Reducing fall risk with combined motor and cognitive training in elderly fallers

Background. Falling is a major clinical problem in elderly people, demanding effective solutions. At present, the only effective intervention is motor training of balance and strength. Executive function-based training (EFt) might be effective at preventing falls according to evidence showing a relationship between executive functions and gait abnormalities. The aim was to assess the effectiveness of a motor and a cognitive treatment developed within the EU co-funded project I-DONT-FALL. Methods. In a sample of 481 elderly people at risk of falls recruited in this multicenter randomised controlled trial, the effectiveness of a motor treatment (pure motor or mixed with EFt) of 24 one-hour sessions delivered through an i-Walker with a non-motor treatment (pure EFt or control condition) was evaluated. Similarly, a 24 one-hour session cognitive treatment (pure EFt or mixed with motor training), delivered through a touch-screen computer was compared with a non-cognitive treatment (pure motor or control condition). Results. Motor treatment, particularly when mixed with EFt, reduced significantly fear of falling (F(1,478) = 6.786, p = 0.009) although to a limited extent (ES -0.25) restricted to the period after intervention. Conclusions. This study suggests the effectiveness of motor treatment empowered by EFt in reducing fear of falling.Peer ReviewedPostprint (published version

A pilot study on brain plasticity of functional connectivity modulated by cognitive training in mild Alzheimer's disease and mild cognitive impairment

Alzheimer's disease (AD) alters the functional connectivity of the default mode network (DMN) but also the topological properties of the functional connectome. Cognitive training (CT) is a tool to slow down AD progression and is likely to impact on functional connectivity. In this pilot study, we aimed at investigating brain functional changes after a period of CT and active control (AC) in a group of 26 subjects with mild AD (mAD), 26 with amnestic mild cognitive impairment (aMCI), and a control group of 29 healthy elderly (HE) people. They all underwent a CT and AC in a counterbalanced order following a crossover design. Resting-state functional MRI and neuropsychological testing were acquired before and after each period. We tested post-CT and post-AC changes of cognitive abilities, of the functional connectivity of the DMN, and of topological network properties derived from graph theory and network-based statistics. Only CT produced functional changes, increasing the functional connectivity of the posterior DMN in all three groups. mAD also showed functional changes in the medial temporal lobe and topological changes in the anterior cingulum, whereas aMCI showed more widespread topological changes involving the frontal lobes, the cerebellum and the thalamus. Our results suggest specific functional connectivity changes after CT for aMCI and mAD

Neuromorphic-Based Neuroprostheses for Brain Rewiring: State-of-the-Art and Perspectives in Neuroengineering.

Neuroprostheses are neuroengineering devices that have an interface with the nervous system and supplement or substitute functionality in people with disabilities. In the collective imagination, neuroprostheses are mostly used to restore sensory or motor capabilities, but in recent years, new devices directly acting at the brain level have been proposed. In order to design the next-generation of neuroprosthetic devices for brain repair, we foresee the increasing exploitation of closed-loop systems enabled with neuromorphic elements due to their intrinsic energy efficiency, their capability to perform real-time data processing, and of mimicking neurobiological computation for an improved synergy between the technological and biological counterparts. In this manuscript, after providing definitions of key concepts, we reviewed the first exploitation of a real-time hardware neuromorphic prosthesis to restore the bidirectional communication between two neuronal populations in vitro. Starting from that 'case-study', we provide perspectives on the technological improvements for real-time interfacing and processing of neural signals and their potential usage for novel in vitro and in vivo experimental designs. The development of innovative neuroprosthetics for translational purposes is also presented and discussed. In our understanding, the pursuit of neuromorphic-based closed-loop neuroprostheses may spur the development of novel powerful technologies, such as 'brain-prostheses', capable of rewiring and/or substituting the injured nervous system

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits

Reducing Fall Risk with Combined Motor and Cognitive Training in Elderly Fallers

Background. Falling is a major clinical problem in elderly people, demanding effective solutions. At present, the only effective intervention is motor training of balance and strength. Executive function-based training (EFt) might be effective at preventing falls according to evidence showing a relationship between executive functions and gait abnormalities. The aim was to assess the effectiveness of a motor and a cognitive treatment developed within the EU co-funded project I-DONT-FALL. Methods. In a sample of 481 elderly people at risk of falls recruited in this multicenter randomised controlled trial, the effectiveness of a motor treatment (pure motor or mixed with EFt) of 24 one-hour sessions delivered through an i-Walker with a non-motor treatment (pure EFt or control condition) was evaluated. Similarly, a 24 one-hour session cognitive treatment (pure EFt or mixed with motor training), delivered through a touch-screen computer was compared with a non-cognitive treatment (pure motor or control condition). Results. Motor treatment, particularly when mixed with EFt, reduced significantly fear of falling (F(1,478) = 6.786, p = 0.009) although to a limited extent (ES −0.25) restricted to the period after intervention. Conclusions. This study suggests the effectiveness of motor treatment empowered by EFt in reducing fear of falling

