Background. Executive function (EF) deficits may increase fall risk, even among older adults with no overt cognitive impairment. Indeed, the effects of dual tasking (DT) on gait, a challenge to ...executive control, are more exaggerated in persons with a history of falls. Prospective evidence is, however, lacking. Methods. We prospectively evaluated whether EF predicts falls over a 2-year period among 262 community-living, healthy, and well-functioning older adults, focusing on the 201 who reported no falls during the previous year. At baseline, participants completed a computerized cognitive battery that generated an index of EF and other cognitive domains. Gait was assessed using performance-based tests and by quantifying walking during single- and dual-task conditions. Results. The 262 participants (mean age: 76.3 ± 4.3 years, 60.3% women) had intact cognitive function on testing, a low comorbidity index, and good mobility. The EF index predicted future falls. Among those who reported no previous falls, participants in the worst EF quartile were three times more likely to fall during the 2 years of follow-up, and they were more likely to transition from nonfaller to faller sooner. DT gait variability also predicted future falls and multiple falls, whereas other measures of cognitive function, gait, and mobility did not. Conclusions. Among healthy older adults, individuals with poorer EF are more prone to falls. Higher-level cognitive functions such as those regulated by the frontal lobes are apparently needed for safe everyday navigation that demands multitasking. Optimal screening, early detection, and treatment of falls should, apparently, also target this cognitive domain.
•In contrast to younger adults, older adults recruit the prefrontal cortex during simple tasks.•Neural activation increases with task complexity, similarly, in young and older adults.•Higher ...prefrontal activation is associated with increased gait variability in older adults.
Deficits in cognitive domains, in particular, those related to the prefrontal cortex, contribute to diminished walking performance in complex conditions in older age. Studies using functional near infra-red spectroscopy (fNIRS) reported inconsistent findings of brain activation age-related changes in response to increased task demands. We aimed to study the effects of aging on gait and prefrontal activation in complex walking tasks with internal and external task demands.
Twenty-three healthy young adults (30.9±3.7yrs) and 20 healthy older adults (69.7±5.8yrs) participated in this study. Gait and prefrontal activation were assessed during three walking conditions: (1) usual walking, (2) dual tasking (internal task demands) and, (3) obstacle negotiation (external task demands). fNIRS measured changes in oxygenated hemoglobin concentrations in the prefrontal cortex.
Several gait measures were worse in older compared to younger adults under all walking conditions (p<0.005). Even at the lowest level of challenge, older adults had significant increases in HbO2 levels during usual walking, relative to standing (p=0.006). Both groups showed increased activation during dual-task (p<0.002) and during obstacle negotiation (p<0.003).
Prefrontal activation during walking is dependent on age and task properties and that older adults apparently rely more on cognitive resources even during usual walking task.
A substantial corpus of evidence suggests that the cognitive involvement in postural control and gait increases with aging. A large portion of such studies were based on dual-task experimental ...designs, which typically use the simultaneous performance of a motor task (e.g., static or dynamic balancing, walking) and a continuous cognitive task (e.g., mental arithmetic, tone detection). This focused review takes a cognitive neuroscience of aging perspective in interpreting cognitive motor dual-task findings. Specifically, we consider the importance of identifying the neural circuits that are engaged by the cognitive task in relation to those that are engaged during motor task performance. Following the principle of neural overlap, dual-task interference should be greatest when the cognitive and motor tasks engage the same neural circuits. Moreover, the literature on brain aging in general, and models of dedifferentiation and compensation, in particular, suggest that in cognitive motor dual-task performance, the cognitive task engages different neural substrates in young as compared to older adults. Also considered is the concept of multisensory aging, and the degree to which the age-related decline of other systems (e.g., vision, hearing) contribute to cognitive load. Finally, we discuss recent work on focused cognitive training, exercise and multimodal training of older adults and their effects on postural and gait outcomes. In keeping with the principle of neural overlap, the available cognitive training research suggests that targeting processes such as dividing attention and inhibition lead to improved balance and gait in older adults. However, more studies are needed that include functional neuroimaging during actual, upright performance of gait and balance tasks, in order to directly test the principle of neural overlap, and to better optimize the design of intervention studies to improve gait and posture.
