Examination on Brain Training Method : Effects of n-back task and dual-task

Alzheimer's dementia (AD) is the most common dementia, Background accounting for more than 60% of all dementia cases. For adults aged >65 years, the incidence rate doubles for every 5 years of increased age; therefore, preserving cognitive function is a pressing issue. Thus, our team screens for AD in older adults with mild cognitive impairment, at 11 public halls in Kashihara City, Japan, and offers follow-up to those with cognitive difficulties. The purpose of this research was to measure the effects of two interventions, a dual-task (requiring the participant to perform two tasks at the same time) and an n-back task (test of memory retention, requiring the participant to identify the item occupying the nth-back position in a sequence of items). A comparison group performed a single learning task in place of the dual-task.  Moreover, the majority of non-drug therapies for the maintenance of cognitive function help promote a positive mood, activating reward systems in the brain and motivating the individual to continue the task. Therefore, the correlation between cognitive function, and positive and negative mood was investigated. : Dual and nback task (n = 304) and single-task (n = 78) groups were Methods compared in a 6-month intervention. Salivary α-amylase concentration was measured, which reflects positive and negative mood, and correlations with cognitive function were analyzed. : Cognitive function improved in both the dual-task and the single-task Results groups, and many cognitive domains had improved in the dual-task group. A correlation between salivary α-amylase and cognitive function was found, indicating that a greater positive mood was associated with greater cognitive function. : The results of this research show that functional decline can be Conclusion improved by a cognitive intervention. Positive mood and cognitive function were correlated, suggesting that encouraging comfort in the participant can increase the effectiveness of the intervention. 1 1 1 2


Introduction
The Ministry of Health, Labour and Welfare estimates that 15% of the Japanese population aged >65 years have dementia, i.e., a total of approximately 4.62 million individuals (estimated in 2012) 1 .Alzheimer's disease (AD) is the most common type of dementia and accounts for 60% or more of dementia cases; vascular dementia is the second most prevalent type of dementia, accounting for 15-20 % of cases 2 .However, many individuals have a mixed dementia type, with lesions characteristic of both AD and vascular dementia 3 .AD has increased year-by-year 4 , and among adults >65 years of age, the incidence rate doubles with every 5 years of increased age 5 .This means that the construction of countermeasures is an urgent issue.For instance, although the amyloid vaccine was developed in 2000, it could not suppress the decline in cognitive function, even after amyloid β is removed from the brain 6 .
Since taking preventive measures before the onset of dementia is important, a worldwide project, the Alzheimer's Disease Neuroimaging Initiative (ADNI; http://www.adni-info.org/), has been implemented to establish a test that can indicate AD before onset, and therefore offer an opportunity for intervention to stop the progression of disease 7 .J-ADNI was also launched in Japan in 2007 (http:// www.alz.org/research/funding/partnerships/WW-ADNI_japan.asp), though regional efforts in Japan are still at an early stage.
With this in mind, we started a brain training preventive intervention for AD in Kashihara City (Nara, Japan), at all 11 of the city's public halls.This initiative is a joint project between Nara Medical University and the dementia prevention project of the Kashihara City Council of Social Welfare, and screens individuals for Mild Cognitive Impairment (MCI), with follow-up for those meeting criteria for an MCI diagnosis.Screening is conducted twice a year, using the Montreal Cognitive Assessment (MoCA), a screening scale for MCI (http://www.mocatest.org/).Public health nurses conduct follow-up visits to participants with low scores.In addition, a brain training class is held once a month, and prevention interventions and cognitive function evaluations are continuously conducted.
The monthly brain training class aims to inform participants how to take precautions against risk factors for AD, and transform their lifestyle.Risk factors for AD that are targeted comprise of the following: high blood pressure, obesity, smoking, dyslipidemia, and lifestyle-related diseases, such as diabetes, and complications of these 8 .It is reported that the probability of developing AD in the future is 2 times as high in people with hypertension, 2.1 times in those who are obese (with a BMI of 30 or more), 1.8 times in those who smoke, 2.9 times in those with dyslipidemia (total cholesterol 250mg/dl or more), and 4.6 times in people with diabetes (HbA1c, 7% or higher) 9 .Furthermore, in the brains of people with AD, there is an increased quantity of oxidatively modified products 10 .Therefore, improving diet is an important part of disease prevention.
Aerobic exercise is also essential in preventing AD.For instance, it has been reported that participation in continuous aerobic exercise is linked to increases in brain derived neurotrophic factor (BDNF) and increases in the capacity of the hippocampus 11 .In addition, brain training has shown some positive effects on the brain: the n-back task (a test of memory retention, requiring the participant to identify the item occupying the nth-back position in a sequence of items) has been validated as an effective brain training task, and a meta-analysis indicates that this task is associated with activation of frontal and parietal cortex 12 .Furthermore, it has been reported that, compared to a single-task (such as exercise or learning only), a dual-task (requiring the participant to perform two activities at the same time) generates more activation in the brain, in particular in the prefrontal cortex 13,14 .
Drawing on the above-mentioned previous studies, in this study we considered that an intervention combining healthy-eating habit guidance, aerobic exercise, an n-back task and a dual-task might be effective.In addition, the majority of non-drug therapies, such as music therapy, for the maintenance of cognitive function promote feelings of comfort.These feelings of comfort activate reward systems in the brain, motivating the individual to continue the task in which they are engaged.For instance, in a study comparing the effects of negative and positive feeling, positive feeling increased an individual's repertoire of thinking, behavior and attention, whereas negative feeling reduced an individual's repertoire of thinking and behavior 15 .In addition, it is reported that improvement in selfefficacy is related to memory improvement 16 .Therefore, we thought it was important that the intervention assessed herein improved positive mood and feelings of comfort; therefore, we decided to use physical recreation in this intervention.The full intervention consisted of diet guidance, recreation, exercise, an n-back task, and a dual-task.The purpose of this study was to measure the effect of this intervention on improving cognitive function, and to clarify whether there is a correlation between cognitive function and positive mood.

