, 0.54] |
| 10 Auditory attention Show forest plot | 2 | 189 | Mean Difference (IV, Random, 95% CI) | ‐0.17 [‐0.83, 0.49] |
| 10.1 Digit span forward | 2 | 189 | Mean Difference (IV, Random, 95% CI) | ‐0.17 [‐0.83, 0.49] |
| 11 Motor function Show forest plot | 2 | 189 | Std. Mean Difference (IV, Random, 95% CI) | 0.08 [‐0.20, 0.37] |
| 11.1 Finger tapping | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | 0.19 [‐0.30, 0.68] |
| 11.2 Pursuit rotor task (tracking error) | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.02 [‐0.33, 0.38] |
| 12 Drop‐out Show forest plot | 4 | 351 | Odds Ratio (M‐H, Random, 95% CI) | 0.99 [0.58, 1.72] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Verbal memory functions (immediate) Show forest plot | 1 | 20 | Mean Difference (IV, Fixed, 95% CI) | 0.30 [‐4.17, 4.77] |
| 1.1 Randt Memory test story recall | 0 | 0 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| 1.2 16 words immediate recall | 0 | 0 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| 1.3 Ross Information Processing Assessment immediate memory | 1 | 20 | Mean Difference (IV, Fixed, 95% CI) | 0.30 [‐4.17, 4.77] |
| 1.4 Wechsler Adult Intelligence Scales logical memory immediate recall | 0 | 0 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| 1.5 Rey auditory verbal learning trial I‐V | 0 | 0 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| 2 Executive functions Show forest plot | 1 | 20 | Mean Difference (IV, Fixed, 95% CI) | ‐2.30 [‐4.49, ‐0.11] |
| 2.1 Trailmaking part B | 0 | 0 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| 2.2 Ross Information Processing Assessment problem solving and abstract reasoning | 1 | 20 | Mean Difference (IV, Fixed, 95% CI) | ‐2.30 [‐4.49, ‐0.11] |
| 2.3 Wechsler Memory Scales mental control | 0 | 0 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| 2.4 Word comparison (#error) | 0 | 0 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| 2.5 Task switching paradigm (accuracy) | 0 | 0 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| 2.6 Verbal fluency | 0 | 0 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| 3 Perception Show forest plot | 1 | 20 | Mean Difference (IV, Fixed, 95% CI) | ‐0.5 [‐2.93, 1.93] |
| 3.1 Face recognition (delayed recall) | 0 | 0 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| 3.2 Ross Information Processing Assessment auditory processing | 1 | 20 | Mean Difference (IV, Fixed, 95% CI) | ‐0.5 [‐2.93, 1.93] |
| 3.3 Wechsler Adult Intelligence Scales visual reproduction | 0 | 0 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| 4 Cognitive speed Show forest plot | 1 | 37 | Mean Difference (IV, Fixed, 95% CI) | ‐4.0 [‐27.93, 19.93] |
| 4.1 Simple reaction time | 1 | 37 | Mean Difference (IV, Fixed, 95% CI) | ‐4.0 [‐27.93, 19.93] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Cognitive speed Show forest plot | 4 | 275 | Std. Mean Difference (IV, Random, 95% CI) | 0.08 [‐0.22, 0.37] |
| 1.1 Simple reaction time | 1 | 37 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.10 [‐0.75, 0.54] |
| 1.2 Choice reaction time | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 1.3 Trailmaking part A | 1 | 49 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.36 [‐0.96, 0.24] |
| 1.4 Digit symbol substitution | 2 | 189 | Std. Mean Difference (IV, Random, 95% CI) | 0.24 [‐0.05, 0.52] |
| 2 Verbal memory functions (immediate) Show forest plot | 5 | 292 | Std. Mean Difference (IV, Random, 95% CI) | 0.08 [‐0.38, 0.55] |
| 2.1 16 words immediate recall | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 2.2 Randt Memory test story recall | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | 0.34 [‐0.15, 0.83] |
| 2.3 Ross Information Processing Assessment immediate memory | 1 | 30 | Std. Mean Difference (IV, Random, 95% CI) | 0.60 [‐0.18, 1.37] |
| 2.4 Wechsler Adult Intelligence Scales logical memory immediate recall | 1 | 24 | Std. Mean Difference (IV, Random, 95% CI) | ‐1.41 [‐2.36, ‐0.45] |
| 2.5 Rey auditory verbal learning trial I‐V | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.10 [‐0.25, 0.45] |
| 2.6 Hopkins Verbal Learning Test (immediate) | 1 | 49 | Std. Mean Difference (IV, Random, 95% CI) | 0.34 [‐0.27, 0.94] |
| 3 Visual memory functions (immediate) Show forest plot | 2 | 89 | Mean Difference (IV, Random, 95% CI) | ‐0.59 [‐2.04, 0.87] |
