Validation of the Dépistage Cognitif de Québec in the Oldest Old.

OBJECTIVE: We aimed to validate the Dépistage Cognitif de Québec (DCQ; www.dcqtest.org), a new cognitive screening tool for atypical degenerative syndromes, in the oldest old. METHODS: The DCQ was developed by expert behavioural neurologists and clinical neuropsychologists based on updated criteria for Alzheimer's disease, primary progressive aphasia, and behavioural variant frontotemporal dementia. It targets five relevant cognitive domains: Memory, Visuospatial, Executive, Language, and Behaviour. Validation was performed using a prospective community-based sample consisting of 53 healthy French-speaking Canadian volunteers aged between 80 and 94 years old. Normative data were derived from participants with no history of cognitive difficulties and a Montreal Cognitive Assessment (MoCA) score ≥ 24. RESULTS: The mean DCQ total score (out of 100) was 84.65 (SD = 6.33). Pearson's correlation coefficient showed a moderate, but significant, correlation (r = 0.36, p < .01) with the MoCA. Normative data shown in percentiles were stratified by age and education for DCQ total score and for each of the five cognitive domains. CONCLUSIONS: This study suggests that the DCQ is a valid cognitive screening test in the oldest old. It is proposed that the DCQ can help early identification of atypical degenerative syndromes.

Non-steroidal anti-inflammatory drugs disturb the osmoregulatory, metabolic and cortisol responses associated with seawater exposure in rainbow trout.

While detectable levels of non-steroidal anti-inflammatory drugs (NSAIDs) have been reported in various aquatic habitats, little is known about the mechanism of action of these pharmaceutical drugs on organisms. Recently we demonstrated that NSAIDs disrupt corticosteroidogenesis in rainbow trout (Oncorhynchus mykiss). As cortisol is a seawater adapting hormone, we hypothesized that exposure to NSAIDs will impair the hyposmoregulatory capacity of this species in seawater. Trout were exposed to either waterborne salicylate or ibuprofen in fresh water for four days and the salinity switched to 50% seawater for two days, followed by 100% seawater and sampled two days later. NSAIDs disturbed the seawater-induced elevation in plasma osmolality and concentrations of Cl(-) and K(+), but not Na(+) in rainbow trout. This was accompanied by enhanced gill glycolytic capacity and reduced liver glycogen content in seawater with NSAIDs, suggesting enhanced metabolic demand to fuel ion pumps. While salicylate did not affect gill Na(+)/K(+)-ATPase activity, ibuprofen inhibited the seawater-induced elevation in gill Na(+)/K(+)-ATPase activity. The drugs also further enhanced the seawater-induced elevation in plasma cortisol concentration; this response was greater with salicylate compared to ibuprofen. There were no changes in the transcript levels of key proteins involved in steroidogenesis with NSAIDs, whereas gill and brain GR protein expression expression was reduced with salicylate. Altogether, salicylate and ibuprofen exposures impaired the hyposmoregulatory capacity of rainbow trout in seawater, but the mode of action of the two drugs in bringing about these changes appears distinct in trout.

Salicylate impacts the physiological responses to an acute handling disturbance in rainbow trout.

While salicylates (non-steroidal anti-inflammatory drugs) have been detected in the aquatic environment, few studies have focused on the mechanism of action of these pharmaceuticals on aquatic organisms. We reported previously that salicylate disrupted the acute trophic hormone-stimulated corticosteroidogenesis in rainbow trout (Oncorhynchus mykiss) interrenal tissue in vitro. Here, we tested the hypothesis that this drug will inhibit the adaptive plasma cortisol response and the associated metabolic response to an acute stressor in trout. Fish were fed salicylate-laced feed (100 mg/kg body weight) for 3 days, subjected to an acute (5 min) handling disturbance and sampled 1, 4 and 24 h after the stressor exposure. Salicylate treatment attenuated the stressor-induced plasma cortisol but not glucose or lactate elevations. The disruption of cortisol response corresponded with a significant reduction in transcript levels of the steroidogenic acute regulatory protein (StAR), but not peripheral-type benzodiazepine receptor, cytochrome P450 side-chain cleavage or 11beta-hydroxylase. Salicylate did not modify the stressor-induced elevation of brain glucocorticoid receptor (GR) protein expression, while liver GR protein content was reduced. Salicylate impact on liver metabolic capacity involved depressed liver glycogen content, whereas no significant changes in liver hexokinase, glucokinase, lactate dehydrogenase, pyruvate kinase, phosphoenolpyruvate carboxykinase, aspartate aminotransferase and alanine aminotransferase activities were observed. Taken together, salicylate impairs the stressor-mediated plasma cortisol response and the associated liver metabolic capacity in trout. The mode of action of salicylate involves disruption of StAR and liver GR, two key proteins critical for cortisol production and target tissue responsiveness to this steroid, respectively.

