Cognitive training for freezing of gait in Parkinson's disease: a randomized controlled trial.

The pathophysiological mechanism of freezing of gait (FoG) has been linked to executive dysfunction. Cognitive training (CT) is a non-pharmacological intervention which has been shown to improve executive functioning in Parkinson's disease (PD). This study aimed to explore whether targeted CT can reduce the severity of FoG in PD. Patients with PD who self-reported FoG and were free from dementia were randomly allocated to receive either a CT intervention or an active control. Both groups were clinician-facilitated and conducted twice-weekly for seven weeks. The primary outcome was percentage of time spent frozen during a Timed Up and Go task, assessed both on and off dopaminergic medications. Secondary outcomes included multiple neuropsychological and psychosocial measures. A full analysis was first conducted on all participants randomized, followed by a sample of interest including only those who had objective FoG at baseline, and completed the intervention. Sixty-five patients were randomized into the study. The sample of interest included 20 in the CT group and 18 in the active control group. The primary outcome of percentage time spent frozen during a gait task was significantly improved in the CT group compared to active controls in the on-state. There were no differences in the off-state. Patients who received CT also demonstrated improved processing speed and reduced daytime sleepiness compared to those in the active control. The findings suggest that CT can reduce the severity of FoG in the on-state, however replication in a larger sample is required

Neurophysiological changes associated with cognitive training in older adults 'at risk' for dementia: application of the mismatch negativity event-related potential

"Research conducted at the Ageing Brain Centre, Brain and Mind Research Institute, University of Sydney, NSW, Australia""Empirical thesis submitted in partial fulfilment of the requirements of the degree of Doctorate of Psychology (Clinical Neuropsychology)"Thesis by publication.Bibliography: pages 159-185.1. General introduction -- 2. Early intervention for cognitive decline: can cognitive training be used as a selective prevention technique? -- 3. Reduced mismatch negativity in mild cognitive impairment: associations with neuropsychological performance -- 4. Reduced temporal mismatch negativity in late-life depression: an event-related potential index of cognitive deficit and functional disability? -- 5. A healthy brain ageing cognitive training program enhances neurophysiological responses in older 'at risk' adults: an event-related potential study -- 6. General discussion.Background: The prevalence of dementia worldwide is expected to increase dramatically with the rapidly expanding ageing population. Research has identified sub-groups of older people with increased risk of dementia, including those with subjective cognitive impairment, depression and mild cognitive impairment. With the current lack of effective treatments for dementia, secondary prevention approaches targeting 'at risk' older individuals are warranted. It has been suggested that cognitive training may have the capacity to delay or slow cognitive decline in these 'at risk' groups. However, the extent to which such interventions also have the capacity to alter underlying brain functioning is largely unknown. -- Aims: This body of research aimed to: 1) examine whether cognitive training may be a viable early intervention strategy for 'at risk' older adults; 2) determine whether utilisation of neurophysiological paradigms may be a viable way to probe underlying brain dysfunction in 'at risk' groups; and 3) investigate the extent to which cognitive training may be associated with altered neurophysiological responses. -- Methods: The first aim of this thesis was achieved with the publication of a literature review exploring evidence for the efficacy of cognitive training. The second aim of this research employed an event-related potential Mismatch Negativity (MMN) paradigm to determine the capacity to detect changes in 'pre-attentive' cognitive processes in 'at risk' groups, which in turn, are thought to recruit distinct neurobiological circuits. Finally, using a randomised controlled trial in 40 'at risk' older people, this research examined the capacity for cognitive training to alter the MMN response. -- Results: The findings of this research confirmed that cognitive training does offer promise as a secondary prevention tool for cognitive decline in 'at risk' cohorts. It also showed that the MMN response is reduced in 'at risk' groups relative to healthy older controls and is also associated with neuropsychological and psychosocial functioning, suggesting its utility as a neural marker of brain dysfunction. Finally, results showed that this marker is enhanced following cognitive training, supporting the notion that neuroplastic changes do occur in relation to this non-pharmacological intervention. -- Implications: Further research exploring the relationship between the MMN marker and underlying pathophysiological brain changes associated with dementia is now warranted, as well as research exploring the capacity of this marker to predict cognitive decline longitudinally.Mode of access: World Wide Web.1 online resource (xv, 185 pages) illustrations (some colour

Mismatch negativity in at risk older adults: Associations with cognitive performance

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Perspectives of general practitioners and memory clinic patients on ageing and cognitive decline to inform the design of a decentralised antihypertensive dementia prevention trial

