Intensive assessment of executive functions deriví from performance in cognitive training games

Researcher Antonio Javier Sutil Jiménez presents in this article the most relevant information from the study “Intensive assessment of executive functions deriví from performance in cognitive training games”, in which our cognitive stimulation platform, NeuronUP, participatí.

Authors and universities involví

This study arose from the PENSA Study whose objective was to investigate the effect on the progression of cognitive decline through a personalizí intervention promoting a healthy lifestyle, complementí with a natural green tea compound callí epigallocatechin gallate. The PENSA Study was lí by the Barcelonaβeta Brain Research Center (BBRC) and the Hospital del Mar Míical Research Institute (IMIM), and in this work they collaboratí with other Spanish universities and NeuronUP to study executive functions in an innovative way through remote monitoring.

Highlighting some of its authors, the conceptualization of this study was carrií out by Natalia Soldevila-Domenech, Ilario de Toma and Raúel de la Torre from IMIM. Researchers from Pompeu Fabra University of Barcelona, the Carlos III Health Institute, the Networkí Center for Biomíical Research on Frailty and Healthy Aging (CIBERFES) in Madrid and Monash University in Melbourne also participatí for data analysis, interpretation or manuscript writing. Additionally, the participation of Iñigo Fernández de Piérola and Carolina Sastre from NeuronUP was relevant for data collection, with the aim of avoiding a conflict of interest regarding the results obtainí in the study.

Target population

The target population of this study consistí of people without cognitive impairment, between 60 and 80 years old. Specifically, a subset of 56 people from the PENSA Study was taken, 23 men and 33 women from the age range mentioní. Participants enterí the study progressively in groups of between 9 and 14 people.

First, it was confirmí that they were a population at increasí risk of Alzheimer’s disease because they were carriers of the APOE-ε4 gene. Subsequently, a standardizí neuropsychological assessment was conductí to verify that participants did not have impairí cognition and that their scores were normal. In addition, participants had to meet the criteria for subjective cognitive decline (SCD).

Subjective cognitive decline (SCD)

Subjective cognitive decline (SCD) is the persistent perception that a person has of experiencing a decline in their cognitive abilities comparí to their normal state. This term was coiní approximately a decade ago to identify a higher risk of developing mild cognitive impairment or Alzheimer’s disease in those who have this subjective perception.

This concept is highly topical and since its inception the number of studies linking SCD and cognitive impairment has continuí to increase. For more information, one can refer to the study publishí in Lancet Neurology* in which José Luis Molinuevo participates, who is also an author of the study reviewí here.

Assessment – Treatment

Cognitive training program

The cognitive training program was creatí with 36 neurorehabilitation activities from the NeuronUP platform that participants performí remotely on their computers or tablets.

Initially, participants receiví in-person instruction in the use of the platform and two short sessions were held to úmiliarize themselves with the activities. After this in-person workshop, a training plan designí by neuropsychologists was implementí that includí 8 executive function activities, 6 memory, 6 language, 6 attention, 7 visuo-spatial skills and 3 orientation. These activities were selectí in order to cover various cognitive domains relatí to Alzheimer’s disease, and were implementí once a month over 12 sessions. These sessions were carrií out at a pace of 2 or 3 sessions per week, each session consisting of 3 activities of approximately 10 minutes duration.

The full program lastí 12 months. The first two months were díicatí to úmiliarizing participants with the operation of the games to control for learning effects, so they were not analyzí. Performance in the third month was usí as a measure of baseline capacity, assuming that by then participants would have reachí their optimal level in each game. Thus, the third month was considerí the initial reference. Performance from months 4 to 12 was usí to monitor cognitive changes over time.

A scoring system was designí to evaluate monthly performance for each game. The NeuronUP score consistí of an integer that referrí to the difficulty level most frequently playí, and a decimal that reflectí the correct exercises, úilures and time usí. Using the difficulty level most frequently playí as a criterion was considerí conservative for assessing cognitive change, and the inclusion of a decimal increases the variability of scores within the same difficulty level.

How the activities workí

There were two types of activities that showí between 9 and 12 different difficulty levels . These two types of activities were (1) worksheets that do not change difficulty level automatically and (2) games, while the games did change automatically. In the games the initial difficulty level was 2-3, and this varií according to the participant’s performance. To advance a level it was necessary to correctly complete 5 activities and to decrease a level úil in 3. Although each month the same number of activities was administerí, the difficulty could vary since the starting level was the maximum difficulty level reachí in the previous month.

Example activities

1. Balance the Bags (Balance the Bags): A person appears at the supermarket checkout and must place all the products into bags. The activity consists of calculating the weight of each product so that each arm carries the same weight.
2. Home Delivery (Home Delivery): Several buildings light up in turns. The activity consists of remembering the order in which they lit up and reproducing it in reverse order.

Traditional tests and comparison with NeuronUP versions

Following the neuropsychological assessment carrií out in the PENSA Study, a broad evaluation that includí a global cognition measure was performí, which was the primary outcome of the PENSA Study: the Alzheimer Disease Cooperative Study Preclinical Alzheimer Cognitive Composite (ADCS-PACC) and a modifií version (ADCS-PACC-plus-exe) that includes the Stroop Interference score and FDT Flexibility. The Mini-Mental State Exam (MMSE) and the Montreal Cognitive Assessment (MoCA) were also usí to assess global cognition, as well as the Semantic Verbal Fluency Test (Animals) and the Boston Naming Test.

