Tag Archives: healthy aging

Morphological changes of the aging brain

During healthy aging, the brain experiences complex structural and biochemical changes, including modification in dendritic morphology, synaptic connectivity (Anderson and Rutledge, 1996), Ca2+ dysregulation (Toescu et al., 2004), gene expression (for review see Burke and Barnes, 2006) and a decrease in the availability and level of neurotransmitters (Roth and Joseph, 1994). Cholinergic and dopaminergic reductions are particularly pronounced compromising motor, attention, and memory processes (Volkow et al., 1998; Braver and Barch, 2002). Furthermore, extensive studies reported that the function of the dopaminergic system gradually declines as we grow older due to degeneration of dopaminergic neurons and receptors (Zaman et al., 2008).

Age-related decreases in white matter integrity appear to be a common process in the brain (Resnick et al., 2003; Stadlbauer et al., 2008). Recent morphological studies using diffusion tensor imaging (DTI, for review see Pierpaoli et al., 1996) in old healthy subjects have consistently shown a correlation between aging and reduction of fractional anisotropy, suggesting a rarefaction of directionally oriented axonal membranes, and increased mean diffusivity reflecting an alteration in cellular membranes and other structures hindering diffusion (Sullivan and Pfefferbaum, 2006).

These age-related differences in white matter integrity are seen throughout the brain, with an increasing magnitude of the difference in anterior white matter structures compared to posterior regions, which most authors refer to as a “anterior–posterior gradient,” with age-related changes occurring earlier in the frontal lobe (Bennett et al., 2010). The corpus callosum represents the largest white matter structure connecting the two hemispheres in the brain. Age-related changes in the topology of the corpus callosum primarily affect the genus; however, recent studies using more sensitive techniques of DTI also demonstrated changes in the splenium (Bastin et al., 2010).

Until now, there is no consensus of the etiology and the functional repercussion of these changes in white matter structure, but recent data from healthy individuals and patients with mild cognitive impairments and dementia converge on highlighting correlations between cognitive performance and fractional anisotropy (Persson et al., 2006), indicating that the decline in white matter might be associated with cognitive impairment.

Healthy aging

Healthy aging is accompanied by changes in cognitive and motor functions that result in impairment of activities of daily living. This process involves a number of modifications in the brain and is associated with metabolic, structural, and physiological changes; some of these serving as adaptive responses to the functional declines. Up to date there are no universally accepted strategies to ameliorate declining functions in this population. An essential basis to develop such strategies is a better understanding of neuroplastic changes during healthy aging. In this context, non-invasive brain stimulation techniques, such as transcranial direct current or transcranial magnetic stimulation, provide an attractive option to modulate cortical neuronal assemblies, even with subsequent changes in neuroplasticity. Thus, in the present review we discuss the use of these techniques as a tool to study underlying cortical mechanisms during healthy aging and as an interventional strategy to enhance declining functions and learning abilities in aged subjects.

During the last century, average life expectancy in developed countries was prolonged approximately 30 years. In addition, a significant decline in fertility generated a shift in the distribution of the population with important socio-economic, political, and public health consequences (UN-Report, 2005). The fact that there are more old people today than ever before, and that this tendency is expected to increase further, underlines the importance of understanding the mechanisms of healthy aging as well as developing novel innovative strategies to adapt for age-relate declines.

Besides age-associated diseases, like cardiovascular diseases or cancer (Balducci and Extermann, 2000), age-related neurobiological changes with consecutive declines in cognitive functions, perceptual, and motor abilities impair activities of daily living, independence, and quality of life (Logsdon et al., 2002; Craik and Bialystok, 2006). In cognition, age-related deficits encompass multiple domains, including attention, memory, reasoning, and executive functions (Celsis, 2000; Hogan et al., 2006). Age-related motor impairments are also ubiquitous, with deficits in the planning, the execution and the control of movement (Krampe et al., 2002; Sawaki et al., 2003). Physiologically, aging consists of a dynamic process in the brain, involving a number of modifications associated with metabolic, structural, and functional changes, part of them hypothesized as adaptive responses to the functional declines (Burke and Barnes, 2006).

In recent years, different forms of non-invasive brain stimulation techniques have been explored in patients and healthy volunteers offering the attractive option to modulate neuronal plasticity and to improve behavior and learning processes (Hummel and Cohen, 2006; Nitsche et al., 2008; Reis et al., 2009). In the present review, we will focus on studies using non-invasive brain stimulation techniques to evaluate cortical mechanisms during healthy aging, especially the one involved in preserving cognitive and motor funcNon-2010.00149tions. Furthermore, the novel field of applying these techniques to increase behavior, neuronal plasticity and learning, e.g., in the sensorimotor domain as a model system, will be presented. Rather than attempting to be comprehensive in terms of reviewed work, this article intends to provide a clearly structured framework of the application of these techniques to understand and support plastic changes in the aging population.