Adverse performance effects of acute lorazepam administration in elderly long-term users: pharmacokinetic and clinical predictors.

BACKGROUND: The benzodiazepine lorazepam is widely utilized in the treatment of elderly individuals with anxiety disorders and related conditions. Negative effects of acute lorazepam administration on cognitive performance, especially memory, have been reported in both previously untreated elderly and in individuals who have received short term (up to three weeks) treatment with therapeutic doses. However, it remains unclear if these adverse cognitive effects also persist after long-term use, which is frequently found in clinical practice. METHODS: Cognitively intact elderly individuals (n=37) on long-term (at least three months) daily treatment with lorazepam were studied using a double-blind placebo-controlled cross-over study design. Subjects were administered their highest daily unit dose of lorazepam (0.25-3.00 mg) or placebo on different days, approximately 1 week apart in a random order, and were assessed on memory, psychomotor speed, and subjective mood states. RESULTS: Subjects had significantly poorer recall and slowed psychomotor performance following acute lorazepam administration. There were no significant effects on self-ratings of mood, sedation, or anxiety in the whole group, but secondary analyses suggested a differential response in subjects with Generalized Anxiety Disorder. CONCLUSIONS: The reduced recall and psychomotor slowing that we observed, along with an absence of significant therapeutic benefits, following acute lorazepam administration in elderly long-term users reinforces the importance of cognitive toxicity as a clinical factor in benzodiazepine use, especially in this population

The evolving role of the European Commission in research on Africa

We examine the EC's role in research related to the African continent, both as a funder of research through the EU research and innovation Framework programmes, and as a producer of research through its Joint Research Centre. We used bibliometrics analyses of 6,849 peer-reviewed scientific articles from the Scopus database to answer three questions. Has the production of research related to Africa changed over time ? How has the collaborative landscape evolved? Has the thematic focus of research changed through the years? We answered these questions separately for EU research funded through the EC, as well as research carried out at the JRC. We presented our main findings on bibliometric trends in the context of science diplomacy between the EU and Africa. We highlighted key policy relevant messages on how and where science helps guiding the implementation of policy instruments, notably the EC Comprehensive Strategy with Africa under the action on scientific capacity. Future paths for the JRC to best support EU-Africa scientific cooperation could possibly include building capacity on the use of machine learning tools and setting taxonomies to capture interdisciplinarity and synthesise content, as well as institutionalise knowledge brokerage. The recently launched Africa Knowledge Platform is presented as one way forward to defragment knowledge and translate science into policy. This study is also available as a narrative within this platform.JRC.D.6 - Knowledge for Sustainable Development and Food Securit

The perceptions of research values and priorities in water resource management from the 3rd Orange River Basin Symposium

Research has played an important role in water resource management and a consensus on research objectives would increase the efficiency of these practices. In this paper we aimed to elicit the views of attendees of the 3rd Orange River Basin Symposium regarding water-related research, by using both quantitative and qualitative responses to a questionnairesurvey, and purposeful sampling methods. Overall, research was perceived to play an important role in water resource management and there was significant agreement on which sectors are responsible for carrying out this research. Although clear strengths in water resource management in southern Africa were identified, we found that most perceived weaknessesrelated to the lack of enforcement or to human resource constraints. Despite this fact, the identified research priorities, which were aligned to those of the Water Research Commission, tended to be technical in nature and would not address these perceived weaknesses. Our recommendations were that, by incorporating previously ignored sectors into research,such as private consultants and non-governmental organisations, and addressing human capacity and enforcement issues, unique and unexplored research opportunities could improve water resource management

Rapid assessment of human population growth, and natural carbon stocks and fluxes in Key Landscapes for Conservation and Development (KLCDs) in Central Africa, in the context of NaturAfrica