Background: The global burden dementia is growing each year. Clinical trials investigating approaches to preventing dementia have been occurring for decades, but they are particularly challenging including the requirement to include large numbers of healthy ‘at-risk’ people who need to be followed up for a long period of time. Community and consumer involvement in trial design helps to ensure that the methods are acceptable to the involved stakeholders, the design and operation of clinical trials are suitable and applicable to the target population, and that key areas of concern are identified and addressed at an early stage. Objectives: To gain insights from samples of memory clinic patients without dementia and general practitioners on the acceptability of, and attitudes towards, the proposed design of a decentralised antihypertensive dementia prevention trial. Topics addressed included the assessment of cognition, antihypertensive medication use, and motivation to participate in research. Methods: Two focus groups (total n = 7) with memory clinic patients and individual interviews with GPs (n = 5) were conducted. Transcripts were analysed using qualitative thematic framework analysis. Results: The proposed design was acceptable, with some possible barriers identified regarding computer use, GP time restraints, and concerns about medication interactions. Additional themes included the importance of communication and social connectedness in research participation and perceptions of ageing in medical settings. Future directions of research into larger studies and consumer-led research practices were discussed. Conclusion: The proposed trial design was agreed to be acceptable with some operational considerations, which were incorporated in the trial design

Stuck in the mud: time for change in the implementation of cognitive training research in ageing?

Over the past two decades, within the field of healthy ageing and dementia prevention there has been a substantial growth of interest in the potential of cognitive training (CT) interventions (see Figure 1). Whilst various studies have employed different methodologies, generally the term refers to programs which provide theoretically driven skills and strategies, involving guided practice on tasks reflecting specific cognitive functions (Mowszowski et al., 2010). The focus of such interventions is to improve functioning of particular cognitive skills such as memory, working memory, attention, and executive functions, as decline in these or other cognitive domains may lead to functional impairment in day-to-day activities as well as contribute to reduced quality of life and disability (Salthouse, 2004). Improvements in these cognitive abilities may lead to more effective or independent functioning and may be instigated through various CT approaches including repetitive computerized exercise, pen and paper tasks, and clinically-driven strategy learning

Cognitive training in Parkinson's disease

Cognitive impairment is now widely accepted as a fundamental aspect of Parkinson's disease (PD). Given the prevalence of cognitive impairment and the associated impact on well-being, evidence-based interventions are needed. However, while research is continually accumulating in order to better understand the pathology and trajectory of cognitive changes, treatment options lag behind. Nonpharmacological approaches are of particular interest in this group, given the typical polypharmacy already present in PD patients. In this regard, cognitive training (CT) is a relatively new and prominent therapeutic option with accumulating scientific support and increasing public awareness. Research has now established benefits across many different populations, and trials investigating the use of CT specifically in PD are becoming more common. We offer a brief summary of CT and its efficacy in PD samples to date, as well as discuss areas requiring further exploration in this group. Crucially, we suggest that CT should be supported as a research priority in PD, given both proven and potential benefits as a noninvasive and well-tolerated behavioral intervention for cognitive impairment

Freezing of gait in Parkinson's disease: current treatments and the potential role for cognitive training

Freezing of gait (FOG) is a complex motor symptom of Parkinson's disease that manifests as an inability to generate effective gait, leading to a significant falls risk and a severe impact on quality of life. Research into effective treatment options has provided relatively limited benefits and is often hindered by substantial limitations. In this article, current treatment and research options are briefly discussed and a proposal for the further exploration of non-invasive therapeutic approaches is given. Recent advances in the literature continue to identify a pattern of selective executive dysfunction in patients with freezing of gait and such findings highlight a possible common underlying pathophysiology. Therefore, cognitive training is of particular interest as it may be able to improve executive processes thus reducing the manifestation of FOG. This article focuses on the existing evidence for such intervention strategies and proposes that targeted cognitive training may offer a novel treatment option for FOG that is worthy of an increased research focus

Hippocampal neuronal integrity and functional connectivity within the default mode network in mild cognitive impairment: a multimodal investigation

Background. In older people with Mild Cognitive Impairment (MCI), the relationship between early changes in functional connectivity and in vivo changes in key neurometabolites is not known. Two established correlates of MCI diagnosis are decreased in N-Acetylaspartate (NAA) in the hippocampus, indicative of decreased neuronal integrity, and changes in the Default Mode Network (DMN) functional network. If and how these measures interrelate is yet to be established, and this understanding may provide insight into the processes underpinning observed cognitive decline. Objectives. To determine the relationship between NAA levels in the left hippocampus and functional connectivity within the DMN in an aging cohort. Methods. In a sample of 51 MCI participants and 30 controls, hippocampal NAA was determined using magnetic resonance spectroscopy, and DMN connectivity was quantified using resting state functional MRI. The association between hippocampal NAA and the DMN functional connectivity was tested independently within in the MCI and separately within the control group. Results. In the DMN, we showed a significant inverse association between functional connectivity and hippocampal NAA in 20 specific brain connections for patients with MCI. This was despite no evidence of any associations in the healthy control group or group differences in either of these measures alone. Conclusions. This study suggests that decreased neuronal integrity in the hippocampus is associated with functional change within the DMN for those with MCI, in contrast to healthy older adults. These results highlight the potential of multimodal investigations to better understand the processes associated with cognitive decline