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

Abstract

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.

Trial registration: German Clinical Trials Register (DRKS), ID: DRKS00013077 . Registered on 19 November 2017.

Keywords: Cognitive training; Neurobiological mechanisms and modulators of transfer; Normal aging; Physical training; Transfer of training gains.

Fig. 1

Age-relation of callosal structural integrity (a) and hypothetical association of callosal structural integrity with transfer probability in cognitively healthy elderly (b). a Fractional anisotropy (FA) of the genu and corpus of the corpus callosum decreases with age in cognitively healthy elderly [11]; higher FA values indicate better structural integrity. b Hypothetical probability of transfer decreases with decreased structural integrity of the corpus callosum

Fig. 2

Joint models of brain structural (b) and functional (a) mechanisms for the explanation of transfer capability in healthy aging. a Fractional anisotropy (FA) of the genu and corpus of the corpus callosum decreases with age in cognitively healthy elderly; higher FA values indicate better structural integrity. Structural integrity of the corpus callosum predicts transfer capability determined by stable success (ST) versus non-transfer (NT) [11]. Categorial transfer was defined as an increase of fluid intelligence performance (transfer task) beyond the retest effect of untrained healthy elderly after successful training of logical reasoning skills [11]. Taken the corpus callosum structural integrity (FA) as surrogate of transfer capability, the model delineates a threshold of structural integrity (− − −) dividing ST and NT. Moreover, the model suggests that (e.g., z-standardized) FA values could be taken as dimensional predictors of the transfer amount in single subjects. b Increased hemispheric cooperation/HAROLD as measured by BOLD lateralization index [70] may mediate transfer capabilities in older adults since both are associated with the structural integrity of the corpus callosum. NT subjects may show less hemispheric cooperation compared to ST subjects at baseline thereby predicting less transfer success while both groups show the general pattern of lateralized to bilateral to disengagement of activity with increasing task demand [17]

Fig. 3

The Hybrid Response Inhibition task. Participants are asked to press a button corresponding to the pointing direction of an arrow. Go trials consist of congruent trials; inhibition trials consist of incongruent trials (interference inhibition), occurrence of a no-go stimulus (blue ellipse; action withholding), or of a stop-signal (blue ellipse after a varying stop-signal delay; action cancelation)