Validation in French of the Montreal Cognitive Assessment 5-Minute, a brief cognitive screening test for phone administration.

BACKGROUND: The prevalence of cognitive impairment and dementia is high and steadily increasing. Early detection of cognitive decline is crucial since some interventions can reduce the risk of progression to dementia. However, there is a lack of manageable scales for assessing cognitive functions outside specialized consultations. Recently, the MoCA-5min, a short version of the Montreal Cognitive assessment (MoCA), phone-administered, was validated for screening for vascular cognitive impairment. The aim of the present study was to validate the MoCA-5min in French in diverse clinical populations. METHODS: The Cantonese version of the MoCA-5min was adapted for French language. Healthy volunteers and patients with possible or established cognitive impairment (Alzheimer's disease or related disorders, Parkinson's disease, Huntington's disease, type-2 diabetes) participated in the study. The original MoCA and the MoCA-5min were administered, by phone, with a 30-day interval. Alternate forms were used to reduce learning effects. RESULTS: The scores of the original MoCA and MoCA-5min correlated significantly (Spearman rho=0.751, P<0.0001, 95% confidence interval 0.657 to 0.819). Internal consistency was good (Cronbach alpha=0.795). The area under the ROC curve was 0.870 and the optimal cut-off value for separating patients with and without cognitive impairment with the MoCA-5min was≤27 with 87.32% sensitivity and 76.09% specificity. Interrater and test-retest reliability were adequate. CONCLUSION: This study demonstrates that the French version of the MoCA-5min is a valid and reliable scale for detecting cognitive impairment in different clinical populations. It is administrable by phone and thus suitable for remote assessment as well as for large-scale screening and epidemiological studies.

Etifoxine impairs neither alertness nor cognitive functions of the elderly: A randomized, double-blind, placebo-controlled crossover study.

Etifoxine hydrochloride (Stresam®), a treatment indicated for psychosomatic manifestations of anxiety, could be an alternative to benzodiazepines. While no impact on alertness and cognitive functions has been proven among youth, data on elderly are lacking. The primary objective of this study was to measure the impact of etifoxine, lorazepam or placebo on alertness in the elderly. The secondary objectives were to evaluate cognitive performances and adverse effects. In this randomized, placebo-controlled, double-blind, 3-way crossover design, 30 healthy volunteers aged 65 to 75 years underwent three one-day sessions. After treatment intake, standardized cognitive tests were conducted using the Cambridge Neuropsychological Test Automated Batteries and other psychological tests (Stroop, Rey Auditory Verbal Learning Test, Digit Span). The reaction time (RTI) as primary endpoint was analysed using a 3 × 3 latin square variance analysis. A 100-mg dose of etifoxine has no deleterious impact on alertness and causes no cognitive disorders as compared to placebo (RTI: 744 ±â€¯146 ms versus 770 ±â€¯153 ms; p = 1.00). As expected, a 2-mg dose of lorazepam impairs alertness (RTI: 957 ±â€¯251 ms versus placebo; p < 0.0001) and cognitive functions. A similar frequency of adverse events was observed with etifoxine and placebo while their incidence was 3-fold higher with lorazepam, drowsiness being the most frequent adverse event. No serious adverse events were observed. This study demonstrates in the elderly that a single dose of etifoxine does neither impair alertness nor any of the cognitive parameters evaluated. Etifoxine may be a good option when anxiolytic treatment is required, especially in elderly people.

[Androgens and cardiovascular risk: A series of case report in the French and Canadian pharmacovigilance databases]. / Androgènes et risque cardiovasculaire : série de cas dans les bases de pharmacovigilance française et canadienne.

INTRODUCTION: Age-related androgenic deficiency (DALA) is a pathology that is increasingly cited in recent publications. The cardiovascular risk of testosterone is debated: present for the FDA, absent for the European Medicines Agency in 2015. Our objective was to analyze the association between androgens and vascular pathologies in adverse reactions reported in pharmacovigilance databases. MATERIAL AND METHOD: We conducted a retrospective case series study of the French and Canadian pharmacovigilance databases for the period 2005-2015. Cases were defined as the association of the occurrence of a cardiovascular event (myocardial infarction or stroke) and the presence of testosterone in the treatment of patients. RESULTS: Of the 10 years analyzed, 12 French cases and 6 Canadian cases (representing 13 MIs and 5 strokes) were recorded in men aged 55 years on average. All were doubtful: differential diagnoses were possible (2.4 confounding conditions on average per patient) and overall cardiovascular risk was high for the majority of cases. CONCLUSION: Our study shows a very low report of cardiovascular effects under testosterone, all doubtful. Pending further studies, it seems reasonable to consider the cardiovascular risk of patients who are candidates for hormone therapy for age-related androgen deficiency. LEVEL OF EVIDENCE: 3.

