Computerised cognitive training for 12 or more weeks for maintaining cognitive function in cognitively healthy people in late life.

BACKGROUND: Increasing age is associated with a natural decline in cognitive function and is the greatest risk factor for dementia. Cognitive decline and dementia are significant threats to independence and quality of life in older adults. Therefore, identifying interventions that help to maintain cognitive function in older adults or that reduce the risk of dementia is a research priority. Cognitive training uses repeated practice on standardised exercises targeting one or more cognitive domains and may be intended to improve or maintain optimal cognitive function. This review examines the effects of computerised cognitive training interventions lasting at least 12 weeks on the cognitive function of healthy adults aged 65 or older and has formed part of a wider project about modifying lifestyle to maintain cognitive function. We chose a minimum 12 weeks duration as a trade-off between adequate exposure to a sustainable intervention and feasibility in a trial setting. OBJECTIVES: To evaluate the effects of computerised cognitive training interventions lasting at least 12 weeks on cognitive function in cognitively healthy people in late life. SEARCH METHODS: We searched to 31 March 2018 in ALOIS (www.medicine.ox.ac.uk/alois), and we performed additional searches of MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov, and the WHO Portal/ICTRP (www.apps.who.int/trialsearch), to ensure that the search was as comprehensive and as up-to-date as possible to identify published, unpublished, and ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs, published or unpublished, reported in any language. Participants were cognitively healthy people, and at least 80% of the study population had to be aged 65 or older. Experimental interventions adhered to the following criteria: intervention was any form of interactive computerised cognitive intervention - including computer exercises, computer games, mobile devices, gaming console, and virtual reality - that involved repeated practice on standardised exercises of specified cognitive domain(s) for the purpose of enhancing cognitive function; the duration of the intervention was at least 12 weeks; cognitive outcomes were measured; and cognitive training interventions were compared with active or inactive control interventions. DATA COLLECTION AND ANALYSIS: We performed preliminary screening of search results using a 'crowdsourcing' method to identify RCTs. At least two review authors working independently screened the remaining citations against inclusion criteria. At least two review authors also independently extracted data and assessed the risk of bias of included RCTs. Where appropriate, we synthesised data in random-effects meta-analyses, comparing computerised cognitive training (CCT) separately with active and inactive controls. We expressed treatment effects as standardised mean differences (SMDs) with 95% confidence intervals (CIs). We used GRADE methods to describe the overall quality of the evidence for each outcome. MAIN RESULTS: We identified eight RCTs with a total of 1183 participants. The duration of the interventions ranged from 12 to 26 weeks; in five trials, the duration of intervention was 12 or 13 weeks. The included studies had moderate risk of bias, and the overall quality of evidence was low or very low for all outcomes. We compared CCT first against active control interventions, such as watching educational videos. Negative SMDs favour CCT over control. Trial results suggest slight improvement in global cognitive function at the end of the intervention period (12 weeks) (standardised mean difference (SMD) -0.31, 95% confidence interval (CI) -0.57 to -0.05; 232 participants; 2 studies; low-quality evidence). One of these trials also assessed global cognitive function 12 months after the end of the intervention; this trial provided no clear evidence of a persistent effect (SMD -0.21, 95% CI -0.66 to 0.24; 77 participants; 1 study; low-quality evidence). CCT may result in little or no difference at the end of the intervention period in episodic memory (12 to 17 weeks) (SMD 0.06, 95% CI -0.14 to 0.26; 439 participants; 4 studies; low-quality evidence) or working memory (12 to 16 weeks) (SMD -0.17, 95% CI -0.36 to 0.02; 392 participants; 3 studies; low-quality evidence). Because of the very low quality of the evidence, we are very uncertain about the effects of CCT on speed of processing and executive function. We also compared CCT to inactive control (no interventions). We found no data on our primary outcome of global cognitive function. At the end of the intervention, CCT may lead to slight improvement in episodic memory (6 months) (mean difference (MD) in Rivermead Behavioural Memory Test (RBMT) -0.90 points, 95% confidence interval (CI) -1.73 to -0.07; 150 participants; 1 study; low-quality evidence) but can have little or no effect on executive function (12 weeks to 6 months) (SMD -0.08, 95% CI -0.31 to 0.15; 292 participants; 2 studies; low-quality evidence), working memory (16 weeks) (MD -0.08, 95% CI -0.43 to 0.27; 60 participants; 1 study; low-quality evidence), or verbal fluency (6 months) (MD -0.11, 95% CI -1.58 to 1.36; 150 participants; 1 study; low-quality evidence). We could not determine any effects on speed of processing because the evidence was of very low quality. We found no evidence on quality of life, activities of daily living, or adverse effects in either comparison. AUTHORS' CONCLUSIONS: We found low-quality evidence suggesting that immediately after completion of the intervention, small benefits of CCT may be seen for global cognitive function when compared with active controls, and for episodic memory when compared with an inactive control. These benefits are of uncertain clinical importance. We found no evidence that the effect on global cognitive function persisted 12 months later. Our confidence in the results was low, reflecting the overall quality of the evidence. In five of the eight trials, the duration of the intervention was just three months. The possibility that more extensive training could yield larger benefit remains to be more fully explored. We found substantial literature on cognitive training, and collating all available scientific information posed problems. Duration of treatment may not be the best way to categorise interventions for inclusion. As the primary interest of older people and of guideline writers and policymakers involves sustained cognitive benefit, an alternative would be to categorise by length of follow-up after selecting studies that assess longer-term effects.

