Altered long-range alpha-band synchronization during visual short-term memory retention in children born very preterm

Children born very preterm, even when intelligence is broadly normal, often experience selective difficulties in executive function and visual-spatial processing. Development of structural cortical connectivity is known to be altered in this group, and functional magnetic resonance imaging (fMRI) evidence indicates that very preterm children recruit different patterns of functional connectivity between cortical regions during cognition. Synchronization of neural oscillations across brain areas has been proposed as a mechanism for dynamically assigning functional coupling to support perceptual and cognitive processing, but little is known about what role oscillatory synchronization may play in the altered neurocognitive development of very preterm children. To investigate this, we recorded magnetoencephalographic (MEG) activity while 7-8 year old children born very preterm and age-matched full-term controls performed a visual short-term memory task. Very preterm children exhibited reduced long-range synchronization in the alpha-band during visual short-term memory retention, indicating that cortical alpha rhythms may play a critical role in altered patterns functional connectivity expressed by this population during cognitive and perceptual processing. Long-range alpha-band synchronization was also correlated with task performance and visual-perceptual ability within the very preterm group, indicating that altered alpha oscillatory mechanisms mediating transient functional integration between cortical regions may be relevant to selective problems in neurocognitive development in this vulnerable population at school age.

Long-range synchronization and local desynchronization of alpha oscillations during visual short-term memory retention in children

Local alpha-band synchronization has been associated with both cortical idling and active inhibition. Recent evidence, however, suggests that long-range alpha synchronization increases functional coupling between cortical regions. We demonstrate increased long-range alpha and beta band phase synchronization during short-term memory retention in children 6-10 years of age. Furthermore, whereas alpha-band synchronization between posterior cortex and other regions is increased during retention, local alpha-band synchronization over posterior cortex is reduced. This constitutes a functional dissociation for alpha synchronization across local and long-range cortical scales. We interpret long-range synchronization as reflecting functional integration within a network of frontal and visual cortical regions. Local desynchronization of alpha rhythms over posterior cortex, conversely, likely arises because of increased engagement of visual cortex during retention.

Subarachnoid haemorrhage (SAH):long-term cognitive outcome in patients treated with surgical clipping or endovascular coiling

Purpose: To compare long-term cognitive outcomes of patients treated with surgical clipping or endovascular coiling after subarachnoid haemorrhage (SAH). Method: Retrospective matched cohort study assessed neuropsychological functioning at least 12 months after aneurysmal SAH treatment. Fourteen patients treated by endovascular coiling and nine patients treated by surgical clipping participated. After gaining written consent, a comprehensive neuropsychological battery was completed. Standardised tests were employed to assess pre-morbid and current intellectual functioning (IQ), attention, speed of information processing, memory and executive function as well as psychosocial functioning and affect. Results: Treatment groups were not significantly different in terms of age, pre-morbid IQ, time from injury to treatment or time since injury. A significant effect of treatment on full-scale IQ score (p = 0.025), performance IQ (p = 0.045) and verbal IQ score (p = 0.029), all favouring the coiled group was observed. A medium effect size between groups difference in immediate memory (p = 0.19, partial ?(2) = 0.08) was also observed. No significant between group differences on attention, executive functioning and speed of information processing measures or mood and psychosocial functioning were noted. Both groups reported increased anxiety and memory, attention and speed of information processing deficits relative to normative data. Conclusions: Study findings indicate fewer cognitive deficits following endovascular coiling. Cognitive deficits in the clipped group may be due in part to the invasive nature of neurosurgical clipping. Further prospective research with regard to long-term cognitive and emotional outcomes is warranted. [Box: see text].

Long-term neuropsychological and psychosocial outcomes of decompressive hemicraniectomy following malignant middle cerebral artery infarctions

Purpose: This study examines long-term neuropsychological and psychosocial outcomes of survivors of malignant middle cerebral artery infarction treated via decompressive hemicraniectomy. Method: A case series design facilitated a detailed analysis of the outcomes among five participants. Neuropsychological domains assessed included premorbid and current IQ, sustained, selective and divided attention, visual and auditory memory, executive functioning and visuo-spatial ability. Psychosocial domains assessed included self-rated depression, anxiety and quality of life. Participants and their main carer were asked about their retrospective view of surgery. Results: All participants showed neuropsychological impairments in multiple cognitive domains, with preserved ability in others. Effects of laterality of brain function were evident in some domains. Clinically significant depression was evident in two participants. Overall quality of life was within average limits in three of four assessed participants. Four participants retrospectively considered surgery as having been a favourable course of action. Conclusion: While neuropsychological impairments are highly likely post-surgery, preserved abilities and social support may serve a protective function against depression and an unacceptably poor quality of life. Results do not support the suggestion that decompressive hemicraniectomy following malignant middle cerebral artery infarction necessarily leads to unacceptable neuropsychological or psychosocial outcomes.

