Subjective memory complaints are common in adults with studies showing that approximately 50% to 75% of adults have at least some minor concerns about their memory [1,2]. Burdens of cognitive impairment include direct effects on the patient (eg. loss of function and relationships, financial misjudgements, and nonadherence with recommended therapies), on caregivers (eg. burden and depression), and on society (eg, costs of care). The National Institute on Aging provides information on the definition, detection, and management of cognitive impairment for patients and clinicians, including links to some screening instruments [3].

United States Preventive Services Task Force (USPSTF) clarified that while there may be important reasons to identify cognitive impairment early, none of the potential benefits mentioned in this section have been clearly demonstrated in controlled trials [4].

Computerized Cognitive Training (CCT) is a safe and inexpensive approach to cognitive training interventions in improving targeted cognitive abilities. Cognitive training support can improve cognitive performance in healthy elderly adults [5-7] and that these gains are robust up to five years after training [8]. In this study, the parameters that change CCT and how these parameters affect daily living activities were investigated by using "BEYNEX", a CCT program that was advertised on the Internet.

This study was conducted under Memory Centers of Memorial Hospital and Maltepe University Hospital. Individuals living within the borders of Turkey were accepted. It was realized with "BEYNEX", a CCT program that was advertised on the Internet. It used the data of 388 healthy people who accepted informed consent on the webpage and registered for free by entering their personal information. The users stated that they did not have a disease that would cause dementia or similar cognitive impairment and that they were not treated for any neurological or psychiatric disease diagnosis.

The data used in the study include a period of 4 years between Jan. /2016 and Dec. /2019. Username and password have been provided only to individuals who meet the working criteria. Individuals who reach the page with their personal computers or tablets have done the BEYNEX exercises. Users were not clinically examined prior to the use of BEYNEX or during the active membership period. There is no direct communication with the user, Membership registration is automatically renewed for members with 100 page visits every year.

BEYNEX is a non-commercial web-application that allows users to do daily cognitive activities, including playing 3 different 5-minute long computer games and answering questions on activities in daily life (ADL). The group completed the activities daily, and exercised with a 3-minute physical exercise video. All exercises designed within the domains used by clinicians and are completely unique. There are "cognitive assessment" games, which are offered to the user less frequently, together with games that do not generate cognitive data that only aim to exercise mental exercise. Users do not know which games that evaluate themselves cognitively.

Users were asked questions about ADL consisting of 17 questions every 15 days. In response to these questions, the user was asked to choose one of the 3 options: "yes", "no" or "not suitable". The questions answered as "not suitable" were not taken into consideration. A score of 1 was given for questions whose ADL evaluation was considered negative. The number of times the user answered ADL questions after starting BEYNEX applications, and the total negative score was divided by that number, and an average value between 0 and 1 was obtained. With this value approaching 1, the user was considered to be quite inactive in that activity. Patients’ total activity time, ADL and game performances were monitored only by clinicians under 9 different graphics (ADL, Memory, Visual Perception, Speed, Problem-solving, Flexibility, Attention, Language Skills, Arithmetic). The acceptance criteria were based on completing at least 1 course (*completing 20 minutes of exercises for 33 times) within any period of time. A regular cognitive performance report was sent to each user quarterly, and information was given about their condition. Individuals who received a BEYNEX username but did not log in for more than 4 weeks were notified and deleted from the system.

In this study, data of 2071 people who declared that they are suffering from forgetfulness were collected with the BEYNEX application and the users were able to access the BEYNEX application with the passwords given to the applications received online. Data from a total of 388 (18%) users out of 2071 were eligible for this study. User retention were low for various reasons. Being tired of regular page visits, repetitive exercises become monotonous and boring in time, concerns about the confidentiality of personal data were the most common criticisms. The study group consists of 157 males and 231 females. The mean age of the group was 63.25 (SD ± 10.95) and the mean duration of education was 14.85 (SD ± 4.1) years. Users were asked to complete a 20-minute BEYNEX application every day. 1 course was completed every 33 days. The average course completed by the group was 3.47 (SD ± 6.96) (Table 1). The duration of using the program of the individuals participating in the research varied between 6 months and 4 years. The cognitive performance of the users was graphically monitored in 8 separate domains. Individuals with suspected dementia were called for clinical examination and those diagnosed with dementia were not included in the study analysis, as their cognitive domains decreased over time.

Table 1: Baseline characteristics of the study population.

The relationship between the age, years of education, the number of courses completed and 8 cognitive domains were statistically evaluated using the ANOVA test. Users' age and years of education affect most of the 8 cognitive domains at a statistically high level of significance. Cognitive domains affected by the age factor were "Memory, Speed, Flexibility, Attention, and Visual Perception". Education is to affect "Flexibility, Attention, Language, Aritmetic, and Visual Perception". No significant relationship was found between the number of courses completed by the users and the cognitive domains we followed in long-term follow-up (Table 2).