Computerised cognitive training for maintaining cognitive function in cognitively healthy people in late life.

BACKGROUND: Increasing age is associated with a natural decline in cognitive function and is also the greatest risk factor for dementia. Cognitive decline and dementia are significant threats to independence and quality of life in older adults. Therefore, identifying interventions that help to maintain cognitive function in older adults or to reduce the risk of dementia is a research priority. Cognitive training uses repeated practice on standardised exercises targeting one or more cognitive domains and is intended to maintain optimum cognitive function. This review examines the effect of computerised cognitive training interventions lasting at least 12 weeks on the cognitive function of healthy adults aged 65 or older. OBJECTIVES: To evaluate the effects of computerised cognitive training interventions lasting at least 12 weeks for the maintenance or improvement of cognitive function in cognitively healthy people in late life. SEARCH METHODS: We searched to 31 March 2018 in ALOIS (www.medicine.ox.ac.uk/alois) and performed additional searches of MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov, and the WHO Portal/ICTRP (www.apps.who.int/trialsearch) to ensure that the search was as comprehensive and as up-to-date as possible, to identify published, unpublished, and ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs, published or unpublished, reported in any language. Participants were cognitively healthy people, and at least 80% of the study population had to be aged 65 or older. Experimental interventions adhered to the following criteria: intervention was any form of interactive computerised cognitive intervention - including computer exercises, computer games, mobile devices, gaming console, and virtual reality - that involved repeated practice on standardised exercises of specified cognitive domain(s) for the purpose of enhancing cognitive function; duration of the intervention was at least 12 weeks; cognitive outcomes were measured; and cognitive training interventions were compared with active or inactive control interventions. DATA COLLECTION AND ANALYSIS: We performed preliminary screening of search results using a 'crowdsourcing' method to identify RCTs. At least two review authors working independently screened the remaining citations against inclusion criteria. At least two review authors also independently extracted data and assessed the risk of bias of included RCTs. Where appropriate, we synthesised data in random-effect meta-analyses, comparing computerised cognitive training (CCT) separately with active and inactive controls. We expressed treatment effects as standardised mean differences (SMDs) with 95% confidence intervals (CIs). We used GRADE methods to describe the overall quality of the evidence for each outcome. MAIN RESULTS: We identified eight RCTs with a total of 1183 participants. Researchers provided interventions over 12 to 26 weeks; in five trials, the duration of intervention was 12 or 13 weeks. The included studies had a moderate risk of bias. Review authors noted a lot of inconsistency between trial results. The overall quality of evidence was low or very low for all outcomes.We compared CCT first against active control interventions, such as watching educational videos. Because of the very low quality of the evidence, we were unable to determine any effect of CCT on our primary outcome of global cognitive function or on secondary outcomes of episodic memory, speed of processing, executive function, and working memory.We also compared CCT versus inactive control (no interventions). Negative SMDs favour CCT over control. We found no studies on our primary outcome of global cognitive function. In terms of our secondary outcomes, trial results suggest slight improvement in episodic memory (mean difference (MD) -0.90, 95% confidence interval (CI) -1.73 to -0.07; 150 participants; 1 study; low-quality evidence) and no effect on executive function (SMD -0.08, 95% CI -0.31 to 0.15; 292 participants; 2 studies; low-quality evidence), working memory (MD -0.08, 95% CI -0.43 to 0.27; 60 participants; 1 study; low-quality evidence), or verbal fluency (MD -0.11, 95% CI -1.58 to 1.36; 150 participants; 1 study; low-quality evidence). We could not determine any effects on speed of processing at trial endpoints because the evidence was of very low quality.We found no evidence on quality of life, activities of daily living, or adverse effects in either comparison. AUTHORS' CONCLUSIONS: We found little evidence from the included studies to suggest that 12 or more weeks of CCT improves cognition in healthy older adults. However, our limited confidence in the results reflects the overall quality of the evidence. Inconsistency between trials was a major limitation. In five of the eight trials, the duration of intervention was just three months. The possibility that longer periods of training could be beneficial remains to be more fully explored.

Computerised cognitive training for maintaining cognitive function in cognitively healthy people in midlife.