[Proper use of apixaban: an outline for clinical practice]. / Bon usage d'apixaban: que retenir pour la pratique.

Apixaban is a direct inhibitor of coagulation factor Xa. Superior efficacy over aspirin and antivitamin K has been shown in the prevention of stroke and systemic embolism during non-valvular atrial fibrillation with a more favorable safety profile, even though the risk of hemorrhage cannot be ignored, considering its mechanism of action. The recommended dose is 5mg twice daily which can be reduced to 2.5mg depending on the individual risk. Apixaban is also indicated for the treatment of venous thromboembolism but reimbursement has not yet been accepted in France for this indication. As with all direct oral anticoagulants, no routine biological monitoring is required, nevertheless their use may have an impact on all coagulation tests, eventually hampering interpretation. In particular clinical circumstances where a measure of anticoagulant efficacy is deemed necessary, specific assay of anti-Xa activity is appropriate, the result being expressed as concentration of the anticoagulant used. It is therefore necessary to state the name of the medicine for which the assay is requested. With these new anticoagulants, management of hemorrhagic events can be more difficult due to the lack of a specific antidote. Pro-hemostatic substances have exhibited efficacy in animal models but results are still insufficiently documented in clinical practice. Local or locoregional hemostasis measurements, when possible, are an essential factor in the treatment of hemorrhagic events.

PPAR: a new pharmacological target for neuroprotection in stroke and neurodegenerative diseases.

PPARs (peroxisome-proliferator-activated receptors) are ligand-activated transcriptional factor receptors belonging to the so-called nuclear receptor family. The three isoforms of PPAR (alpha, beta/delta and gamma) are involved in regulation of lipid or glucose metabolism. Beyond metabolic effects, PPARalpha and PPARgamma activation also induces anti-inflammatory and antioxidant effects in different organs. These pleiotropic effects explain why PPARalpha or PPARgamma activation has been tested as a neuroprotective agent in cerebral ischaemia. Fibrates and other non-fibrate PPARalpha activators as well as thiazolidinediones and other non-thiazolidinedione PPARgamma agonists have been demonstrated to induce both preventive and acute neuroprotection. This neuroprotective effect involves both cerebral and vascular mechanisms. PPAR activation induces a decrease in neuronal death by prevention of oxidative or inflammatory mechanisms implicated in cerebral injury. PPARalpha activation induces also a vascular protection as demonstrated by prevention of post-ischaemic endothelial dysfunction. These vascular effects result from a decrease in oxidative stress and prevention of adhesion proteins, such as vascular cell adhesion molecule 1 or intercellular cell-adhesion molecule 1. Moreover, PPAR activation might be able to induce neurorepair and endothelium regeneration. Beyond neuroprotection in cerebral ischaemia, PPARs are also pertinent pharmacological targets to induce neuroprotection in chronic neurodegenerative diseases.

Prior TIA, lipid-lowering drug use, and physical activity decrease ischemic stroke severity.

OBJECTIVE: To determine clinical and pharmacologic factors that could influence the initial severity and short-term outcome of cerebral ischemia. METHODS: In a cross-sectional hospital-based study of patients with acute supratentorial ischemic stroke, we systematically collected medical history, previous leisure-time physical activity, current and previous treatments, blood pressure, temperature, blood glucose, fibrinogen, NIH Stroke Scale (NIHSS) score at admission, and outcome at day 8. Factors potentially associated with initial stroke severity and outcome were selected by univariate analyses and then validated in logistic regression analyses with lower severity of stroke at admission (NIHSS 0 to 5) or good outcome at day 8 (modified Rankin Scale 0 to 1, Barthel Index 95 to 100) as dependent variables. RESULTS: In 362 consecutive patients (median age 70 years, range 16 to 97 years; 195 women), independent factors associated with a lower severity at admission were previous leisure-time physical activity (adjusted odds ratio [OR] 1.67, 95% CI 1.07 to 2.66), TIA (adjusted OR 2.28, 95% CI 1.06 to 4.87) and treatment with lipid-lowering drug (adjusted OR 1.76, 95% CI 1.02 to 3.03). Previous treatment with lipid-lowering drug and leisure-time physical activity were also independent factors associated with a good short-term outcome. CONCLUSION: Both regular physical activity and lipid-lowering drugs should be prospectively evaluated to determine whether they reduce the severity of ischemic stroke.

