Brain Plasticity and Functional Losses in the Aged: Scientific Bases for a Novel Intervention

University of California, San Francisco, San Francisco, California, United States
Progress in brain research (Impact Factor: 2.83). 02/2006; 157:81-109. DOI: 10.1016/S0079-6123(06)57006-2
Source: PubMed


Aging is associated with progressive losses in function across multiple systems, including sensation, cognition, memory, motor control, and affect. The traditional view has been that functional decline in aging is unavoidable because it is a direct consequence of brain machinery wearing down over time. In recent years, an alternative perspective has emerged, which elaborates on this traditional view of age-related functional decline. This new viewpoint--based upon decades of research in neuroscience, experimental psychology, and other related fields--argues that as people age, brain plasticity processes with negative consequences begin to dominate brain functioning. Four core factors--reduced schedules of brain activity, noisy processing, weakened neuromodulatory control, and negative learning--interact to create a self-reinforcing downward spiral of degraded brain function in older adults. This downward spiral might begin from reduced brain activity due to behavioral change, from a loss in brain function driven by aging brain machinery, or more likely from both. In aggregate, these interrelated factors promote plastic changes in the brain that result in age-related functional decline. This new viewpoint on the root causes of functional decline immediately suggests a remedial approach. Studies of adult brain plasticity have shown that substantial improvement in function and/or recovery from losses in sensation, cognition, memory, motor control, and affect should be possible, using appropriately designed behavioral training paradigms. Driving brain plasticity with positive outcomes requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis, in a behavioral context designed to re-engage and strengthen the neuromodulatory systems that control learning in adults, with the goal of increasing the fidelity, reliability, and power of cortical representations. Such a training program would serve a substantial unmet need in aging adults. Current treatments directed at age-related functional losses are limited in important ways. Pharmacological therapies can target only a limited number of the many changes believed to underlie functional decline. Behavioral approaches focus on teaching specific strategies to aid higher order cognitive functions, and do not usually aspire to fundamentally change brain function. A brain-plasticity-based training program would potentially be applicable to all aging adults with the promise of improving their operational capabilities. We have constructed such a brain-plasticity-based training program and conducted an initial randomized controlled pilot study to evaluate the feasibility of its use by older adults. A main objective of this initial study was to estimate the effect size on standardized neuropsychological measures of memory. We found that older adults could learn the training program quickly, and could use it entirely unsupervised for the majority of the time required. Pre- and posttesting documented a significant improvement in memory within the training group (effect size 0.41, p<0.0005), with no significant within-group changes in a time-matched computer using active control group, or in a no-contact control group. Thus, a brain-plasticity-based intervention targeting normal age-related cognitive decline may potentially offer benefit to a broad population of older adults.