The cortical control of gait and mobility involves multiple brain regions. Therefore, one could speculate that the association between specific spatial patterns of cortical thickness may be ...differentially associated with different mobility domains. To test this possibility, 115 healthy participants aged 27-82 (mean 60.5 ± 13.8) underwent a mobility assessment (usual-walk, dual-task walk, Timed Up and Go) and MRI scan. Ten mobility domains of relatively simple (e.g., usual-walking) and complex tasks (i.e., dual task walking, turns, transitions) and cortical thickness of 68 ROIs were extracted. All associations between mobility and cortical thickness were controlled for age and gender. Scaled Subprofile Modelling (SSM), a PCA-regression, identified thickness patterns that were correlated with the individual mobility domains, controlling for multiple comparisons. We found that lower mean global cortical thickness was correlated with worse general mobility (r = - 0.296, p = 0.003), as measured by the time to complete the Timed Up and Go test. Three distinct patterns of cortical thickness were associated with three different gait domains during simple, usual-walking: pace, rhythm, and symmetry. In contrast, cortical thickness patterns were not related to the more complex mobility domains. These findings demonstrate that robust and topographically distinct cortical thickness patterns are linked to select mobility domains during relatively simple walking, but not to more complex aspects of mobility. Functional connectivity may play a larger role in the more complex aspects of mobility.
Summary Background Age-associated motor and cognitive deficits increase the risk of falls, a major cause of morbidity and mortality. Because of the significant ramifications of falls, many ...interventions have been proposed, but few have aimed to prevent falls via an integrated approach targeting both motor and cognitive function. We aimed to test the hypothesis that an intervention combining treadmill training with non-immersive virtual reality (VR) to target both cognitive aspects of safe ambulation and mobility would lead to fewer falls than would treadmill training alone. Methods We carried out this randomised controlled trial at five clinical centres across five countries (Belgium, Israel, Italy, the Netherlands, and the UK). Adults aged 60–90 years with a high risk of falls based on a history of two or more falls in the 6 months before the study and with varied motor and cognitive deficits were randomly assigned by use of computer-based allocation to receive 6 weeks of either treadmill training plus VR or treadmill training alone. Randomisation was stratified by subgroups of patients (those with a history of idiopathic falls, those with mild cognitive impairment, and those with Parkinson's disease) and sex, with stratification per clinical site. Group allocation was done by a third party not involved in onsite study procedures. Both groups aimed to train three times per week for 6 weeks, with each session lasting about 45 min and structured training progression individualised to the participant's level of performance. The VR system consisted of a motion-capture camera and a computer-generated simulation projected on to a large screen, which was specifically designed to reduce fall risk in older adults by including real-life challenges such as obstacles, multiple pathways, and distracters that required continual adjustment of steps. The primary outcome was the incident rate of falls during the 6 months after the end of training, which was assessed in a modified intention-to-treat population. Safety was assessed in all patients who were assigned a treatment. This study is registered with ClinicalTrials.gov , NCT01732653. Findings Between Jan 6, 2013, and April 3, 2015, 302 adults were randomly assigned to either the treadmill training plus VR group (n=154) or treadmill training alone group (n=148). Data from 282 (93%) participants were included in the prespecified, modified intention-to-treat analysis. Before training, the incident rate of falls was similar in both groups (10·7 SD 35·6 falls per 6 months for treadmill training alone vs 11·9 39·5 falls per 6 months for treadmill training plus VR). In the 6 months after training, the incident rate was significantly lower in the treadmill training plus VR group than it had been before training (6·00 95% CI 4·36–8·25 falls per 6 months; p<0·0001 vs before training), whereas the incident rate did not decrease significantly in the treadmill training alone group (8·27 5·55–12·31 falls per 6 months; p=0·49). 6 months after the end of training, the incident rate of falls was also significantly lower in the treadmill training plus VR group than in the treadmill training group (incident rate ratio 0·58, 95% CI 0·36–0·96; p=0·033). No serious training-related adverse events occurred. Interpretation In a diverse group of older adults at high risk for falls, treadmill training plus VR led to reduced fall rates compared with treadmill training alone. Funding European Commission.
