Memory consolidation — Mechanisms and opportunities for enhancement

Abstract Memory consolidation is the process by which relevant information is selected and transferred from a short-term, fragile state, into a stable, longer term domain from which it can be recalled. Effective memory underpins our ability to carry out everyday activities. When memory consolidation fails, such as in Alzheimer’s disease, the consequences can be devastating. Understanding the neurobiology of memory will help develop treatments for patients with memory loss. Here we describe the myriad processes involved in memory consolidation, including cholinergic and dopaminergic neurotransmission predominantly in hippocampal networks. We discuss established therapies as well as potential novel strategies for boosting cognition. Future approaches to enhancement of memory consolidation include not only pharmacological and neurosurgical treatments, but also lifestyle interventions — for example, modifications to sleep, exercise and diet.</jats:p

In search of ‘lost’ knowledge and outsourced expertise in flood risk management

This paper examines the parallel discourses of ‘lost’ local flood expertise and the growing use of commercial consultancies to outsource aspects of flood risk work. We critically examine the various claims and counter-claims about lost, local and external expertise in flood management, focusing on the aftermath of the 2007 floods in East Yorkshire, England. Drawing on interviews with consultants, drainage engineers and others, we caution against claims that privilege ‘local’ floods knowledge as ‘good’ and expert knowledge as somehow suspect. This paper urges carefulness in interpreting claims about local knowledge, arguing that it is important always to think instead of hybrid knowledge formations. We conclude by arguing that experiments in the co-production of flood risk knowledge need to be seen as part of a spectrum of ways for producing shared knowledge

APOE ε4, Alzheimer's disease neuropathology, and sleep disturbance, in individuals with and without dementia

BACKGROUND: Apolipoprotein E epsilon 4 (APOE-ε4) carrier status is an established risk factor for Alzheimer’s disease (AD) dementia. It has also been linked with sleep disturbance in healthy older adults and increased insomnia risk. This association may be driven by the effect of APOE-ε4 on AD pathological change, itself associated with sleep abnormalities. To assess this relationship, we have evaluated post-mortem neuropathological findings in patients with and without cognitive impairment and AD pathology, who had extensive clinical assessment within 12 months of death. METHODS: This retrospective cohort study used UK Brain Banks Network data. Eligible subjects were aged over 50, with pre-mortem neuropsychiatry inventory scores of sleep disturbance (NPI-K), neurocognitive testing and functional cognitive status assessment (Clinical Dementia Rating scale). Neuropathological data included Thal phase, Braak stage and CERAD scores (measures of Aβ plaque distribution, tangle distribution and neuritic plaque density, respectively) combined to form the National Institute on Aging Alzheimer’s Association (NIA-AA) ABC score reflecting AD neuropathology. Participants with other significant intracerebral pathology or pathological features of non-AD dementia were excluded. Multivariate linear regression was performed with NPIK Global Score (NPIK frequency score multiplied by severity score) as the dependent variable and APOE-ε4 heterozygosity or homozygosity as independent variables. Covariates included age, gender, APOE-ε2 status and ABC NPI measures reflecting depression and anxiety. Further models stratified by ABC score and functional cognitive status were also produced. RESULTS: Seven hundred twenty-eight records were identified. Two hundred two participants were included in the final analysis: mean (SD) age 84.0 (9.2) and MMSE 14.0 (11.8). Mean sleep disturbance scores were highest in ε4 homozygosity (n=11), 4.55 (5.4); intermediate in ε4 heterozygosity (n=95), 2.03 (4.0); and lowest in non-ε4 carriers (n=96), 1.36 (3.3). Within the full sample, controlling for pathological status, age, gender, depression, anxiety and CDR-SOB status, APOE-ε4 homozygosity was associated with sleep disturbance (β 2.53, p=0.034). APOE-ε4 heterozygosity was similarly associated in individuals without dementia (β 1.21, p=0.048). CONCLUSION: These findings lend weight to the hypothesis that APOE-ε4 affects sleep by mechanisms independent of AD pathological change. Evaluation of those mechanisms would enhance understanding of sleep disturbance pathways and potentially provide treatment targets. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-022-00992-y

Improving estuary models by reducing uncertainties associated with river flows

© 2018 The Authors To mitigate against future changes to estuaries such as water quality, catchment and estuary models can be coupled to simulate the transport of harmful pathogenic viruses, pollutants and nutrients from their terrestrial sources, through the estuary and to the coast. To predict future changes to estuaries, daily mean river flow projections are typically used. We show that this approach cannot resolve higher frequency discharge events that have large impacts to estuarine dilution, contamination and recovery for two contrasting estuaries. We therefore characterise sub-daily scale flow variability and propagate this through an estuary model to provide robust estimates of impacts for the future. River flow data (35-year records at 15-min sampling) were used to characterise variabilities in storm hydrograph shapes and simulate the estuarine response. In particular, we modelled a fast-responding catchment-estuary system (Conwy, UK), where the natural variability in hydrograph shapes generated large variability in estuarine circulation that was not captured when using daily-averaged river forcing. In the extreme, the freshwater plume from a ‘flash’ flood (lasting < 12 h) was underestimated by up to 100% – and the response to nutrient loading was underestimated further still. A model of a slower-responding system (Humber, UK), where hydrographs typically last 2–4 days, showed less variability in estuarine circulation and good approximation with daily-averaged flow forcing. Our result has implications for entire system impact modelling; when we determine future changes to estuaries, some systems will need higher resolution future river flow estimates

Num. 11

Emerging evidence suggests that dopamine may modulate learning and memory with important implications for understanding the neurobiology of memory and future therapeutic targeting. An influential hypothesis posits that dopamine biases reinforcement learning. More recent data also suggest an influence during both consolidation and retrieval. Eighteen Parkinson’s disease patients learned through feedback ON or OFF medication with memory tested 24 hours later ON or OFF medication (4 conditions, within-subjects design with matched healthy control group). Patients OFF medication during learning decreased in memory accuracy over the following 24 hours. In contrast to previous studies, however, dopaminergic medication during learning and testing did not affect expression of positive or negative reinforcement. Two further experiments were run without the 24-hour delay, but they too failed to reproduce effects of dopaminergic medication on reinforcement learning. While supportive of a dopaminergic role in consolidation, this study failed to replicate previous findings on reinforcement learning