BACKGROUND: Normal aging is associated with changes in cognitive function that are non-pathological and are not necessarily indicative of future neurocognitive disease. Low cognitive and brain reserve and limited cognitive stimulation are associated with increased risk of dementia. Emerging evidence now suggests that subtle cognitive changes, detectable years before criteria for mild cognitive impairment are met, may be predictive of future dementia. Important for intervention and reduction in disease risk, research also suggests that engaging in stimulating mental activity throughout adulthood builds cognitive and brain reserve and reduces dementia risk. Therefore, midlife (defined here as 40 to 65 years) may be a suitable time to introduce cognitive interventions for maintaining cognitive function and, in the longer term, possibly preventing or delaying the onset of clinical dementia. OBJECTIVES: To evaluate the effects of computerised cognitive training interventions lasting at least 12 weeks for maintaining or improving cognitive function in cognitively healthy people in midlife. SEARCH METHODS: We searched up to 31 March 2018 in ALOIS (www.medicine.ox.ac.uk/alois), the specialised register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG). We ran additional searches in MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov, and the WHO Portal/ICTRP at www.apps.who.int/trialsearch, to ensure that the search was as comprehensive and as up-to-date as possible, to identify published, unpublished, and ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs, published or unpublished, reported in any language. Participants were cognitively healthy people between 40 and 65 years of age (80% of study population within this age range). Experimental interventions adhered to the following criteria: intervention was any form of interactive computerised cognitive intervention - including computer exercises, computer games, mobile devices, gaming console, and virtual reality - that involved repeated practice on standardised exercises of specified cognitive domain(s) for the purpose of enhancing cognitive function; duration of the intervention was at least 12 weeks; cognitive outcomes were measured; and cognitive training interventions were compared with active or inactive control interventions. DATA COLLECTION AND ANALYSIS: For preliminary screening of search results, we used a 'crowd' method to identify RCTs. At least two review authors working independently screened remaining citations against inclusion criteria; independently extracted data; and assessed the quality of the included trial, using the Cochrane risk of bias assessment tool. We used GRADE to describe the overall quality of the evidence. MAIN RESULTS: We identified one eligible study that examined the effect of computerised cognitive training (CCT) in 6742 participants over 50 years of age, with training and follow-up duration of six months. We considered the study to be at high risk of attrition bias and the overall quality of the evidence to be low.Researchers provided no data on our primary outcome. Results indicate that there may be a small advantage for the CCT group for executive function (mean difference (MD) -1.57, 95% confidence interval (CI) -1.85 to -1.29; participants = 3994; low-quality evidence) and a very small advantage for the control group for working memory (MD 0.09, 95% CI 0.03 to 0.15; participants = 5831; low-quality evidence). The intervention may have had little or no effect on episodic memory (MD -0.03, 95% CI -0.10 to 0.04; participants = 3090; low-quality evidence). AUTHORS' CONCLUSIONS: We found low-quality evidence from only one study. We are unable to determine whether computerised cognitive training is effective in maintaining global cognitive function among healthy adults in midlife. We strongly recommend that high-quality studies be undertaken to investigate the effectiveness and acceptability of cognitive training in midlife, using interventions that last long enough that they may have enduring effects on cognitive and brain reserve, and with investigators following up long enough to assess effects on clinically important outcomes in later life.

Computerised cognitive training for preventing dementia in people with mild cognitive impairment.

BACKGROUND: The number of people living with dementia is increasing rapidly. Clinical dementia does not develop suddenly, but rather is preceded by a period of cognitive decline beyond normal age-related change. People at this intermediate stage between normal cognitive function and clinical dementia are often described as having mild cognitive impairment (MCI). Considerable research and clinical efforts have been directed toward finding disease-modifying interventions that may prevent or delay progression from MCI to clinical dementia. OBJECTIVES: To evaluate the effects of at least 12 weeks of computerised cognitive training (CCT) on maintaining or improving cognitive function and preventing dementia in people with mild cognitive impairment. SEARCH METHODS: We searched to 31 May 2018 in ALOIS (www.medicine.ox.ac.uk/alois) and ran additional searches in MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov, and the WHO portal/ICTRP (www.apps.who.int/trialsearch) to identify published, unpublished, and ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs in which cognitive training via interactive computerised technology was compared with an active or inactive control intervention. Experimental computerised cognitive training (CCT) interventions had to adhere to the following criteria: minimum intervention duration of 12 weeks; any form of interactive computerised cognitive training, including computer exercises, computer games, mobile devices, gaming console, and virtual reality. Participants were adults with a diagnosis of mild cognitive impairment (MCI) or mild neurocognitive disorder (MND), or otherwise at high risk of cognitive decline. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias of the included RCTs. We expressed treatment effects as mean differences (MDs) or standardised mean differences (SMDs) for continuous outcomes and as risk ratios (RRs) for dichotomous outcomes. We used the GRADE approach to describe the overall quality of evidence for each outcome. MAIN RESULTS: Eight RCTs with a total of 660 participants met review inclusion criteria. Duration of the included trials varied from 12 weeks to 18 months. Only one trial used an inactive control. Most studies were at unclear or high risk of bias in several domains. Overall, our ability to draw conclusions was hampered by very low-quality evidence. Almost all results were very imprecise; there were also problems related to risk of bias, inconsistency between trials, and indirectness of the evidence.No trial provided data on incident dementia. For comparisons of CCT with both active and inactive controls, the quality of evidence on our other primary outcome of global cognitive function immediately after the intervention period was very low. Therefore, we were unable to draw any conclusions about this outcome.Due to very low quality of evidence, we were also unable to determine whether there was any effect of CCT compared to active control on our secondary outcomes of episodic memory, working memory, executive function, depression, functional performance, and mortality. We found low-quality evidence suggesting that there is probably no effect on speed of processing (SMD 0.20, 95% confidence interval (CI) -0.16 to 0.56; 2 studies; 119 participants), verbal fluency (SMD -0.16, 95% CI -0.76 to 0.44; 3 studies; 150 participants), or quality of life (mean difference (MD) 0.40, 95% CI -1.85 to 2.65; 1 study; 19 participants).When CCT was compared with inactive control, we obtained data on five secondary outcomes, including episodic memory, executive function, verbal fluency, depression, and functional performance. We found very low-quality evidence; therefore, we were unable to draw any conclusions about these outcomes. AUTHORS' CONCLUSIONS: Currently available evidence does not allow us to determine whether or not computerised cognitive training will prevent clinical dementia or improve or maintain cognitive function in those who already have evidence of cognitive impairment. Small numbers of trials, small samples, risk of bias, inconsistency between trials, and highly imprecise results mean that it is not possible to derive any implications for clinical practice, despite some observed large effect sizes from individual studies. Direct adverse events are unlikely to occur, although the time and sometimes the money involved in computerised cognitive training programmes may represent significant burdens. Further research is necessary and should concentrate on improving methodological rigour, selecting suitable outcomes measures, and assessing generalisability and persistence of any effects. Trials with long-term follow-up are needed to determine the potential of this intervention to reduce the risk of dementia.

