Mechanisms and modulators of cognitive training gain transfer in cognitively healthy aging: study protocol of the AgeGain study

Background: Cognitively healthy older people can increase their performance in cognitive tasks through training. However, training effects are mostly limited to the trained task; thus, training effects only poorly transfer to untrained tasks or other contexts, which contributes to reduced adaptation abilities in aging. Stabilizing transfer capabilities in aging would increase the chance of persistent high performance in activities of daily living including longer independency, and prolonged active participation in social life. The trial AgeGain aims at elaborating the physiological brain mechanisms of transfer in aging and supposed major modulators of transfer capability, especially physical activity, cerebral vascular lesions, and amyloid burden. Methods: This 4-year interventional, multicenter, phase 2a cognitive and physical training study will enroll 237 cognitively healthy older subjects in four recruiting centers. The primary endpoint of this trial is the prediction of transfer of cognitive training gains. Secondary endpoints are the structural connectivity of the corpus callosum, Default Mode Network activity, brain-derived neurotrophic factors, motor fitness, and maximal oxygen uptake. Discussion: Cognitive transfer allows making use of cognitive training gains in everyday life. Thus, maintenance of transfer capability with aging increases the chance of persistent self-guidance and prolonged active participation in social life, which may support a good quality of life. The AgeGain study aims at identifying older people who will most benefit from cognitive training. It will increase the understanding of the neurobiological mechanisms of transfer in aging and will help in determining the impact of physical activity and sport as well as pathologic factors (such as cerebrovascular disease and amyloid load) on transfer capability.