The researcher Antonio Javier Sutil Jiménez presents in this article the most relevant information from the study “Intensive Evaluation of Executive Functions Derived from Performance in Cognitive Training Games”, in which our cognitive stimulation platform, NeuronUP, participated.

Authors and Universities Involved

This study originated from the PENSA Study, which aimed to investigate the effect on the progression of cognitive decline through a personalized intervention promoting a healthy lifestyle, complemented by a natural compound from green tea called epigallocatechin gallate. The PENSA Study was led by the Barcelonaβeta Brain Research Center (BBRC) and the Hospital del Mar Medical Research Institute (IMIM), collaborating with other Spanish universities and NeuronUP to innovatively study executive functions through remote monitoring.

Highlighting some of the authors, the conceptualization of this study was carried out by Natalia Soldevila-Domenech, Ilario de Toma, and Rafael de la Torre from IMIM. Researchers from the Pompeu Fabra University of Barcelona, the Carlos III Health Institute, the Biomedical Research Network Center for Frailty and Healthy Aging (CIBERFES) in Madrid, and Monash University in Melbourne also participated in data analysis, interpretation, or manuscript writing. Additionally, the participation of Iñigo Fernández de Piérola and Carolina Sastre from NeuronUP was significant for data collection, ensuring no conflict of interest regarding the study results.

Target Population

The target population of this study consisted of individuals without cognitive decline, aged 60 to 80 years. Specifically, a subset of 56 participants from the PENSA Study was selected, including 23 men and 33 women within the mentioned age range. Participants were progressively enrolled in groups of 9 to 14 individuals.

Initially, it was verified that they were a population with increased Alzheimer’s risk as they were carriers of the APOE-ε4 gene. Subsequently, a standardized neuropsychological evaluation was conducted to ensure participants did not have impaired cognition and their scores were normal. Additionally, participants had to meet the criteria for subjective cognitive decline (SCD).

Subjective Cognitive Decline (SCD)

Subjective cognitive decline (SCD) is the persistent perception by an individual of experiencing a decrease in cognitive abilities compared to their normal state. This term was coined approximately a decade ago to identify the increased risk of developing mild cognitive impairment or Alzheimer’s disease among those with this subjective perception.

This concept is highly relevant today, and since its introduction, the number of studies linking SCD and cognitive decline has continued to grow. For more information, refer to the study published in *Lancet Neurology*, where José Luis Molinuevo, also an author of the study reviewed here, participated.

Evaluation – Treatment

Cognitive Training Program

The cognitive training program was created using 36 neurorehabilitation activities from the NeuronUP platform that participants performed remotely on their computers or tablets.

Participants were first given in-person instructions on using the platform, followed by two short sessions to familiarize themselves with the activities. After this in-person workshop, a training plan designed by neuropsychologists was implemented, including 8 executive function activities, 6 memory activities, 6 language activities, 6 attention activities, 7 visuospatial skills activities, and 3 orientation activities. These activities were chosen to cover various cognitive domains related to Alzheimer’s disease and were implemented once a month over 12 sessions. Each session involved 2 to 3 weekly activities, each lasting approximately 10 minutes.

The entire program lasted 12 months. The first two months were dedicated to familiarizing participants with the games’ functionality to control for learning effects, so these months were not analyzed. Performance in the third month was used as a baseline measure, assuming participants had reached their optimal level in each game by then. Thus, the third month was considered the initial reference. Performance from months 4 to 12 was used to monitor cognitive changes over time.

Convergent and Discriminant Validity of the Model

To study the convergent and discriminant validity of the model, global scores for executive functions and memory were used, employing both 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 showed a strong correlation with global cognition measures, such as the ADCS-PACC (r = 0.65), ADCS-PACC-plus-exe (r = 0.63), and MoCA (r = 0.47), and a moderate correlation with the MMSE (r = 0.42). Finally, a table of correlations between the NeuronUP EXE measure and some traditional measures is presented.

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%. Nearly all participants (94.6%) completed at least half of the training sessions. In summary, the following table shows the evolution of adherence over the 12 months of training.

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

Moreover, most participants (48 out of 56) completed an online survey about the intervention. In this survey, nearly all indicated that they had the necessary knowledge to use the platform, with more than 80% affirming that it was easy to use. Additionally, up to 70% of them considered that their motivation remained high throughout the study, deeming the frequency appropriate.

Conclusion

Based on the PENSA study, it was decided to study a cohort of SCD patients to prevent potential progression to a neurodegenerative disease. This study validated the creation of an executive functions measure based on cognitive performance in games conducted on the digital platform NeuronUP.

The study results support the validity of conducting these measurements through monthly remote monitoring, enabling the detection of changes in executive functions while minimizing learning effects. Minimization of learning effects is achieved by automatically adjusting difficulty to individual capacity, ensuring reliable measurements of each participant’s optimal performance after repeated testing. This suggests that this measure could be useful for overcoming limitations of traditional neuropsychological evaluation methods. Additionally, adherence to the cognitive training intervention was high, and participants rated the digital platform’s usefulness positively.

References

• 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, Rafael de la Torre. Intensive assessment of executive functions derived 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 characterization of subjective cognitive decline. Jessen, Frank et al. The Lancet Neurology, Volume 19, Issue 3, 271 – 278

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