Participants
A total of 382 adults of 65 years or older participated in the present study between June 2015 and June 2016, who volunteered for the intervention.We distributed public information to all houses in Kashihara city and invited participants.The participants were split into two groups: 304 people in a dual-task group, and 78 people in a single-task group.
The dual-task group focused on dietary guidance and recreation, combined with exercise, the n-back task and the dual-task.The single-task group performed learning tasks only.
We explained the contents of the intervention program and divided people who chose composite tasks combining dual-task and nback task, and those who chose a single task of learning alone.Participants chose the program by themselves, so they were divided into unbalanced groups.
The exclusion requirement for intervention was people who could not move by themselves; however, all participants that volunteered were able to clear the requirement.
The intervention is once a month, the evaluation of cognitive function is before intervention and once every six months after intervention.Stress checks were carried out using salivary amylase before intervention.

Intervention
Intervention method.As an intervention method, the cognitive prevention class was held once a month and focused on diet guidance and recreation, combined with exercise, the n-back task, and the dual-task.Subjects received 12 interventions a year.Diet guidance was carried out using the following content: 1. Correlation between vascular age and cognitive function: Diet that prevents arteriosclerosis.
2. Reduced salt and reduced trans fatty acids.

Food containing antioxidants.
This has been continued for about 20 minutes.
For the exercise requirement, aerobic exercise was conducted under the guidance of an occupational therapist.The aerobic exercise undertaken was rhythmic gymnastics tailored to music, and was continued for about 20 minutes at a time.
The n-back task is a delayed recall task, in which subjects answer tasks a certain number of times.Subjects started this experiment from a set of back tasks and kept adding an extra set of back task each time for 40 minutes.Gradually, the difficulty of the tasks increased.
For a set of back tasks, subjects first memorized ten random words by reading them aloud.Subjects were not allowed to write them down.After that, subjects performed a dual task game and then wrote down what they remembered from those ten words.For the second set of back tasks, subjects memorized a new set of ten words and then played two dual task games.After playing two games, they tried to write down as many words as possible from those new ten words that they had memorized.For the third set of back tasks, they again memorized a new set of ten words, played an additional dual task game and did the same thing.They continued this process for 40 minutes and increased the difficulty of the n-back task.
The dual-task requires the participant to perform two activities at the same time, such as arithmetic calculations while stepping.
As a comparison to the dual-task, a single learning task was conducted.In this method, we conducted a lecture style learning task for 90 minutes with a 10 minute break in the middle.
Evaluation methods MCI screening.MCI screening was used for comparison before intervention and after 6 months and was conducted using the Montreal Cognitive Assessment (MoCA: http://www.mocatest.org/pdf_files/instructions/MoCA-Instructions-English_2010.pdf).
This is a 30-point scale; a higher score indicates higher cognitive function.The cut-off value for MCI is 26 points.We obtained a license to use the scale from Dr. Ziad Nasreddine, the developer of the original version.
Measurement of positive and negative mood.Positive and negative mood was measured by collecting sublingual saliva and measuring salivary α-amylase concentration (NIPRO; catalog number, 34549000).This was measured before intervention.Salivary αamylase reflects sympathetic nervous activity.It rises following a negative stimulus, and reduces following a positive one 17 .The reference values of salivary αamylase by NIPRO, the manufacturer of the measurement device, is as follows: -0-30 KU/L: There is no negative stress.
-61 KU/L or more: There is a high amount of negative stress.

Analytical methods
To compare MoCA scores before and after the intervention, paired t-test were conducted.Correlations of MoCA scores with age and salivary α-amylase were computed using Pearson product-moment correlation coefficients.SPSS 21.0 for Windows was used for analysis.

Ethical considerations
This study was approved by the Ethics Committee of the Nara Medical University (approval number: 741).For the benefit of the participants, we explained in speech and writing: (i) the purpose and method of the study; (ii) the freedom and veto each individual had over participation; (iii) the measures taken to protect privacy; (iv) the approach to data management; (v) and our intentions regarding publication of the results.Written informed consent was required for participation.

