Impact of a Cognitive Intervention Enriched With Leisure Activities on Cognition, Daily Life Functioning and Brain Structure and Function in Persons With Subjective Cognitive Decline: The ENGAGE Program

In the absence of a cure for Alzheimer's disease (AD), there is paramount interest for non-pharmacological cognitive interventions that are designed to restore, increase, or optimize capacities and adaptation. Numerous epidemiological studies have shown that education, cognitively engaging leisure activities, and cognitively demanding professions are associated with a lower risk of cognitive decline and dementia. When estimating the proportion of AD cases attributable to modifiable risk factors, it was found that cognitive inactivity was the factor that contributed to many of the cases worldwide (19.1% or 6.5 million cases). Thus, the level of cognitive stimulation that individuals receive throughout their life is a critical protective factor against cognitive decline and AD, which suggests potentially powerful avenues for intervention. In a number of influential papers, Stern suggested that differences in cognitive lifestyle contribute to cognitive reserve, defined as the built-up resilience of the brain against the detrimental effect of age-related brain damage. Cognitive stimulation is thought to create richer brain networks and facilitate the recruitment of alternative regions or networks. Barnes and Yaffe projected that 1.375 million AD cases worldwide might be prevented by reducing by 25% the prevalence of cognitive inactivity. These findings have tremendous consequences when designing strategies against dementia. Thus, the goal of Team 10 is to design and test an innovative cognitive training program to increase cognitive reserve and reduce decline in persons with a high risk of AD.

Many studies have shown that cognitive training can increase cognitive abilities in healthy older adults, or persons with mild cognitive impairment (MCI). Studies with MCI also show that cognitive training in MCI results in greater brain activation and connectivity, as well as the recruitment of alternative networks, which supports the view that it contributes to the creation of cognitive reserve.

There are different types of cognitive interventions that are potentially available. Choosing the proper one necessitates a fine understanding of their mechanisms of action and their match to the individual's needs and capabilities. Furthermore, many of the existing programs have not received empirical support from studies relying on good quality methodology and there is a lack of evidence regarding their capacity to reduce cognitive decline and dementia. Hence, previous studies have been limited by some or all of the following methodological issues: 1) they most often relied on a small number of participants; 2) they had time-limited follow-up; 3) many did not use a randomized controlled design or provided limited information on their randomization process; 4) very few have assessed the participant characteristics that define best responders (i.e., the profile of individuals that benefit the most from the intervention). Another important aspect is that the programs that are typically used in those studies are often not optimally adapted to seniors' needs and preferences and are not grounded in real life, limiting adherence and generalization to everyday life. Emotional and cognitive engagement refers to participants enjoying as well as actively participating to the learning experience and has been shown to be a critical factor in determining learning outcomes. Thus, our program will be designed to promote engagement, which is absent in the previous studies. Finally, one other important gap is that there are still a lot that is unknown about the brain processes involved in these interventions and how they alter brain structure and/or function, especially in healthy older adults. Thus, an additional important issue is to understand the brain plasticity processes resulting from cognitive training. Brain plasticity refers to the remarkable ability of the central nervous system to spontaneously re-organize or expand during normal learning processes, or to self-repair in acute or progressive brain diseases. This is critical given that an increasing number of studies has revealed that non-pharmacological interventions can have a positive impact in AD and that intermediate mechanisms of neural plasticity and functional compensation likely modulate the detrimental effect of the disease on symptoms.

The investigators will develop ENGAGE, a program to increase cognitive reserve and reduce decline over a 2-year period in persons with a high risk of AD. The investigators propose a multi-faceted intervention program meant to increase reserve by providing cognitive stimulation through participation in engaging cognitive and leisure activities. This ground-breaking program proposes for the first time to combine (1) hands-on training to improve memory and attention through teaching strategies to optimize efficiency, and (2) selected engaging leisure activities that are known to increase brain functions in younger and older adults, such as learning music, learning a second language, and playing carefully selected casual video-games. There are many reasons to combine brain training and leisure activities. First, one limitation of brain training for memory and attention is that participants sometimes fail to generalize the strategies learned in a lab setting and to apply them in their everyday life. Thus, the investigators propose to practice these strategies in the leisure activities, e.g., to learn information relevant to the music or Spanish lessons. Providing natural, ecologically-valid situations to apply and practice the cognitive strategies is done to train participants to use them more spontaneously outside the formal brain training setting. Second, these leisure activities correspond to the cognitively demanding activities that are identified as protective in epidemiological studies, and thus likely to promote brain plasticity. Third, they are attractive and will therefore improve motivation for training. The enjoyable characteristic of the leisure activities will also make them attractive to older adults with lower education, a segment of population which may especially benefit from such intervention. Finally, if proven effective, the training program will have the important advantage of being easy to implement in the community and will be relatively low-cost relative to formal health care. Another objective of this research project is to provide recommendations regarding profiles of participants which may benefit the most from the intervention. The investigators will thus measure whether the effect of the training is modulated by sex differences as women have been suggested to have less brain reserve than men as well as age, education or socio-cultural background, lifestyle habits, genetic factors and other markers of cognitive reserve.

The research team benefits from the contribution of clinicians and researchers from across Canada who will combine their unique expertise on brain training and on the effects of leisure activities on the brain to provide the most innovative and potentially meaningful approach to cognitive intervention. Overall, this innovative program will provide brain training through specific cognitive training and carefully selected leisure activities that are known to have a positive impact on cognition and will be particularly attractive to older adults from varied backgrounds.