| 3.1 Benton visual retention (#error) | 1 | 65 | Mean Difference (IV, Random, 95% CI) | 0.05 [‐1.65, 1.76] |
| 3.2 Wechsler Memory Scales visual reproduction | 1 | 24 | Mean Difference (IV, Random, 95% CI) | ‐1.45 [‐3.50, 0.60] |
| 4 Working memory Show forest plot | 3 | 238 | Std. Mean Difference (IV, Random, 95% CI) | 0.10 [‐0.16, 0.36] |
| 4.1 Digit span backward | 2 | 189 | Std. Mean Difference (IV, Random, 95% CI) | 0.16 [‐0.13, 0.45] |
| 4.2 2‐Back (accuracy, Hits ‐ False Alarms) | 1 | 49 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.14 [‐0.74, 0.46] |
| 5 Memory functions (delayed) Show forest plot | 2 | 173 | Mean Difference (IV, Random, 95% CI) | 0.48 [‐0.29, 1.25] |
| 5.1 16 words delayed recall | 0 | 0 | Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 5.2 Rey auditory verbal learning delayed recall trial | 1 | 124 | Mean Difference (IV, Random, 95% CI) | 0.5 [‐0.44, 1.44] |
| 5.3 10 words delayed recall | 0 | 0 | Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 5.4 Hopkins Verbal Learning Test ‐ 12 words (delayed) | 1 | 49 | Mean Difference (IV, Random, 95% CI) | 0.44 [‐0.94, 1.82] |
| 6 Executive functions Show forest plot | 5 | 291 | Std. Mean Difference (IV, Random, 95% CI) | 0.48 [‐0.18, 1.15] |
| 6.1 Trailmaking part B | 2 | 113 | Std. Mean Difference (IV, Random, 95% CI) | 0.27 [‐0.11, 0.65] |
| 6.2 Ross Information Processing Assessment problem solving and abstract reasoning | 1 | 30 | Std. Mean Difference (IV, Random, 95% CI) | 2.75 [1.69, 3.82] |
| 6.3 Wechsler Memory Scales mental control | 1 | 24 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.31 [‐1.16, 0.55] |
| 6.4 Task switching paradigm (accuracy) | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.03 [‐0.32, 0.38] |
| 6.5 Verbal fluency | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 6.6 Letter number sequencing | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 7 Perception Show forest plot | 3 | 178 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.01 [‐0.50, 0.48] |
| 7.1 Face recognition (delayed recall) | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.17 [‐0.18, 0.53] |
| 7.2 Ross Information Processing Assessment auditory processing | 1 | 30 | Std. Mean Difference (IV, Random, 95% CI) | 0.21 [‐0.55, 0.97] |
| 7.3 Wechsler Adult Intelligence Scales visual reproduction | 1 | 24 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.73 [‐1.61, 0.15] |
| 8 Cognitive inhibition Show forest plot | 3 | 238 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.02 [‐0.27, 0.24] |
| 8.1 Stroop colour word (interference) | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.07 [‐0.55, 0.42] |
| 8.2 Stopping task (accuracy choice RT) | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.01 [‐0.35, 0.36] |
| 8.3 Flanker Task (Incongruent RT) | 1 | 49 | Std. Mean Difference (IV, Random, 95% CI) | 0.00 [‐0.59, 0.60] |
| 9 Visual attention Show forest plot | 2 | 189 | Std. Mean Difference (IV, Random, 95% CI) | 0.27 [‐0.02, 0.56] |
| 9.1 Digit vigilance | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 9.2 Tracking (accuracy index) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 9.3 2&7 test | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | 0.30 [‐0.19, 0.79] |
| 9.4 Visual search (accuracy) | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.25 [‐0.10, 0.60] |
| 9.5 Covert orienting of visuospatial attention | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 10 Auditory attention Show forest plot | 3 | 213 | Mean Difference (IV, Random, 95% CI) | 0.15 [‐0.49, 0.79] |
| 10.1 Digit span forward | 3 | 213 | Mean Difference (IV, Random, 95% CI) | 0.15 [‐0.49, 0.79] |
| 11 Motor function Show forest plot | 2 | 189 | Std. Mean Difference (IV, Random, 95% CI) | 0.08 [‐0.20, 0.37] |
| 11.1 Finger tapping | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | 0.19 [‐0.30, 0.68] |
| 11.2 Pursuit rotor task (tracking error) | 1 | 124 | Std. Mean Difference (IV, Random, 95% CI) | 0.02 [‐0.33, 0.38] |
| 12 Drop‐out Show forest plot | 5 | 330 | Odds Ratio (M‐H, Random, 95% CI) | 1.22 [0.66, 2.25] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Cognitive speed Show forest plot | 4 | 180 | Std. Mean Difference (IV, Random, 95% CI) | 0.25 [‐0.05, 0.55] |
| 1.1 Simple reaction time | 1 | 29 | Std. Mean Difference (IV, Random, 95% CI) | 0.02 [‐0.71, 0.76] |