Results
The intervention had a 100% completion rate.The average age of the subjects was 72.3 (± 6.6) years old.The group consisted of 129 men and 253 women.The MoCA scores for each age category (50s, 60s, 70s, and 80s) are shown in Figure 1.This was measured before intervention.The correlation coefficients between age and each cognitive function at the beginning of the intervention are also shown in Figure 1.These are classified by MoCA Assessment items.
As shown in Figure 1, the cognitive function with the strongest negative correlation with age at the start of the intervention was the short-term memory recall task; the MoCA score rapidly decreased in participants in their 70s and 80s compared to participants in their 50s and 60s (r = -0.56).Other tests whose results were negatively correlated with age were the trail making task and the clock-task (together indicating visuospatial cognitive ability, r = -0.38,-0.49), verbal fluency (memory retrieval ability, r = -0.46),attention, concentration and working memory (ability to concentrate and attention and memory, r = 0.53), repetition task (memory, r = -0.49),abstract thinking (r = -0.31),and orientation (r = -0.34).
Cognitive functions that were maintained with increasing age were visuoconstructional skills (cube: graphic replication) and naming (animal name recall).
With an intervention once a month, an evaluation can be seen before and six months after the intervention in Table 1.This is a comparison of the results of all ages.The average of the total scores before the intervention was >26 points in both the dual-task group and the single-task group; this met the cut-off value for MCI (26 points).After the intervention, there was significant improvement in both the dual-task group and single-task group, and the average value on the MoCA was above the cutoff value for MCI (p < 0.01).
Comparing the results of the dual-task group and the single-task group, only the dual-task group showed a significant improvement in the trail making and the cube drawing tests (visual-spatial cognitive abilities), and in abstract thinking, speaking in order, speaking in reverse, sustained attention, and calculation (ability to concentrate & attention & memory) (p < 0.01).There were significant improvements in both the dual-task and single-task groups in the verbal fluency, the repetition task (memory), delayed recall task (memory playback capability), and in the overall score on the MoCA (the presence or absence of MCI) (p < 0.05).
Regarding collection of salivary amylase, was taken at a briefing session before the intervention.At that time, the subjects, after receiving the MoCA test, remained in the venue and collected saliva.As it takes time to collect individual saliva and measure alpha amylase, only subjects with time remained in the venue.
In addition, there were subjects who were unable to measure α-amylase (measurement error) subject to influence of hypertensive internal medicine and others.For this reason, the number of subjects that were able to collect the salivary α-amylase, is 280 people.In the measurement of salivary α-amylase, the minimum value was 2 KU/L and the maximum value was 216 KU/L (mean, 49.7 ± 47.0).The correlation of salivary α-amylase and MoCA total score was negative (r = -0.31).
Therefore, there was a trend for MoCA scores to be lower in individuals experiencing greater stress (Figure 2).Performance on the trail making and clock-drawing tasks (both measuring visuospatial cognitive ability) also rapidly decreased with age.Visuospatial cognition refers to the brain's ability to process visual information.When this ability declines, people tend to get lost 18 .There were also correlations between age and word recall (thinking ability), speaking in order, speaking in reverse, sustained attention and calculation (ability to concentrate & attention & memory), and the repetition task (memory).Decreased performance in the word recall task indicates that an individual may have trouble recalling words during a conversation.Decreasing ability to concentrate affects safety and the continuity of actions; when attention is impaired, people struggle to maintain attention on stimuli, so their actions become distracted 19 .Memory was assessed in this study through tasks requiring the participants to speak in order, to speak in reverse, and to listen to and reproduce sentences.