This study was on request by the European Union Delegation to Cameroon, through the policy request ticketing system by the European Commission Knowledge Centre for Biodiversity and the Science Service for Biodiversity. We summarised changes in human population density (2010 – 2020), irrecoverable carbon stocks (2010 – 2018), and carbon fluxes (2001 – 2022) in Key Landscape for Conservation and Development (KLCD) in Central Africa, which are prioritised by the European Union’s NaturAfrica initiative. Results indicated geographical variation in population growth, both within and between KLCD. The Great Sangha Trinational (TNS) transboundary conservation area had the highest population growth rates (~7.96 % per annum), while the Greater Virunga-Murchison had the greatest total population (~15.4 million in 2020). Irrecoverable carbon stocks were relatively stable between 2010 and 2018 and were highest in the dense moist forests of the Great TNS (~11,160 Mt) and the peatlands of Ngiri-Tumba-Maindombe (~8,271 Mt). The majority of landscapes were net carbon sinks, though biomass removal has turned Lomami-Yangambi-Rubi-Tele KLCD into a net carbon source (net emissions ~0.24 Mt carbon per annum). Since this rapid assessment covered such a large geographical area, it did not identify consistent trends between human populations and biomass carbon across all KLCD. Therefore, trend analyses could be tailored to narrower geographical contexts to support specific NaturAfrica Interventions within individual KLCD.JRC.D.6 - Nature Conservation and Observation

A study on the specificity of the association between hippocampal volume and delayed primacy performance in cognitively intact elderly individuals.

Delayed recall at the primacy position (first few items on a list) has been shown to predict cognitive decline in cognitively intact elderly participants, with poorer delayed primacy performance associated with more pronounced generalized cognitive decline during follow-up. We have previously suggested that this association is due to delayed primacy performance indexing memory consolidation, which in turn is thought to depend upon hippocampal function. Here, we test the hypothesis that hippocampal size is associated with delayed primacy performance in cognitively intact elderly individuals. Data were analyzed from a group (N=81) of cognitively intact participants, aged 60 or above. Serial position performance was measured with the Buschke selective reminding test (BSRT). Hippocampal size was automatically measured via MRI, and unbiased voxel-based analyses were also conducted to explore further regional specificity of memory performance. We conducted regression analyses of hippocampus volumes on serial position performance; other predictors included age, family history of Alzheimer's disease (AD), APOE ε4 status, education, and total intracranial volume. Our results collectively suggest that there is a preferential association between hippocampal volume and delayed primacy performance. These findings are consistent with the hypothesis that delayed primacy consolidation is associated with hippocampal size, and shed light on the relationship between delayed primacy performance and generalized cognitive decline in cognitively intact individuals, suggesting that delayed primacy consolidation may serve as a sensitive marker of hippocampal health in these individuals

Abnormality in glutamine-glutamate cycle in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder: a 3-year follow-up study

Major depressive disorder (MDD), common in the elderly, is a risk factor for dementia. Abnormalities in glutamatergic neurotransmission via the N-methyl-D-aspartate receptor (NMDA-R) have a key role in the pathophysiology of depression. This study examined whether depression was associated with cerebrospinal fluid (CSF) levels of NMDA-R neurotransmission-associated amino acids in cognitively intact elderly individuals with MDD and age- and gender-matched healthy controls. CSF was obtained from 47 volunteers (MDD group, N = 28; age- and gender-matched comparison group, N = 19) at baseline and 3-year follow-up (MDD group, N = 19; comparison group, N = 17). CSF levels of glutamine, glutamate, glycine, L-serine and D-serine were measured by highperformance liquid chromatography. CSF levels of amino acids did not differ across MDD and comparison groups. However, the ratio of glutamine to glutamate was significantly higher at baseline in subjects with MDD than in controls. The ratio decreased in individuals with MDD over the 3-year follow-up, and this decrease correlated with a decrease in the severity of depression. No correlations between absolute amino-acid levels and clinical variables were observed, nor were correlations between amino acids and other biomarkers (for example, amyloid-β42, amyloid-β40, and total and phosphorylated tau protein) detected. These results suggest that abnormalities in the glutamine–glutamate cycle in the communication between glia and neurons may have a role in the pathophysiology of depression in the elderly. Furthermore, the glutamine/glutamate ratio in CSF may be a state biomarker for depression

Mood is a key determinant of cognitive performance in community-dwelling older adults: a cross-sectional analysis