Designing for dementia : an assessment of the impact of the physical environment on wayfinding success for residents in long term care settings

It is acknowledged that one of the consequences of the ageing process is cognitive decline, which leads to an increase in the incidence of illnesses such as dementia. This has become ever more relevant due to the projected increase in the ageing demographic. Dementia affects visuo-spatial perception, causing difficulty with wayfinding, even during the early stages of the disease. The literature widely recognises the physical environment’s role in alleviating symptoms of dementia and improving quality of life for residents. It also identifies the lack of available housing options for older people with dementia and consequently the current stock is ill-equipped to provide adequate support.
Recent statistics indicate that 80% of those residing in nursing or residential care homes have some form of dementia or severe memory problems. The shift towards institutional care settings, the need for specialist support and care, places a greater impetus on the need for a person-centred approach to tackle issues related to wayfinding and dementia.
This thesis therefore aims to improve design for dementia in nursing and residential care settings in the context of Northern Ireland. This will be undertaken in order to provide a better understanding of how people with dementia experience the physical environment and to highlight features of the design that assist with wayfinding. Currently there are limited guidelines on design for dementia, meaning that many of these are theoretical, anecdotal and not definitive. Hence a greater verification to address the less recognised design issues is required. This is intended to ultimately improve quality of life, wellbeing, independence and uphold the dignity of people with dementia living in nursing or residential care homes.
The research design uses a mixed methods approach. A thorough preparation and consideration of ethical issues informed the methodology. The various facets were also trialled and piloted to identify any ethical, technological, methodological, data collection and analysis issues. The protocol was then amended to improve or resolve any of the aforementioned issues. Initially a questionnaire based on leading design recommendations was conducted with home managers. Semi-structured interviews were developed from this and conducted with staff and resident’s next of kin. An evidence-based approach was used to design a study which used ethnographic methods, including a wayfinding task. This followed a repeated measures design which would be used to actively engage residents with dementia in the research. Complementary to the wayfinding task, conversational and semi-structured interviews were used to promote dialogue and direct responses with the person with dementia. In addition to this, Space Syntax methodologies were used to examine the physical properties of the architectural layout. This was then cross-examined with interview responses and data from the wayfinding tasks.
A number of plan typologies were identified and were determined as synonymous with decision point types which needed to be made during the walks. The empirical work enabled the synthesis of environmental features which support wayfinding.
Results indicate that particular environmental features are associated with improved performance on the wayfinding tasks. By enhancing design for dementia, through identifying the attributes, challenges with wayfinding may be overcome and the benefits of the physical environment can be seen to promote wellbeing.
The implications of this work mean that the environmental features which have been highlighted from the project can be used to inform guidelines, thus adding to existing knowledge. Future work would involve the dissemination of this information and the potential for it to be made into design standards or regulations which champion design for dementia. These would increase awareness for designers and stakeholders undertaking new projects, extensions or refurbishments.
A person-centred, evidence-based design was emphasised throughout the project which guaranteed an in-depth study. There were limitations due to the available resources, time and funding. Future research would involve testing the identified environmental features within a specific environment to enable measured observation of improvements.

Finding a way: Long term care homes to support dementia

An ageing demographic has increased the number of people with dementia. Although dementia is commonly associated with memory loss, other early symptoms include difficulty with wayfinding. Dementia alters visuo-spatial perception and the processes used to interpret the physical environment. The role of the design of the physical environment for people with dementia has gained increased recognition. Despite this, design for dementia is often overlooked, focusing on issues relating to physical impairment. This paper presents the results of a PhD study and aims to examine the role of the design of the physical environment in supporting wayfinding for people with dementia living in long-term care settings in Northern Ireland. Mixed methods combined the observation of wayfinding walks and conversational style interviews to elicit perspectives and experiences of residents with dementia. The findings aim to promote well-being for those with dementia living in long-term care settings.

MRZ-99030 – a novel modulator of Aβ aggregation: II – reversal of Aβ oligomer-induced deficits in long-term potentiation (LTP) and cognitive performance in rats and mice.

β-amyloid1-42 (Aβ1-42) is a major endogenous pathogen underlying the aetiology of Alzheimer's disease (AD). Recent evidence indicates that soluble Aβ oligomers, rather than plaques, are the major cause of synaptic dysfunction and neurodegeneration. Small molecules that suppress Aβ aggregation, reduce oligomer stability or promote off-pathway non-toxic oligomerization represent a promising alternative strategy for neuroprotection in AD. MRZ-99030 was recently identified as a dipeptide that modulates Aβ1-42 aggregation by triggering a non-amyloidogenic aggregation pathway, thereby reducing the amount of intermediate toxic soluble oligomeric Aβ species. The present study evaluated the relevance of these promising results with MRZ-99030 under pathophysiological conditions i.e. against the synaptotoxic effects of Aβ oligomers on hippocampal long term potentiation (LTP) and two different memory tasks. Aβ1-42 interferes with the glutamatergic system and with neuronal Ca2+ signalling and abolishes the induction of LTP. Here we demonstrate that MRZ-99030 (100–500 nM) at a 10:1 stoichiometric excess to Aβ clearly reversed the synaptotoxic effects of Aβ1-42 oligomers on CA1-LTP in murine hippocampal slices. Co-application of MRZ-99030 also prevented the two-fold increase in resting Ca2+ levels in pyramidal neuron dendrites and spines triggered by Aβ1-42 oligomers. In anaesthetized rats, pre-administration of MRZ-99030 (50 mg/kg s.c.) protected against deficits in hippocampal LTP following i.c.v. injection of oligomeric Aβ1-42. Furthermore, similar treatment significantly ameliorated cognitive deficits in an object recognition task and under an alternating lever cyclic ratio schedule after the i.c.v. application of Aβ1-42 and 7PA2 conditioned medium, respectively. Altogether, these results demonstrate the potential therapeutic benefit of MRZ-99030 in AD.