The epidemiologic evidence suggests that experiences at all stages, even in late life, can impart such reserve. These findings support the possibility that it may be possible to intervene even later in life in order to impart reserve, slow age-related cognitive decline, and prolonged healthy aging. The most successful remediation approach to date has been aerobic exercise. Many controlled studies in elderly individuals have demonstrated that, in individuals with below median respiratory capacity, aerobic exercise that increases this respiratory capacity also results in increases in cognitive performance47, 48
. The results of cognitive intervention studies have been more mixed. In one of the largest such studies there was no evidence that training in one cognitive domain generalized to performance in two other domains. In addition, there is no convincing evidence that training resulted in any improvement in activities of daily living49
. More promising have been studies that have immersed subjects in complex gameplay. For example, Basak et al.50
had elders play a complex role-playing game, "Rise of Nations" for 23.5 hours, and demonstrated that gameplay was associated with improved performance on a wide range of cognitive tasks. Similarly, focused training has improved working memory capacity and shown transfer of training to nontrained working memory tasks51
. In schizophrenia, small effects of cognitive remediation were noted, particularly in stable patients and when combined with adjunctive rehabilitation52
. Similar conclusions about the limitations and promise of cognitive intervention were reached by a recent working group53
Our group has been working with another complex game, "Space Fortress," that was designed by human operations psychologists as a test bed for training approaches to teach young adults complex tasks54
. In research with young adults, one particular training approach produced excellent improvement in gameplay, but, more importantly, also showed transfer of training to other tasks. In this approach, which is called emphasis change training, players are instructed to focus on all of the features of the game, but to give specific emphasis to one particular feature during each individual game. By shifting emphasis from game to game, participants cannot fall into a fixed strategy. They must develop the ability to deal with the entire task as a whole – skills that might be termed attentional allocation or executive control. Younger people who learn to play the game using this training approach were more able to incorporate new demands while playing the game55
. In addition, they showed more successful performance on real-world tasks such as flight simulator or flight training performance56, 57
. In a preliminary study with older adults, we explored the capacity of the elders to learn to play the game, and the possibility that gameplay might improve cognitive performance58
. 90 subjects were divided into three groups: a non-gameplay condition, gameplay without emphasis change training, and gameplay with emphasis change training. The two gameplay groups played the game three times a week for 12 weeks. Interestingly, although the game itself was very challenging for the elders, there were few dropouts and performance improved over time. Analysis of various features of gameplay indicated that elders in the pure gameplay condition were not as focused on the key goals of the game as the emphasis change group; they were more likely to respond to signals for bonus points as opposed to attempt to destroy the space fortress. In contrast, the elders in the emphasis change condition were more likely to focus on features central to the game, in particular they were eventually more successful at destroying the space fortress than elders and the other group. Our primary cognitive measures were five tasks that involve executive control. On one of these tasks, a test of working memory, the emphasis change group showed greater improvement from pre- to post-testing than the other two groups. We consider this a promising finding, and are currently conducting a study which combines space fortress gameplay with aerobic exercise. By combining a cognitive intervention with aerobic exercise we are hoping for a synergistic effect. The aerobic exercise may in effect boost brain reserve, for example by improving plasticity via upregulation of BDNF. The cognitive intervention, in turn, may help increase CR by staying the efficiency of the cognitive networks underlying executive control. This cognitive data fit would be facilitated by the improved level of brain reserve.
More generally, the epidemiologic data clearly suggest that aspects of life experience can impart reserve against age- or disease-related pathology. However, the exact "recipe" for helping to create this reserve is still unknown. A generic recommendation would be to maintain educational and mentally stimulating activities throughout life59
. Specific recommendations await more focused, large-scale research interventions. The most meaningful endpoints for such an intervention would be slowed rate of cognitive decline in aging or reduced risk of developing Alzheimer's disease. No study to date has shown change in either of these endpoints. Optimally they would begin with cognitively intact elders, and follow them over a suitable period of time. Most likely, these studies should use multiple intervention strategies including exercise, cognitive stimulation and social stimulation. Studies using these endpoints will be very expensive because they will require a large number of participants and will have to be conducted over several years.