A decline in memory due to aging (age-associated memory impairment) is caused by a decline in the function of cranial nerve 20 and a failure in the network of the brain 21 .Disruption to the cognitive functions considered above adversely affects daily life and lowers safety.Therefore, reducing the risks associated with cognitive decline is an important issue.By contrast, some cognitive functions were maintained even with increasing age, as indicated by performance on the tasks requiring shape replication, animal name recall.These tasks require the reproduction of familiar forms, learned from a young age, and are not tasks in which the participant memorizes new things.Abstract thinking is also a common task of the situations that require common knowledge.In tasks based on familiar stimuli, cognitive function is maintained with increasing age.Due to this, familiar experiences are easier to retrieve 22 .
Comparing scores before and after the intervention, the cognitive tasks that improved significantly in the course of the invention were the trail making and clock drawing tests (visual-spatial cognitive ability), abstract thinking, speaking in order, speaking in reverse, sustained attention and calculation (ability to concentrate & attention & memory), the repetition task (memory), the delayed recall task (memory playback capability).All these cognitive functions decrease with age, but here showed an improvement throughout the intervention; importantly, these functions are associated with the ability of an older person to keep safe and secure in their everyday life.
On comparing the results of the dual-task group and the single-task group, a greater number of cognitive functions showed significant improvement in the dual-task group.Comparing the results after intervention, visuospatial cognition, abstract thinking, concentration, attention, and memory, only those within the dual-task group showed significant improvement.To run two tasks at the same time, the frontal lobe, and in particular the most anterior region, the prefrontal cortex, is essential 23 .Based on this understanding, the dual-task is considered to train the frontal lobe, and this view has been supported by neuroscience studies that show frontal activation during the dual-task 24,25 .The prefrontal cortex ages earlier than other brain regions 26 , meaning that cognitive training for the elderly needs to be considered a priority on maintaining the function on the prefrontal cortex.Interestingly, it has been found that the number of neural stem cells, which are needed for the regeneration of nerve cells, is maintained, even with increasing age 27,28 .Thus, it is reasonable to expect that cognitive training can maintain cognitive function by drawing on these neural stem cells.
The n-back task, first introduced by Wayne Kirchner in 1958 29 , measures the capacity of an individual's working memory.It has been demonstrated that the n-back task not only measures working memory, but also can improve it when structured in a brain training intervention.Improvements in fluid intelligence 30 , and increased density of dopamine 31 have been demonstrated.A synergistic effect in combination with dual-task can be expected.
In addition, the present intervention improved positive mood, presumably activating the brain's reward system.An increase in positive feelings is reported to have effects on body and mind, such as increasing satisfaction and success 32 , improving immune function 33 , increasing confidence towards others and fostering closer relationships 34 , positively affecting physical and mental health 35 , and speeding up recovery from disease 36 .Thus, by targeting an improved positive mood, other positive effects might be expected.In the present study, a correlation was found between salivary α-amylase, which reflects mood, and cognitive function; when negative stress was high, the MoCA was low.Our research group, in a study in the last year, demonstrated a correlation between the ability to cope with stress (Sense of Coherence SOC) and cognitive functions 37 , and the current study supports this finding.