Reliability and validity of a Mediterranean diet and culinary index (MediCul) tool in an older population with mild cognitive impairment.

Dementia is a leading cause of morbidity and mortality without pharmacologic prevention or cure. Mounting evidence suggests that adherence to a Mediterranean dietary pattern may slow cognitive decline, and is important to characterise in at-risk cohorts. Thus, we determined the reliability and validity of the Mediterranean Diet and Culinary Index (MediCul), a new tool, among community-dwelling individuals with mild cognitive impairment (MCI). A total of sixty-eight participants (66 % female) aged 75·9 (sd 6·6) years, from the Study of Mental and Resistance Training study MCI cohort, completed the fifty-item MediCul at two time points, followed by a 3-d food record (FR). MediCul test-retest reliability was assessed using intra-class correlation coefficients (ICC), Bland-Altman plots and κ agreement within seventeen dietary element categories. Validity was assessed against the FR using the Bland-Altman method and nutrient trends across MediCul score tertiles. The mean MediCul score was 54·6/100·0, with few participants reaching thresholds for key Mediterranean foods. MediCul had very good test-retest reliability (ICC=0·93, 95 % CI 0·884, 0·954, P<0·0001) with fair-to-almost-perfect agreement for classifying elements within the same category. Validity was moderate with no systematic bias between methods of measurement, according to the regression coefficient (y=-2·30+0·17x) (95 % CI -0·027, 0·358; P=0·091). MediCul over-estimated the mean FR score by 6 %, with limits of agreement being under- and over-estimated by 11 and 23 %, respectively. Nutrient trends were significantly associated with increased MediCul scoring, consistent with a Mediterranean pattern. MediCul provides reliable and moderately valid information about Mediterranean diet adherence among older individuals with MCI, with potential application in future studies assessing relationships between diet and cognitive function.

Non-Pharmacologic Interventions for Older Adults with Subjective Cognitive Decline: Systematic Review, Meta-Analysis, and Preliminary Recommendations.

In subjective cognitive decline (SCD), older adults present with concerns about self-perceived cognitive decline but are found to have clinically normal function. However, a significant proportion of those adults are subsequently found to develop mild cognitive impairment, Alzheimer's dementia or other neurocognitive disorder. In other cases, SCD may be associated with mood, personality, and physical health concerns. Regardless of etiology, adults with SCD may benefit from interventions that could enhance current function or slow incipient cognitive decline. The objective of this systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, is to examine the benefits of non-pharmacologic intervention (NPI) in persons with SCD. Inclusion criteria were studies of adults aged 55 + with SCD defined using published criteria, receiving NPI or any control condition, with cognitive, behavioural, or psychological outcomes in controlled trails. Published empirical studies were obtained through a standardized search of CINAHL Complete, Cochrane Central Register of Controlled Trials, MEDLINE with Full Text, PsycINFO, and PsycARTICLES, supplemented by a manual retrieval of relevant articles. Study quality and bias was determined using PEDro. Nine studies were included in the review and meta-analysis. A wide range of study quality was observed. Overall, a small effect size was found on cognitive outcomes, greater for cognitive versus other intervention types. The available evidence suggests that NPI may benefit current cognitive function in persons with SCD. Recommendations are provided to improve future trials of NPI in SCD.

A Neuropsychologist's Guide To Undertaking a Systematic Review for Publication: Making the most of PRISMA Guidelines.