Non-steroidal anti-inflammatory drugs disrupt the heat shock response in rainbow trout.

Non-steroidal anti-inflammatory drugs (NSAIDS) have been detected in the aquatic environment, but little is known about either their impact or mode of action in aquatic organisms. We tested the hypothesis that NSAIDs disrupt the evolutionarily conserved heat shock response, critical for defense against stressor-mediated proteotoxicity, in rainbow trout (Oncorhynchus mykiss). Trout fry were exposed by immersion to a range of salicylate or ibuprofen concentrations (1, 10, 100 or 1000 microg/L) for 4d. Ibuprofen, but not salicylate, at all concentrations induced heat shock protein 70 (hsp70) in trout liver. We used the highest concentration of the drugs to investigate their mode of action on the heat shock response. Fry were subjected to a standardized heat shock, 10 degrees C above ambient (13 degrees C) for 1h, and the temporal changes in liver hsp70 mRNA and protein content as well as glucose dynamics during recovery from the heat stressor assessed. Ibuprofen exposure did not modify hsp70 mRNA abundance, but significantly depressed the heat shock-induced hsp70 protein expression in the liver and gill of trout. Salicylate exposure elevated hsp70 mRNA abundance and delayed the hsp70 expression after a heat shock. Liver glucose levels and the activities of hexokinase, pyruvate kinase and lactate dehydrogenase, were elevated by NSAIDs suggesting enhanced tissue glycolytic capacity. Effects on whole body glucose dynamics, induced by the heat shock, were either absent with ibuprofen or completely modified by salicylate. Overall, NSAIDs disrupt the heat shock response in rainbow trout, while the mode of action of salicylate and ibuprofen in impacting the cellular stress response appears distinct.

Salicylate disrupts interrenal steroidogenesis and brain glucocorticoid receptor expression in rainbow trout.

Varying levels of pharmaceuticals, including salicylate, ibuprofen, and acetaminophen, have been reported in the aquatic environment, but few studies have actually addressed the impact of these drugs on aquatic organisms. We tested the hypothesis that these pharmaceuticals are endocrine disruptors in fish by examining their impact on interrenal corticosteroidogenesis in rainbow trout. Indeed, acute adrenocorticotrophic hormone (ACTH)-mediated cortisol production in trout interrenal cells in vitro was significantly depressed (20-40%) by these pharmaceutical drugs. Furthermore, we investigated whether this interrenal dysfunction involved inhibition of the steroidogenic capacity in rainbow trout. To this end, we fed trout salicylate-laced feed (100 mg/kg body weight) for 3 days and assessed the transcript levels of key proteins involved in corticosteroidogenesis, including steroidogenic acute regulatory protein (StAR), peripheral-type benzodiazepine receptor (PBR), cytochrome P450 cholesterol side chain cleavage (P450scc), and 11beta-hydroxylase. Salicylate treatment did not affect the resting plasma cortisol or glucose levels, whereas the acute ACTH-stimulated cortisol production was significantly depressed in the interrenal tissue. This disruption of steroidogenesis by salicylate corresponded to a significant drop in the gene expression of StAR and PBR, but not P450scc or 11beta-hydroxylase, compared to the sham-treated fish. Also, brain glucocorticoid receptor (GR) protein content and not GR mRNA level was significantly reduced by salicylate. Taken together, salicylate is a corticosteroid disruptor in trout and the targets include the key rate-limiting step in interrenal steroidogenesis and brain glucocorticoid signaling.