There are declines with age in speed of processing, working memory, inhibitory function, and long-term memory, as well as decreases in brain structure size and white matter integrity. In the face of these decreases, functional imaging studies have demonstrated, somewhat surprisingly, reliable increases in prefrontal activation. To account for these joint phenomena, we propose the scaffolding theory of aging and cognition (STAC). STAC provides an integrative view of the aging mind, suggesting that pervasive increased frontal activation with age is a marker of an adaptive brain that engages in compensatory scaffolding in response to the challenges posed by declining neural structures and function. Scaffolding is a normal process present across the lifespan that involves use and development of complementary, alternative neural circuits to achieve a particular cognitive goal. Scaffolding is protective of cognitive function in the aging brain, and available evidence suggests that the ability to use this mechanism is strengthened by cognitive engagement, exercise, and low levels of default network engagement.

The most unexpected and intriguing result from functional brain imaging studies of cognitive aging is evidence for age-related overactivation: greater activation in older adults than in younger adults, even when performance is age-equivalent. Here we examine the hypothesis that age-related overactivation is compensatory and discuss the compensation-related utilization of neural circuits hypothesis (CRUNCH). We review evidence that favors a compensatory account, discuss questions about strategy differences, and consider the functions that may be served by overactive brain areas. Future research directed at neurocognitively informed training interventions may augment the potential for plasticity that persists into the later years of the human lifespan.

Human neuroimaging research on cognitive aging has brought significant advances to our understanding of the neural mechanisms underlying age-related cognitive decline and successful aging. However, interpreting age-related changes and differences in brain structure, activation, and functional connectivity is an ongoing challenge. Ambiguous terminology is a major source of this challenge. For example, the terms ‘compensation,’ ‘maintenance,’ and ‘reserve’ are used in different ways and researchers disagree about the kinds of evidence or patterns of results required to interpret findings related to these concepts. As such inconsistencies can impede theoretical and empirical progress, we here aim to clarify these key terms and to propose consensual definitions of maintenance, reserve, and compensation.

Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections. Major advances in the understanding of neuroplasticity have to date yielded few established interventions. To advance the translation of neuroplasticity research towards clinical applications, the National Institutes of Health Blueprint for Neuroscience Research sponsored a workshop in 2009. Basic and clinical researchers in disciplines from central nervous system injury/stroke, mental/addictive disorders, paediatric/developmental disorders and neurodegeneration/ageing identified cardinal examples of neuroplasticity, underlying mechanisms, therapeutic implications and common denominators. Promising therapies that may enhance training-induced cognitive and motor learning, such as brain stimulation and neuropharmacological interventions, were identified, along with questions of how best to use this body of information to reduce human disability. Improved understanding of adaptive mechanisms at every level, from molecules to synapses, to networks, to behaviour, can be gained from iterative collaborations between basic and clinical researchers. Lessons can be gleaned from studying fields related to plasticity, such as development, critical periods, learning and response to disease. Improved means of assessing neuroplasticity in humans, including biomarkers for predicting and monitoring treatment response, are needed. Neuroplasticity occurs with many variations, in many forms, and in many contexts. However, common themes in plasticity that emerge across diverse central nervous system conditions include experience dependence, time sensitivity and the importance of motivation and attention. Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.

Age-related decline in working memory figures prominently in theories of cognitive aging. However, the effects of aging on the neural substrate of working memory are largely unknown. Positron emission tomography (PET) was used to investigate verbal and spatial short-term storage (3 sec) in older and younger adults. Previous investigations with younger subjects performing these same tasks have revealed asymmetries in the lateral organization of verbal and spatial working memory. Using volume of interest (VOI) analyses that specifically compared activation at sites identified with working memory to their homologous twin in the opposite hemisphere, we show pronounced age differences in this organization, particularly in the frontal lobes: In younger adults, activation is predominantly left lateralized for verbal working memory, and right lateralized for spatial working memory, whereas older adults show a global pattern of anterior bilateral activation for both types of memory. Analyses of frontal subregions indicate that several underlying patterns contribute to global bilaterality in older adults: most notably, bilateral activation in areas associated with rehearsal, and paradoxical laterality in dorsolateral prefrontal sites (DLPFC; greater left activation for spatial and greater right activation for verbal). We consider several mechanisms that could account for these age differences including the possibility that bilateral activation reflects recruitment to compensate for neural decline.