There is increasing impetus to improve the quality of research and scientific writing. Systematic reviews provide Class 1 research evidence, are based upon an established rigor and communicate results in a comprehensive manner, and are therefore particularly relevant to clinicians and researchers. Clinician requirements for quality systematic reviews are twofold: to keep up to date with research and to make informed decisions including those required for diagnoses, disease or risk assessment, and treatment. Researchers rely upon quality systematic reviews to compete for diminishing research funds, prove efficacy for intervention trials, and to meet increasing demand for evidence based intervention. However, insufficient systematic reviews are undertaken, and the methodological rigor and quality are often variable. The aim of this article is to guide researchers through the iterative systematic review process in order to improve quality and thereby increase publication rates. The step by step guide provides a road map through the EQUATOR network and practical suggestions in order to meet the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (Moher et al. 2009) as well as encouraging high standards through the use of quality rating scales. Lastly, information is provided to encourage quantitative analysis to improve the synthesis of results and qualitative interpretation, such as calculating effect sizes or conducting a meta-analyses as the ultimate goal of a systematic review.

The effect of exercise training on cognitive function in older adults with mild cognitive impairment: a meta-analysis of randomized controlled trials.

OBJECTIVES: Investigations of exercise and cognition have primarily focused on healthy or demented older adults, and results have been equivocal in individuals with mild cognitive impairment (MCI). Our aim was to evaluate efficacy of exercise on cognition in older adults with MCI. DESIGN: We conducted a meta-analysis of random controlled trials (RCTs) of exercise effects on cognitive outcomes in adults with MCI. Searches were conducted in Medline, EMBASE, CINAHL, PEDro, SPORTSDICUS, PsychInfo, and PubMed. PARTICIPANTS: Adults aged over 65 years with MCI or Mini-Mental State Exam mean score 24-28 inclusive. MEASUREMENTS: Study quality was assessed using the PEDro scale; data on participant and intervention characteristics and outcomes were extracted, followed by meta-analysis. RESULTS: Fourteen RCTs (1,695 participants; age 65-95 years) met inclusion criteria. Quality was modest and under-powering for small effects prevalent. Overall, 42% of effect sizes (ESs) were potentially clinically relevant (ES >0.20) with only 8% of cognitive outcomes statistically significant. Meta-analysis revealed negligible but significant effects of exercise on verbal fluency (ES: 0.17 [0.04, 0.30]). No significant benefit was found for additional executive measures, memory, or information processing. Overall results were inconsistent with benefits varying across exercise types and cognitive domains. CONCLUSIONS: There is very limited evidence that exercise improves cognitive function in individuals with MCI, although published research is of moderate quality and inconclusive due to low statistical power. Questions remain regarding the magnitude, generalization, persistence, and mechanisms of benefits. Large-scale, high-quality RCTs are required to determine if exercise improves cognition or reduces dementia incidence in those with MCI.

Cognitive and memory training in adults at risk of dementia: a systematic review.

BACKGROUND: Effective non-pharmacological cognitive interventions to prevent Alzheimer's dementia or slow its progression are an urgent international priority. The aim of this review was to evaluate cognitive training trials in individuals with mild cognitive impairment (MCI), and evaluate the efficacy of training in memory strategies or cognitive exercises to determine if cognitive training could benefit individuals at risk of developing dementia. METHODS: A systematic review of eligible trials was undertaken, followed by effect size analysis. Cognitive training was differentiated from other cognitive interventions not meeting generally accepted definitions, and included both cognitive exercises and memory strategies. RESULTS: Ten studies enrolling a total of 305 subjects met criteria for cognitive training in MCI. Only five of the studies were randomized controlled trials. Meta-analysis was not considered appropriate due to the heterogeneity of interventions. Moderate effects on memory outcomes were identified in seven trials. Cognitive exercises (relative effect sizes ranged from .10 to 1.21) may lead to greater benefits than memory strategies (.88 to -1.18) on memory. CONCLUSIONS: Previous conclusions of a lack of efficacy for cognitive training in MCI may have been influenced by not clearly defining the intervention. Our systematic review found that cognitive exercises can produce moderate-to-large beneficial effects on memory-related outcomes. However, the number of high quality RCTs remains low, and so further trials must be a priority. Several suggestions for the better design of cognitive training trials are provided.

Study of Mental Activity and Regular Training (SMART) in at risk individuals: a randomised double blind, sham controlled, longitudinal trial.