First Online: 06 October 2012Identification of predictors of cognitive trajectories through the establishment of composite or single-parameter dimensional categories of cognition and mood may facilitate development of strategies to improve quality of life in the elderly. Participants (n = 487, aged 50+ years) were representative of the Portuguese population in terms of age, gender, and educational status. Cognitive and mood profiles were established using a battery of neurocognitive and psychological tests. Data were subjected to principal component analysis to identify core dimensions of cognition and mood, encompassing multiple test variables. Dimensions were correlated with age and with respect to gender, education, and occupational status. Cluster analysis was applied to isolate distinct patterns of cognitive performance and binary logistic regression models to explore interrelationships between aging, cognition, mood, and socio-demographic characteristics. Four main dimensions were identified: memory, executive function, global cognitive status, and mood. Based on these, strong and weak cognitive performers were distinguishable. Cluster analysis revealed further distinction within these two main categories into very good, good, poor, and very poor performers. Mood was the principal factor contributing to the separation between very good and good, as well as poor and very poor, performers. Clustering was also influenced by gender and education, albeit to a lesser extent; notably, however, female gender × lower educational background predicted significantly poorer cognitive performance with increasing age. Mood has a significant impact on the rate of cognitive decline in the elderly. Gender and educational level are early determinants of cognitive performance in later life.This work was funded by the European Commission (FP7) “SwitchBox” (Contract HEALTH-F2-2010-259772). NCS is supported by a SwitchBox post-doctoral fellowship. We are thankful to all study participants. The authors would like to acknowledge all colleagues who assisted with participant recruitment and evaluation

The use of Bayesian latent class cluster models to classify patterns of cognitive performance in healthy ageing

The main focus of this study is to illustrate the applicability of latent class analysis in the assessment of cognitive performance profiles during ageing. Principal component analysis (PCA) was used to detect main cognitive dimensions (based on the neurocognitive test variables) and Bayesian latent class analysis (LCA) models (without constraints) were used to explore patterns of cognitive performance among community-dwelling older individuals. Gender, age and number of school years were explored as variables. Three cognitive dimensions were identified: general cognition (MMSE), memory (MEM) and executive (EXEC) function. Based on these, three latent classes of cognitive performance profiles (LC1 to LC3) were identified among the older adults. These classes corresponded to stronger to weaker performance patterns (LC1>LC2>LC3) across all dimensions; each latent class denoted the same hierarchy in the proportion of males, age and number of school years. Bayesian LCA provided a powerful tool to explore cognitive typologies among healthy cognitive agers.The study is integrated in the "Maintaining health in old age through homeostasis (SWITCHBOX)" collaborative project funded by the European Commission FP7 initiative (grant HEALTH-F2-2010-259772). NS and JAP are main team members of the European consortium SWITCHBOX (http://www.switchbox-online.eu/). NCS is supported by a SwitchBox post-doctoral fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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Validation of the Argentine version of the memory binding test (MBT) for early detection of mild cognitive impairment

Background: “Forgetfulness” is frequent in normal aging and characteristic of the early stages of dementia syndromes. The episodic memory test is central for detecting amnestic mild cognitive impairment (MCI). The Memory Binding Test (MBT) is a simple, easy and brief memory test to detect the early stage of episodic memory impairment. Objective: To validate the Argentine version of the MBT in a Latin American population and to estimate the diagnostic accuracy as a tool for early detection of MCI. Methods: 88 subjects (46 healthy controls and 42 patients with amnestic MCI) matched for age and educational level were evaluated by an extensive neuropsychological battery and the memory binding test. Results: A significantly better performance was detected in the control group; all MBT scales were predictive of MCI diagnosis (p<.01). The MBT showed high sensitivity (69%) and high specificity (88%), with a PPV of 93% and a NPV of 55% for associative paired recall. A statistically significant difference (χ2=14,164, p<.001) was obtained when comparing the area under the curve (AUC) of the MBT (0.88) and the MMSE (0.70). Conclusion: The Argentine version of the MBT correlated significantly with the MMSE and the memory battery and is a useful tool in the detection of MCI. The operating characteristics of the MBT are well suited, surpassing other tests commonly used for detecting MCI. © 2016, Academia Brasileira de Neurologia. All rights reserved