| 1.2 Choice reaction time | 1 | 14 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.53 [‐1.60, 0.54] |
| 1.3 Trailmaking part A | 1 | 72 | Std. Mean Difference (IV, Random, 95% CI) | 0.31 [‐0.15, 0.78] |
| 1.4 Digit symbol substitution | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | 0.44 [‐0.05, 0.94] |
| 2 Verbal memory functions (immediate) Show forest plot | 2 | 137 | Std. Mean Difference (IV, Random, 95% CI) | 0.09 [‐0.24, 0.43] |
| 2.1 Randt Memory test story recall | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.04 [‐0.53, 0.45] |
| 2.2 16 words immediate recall | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 2.3 Ross Information Processing Assessment immediate memory | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 2.4 Wechsler Adult Intelligence Scales logical memory immediate recall | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 2.5 Rey auditory verbal learning trial I‐V | 1 | 72 | Std. Mean Difference (IV, Random, 95% CI) | 0.21 [‐0.25, 0.67] |
| 2.6 Hopkins Verbal Learning Test (immediate) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 3 Visual memory functions (immediate) Show forest plot | 1 | 65 | Mean Difference (IV, Random, 95% CI) | ‐0.28 [‐1.87, 1.30] |
| 3.1 Benton visual retention (#error) | 1 | 65 | Mean Difference (IV, Random, 95% CI) | ‐0.28 [‐1.87, 1.30] |
| 3.2 Wechsler Memory Scales visual reproduction | 0 | 0 | Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 4 Working memory Show forest plot | 2 | 137 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.21, 0.46] |
| 4.1 Digit span backward | 2 | 137 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.21, 0.46] |
| 4.2 2‐Back (accuracy, Hits ‐ False Alarms) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 5 Memory functions (delayed) Show forest plot | 1 | 72 | Mean Difference (IV, Fixed, 95% CI) | 0.92 [‐0.75, 2.59] |
| 5.1 Rey auditory verbal learning delayed recall trial | 1 | 72 | Mean Difference (IV, Fixed, 95% CI) | 0.92 [‐0.75, 2.59] |
| 6 Executive functions Show forest plot | 2 | 137 | Std. Mean Difference (IV, Random, 95% CI) | 0.30 [‐0.16, 0.76] |
| 6.1 Trailmaking part B | 2 | 137 | Std. Mean Difference (IV, Random, 95% CI) | 0.30 [‐0.16, 0.76] |
| 6.2 Ross Information Processing Assessment problem solving and abstract reasoning | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 6.3 Wechsler Memory Scales mental control | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 6.4 Task switching paradigm (accuracy) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 6.5 Verbal fluency | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 6.6 Letter number sequencing | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 7 Cognitive inhibition Show forest plot | 2 | 137 | Std. Mean Difference (IV, Random, 95% CI) | 0.29 [‐0.04, 0.63] |
| 7.1 Stroop colour word (interference) | 2 | 137 | Std. Mean Difference (IV, Random, 95% CI) | 0.29 [‐0.04, 0.63] |
| 7.2 Stopping task (accuracy choice RT) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 7.3 Flanker Task (Incongruent RT) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 8 Visual attention Show forest plot | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | 0.04 [‐0.44, 0.53] |
| 8.1 Digit vigilance | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 8.2 Tracking (accuracy index) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 8.3 2&7 test | 1 | 65 | Std. Mean Difference (IV, Random, 95% CI) | 0.04 [‐0.44, 0.53] |
| 8.4 Visual search (accuracy) | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 8.5 Covert orienting of visuospatial attention | 0 | 0 | Std. Mean Difference (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 9 Auditory attention Show forest plot | 1 | 65 | Mean Difference (IV, Fixed, 95% CI) | 0.16 [‐1.01, 1.33] |
| 9.1 Digit span forward | 1 | 65 | Mean Difference (IV, Fixed, 95% CI) | 0.16 [‐1.01, 1.33] |
| 10 Motor function Show forest plot | 1 | 65 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐7.87, 8.08] |
| 10.1 Finger tapping | 1 | 65 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐7.87, 8.08] |
| 10.2 Pursuit rotor task (tracking error) | 0 | 0 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| 11 Drop‐out Show forest plot | 3 | 164 | Odds Ratio (IV, Random, 95% CI) | 1.50 [0.50, 4.50] |