BACKGROUND: The extent to which mental and physical exercise may slow cognitive decline in adults with early signs of cognitive impairment is unknown. This article provides the rationale and methodology of the first trial to investigate the isolated and combined effects of cognitive training (CT) and progressive resistance training (PRT) on general cognitive function and functional independence in older adults with early cognitive impairment: Study of Mental and Regular Training (SMART). Our secondary aim is to quantify the differential adaptations to these interventions in terms of brain morphology and function, cardiovascular and metabolic function, exercise capacity, psychological state and body composition, to identify the potential mechanisms of benefit and broader health status effects. METHODS: SMART is a double-blind randomized, double sham-controlled trial. One hundred and thirty-two community-dwelling volunteers will be recruited. Primary inclusion criteria are: at risk for cognitive decline as defined by neuropsychology assessment, low physical activity levels, stable disease, and age over 55 years. The two active interventions are computerized CT and whole body, high intensity PRT. The two sham interventions are educational videos and seated calisthenics. Participants are randomized into 1 of 4 supervised training groups (2 d/wk×6 mo) in a fully factorial design. Primary outcomes measured at baseline, 6, and 18 months are the Alzheimer's Disease Assessment Scale (ADAS-Cog), neuropsychological test scores, and Bayer Informant Instrumental Activities of Daily Living (B-IADLs). Secondary outcomes are psychological well-being, quality of life, cardiovascular and musculoskeletal function, body composition, insulin resistance, systemic inflammation and anabolic/neurotrophic hormones, and brain morphology and function via Magnetic Resonance Imaging (MRI) and Spectroscopy (fMRS). DISCUSSION: SMART will provide a novel evaluation of the immediate and long term benefits of CT, PRT, and combined CT and PRT on global cognitive function and brain morphology, as well as potential underlying mechanisms of adaptation in older adults at risk of further cognitive decline. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ANZCTRN12608000489392.

Cognitive exercise and its role in cognitive function in older adults.

Converging lines of research indicate that complex mental activity is associated with reduced dementia risk. Thus, intense interest exists in whether different forms of cognitive exercise can help protect against cognitive decline and dementia. However, there is considerable confusion in terminology that is hindering progress in the field. We therefore introduce a concrete definition of cognitive training (CT) and make this the focus of our article. Clinical research that has evaluated CT in normal aging, mild cognitive impairment, and dementia is then critically reviewed. Despite many methodological shortcomings, the overall findings indicate that multidomain CT has the potential to improve cognitive function in healthy older adults and slow decline in affected individuals. Finally, practical issues, including the strengths and weaknesses of commercial products, are explored, and recommendations for further research and clinical implementation are made.

A randomised double-blind trial of cognitive training for the prevention of psychopathology in at-risk youth.

BACKGROUND: The aim of this study was to evaluate the effectiveness of online cognitive training as a means of reducing psychopathology in at-risk youth. METHODS: In a double-blind randomised controlled trial, 228 youths (mean age = 18.6, 74.6% female) were randomly allocated to either an intervention group (n = 114; online cognitive training focused on executive functioning) and a control group (n = 114; online cognitive training focused on other cognitive abilities). Participants were assessed online at baseline, post-training, 3-, 6- and 12-month follow-up. The primary outcome of the study was overall psychopathology as measured by the Strengths and Difficulties Questionnaire. Secondary outcomes were executive functioning ability (assessed using the n-back, trail-making and Stroop tasks), day-to-day functioning and risky drinking. RESULTS: Mixed model intention-to-treat analyses indicated that psychopathology increased and day-to-day functioning decreased, regardless of intervention group. Those in the intervention group improved more than those in the control group in terms of the n-back task, but this was not statistically significant after adjusting for multiple comparisons. There were no statistically significant effects on risky drinking, or the trail-making and Stroop tasks. CONCLUSION: This study failed to provide evidence for the efficacy of cognitive training as a stand-alone intervention for psychopathology.

Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI.

Dementia affects 47 million individuals worldwide, and assuming the status quo is projected to rise to 150 million by 2050. Prevention of age-related cognitive impairment in older persons with lifestyle interventions continues to garner evidence but whether this can combat underlying neurodegeneration is unknown. The Study of Mental Activity and Resistance Training (SMART) trial has previously reported within-training findings; the aim of this study was to investigate the long-term neurostructural and cognitive impact of resistance exercise in Mild Cognitive Impairment (MCI). For the first time we show that hippocampal subareas particularly susceptible to volume loss in Alzheimer's disease (AD) are protected by resistance exercise for up to one year after training. One hundred MCI participants were randomised to one of four training groups: (1) Combined high intensity progressive resistance and computerised cognitive training (PRT+CCT), (2) PRT+Sham CCT, (3) CCT+Sham PRT, (4) Sham physical+sham cognitive training (SHAM+SHAM). Physical, neuropsychological and MRI assessments were carried out at baseline, 6 months (directly after training) and 18 months from baseline (12 months after intervention cessation). Here we report neuro-structural and functional changes over the 18-month trial period and the association with global cognitive and executive function measures. PRT but not CCT or PRT+CCT led to global long-term cognitive improvements above SHAM intervention at 18-month follow-up. Furthermore, hippocampal subfields susceptible to atrophy in AD were protected by PRT revealing an elimination of long-term atrophy in the left subiculum, and attenuation of atrophy in left CA1 and dentate gyrus when compared to SHAM+SHAM (p = 0.023, p = 0.020 and p = 0.027). These neuroprotective effects mediated a significant portion of long-term cognitive benefits. By contrast, within-training posterior cingulate plasticity decayed after training cessation and was unrelated to long term cognitive benefits. Neither general physical activity levels nor fitness change over the 18-month period mediated hippocampal trajectory, demonstrating that enduring hippocampal subfield plasticity is not a simple reflection of post-training changes in fitness or physical activity participation. Notably, resting-state fMRI analysis revealed that both the hippocampus and posterior cingulate participate in a functional network that continued to be upregulated following intervention cessation. Multiple structural mechanisms may contribute to the long-term global cognitive benefit of resistance exercise, developing along different time courses but functionally linked. For the first time we show that 6 months of high intensity resistance exercise is capable of not only promoting better cognition in those with MCI, but also protecting AD-vulnerable hippocampal subfields from degeneration for at least 12 months post-intervention. These findings emphasise the therapeutic potential of resistance exercise; however, future work will need to establish just how long-lived these outcomes are and whether they are sufficient to delay dementia.

