Towards Combinatorial Approaches for Preserving Cognitive Fitness in Aging.

Aging-related cognitive decline represents a critical risk factor for the development of dementia and is associated with global neurophysiological changes. It is imperative to act early, while the neural reserve is still sufficient, to prevent or postpone cognitive decline. Given that no significant modifying pharmacological intervention is available, a focus on pharmacological agents alone seems insufficient. We argue that combinations of different approaches are most effective in stimulating long-lasting molecular changes that restore, promote, and preserve cognition through the modulation of cognitively relevant neurotransmitter systems that ultimately converge in driving neurotrophic signaling. Considering recent technological advances, several interventions apart from cognitive enhancing drugs, including noninvasive brain stimulation, physical exercise/vascular interventions, and cognitive training, seem well positioned to possibly prolong optimal brain functioning upon aging.