Abstract
Deterioration of motor and cognitive performance with advancing age is well documented, but its cause remains unknown. Animal studies dating back to the late 1970s reveal that age-associated neurocognitive changes are linked to age-dependent changes in synaptic plasticity, including alterations of long-term potentiation and depression (LTP and LTD). Non-invasive brain stimulation techniques enable measurement of LTP- and LTD-like mechanisms of plasticity, in vivo, in humans, and may thus provide valuable insights. We examined the effects of a 40-s train of continuous theta-burst stimulation (cTBS) to the motor cortex (600 stimuli, three pulses at 50 Hz applied at a frequency of 5 Hz) on cortico-spinal excitability as measured by the motor evoked potentials (MEPs) induced by single-pulse transcranial magnetic stimulation before and after cTBS in the contralateral first dorsal interosseus muscle. Thirty-six healthy individuals aged 19–81 years old were studied in two sites (Boston, USA and Barcelona, Spain). The findings did not differ across study sites. We found that advancing age is negatively correlated with the duration of the effect of cTBS (r = −0.367; p = 0.028) and the overall amount of corticomotor suppression induced by cTBS (r = −0.478; p = 0.003), and positively correlated with the maximal suppression of amplitude on motor evoked responses in the target muscle (r = 0.420; p = 0.011). We performed magnetic resonance imaging (MRI)-based individual morphometric analysis in a subset of subjects to demonstrate that these findings are not explained by age-related brain atrophy or differences in scalp-to-brain distance that could have affected the TBS effects. Our findings provide empirical evidence that the mechanisms of cortical plasticity area are altered with aging and their efficiency decreases across the human lifespan. This may critically contribute to motor and possibly cognitive decline.
Highlights
The average age of the world’s population is increasing at an unprecedented rate
We examined the effects of a 40-s train of continuous theta-burst stimulation to the motor cortex (600 stimuli, three pulses at 50 Hz applied at a frequency of 5 Hz) on cortico-spinal excitability as measured by the motor evoked potentials (MEPs) induced by single-pulse transcranial magnetic stimulation before and after cTBS in the contralateral first dorsal interosseus muscle.Thirty-six healthy individuals aged 19–81 years old were studied in two sites (Boston, USA and Barcelona, Spain)
Our findings provide empirical evidence that the mechanisms of cortical plasticity area are altered with aging and their efficiency decreases across the human lifespan.This may critically contribute to motor and possibly cognitive decline
Summary
The average age of the world’s population is increasing at an unprecedented rate. Demographic projections suggest that the number of people aged over 65 years will nearly triple by 2050, accounting for 14% of the world and 20% of the US population (Lutz et al, 2008). Aging is the major risk factor for Alzheimer’s disease (AD) and is associated with a more or less pronounced decline of many cognitive, motor, and other brain functions (e.g., Deary et al, 2009). This has been behaviorally well-established for decades (e.g., Feier and Gerstman, 1980), but it is unclear that functional decline is an obligatory consequence of aging and the underlying neurophysiologic correlates remain elusive. A greater understanding of the neurobiology underlying age-related decline of function is urgently needed, as it may lead to novel interventions to prevent cognitive decline and minimize the consequences of AD. Unless we work to reduce age-related functional decline and the impact of AD, we will succumb to the staggering personal, social, and economic burden of aging and dementia
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