A Pilot Double-Blind Randomized Controlled Trial of Cognitive Training Combined with Transcranial Direct Current Stimulation for Amnestic Mild Cognitive Impairment.

BACKGROUND: There is currently no effective intervention for improving memory in people at increased risk for dementia. Cognitive training (CT) has been promising, though effects are modest, particularly at follow-up. OBJECTIVE: To investigate whether adjunctive non-invasive brain stimulation (transcranial direct current stimulation, tDCS) could enhance the memory benefits of CT in amnestic mild cognitive impairment (aMCI). METHODS: Participants with aMCI were randomized to receive CT with either Active tDCS (2 mA for 30 min and 0.016 mA for 30 min) or Sham tDCS (0.016 mA for 60 min) for 15 sessions over a period of 5 weeks in a double-blind, sham-controlled, parallel group clinical trial. The primary outcome measure was the California Verbal Learning Task 2nd Edition. RESULTS: 68 participants commenced the intervention. Intention-to-treat (ITT) analysis showed that the CT+Active tDCS group significantly improved at post treatment (p = 0.033), and the CT+Sham tDCS group did not (p = 0.050), but there was no difference between groups. At the 3-month follow-up, both groups showed large-sized memory improvements compared to pre-treatment (CT+Active tDCS: p < 0.01, d = 0.99; CT+Sham tDCS: p < 0.01, d = 0.74), although there was no significant difference between groups. CONCLUSION: This study found that CT+Active tDCS did not produce greater memory improvement compared to CT+Sham tDCS. Large-sized memory improvements occurred in both conditions at follow-up. One possible interpretation, based on recent novel findings, is that low intensity tDCS (used as 'sham') may have contributed biological effects. Further work should use a completely inert tDCS sham condition.

The Brain Games study: protocol for a randomised controlled trial of computerised cognitive training for preventing mental illness in adolescents with high-risk personality styles.

INTRODUCTION: A broad range of mental disorders are now understood as aberrations of normal adolescent brain development. In both adolescents and adults, executive dysfunction has been implicated across a range of mental illnesses, and enhancing executive functioning may prove to be a useful prevention strategy for adolescents at risk for a range of psychopathology. METHODS AND ANALYSIS: This study will consist of a double-blind, randomised controlled trial with a 12-month follow-up period. Participants will consist of 200 people aged 16-24 years who are at risk for a range of mental disorders based on personality risk factors, but have not experienced a lifetime mental illness as determined by a structured diagnostic interview. Participants will be randomly allocated to either an intervention group who complete an online cognitive training programme specifically targeting executive functioning ability or a control group who complete an online cognitive training programme that has limited executive functioning training potential. Superiority of the executive functioning training programme compared with the control training programme will be assessed at baseline, post-training and at 3-month, 6-month and 12-month follow-up. All assessments will be conducted online. The primary outcome of the study will be general psychopathology as measured by the Strengths and Difficulties Questionnaire. Secondary outcomes will include executive functioning ability, day-to-day functioning and alcohol consumption. All analyses will be undertaken using mixed-model repeated measures analysis of variance with planned contrasts. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the University of New South Wales Human Research Ethics Committee (HC15094). Results of the trial immediately post-treatment and at 12 months follow-up will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12616000127404; Pre-results.

Mediation of Cognitive Function Improvements by Strength Gains After Resistance Training in Older Adults with Mild Cognitive Impairment: Outcomes of the Study of Mental and Resistance Training.