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Available from: Henry Mahncke, Jul 30, 2014
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    • "Programs with the most robust empirical evidence for transfer effects on cognitive functions in older adults were implemented in this system. A Greek version of a well-validated neuroplasticity-based training program (Brain Fitness Program; Posit Science Corporation, San Francisco, CA, USA) was used as the cognitive training component (Mahncke et al., 2006a). "
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    ABSTRACT: Physical as well as cognitive training interventions improve specific cognitive functions but effects barely generalize on global cognition. Combined physical and cognitive training may overcome this shortcoming as physical training may facilitate the neuroplastic potential which, in turn, may be guided by cognitive training. This study aimed at investigating the benefits of combined training on global cognition while assessing the effect of training dosage and exploring the role of several potential effect modifiers. In this multi-center study, 322 older adults with or without neurocognitive disorders (NCDs) were allocated to a computerized, game-based, combined physical and cognitive training group (n = 237) or a passive control group (n = 85). Training group participants were allocated to different training dosages ranging from 24 to 110 potential sessions. In a pre-post-test design, global cognition was assessed by averaging standardized performance in working memory, episodic memory and executive function tests. The intervention group increased in global cognition compared to the control group, p = 0.002, Cohen's d = 0.31. Exploratory analysis revealed a trend for less benefits in participants with more severe NCD, p = 0.08 (cognitively healthy: d = 0.54; mild cognitive impairment: d = 0.19; dementia: d = 0.04). In participants without dementia, we found a dose-response effect of the potential number and of the completed number of training sessions on global cognition, p = 0.008 and p = 0.04, respectively. The results indicate that combined physical and cognitive training improves global cognition in a dose-responsive manner but these benefits may be less pronounced in older adults with more severe NCD. The long-lasting impact of combined training on the incidence and trajectory of NCDs in relation to its severity should be assessed in future long-term trials.
    Frontiers in Aging Neuroscience 08/2015; 7(152). DOI:10.3389/fnagi.2015.00152 · 4.00 Impact Factor
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    • "These questions should be taken into account when considering problems of sensorimotor integration in elderly subjects or patients, and when designing simulation models of human balance. In perspective, aged persons (Nardone et al., 1995), Parkinsonian patients, and patients affected by peripheral neuropathies, and blind subjects (Bugnariu and Fung, 2007; Striem-Amit et al., 2012; Maidenbaum et al., 2014) represent examples of different conditions liable to affect the variable at hand, i.e., the sensori-motor processing time, due to progressive losses in function across multiple systems, including sensation, cognition, memory, motor control (Mahncke et al., 2006; De Nunzio et al., 2007; Nardone et al., 2007; Konczak et al., 2008, 2012; Schmid et al., 2008; Aman et al., 2014). A rough attempt at identifying possible steps of the sensorimotor integration process is reported in graphic form in Figure 2, where different reweighting coefficients are assumed for different modalities of posturestabilizing information. "
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    ABSTRACT: Maintaining equilibrium is basically a sensorimotor integration task. The central nervous system (CNS) continually and selectively weights and rapidly integrates sensory inputs from multiple sources, and coordinates multiple outputs. The weighting process is based on the availability and accuracy of afferent signals at a given instant, on the time-period required to process each input, and possibly on the plasticity of the relevant pathways. The likelihood that sensory inflow changes while balancing under static or dynamic conditions is high, because subjects can pass from a dark to a well-lit environment or from a tactile-guided stabilization to loss of haptic inflow. This review article presents recent data on the temporal events accompanying sensory transition, on which basic information is fragmentary. The processing time from sensory shift to reaching a new steady state includes the time to (a) subtract or integrate sensory inputs; (b) move from allocentric to egocentric reference or vice versa; and (c) adjust the calibration of motor activity in time and amplitude to the new sensory set. We present examples of processes of integration of posture-stabilizing information, and of the respective sensorimotor time-intervals while allowing or occluding vision or adding or subtracting tactile information. These intervals are short, in the order of 1-2 s for different postural conditions, modalities and deliberate or passive shift. They are just longer for haptic than visual shift, just shorter on withdrawal than on addition of stabilizing input, and on deliberate than unexpected mode. The delays are the shortest (for haptic shift) in blind subjects. Since automatic balance stabilization may be vulnerable to sensory-integration delays and to interference from concurrent cognitive tasks in patients with sensorimotor problems, insight into the processing time for balance control represents a critical step in the design of new balance- and locomotion training devices.
    Frontiers in Systems Neuroscience 10/2014; 8:190. DOI:10.3389/fnsys.2014.00190
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    • "The most widely known and largest (n = 2,802) CT trial in healthy adults, the ACTIVE (Advanced Cognitive Training for Independent and Vital Elderly) trial, identified immediate gains on corresponding cognitive domains [40]. Subsequent CT trials in healthy adults also indicate significant improvements in cognitive function compared to baseline [41] [42] [43]. Therefore, in healthy adults, CT can enhance cognitive function and may potentially be effective as a preventative intervention. "
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    ABSTRACT: There is much interest in early intervention for the prevention or postponement of dementia in Alzheimer's disease (AD). The results of drugs trials in this regard have thus far been disappointing, and non-pharmacological interventions are receiving increased attention. One such intervention is complex cognitive activity. Evidence from epidemiological studies suggests that participation in stimulating mental activities is associated with lowered dementia risk. The introduction of novel and complex cognitive interventions to healthy adults and those with cognitive impairment may represent an efficacious treatment option to improve cognition, lower dementia incidence, and slow rate of decline. This review examines the evidence for restorative cognitive training (CT) and addresses a number of clinically relevant issues regarding cognitive benefit and its transfer and persistence. Although the number of randomized controlled trials is limited, preliminary evidence suggests that CT may provide immediate and longer term cognitive benefits which generalize to non-trained domains and non-cognitive functions, with supervised small group multi-domain training providing greatest benefits. Possible neuroplastic mechanisms are discussed, and recommendations for further research and clinical implementation provided.
    Journal of Alzheimer's disease: JAD 08/2014; 42(Suppl 4):S551-S559. DOI:10.3233/JAD-141302 · 4.15 Impact Factor
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