Freezing of Gait (FOG) is one of the most debilitating gait impairments in Parkinson’s disease (PD), leading to increased fall risk and reduced health-related quality of life. The utility of ...parkinsonian medications is often limited in the case of FOG and it frequently becomes dopamine resistant. Recent studies have suggested that pre-frontal cortex (PFC) dysfunction contributes to FOG; however, most previous findings provide only indirect evidence. To better understand the role of the PFC, we aimed to investigate the impact of high frequency, deep, repetitive transcranial magnetic stimulation (drTMS) of the medial PFC on FOG and its mediators. Nine patients with advanced PD participated in a randomized, cross-over exploratory study. We applied drTMS over the medial PFC for 16 weeks, with real and sham conditions; each condition included an intensive (i.e., 3 times a week) phase and a maintenance (once a week) phase. Scores on a FOG-provoking test, the motor part of the Unified Parkinson’s Disease Rating Scale, and gait variability significantly improved after real drTMS, but not after the sham condition. Self-report of FOG severity and cognitive scores did not improve. Due to discomfort and pain during treatment, two patients dropped out and the study was halted. These initial findings support the cause-and-effect role of the pre-frontal cortex in FOG among patients with PD. Due to the small sample size, findings should be interpreted cautiously. Further studies are needed to more fully assess the role of the medial PFC in the underlying mechanism of FOG and the possibility of using non-invasive brain stimulation to modify FOG.
Recent findings suggest that executive function (EF) plays a critical role in the regulation of gait in older adults, especially under complex and challenging conditions, and that EF deficits may, ...therefore, contribute to fall risk. The objective of this study was to evaluate if reduced EF is a risk factor for future falls over the course of 5 years of follow-up. Secondary objectives were to assess whether single and dual task walking abilities, an alternative window into EF, were associated with fall risk.
We longitudinally followed 256 community-living older adults (age: 76.4±4.5 yrs; 61% women) who were dementia free and had good mobility upon entrance into the study. At baseline, a computerized cognitive battery generated an index of EF, attention, a closely related construct, and other cognitive domains. Gait was assessed during single and dual task conditions. Falls data were collected prospectively using monthly calendars. Negative binomial regression quantified risk ratios (RR). After adjusting for age, gender and the number of falls in the year prior to the study, only the EF index (RR: .85; CI: .74-.98, p = .021), the attention index (RR: .84; CI: .75-.94, p = .002) and dual tasking gait variability (RR: 1.11; CI: 1.01-1.23; p = .027) were associated with future fall risk. Other cognitive function measures were not related to falls. Survival analyses indicated that subjects with the lowest EF scores were more likely to fall sooner and more likely to experience multiple falls during the 66 months of follow-up (p<0.02).
These findings demonstrate that among community-living older adults, the risk of future falls was predicted by performance on EF and attention tests conducted 5 years earlier. The present results link falls among older adults to cognition, indicating that screening EF will likely enhance fall risk assessment, and that treatment of EF may reduce fall risk.
Creutzfeldt-Jakob Disease (CJD) is the most common prion disease in humans causing a rapidly progressive neurological decline and dementia and is invariably fatal. The familial forms (genetic CJD, ...gCJD) are caused by mutations in the PRNP gene encoding for the prion protein (PrP). In Israel, there is a large cluster of gCJD cases, carriers of an E200K mutation in the PRNP gene, and therefore the largest population of at-risk individuals in the world. The mutation is not necessarily sufficient for the formation and accumulation of the pathological prion protein (PrP
), suggesting that other, genetic and non-genetic factors affect the age at symptoms onset. Here we present the protocol of a cross-sectional and longitudinal natural history study of gCJD patients and first-degree relatives of gCJD patients, aiming to identify biological markers of preclinical CJD and risk factors for phenoconversion.
The study has two groups: Patients diagnosed with gCJD, and first-degree healthy relatives (HR) (both carriers and non-carriers of the E200K mutation in the PRNP gene) of patients diagnosed with gCJD. At baseline, and at the end of every year, healthy participants are invited for an "in-depth" visit, which includes a clinical evaluation, blood and urine collection, gait assessment, brain MRI, lumbar puncture (LP), and Polysomnography (PSG). At 6 months from baseline, and then halfway through each year, participants are invited for a "brief" visit, which includes a clinical evaluation, short cognitive assessment, and blood and urine collection. gCJD patients will be invited for one "in-depth" visit, similar to the baseline visit of healthy relatives.
This continuous follow-up of the participants and the frequent assessments will allow early identification and diagnosis in case of conversion into disease. The knowledge generated from this study is likely to advance the understanding of the underlying clinicopathological processes that occur at the very beginning of CJD, as well as potential genetic and environmental risk factors for the development of the disease, therefore advancing the development of safe and efficient interventions.
The study is an observational study. It has registered retrospectively in https://clinicaltrials.gov/ and has been assigned an identification number NCT05746715.
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