Conclusion
An intervention, combining exercise, an n-back task, and a dualtask, improved performance in a greater number of areas of cognitive function, compared with a similar intervention in which a single learning task was substituted for the dual-task.

Examination on brain training method: Effects of n-back task and dual task
Although the authors have a large sample and an innovative approach providing Summary of overview: their participants with several interventions in a monthly session, the groups are poorly defined and do not adhere to the literature on dual-task (see meta-analysis or reviews on the topic, for example: Verhaeghen , 2003 , Fraser & Bherer, 2013 ).Dual task is a combination of two tasks and when these two tasks et al. are examined alone these are the single tasks.In the study described, I believe that the authors are comparing a combined intervention group (including dual-task, n-back, education, etc.) and an active control group (that listened to lectures), but the manuscript does not present it this way.The rationale for examining the individual components of the MoCA between the groups and correlating salivary samples is also not clear to the reader from the overview provided.There is a possible self-selection bias and confound that the "dual task group" has lower MoCA scores at baseline.There is no indication of whether or not the individual components of the combined intervention group (dual task group) improved...Did those that completed dual task training, n-back training get better on those tasks?The paper needs to be completely revised properly labelling the two groups and identifying the MoCA and the salivary measures as the primary outcome measures of interest in this study.
Examination on brain training method: Effects of n-back task and dual task Title: This title does not reflect the contents of the paper

Abstract:
Rationale for mood measures not clearly stated.Perhaps: The majority of non-drug Background: interventions (this way there is a link with the 2 interventions (dual task + n-back studied)) 6 month intervention?Was this conducted in groups?How many times per week?Methods: Many cognitive domains improved -What cognitive domains were measured?In methods, Results: should state that participants had neuropsychological testing (if this is the measure of cognitive domains).Correlations with cognitive function and salivary α-amylase: Which cognitive functions?N-back performance, dual task performance or single task?The statement of these results is too vague.
First sentence…perhaps functional decline can be reduced with cognitive intervention?Conclusions: Second sentence: "Positive mood and cognitive function were correlated, suggesting that encouraging comfort in the participant can increase the effectiveness of the intervention."I do not understand how this conclusion stems from the correlation between salivary α-amylase and cognitive function.To my knowledge, the n-back task has not been validated as an effective brain training task -Can you provide a reference for this statement?There has been specific demonstration n-back training on fluid intelligence (Jaeggi and colleagues)…but broadly stating that it is valid and effective based on these results is not accurate.
Rationale for all the different "interventions" is not clear.In the one session of brain training, all participants got aerobic training, n-back, dual task, lifestyle education for brain health, recreation?
The distinction between what has been labeled dual task group and single task group is not Methods: clear.I believe these groups have not been appropriately labeled.Especially since the dual task group is doing more than a dual task.This is a combined intervention group that is exposed to many different interventions including dual task but is not a dual-task specific intervention group.And single task, typically this means that the person would only complete one component of the dual task -so if the task is walking and talking, then participants would only walk alone and talk alone but never perform the two tasks together.
The participants chose the groups themselves?This creates a selection bias -how do you control for this?Description of the n-back task unclear.Did they have to remember one item back, two items back?See Jaeggi ., 2003 for visual description of one type of n-back task…Was this an auditory n-back task?et al For the dual-task, the example provided is stepping with arithmetic -were there other combinations of tasks?This is not clear from the description.Typically dual task performance is compared to single task performance on the component tasks (i.e., if stepping and arithmetic as dual task then this would be compared to performance on arithmetic alone (no stepping) or stepping alone (no arithmetic).
The use of a completely different task: lecture style learning task is not an appropriate comparison for the dual task performance.Also what is a lecture style learning task?Are participants presented a lecture on some topic?Was anything measured in these trained tasks?Reaction times?Accuracy?Steps taken?