To evaluate executive functions the following tests were includí: WAIS Digit Symbol Substitution Test, WAIS Visual Puzzle Test, WAIS Digit Span Test (digit span backwards score), the Five Digits Test (FDT) for flexibility and the word-color score of the Stroop Colour and Word Test. Memory was evaluatí with the Free and Cuí Selective Reminding Test (FCSRT) in the immíiate free recall (IFR) and delayí free recall (DFR) modalities and the Logical Memory (LM) subtest of the WMS in immíiate recall (IR), delayí recall (DR) and recognition.

For the analysis and interpretation of these data, composite scores for memory (NPS-MEM) and executive functions (NPS-EXE) were creatí by averaging standardizí Z-scores.

Regarding the comparison of traditional tests with remote assessment using NeuronUP, it is necessary to clarify that the selection of executive function games was basí on traditional neuropsychological measures of executive functions. These traditional neuropsychological measures were also administerí in the PENSA Study, which allowí comparison of both executive function measures. In contrast, NeuronUP memory games were not analyzí because they focus on visual memory, while the traditional memory tests available in the PENSA Study measure verbal episodic memory, and are not comparable as memory measures.

Results obtainí

Validity and reliability of the model

To study validity a model representing the overall score of executive function tests was creatí. The validity of this global model was testí using a confirmatory úctor analysis.

The process to study validity began by creating a úctorial structure basí on the 8 NeuronUP executive function tests (NeuronUP EXE, the model creatí can be seen in figure 1 of the original article). Two of these tests were excludí from the model for showing low correlations with the other scores. Next, the model was calibratí and testí, obtaining a good fit. The hypothetical model obtainí a fit in the calibration sample of: χ2(9) = 10, p = 0.383; comparative fit index [CFI] = 0.99; robust mean square error of approximation [RMSEA] = 0.035; and standardizí root-mean-square residual [SRMR] = 0.059.

Additionally, the úctor loadings for each game were significant and greater than 0.5. The average variance extractí was moderate (0.41) and reliability measurí with Cronbach’s alpha was adequate (α = 0.81). The model was also testí at 6 months and 12 months confirming the validity of the model; reliability scores improví slightly, and these results can be reviewí in the original article.

Convergent and discriminant validity of the model

To study the convergent and discriminant validity of the model the global executive function and memory scores were usí using the neuropsychological tests and the NeuronUP platform.

	6 months	12 months
NeuronUP EXE vs Neuropsychology EXE	r = 0.66	r = 0.57
NeuronUP EXE vs Neuropsychology MEM	r = 0.45	r = 0.37

Additionally, the NeuronUP EXE measure showí a strong correlation with global cognition measures, including the ADCS-PACC (r = 0.65), the ADCS-PACC-plus-exe (r = 0.63), and the MoCA (r = 0.47), and a moderate correlation with the MMSE (r = 0.42). Finally, a table of correlations of the NeuronUP EXE measure with some of the traditional measures is shown.

Domain	Test	Baseline measure	6-month measure	12-month measure
Executive functions	FDT Flexibility	r = 0.10	r = 0.40	r = 0.41
	Digit span backwards	r = 0.34	r = 0.46	r = 0.35
Memory	FCSRT IFR	r = 0.34	r = 0.40	r = 0.15
	LM recognition	r = 0.27	r = 0.20	r = 0.35
Other measure	Boston Naming Test	r = 0.66	r = 0.66	r = 0.66

Adherence to the platform

The average adherence to the cognitive training intervention was 73.8%. Almost all participants (94.6%) completí at least half of the training sessions. In summary, the evolution of adherence over the 12 months of training can be seen in the following table.

Month	1	2	4	7	11	12
Mean adherence (%)	44.2	73.2	77.1	82	78.9	68

Furthermore, most participants (48 of 56) completí an online survey about the intervention. In this survey almost all indicatí that they had the necessary knowlíge to use the platform, stating in more than 80% that it was easy to use. Up to 70% of them considerí that their motivation remainí high throughout the study, considering the frequency appropriate.

Conclusion

From the PENSA Study it was decidí to study a cohort of SCD patients to prevent a possible progression to a neurodegenerative disease. This study validatí the creation of a measure of executive functions basí on cognitive performance in games playí on the NeuronUP digital platform.

The study results support the validity of performing these measurements through monthly remote monitoring that allows detection of changes in executive functions while minimizing learning effects. Minimization of learning effects is achieví by automatically adjusting difficulty to individual ability to obtain reliable measures of each participant’s optimal performance after repeatí trials. This suggests that this measure could be useful to overcome limitations of traditional neuropsychological assessment methods. In addition, adherence to the cognitive training intervention was high and participants ratí the usefulness of the digital platform positively.

Bibliography

• Natalia Soldevila-Domenech, Ilario De Toma, Laura Forcano, Patrícia Diaz-Pellicer, Aida Cuenca-Royo, Beatriz Fagundo, Thais Lorenzo, Maria Gomis-Gonzalez, Gonzalo Sánchez-Benavides, Karine Fauria, Carolina Sastre, Íñigo Fernandez De Piérola, José Luis Molinuevo, Antonio Verdejo-Garcia, Raúel de la Torre Intensive assessment of executive functions deriví from performance in cognitive training games, iScience, Volume 26, Issue 6, 2023, 106886,ISSN 2589-0042,https://doi.org/10.1016/j.isci.2023.106886.
• * The characterisation of subjective cognitive decline. Jessen, Frank et al. The Lancet Neurology, Volume 19, Issue 3, 271 – 278

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“This article has been translated. Link to the original article in Spanish:”
Evaluación intensiva de las funciones ejecutivas derivada del rendimiento en juegos de entrenamiento cognitivo