Cognitive decline in dementia with Lewy bodies: a 5-year prospective cohort study

OBJECTIVES: We report the cognitive decline in persons diagnosed with mild dementia with Lewy bodies (DLB) and mild Alzheimer's disease (AD) during 5 years of annual follow-ups. METHODS: Patients were recruited into the study from geriatric, psychiatric and neurology clinics in Western Norway during 2005–2013. They were diagnosed according to clinical consensus criteria, based on standardised clinical rating scales. Autopsy-based diagnoses were available for 20 cases. Cognitive decline for up to 5 years was assessed using the Clinical Dementia Rating (CDR) scale and the Mini-Mental State Examination (MMSE). Survival analysis including Cox regression (time to reach severe dementia) and linear mixed-effects (lme) modelling were used to model the decline on MMSE. RESULTS: At least one follow-up assessment was available for 67 patients with DLB and 107 patients with AD, with a median follow-up time of 4.3 years. The time to reach severe dementia was significantly shorter in DLB (median 1793 days) compared with AD (1947 days; p=0.033), and the difference remained significant in the multiple Cox regression analysis (HR=2.0, p<0.02). In the adjusted lme model, MMSE decline was faster in DLB (annual decline 4.4 points) compared with AD (3.2 points; p<0.008). CONCLUSIONS: Our findings show that from the mild dementia stage, patients with DLB have a more rapid cognitive decline than in AD. Such prognostic information is vital for patients and families and crucial for planning clinical trials and enabling health economic modelling

Efficacy of Memantine for Agitation in Alzheimer’s Dementia: A Randomised Double-Blind Placebo Controlled Trial

Agitation in Alzheimer's disease (AD) is common and associated with poor patient life-quality and carer distress. The best evidence-based pharmacological treatments are antipsychotics which have limited benefits with increased morbidity and mortality. There are no memantine trials in clinically significant agitation but post-hoc analyses in other populations found reduced agitation. We tested the primary hypothesis, memantine is superior to placebo for clinically significant agitation, in patients with moderate-to-severe AD

Differential HMG-CoA lyase expression in human tissues provides clues about 3-hydroxy-3-methylglutaric aciduria

3-Hydroxy-3-methylglutaric aciduria is a rare human autosomal recessive disorder caused by deficiency of 3-hydroxy-3-methylglutaryl CoA lyase (HL). This mitochondrial enzyme catalyzes the common final step of leucine degradation and ketogenesis. Acute symptoms include vomiting, seizures and lethargy, accompanied by metabolic acidosis and hypoketotic hypoglycaemia. Such organs as the liver, brain, pancreas, and heart can also be involved. However, the pathophysiology of this disease is only partially understood. We measured mRNA levels, protein expression and enzyme activity of human HMG-CoA lyase from liver, kidney, pancreas, testis, heart, skeletal muscle, and brain. Surprisingly, the pancreas is, after the liver, the tissue with most HL activity. However, in heart and adult brain, HL activity was not detected in the mitochondrial fraction. These findings contribute to our understanding of the enzyme function and the consequences of its deficiency and suggest the need for assessment of pancreatic damage in these patients

More warm‐adapted species in soil seed banks than in herb layer plant communities across Europe

Responses to climate change have often been found to lag behind the rate of warming that has occurred. In addition to dispersal limitation potentially restricting spread at leading range margins, the persistence of species in new and unsuitable conditions is thought to be responsible for apparent time-lags. Soil seed banks can allow plant communities to temporarily buffer unsuitable environmental conditions, but their potential to slow responses to long-term climate change is largely unknown. As local forest cover can also buffer the effects of a warming climate, it is important to understand how seed banks might interact with land cover to mediate community responses to climate change. We first related species-level seed bank persistence and distribution-derived climatic niches for 840 plant species. We then used a database of plant community data from grasslands, forests and intermediate successional habitats from across Europe to investigate relationships between seed banks and their corresponding herb layers in 2763 plots in the context of climate and land cover. We found that species from warmer climates and with broader distributions are more likely to have a higher seed bank persistence, resulting in seed banks that are composed of species with warmer and broader climatic distributions than their corresponding herb layers. This was consistent across our climatic extent, with larger differences (seed banks from even warmer climates relative to vegetation) found in grasslands. Synthesis. Seed banks have been shown to buffer plant communities through periods of environmental variability, and in a period of climate change might be expected to contain species reflecting past, cooler conditions. Here, we show that persistent seed banks often contain species with relatively warm climatic niches and those with wide climatic ranges. Although these patterns may not be primarily driven by species' climatic adaptations, the prominence of such species in seed banks might still facilitate climate-driven community shifts. Additionally, seed banks may be related to ongoing trends regarding the spread of widespread generalist species into natural habitats, while cool-associated species may be at risk from both short- and long-term climatic variability and change

Xenophobia, the unconscious, the public sphere and Brexit

We examine xenophobia from the perspective of the unconscious of individuals, groups and nations, emphasizing the role of fantasy, and arguing that some leaders use xenophobic discourse to exploit fantasies arising from emotions such as anxiety, fear and anger. We discuss this in the context of the public sphere as conceptualized by Habermas. We illustrate this with reference to an analysis of the psychic life of ‘Brexit’, the UK decision to exit the European Union (EU) in 2016, arguing that Brexit was one expression of the unconscious life of a nation. We contribute to our understanding of xenophobia and the role of psychodynamic forces within the public sphere by highlighting the key role of the unconscious and its ability to be influenced by leaders. We conclude by reflecting on how we might work to counter xenophobia and its fantasies