OBJECTIVES: To determine whether improvements in aerobic capacity (VO2peak ) and strength after progressive resistance training (PRT) mediate improvements in cognitive function. DESIGN: Randomized, double-blind, double-sham, controlled trial. SETTING: University research facility. PARTICIPANTS: Community-dwelling older adults (aged ≥55) with mild cognitive impairment (MCI) (N = 100). INTERVENTION: PRT and cognitive training (CT), 2 to 3 days per week for 6 months. MEASUREMENTS: Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog); global, executive, and memory domains; peak strength (1 repetition maximum); and VO2peak . RESULTS: PRT increased upper (standardized mean difference (SMD) = 0.69, 95% confidence interval = 0.47, 0.91), lower (SMD = 0.94, 95% CI = 0.69-1.20) and whole-body (SMD = 0.84, 95% CI = 0.62-1.05) strength and percentage change in VO2peak (8.0%, 95% CI = 2.2-13.8) significantly more than sham exercise. Higher strength scores, but not greater VO2peak , were significantly associated with improvements in cognition (P < .05). Greater lower body strength significantly mediated the effect of PRT on ADAS-Cog improvements (indirect effect: ß = -0.64, 95% CI = -1.38 to -0.004; direct effect: ß = -0.37, 95% CI = -1.51-0.78) and global domain (indirect effect: ß = 0.12, 95% CI = 0.02-0.22; direct effect: ß = -0.003, 95% CI = -0.17-0.16) but not for executive domain (indirect effect: ß = 0.11, 95% CI = -0.04-0.26; direct effect: ß = 0.03, 95% CI = -0.17-0.23). CONCLUSION: High-intensity PRT results in significant improvements in cognitive function, muscle strength, and aerobic capacity in older adults with MCI. Strength gains, but not aerobic capacity changes, mediate the cognitive benefits of PRT. Future investigations are warranted to determine the physiological mechanisms linking strength gains and cognitive benefits.

Computerized and on-line neuropsychological testing for late-life cognition and neurocognitive disorders: are we there yet?

PURPOSE OF REVIEW: Cost-effective, valid, efficient and accessible tests for the detection of late-life neurocognitive disorders are crucial, as early identification facilitates appropriate early intervention. Proponents of computerized neuropsychological assessment devices (CNADs) assert that technology-based assessments improve upon traditional neuropsychological tests. However, there remain fundamental questions of validity, reliability, normative data and administration, raising the question of whether CNADs are appropriate alternatives. RECENT FINDINGS: Since publication of the 2012 American Academy of Clinical Neuropsychology and National Academy of Neuropsychology joint position paper outlining appropriate standards for CNAD development, the field has not significantly advanced, with the majority of recommendations inadequately addressed. SUMMARY: Whilst there is a pressing need for innovative and readily applicable cognitive tests, these requirements do not outweigh the necessity for valid measures. Overall, the psychometric quality, standardization, normative data and administration advice of CNADs for neurocognitive disorders are lacking. Therefore, the risk of diagnostic errors is potentially high and poor clinical decisions could potentially arise, having significant impact upon individuals in terms of their well being and access to treatment. We recommend clinicians and researchers make informed decisions about CNAD suitability for their clients and their individual requirements based upon published psychometric and other test information.

Is cognitive training an effective treatment for preclinical and early Alzheimer's disease?

There is much interest in early intervention for the prevention or postponement of dementia in Alzheimer's disease (AD). The results of drug trials in this regard have thus far been disappointing, and non-pharmacological interventions are receiving increased attention. One such intervention is complex cognitive activity. Evidence from epidemiological studies suggests that participation in stimulating mental activities is associated with lowered dementia risk. The introduction of novel and complex cognitive interventions to healthy adults and those with cognitive impairment may represent an efficacious treatment option to improve cognition, lower dementia incidence, and slow rate of decline. This review examines the evidence for restorative cognitive training (CT) and addresses a number of clinically relevant issues regarding cognitive benefit and its transfer and persistence. Although the number of randomized controlled trials is limited, preliminary evidence suggests that CT may provide immediate and longer term cognitive benefits which generalize to non-trained domains and non-cognitive functions, with supervised small group multi-domain training providing greatest benefits. Possible neuroplastic mechanisms are discussed, and recommendations for further research and clinical implementation provided.

Psychological well-being in individuals with mild cognitive impairment.

OBJECTIVES: Cognitive impairments associated with aging and dementia are major sources of burden, deterioration in life quality, and reduced psychological well-being (PWB). Preventative measures to both reduce incident disease and improve PWB in those afflicted are increasingly targeting individuals with mild cognitive impairment (MCI) at early disease stage. However, there is very limited information regarding the relationships between early cognitive changes and memory concern, and life quality and PWB in adults with MCI; furthermore, PWB outcomes are too commonly overlooked in intervention trials. The purpose of this study was therefore to empirically test a theoretical model of PWB in MCI in order to inform clinical intervention. METHODS: Baseline data from a convenience sample of 100 community-dwelling adults diagnosed with MCI enrolled in the Study of Mental Activity and Regular Training (SMART) trial were collected. A series of regression analyses were performed to develop a reduced model, then hierarchical regression with the Baron Kenny test of mediation derived the final three-tiered model of PWB. RESULTS: Significant predictors of PWB were subjective memory concern, cognitive function, evaluations of quality of life, and negative affect, with a final model explaining 61% of the variance of PWB in MCI. DISCUSSION: Our empirical findings support a theoretical tiered model of PWB in MCI and contribute to an understanding of the way in which early subtle cognitive deficits impact upon PWB. Multiple targets and entry points for clinical intervention were identified. These include improving the cognitive difficulties associated with MCI. Additionally, these highlight the importance of reducing memory concern, addressing low mood, and suggest that improving a person's quality of life may attenuate the negative effects of depression and anxiety on PWB in this cohort.