Table 2: Correlation of cognitive domains with Age, Education, and Completed Course Number.

Depicted are means standard deviations (SD).

Statistical analysis was performed using one-way ANOVA test; *P < 0.05, **P < 0.01, ***P < 0.001.

The reliability and validity of the ADL questions have been demonstrated in a study of older adults (aged 50 years and over), with an internal consistency of 0.70 (Cronbach’s alpha) and a test-retest reliability of 0.80 (infraclass correlation coefficient). When we look at how ADL questions are affected by the age variable, it mostly affects the answers given to the questions about "mood" and "regular medication use". In addition, we found that "spending time for hobbies" was different from other questions, even though the statistical significance level was low. We found that users responded significantly differently to questions about emotional state, time allocated for daily reading and waking up early in the morning in relation to their education level. With the increase in the number of BEYNEX courses completed by the user, in other words, in individuals with high usage of application, only “time allocated for physical exercises” was answered differently from ADL questions (Table 3) SPSS 16.0 (SPSS Inc., Chicago, IL, USA) was used for statistical analyses. Statistical analysis was performed using one-way ANOVA test with post hoc analysis using the Turkey test.

Table 3: Correlation of activity of daily living assessments with Age, Education, and Completed Course Number.

From a healthcare perspective, a major concern with an aging population is the higher prevalence of age-related impairment in cognitive function. This expanding aging population highlights the need to identify quick, effective, low-cost solutions to delay pathological cognitive decline associated with aging [9-11]. Many screening tests for AD are available. However, most tests are only validated in a memory clinic setting and the description of the psychometric properties of the instruments is limited. Especially, computer tests require further research. The MoCA is a promising instrument, but the specificity to detect early AD is rather low [12]. One of the main goals of detecting at-risk individuals is the identification of targets for testing therapeutic interventions that have the potential of attenuating the rate of cognitive decline, such as individualized cognitive rehabilitation programs or modification of lifestyle [13].

USPSTF claims that potential benefits of screening for cognitive impairment is limited by several factors. These include the short duration of most trials (often 6 months or pharmacologic agents and 1 year for nonpharmacologic interventions), as well as the heterogeneous nature of interventions and inconsistency in the outcomes reported, which make cross-study comparisons difficult [4]. Regularly practiced internet-based activities positively affect memory related cognitive domains in elderly individuals with memory impairment. Clinical trials conducted on the efficacy of computerized cognitive training have not led to any important breakthroughs. CCT studies are highly contested on application of preventive or deferring dementia processes. There is a growing consensus that this can, at least partially, be explained by methodological difficulties. However, the long-term cognitive performance data can be utilized as a perfect early notification system, even a diagnostic tool.

What are the factors affecting CCT? If a long-term follow-up is to be done, what factors should we pay attention to while preparing the exercises?

In this study, effective factors on CCT revealed by many clinical studies were analyzed. Our data shows that these factors do not affect cognitive domains equally. For example, the memory and speed domains of people given CCT are greatly affected by age. Increase of years of education does not affect the speed and memory performance of the user in CCT games but only 2 domains changes, specific to the years of education, and these are only language and attention domains. Flexibility, attention, and visual perception domains are common domains that are affected by both age and education. Interestingly, multiple repetitions of CCT exercises did not significantly change any cognitive domain.

Do age and education parameters that affect cognitive domains in CCT also affect daily living activities? We asked users 17 questions about daily life and age and years of education differ in only one question. We see that as the age and duration of education increase, the users may show more emotional reflex behaviors. We do not want to attribute this emotional state meaning to depression because the data we have is not sufficient for this diagnosis. Therefore, we cannot comment on the effect of emotional state on cognition. “Regular medication use” deteriorates as age progresses, and this may be explained by the change in attention and memory CCT scores. The time allocated to hobbies decreases with age, but it is not possible to comment on how this is reflected in CCT scores. It is easily predictable that highly educated people will spend more time reading and wake up early, but the reflection of this on CCT scores is not easy. If the high number of completed CCT courses reflects a group that spends more time on the internet, it can be explained by the shortening of the time this group devotes to physical exercise.

In another clinical study conducted with the same BEYNEX application, we saw that the efficacy of CCT is negligible in subjective cognitive impairment (SCI) group, but it shows significant efficacy for AD patients [14]. CCT could not improve the cognitive abilities of the user in forgetful individuals without dementia and we decided to investigate which parameters affected their performances and how? In this study, it was observed that cognitive domains after CCT were not equally affected. Our aim is not to realize how cognitive domains change, but rather to identify other factors that affect these domains. Interestingly, excessive use of the CCT application does not affect cognitive performance very much, whereas age and total years of education are very strong factors, and therefore, it is necessary to work in small segments of age and education groups to interpret CCT effectiveness.

This research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors have no conflicts of interest to declare.

Funding Sources

No Funding.

Author Contributions

All authors have equal contribution in the research and the manuscript.

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