Results:
All participants are pooled for the correlational results?Initially you mentioned having 2 groups (dual task and single task).
The MoCA is typically a global cognitive function score on 30…I have never seen this broken down by each item…it is not a neuropsychological battery -it is a global score.Can you provide rationale for this type of analysis?Was there a significant correlation between age and the global score on 30?
In Table 1

Figure 1 .
Figure 1.The relationship between MoCA scores and age Pearson moment correlation coefficient, n = 382.

"
In addition, a brain training class is held once a month, and prevention interventions and Introduction: cognitive function evaluations are continuously conducted."This sentence from the introduction sounds 1 2 cognitive function evaluations are continuously conducted."This sentence from the introduction sounds like methodology…perhaps stated differently: In these public halls brain training classes were offered once a month and prevention interventions….Also, how is brain training and prevention interventions different here?And what is meant by continuously conducted?Is this every week, every day?Brain training -is risk prevention class?The description that follows brain training suggests that it is an educational class not a training class.
. Based on the global score the combined intervention group (or dual task group) had lower overall MoCA scores than the Single task group at baseline.But the change from pre to post in the global score on 30, seems larger in the dual task group (up by 4.21 points) versus single (up by only 1.49 3 The benefits of publishing with F1000Research: Your article is published within days, with no editorial bias You can publish traditional articles, null/negative results, case reports, data notes and more The peer review process is transparent and collaborative Your article is indexed in PubMed after passing peer review Dedicated customer support at every stage For pre-submission enquiries, contact research@f1000.com

Table 1 . Comparisons of the dual-task and single-task groups before and after the intervention.
Corresponding paired t-test, n=382 (dual task, n= 304; single task, n= 78).These are the average scores of all participants in all age groups (mean).This is the data showing the score of the MoCA test before the intervention and the measured value of salivary α-amylase.
OrientationThe participant is asked to give precisely the current date as well as their present location (6)TOTAL SCOREThe total possible score is 30 points.A score of 26 or above is considered normal.Figure 2. Correlation between salivary α-amylase and MoCA total score.N=280.Discussion Prophylactic interventions of AD, which were carried out in each municipality, are still at the stage of trial and error (http:// www.mhlw.go.jp/file/06-Seisakujouhou-12300000-Roukenkyoku/0000136616.pdf).As shown in this study, dementia preventive measures in Japan, there is a disparity of each municipality.A preventive program for dementia has not been established yet.It can be noted that general cognitive function, which decreased along with age, can be dissociated from specific cognitive functions, some of which were relatively maintained with increasing age.The specific cognitive function that had the strongest negative correlation with age was the delayed recall task, which requires the individual to memorize five nouns and to recall them after about five minutes.The brain's ability to memorize new things, maintain them, and reproduce them rapidly decreased in proportion to age.

review discontinued At the request of the author(s), this article is no longer under peer review. What does this mean? Version 1
The cognitive functions that decreased most with increasing age were delayed recall, visuospatial cognition, thinking, concentration, attention, and memory.The cognitive tasks that had no correlation with age, and were maintained even with age, were graphic replication, animal name recall, abstract thinking, and orientation -all of which require the reproduction of familiar forms or names.The results of this study show that it is possible to improve cognition by a structured intervention.In addition, a correlation between cognitive function and positive mood has been demonstrated by the present study.It would be interesting to investigate whether improvement in positive feeling directly improves the effectiveness of brain training.