Classifying life course trajectories: A comparison of latent class and sequence analysis

In this article we compare two techniques that are widely used in the analysis of life course trajectories, latent class analysis (LCA) and sequence analysis (SA). In particular, we focus on the use of these techniques as devices to obtain classes of individual life course trajectories. We first compare the consistency of the classification obtained via the two techniques using an actual dataset on the life course trajectories of young adults. Then, we adopt a simulation approach to measure the ability of these two methods to correctly classify groups of life course trajectories when specific forms of "random" variability are introduced within pre-specified classes in an artificial dataset. In order to do so, we introduce simulation operators that have a life course and/or observational meaning. Our results contribute on the one hand to outline the usefulness and robustness of findings based on the classification of life course trajectories through LCA and SA, on the other hand to illuminate the potential pitfalls of actual applications of these techniques.sequence analysis; latent class analysis; life course analysis; categorical time series

Classifying life course trajectories:a comparison of latent class and sequence analysis

We compare two techniques that are widely used in the analysis of life course trajectories: latent class analysis and sequence analysis. In particular, we focus on the use of these techniques as devices to obtain classes of individual life course trajectories. We first compare the consistency of the classification that is obtained via the two techniques by using a data set on the life course trajectories of young adults. Then, we adopt a simulation approach to measure the ability of these two methods to classify groups of life course trajectories correctly when specific forms of random variability are introduced within prespecified classes in an artificial data set. To do so, we introduce simulation operators that have a life course and/or observational meaning. Our results contribute on the one hand to outline the usefulness and robustness of findings based on the classification of life course trajectories through latent class analysis and sequence analysis and on the other hand to illuminate the potential pitfalls in applications of these techniques

Slowing of Information Processing in Alzheimer Disease

Objective: To use Sternberg's Additive Factor Method to determine whether patients with mild Alzheimer disease (AD) are slow in information processing and/or response execution. Methods: We gave an odd-even categorization task to 16 patients with probable mild AD and 17 age-matched healthy controls. We recorded reaction and movement times to stimuli varying for noise, target set size, stimulus-response compatibility, and fore-period interval, to probe the cognitive and motor stages of information processing. Results: Both groups performed the task accurately, indicating good preservation of odd-even categorization in mild AD. The AD group's reaction times were similar to the controls' across conditions, and not selectively affected in any of the cognitive stages of the Additive Factor Method. However, the AD group's movement times were slower than the controls' across conditions. Conclusions: AD patients' performance on a task requiring categorization ability was slowed more by motor than cognitive components of information processing. When evaluating the performance of patients with AD in reaction-time paradigms, we should not attribute group differences solely to differences in cognitive processing. Execution components should also be considered

The right frontopolar cortex is involved in visual-spatial prospective memory.

The involvement of frontopolar cortex in mediating prospective memory processes has been evidenced by various studies, mainly by means of neuroimaging techniques. Recently, one transcranial magnetic stimulation study documented that transient inhibition of left Brodmann Area (BA) 10 impaired verbal prospective memory. This result raises the issue of whether the BA 10 involvement in prospective memory functioning may be modulated by the physical characteristics of the stimuli used. The present study aimed to investigate the role of the frontopolar cortex in visual-spatial PM by means of the application of inhibitory theta-burst stimulation. Twelve volunteers were evaluated after inhibitory theta-burst stimulation over left BA 10, right BA10 and CZ (control condition). In the prospective memory procedure, sequences of four spatial positions (black squares) each were presented. During the inter-sequence delay, subjects had to reproduce the sequence in the observed order (ongoing task forward) or the reverse order (backward). At the occurrence of a target position, subjects had to press a key on the keyboard (prospective memory score). Recall and recognition of the target positions were also tested. We found that prospective memory accuracy was lower after theta-burst stimulation over right BA10 than CZ (p<0.01), whereas it was comparable in left BA10 and CZ conditions. No significant difference was found among the three conditions on recall and recognition of target positions and on ongoing task performance. Our findings provide a novel strong evidence for a specific involvement of right frontopolar cortex in visual-spatial prospective memory. In the context of previous data providing evidence for left BA 10 involvement in verbal prospective memory, our results also suggest material-specific lateralization of prospective memory processes in BA 10