Lipid lowering agents are associated with a slower cognitive decline in Alzheimer's disease.

BACKGROUND: Data from epidemiological studies and animal models imply that disturbances in cholesterol metabolism are linked to Alzheimer's disease susceptibility. Lipid lowering agents (LLAs) may have implications for the prevention of Alzheimer's disease. OBJECTIVE: To investigate whether LLAs are associated with a slower cognitive decline in Alzheimer's disease. METHODS: An observational study in 342 Alzheimer patients followed in a memory clinic for 34.8 months (mean age 73.5 years, mini-mental state examination score (MMSE) 21.3 at entry); 129 were dyslipaemic treated with LLAs (47% with statins), 105 were untreated dyslipaemic, and 108 were normolipaemic. The rate of cognitive decline was calculated as the difference between the first and last MMSE score, divided by the time between the measurements, expressed by year. Patients were divided into slow and fast decliners according to their annual rate of decline (lower or higher than the median annual rate of decline in the total population). RESULTS: Patients treated with LLAs had a slower decline on the MMSE (1.5 point/year, p = 0.0102) than patients with untreated dyslipaemia (2.4 points/year), or normolipaemic patients (2.6 points/year). Patients with a slower decline were more likely to be treated with LLAs. Logistic regression analysis, with low annual cognitive decline as the dependent variable, showed that the independent variable LLA (treated with or not) was positively associated with the probability of lower cognitive decline (odds ratio = 0.45, p = 0.002). CONCLUSIONS: LLAs may slow cognitive decline in Alzheimer's disease and have a neuroprotective effect. This should be confirmed by placebo controlled randomised trials in patients with Alzheimer's disease and no dyslipaemia.

Prestroke dementia in patients with atrial fibrillation. Frequency and associated factors.

BACKGROUND AND PURPOSE: Prestroke dementia is frequent but usually not identified. Non-valvular atrial fibrillation (NVAF) is independently associated with an increased risk for dementia. However, the frequency and determinants of prestroke dementia in patients with NVAF have never been evaluated. OBJECTIVE: The aim of this study was to determine the frequency of prestroke dementia and associated factors in patients with a previously known NVAF. METHODS: This is an ancillary study of Stroke in Atrial Fibrillation Ensemble II (SAFE II), an observational study conducted in patients with a previously known NVAF, consecutively admitted for an acute stroke in French and Italian centers. Prestroke dementia was evaluated by the IQCODE in patients with a reliable informant. Patients were considered as demented before stroke when their IQCODE score was > or = 104. RESULTS: of 204 patients, 39 (19.1%; 95% confidence interval [CI]: 13.7%-24.5%) patients met criteria for prestroke dementia. The only variable independently associated with prestroke dementia was increasing age (adjusted odds ratio for 1 year increase in age: 1.10; 95 % CI: 1.04-1.17), and there was a nonsignificant tendency for previous ischemic stroke or TIA and arterial hypertension. CONCLUSION: One fifth of stroke patients with a previously known NVAF were already demented before stroke. The main determinant of prestroke dementia is increasing age. A large cohort is necessary to identify other determinants.

Angioplasty and stenting for high-grade internal carotid artery stenosis: safety study in 39 selected patients.

BACKGROUND: Carotid angioplasty and stenting (CAS) is sometimes used as an alternative to surgery, despite the lack of evidence for its safety and efficacy. METHOD: Over a 33-month period, 39 consecutive patients with a stenosis >/=70% underwent CAS (4 in a randomized trial and 35 because of contra-indications for surgery). RESULTS: In 5 patients (13%; 95% CI: 3-23), a major complication occurred (3 disabling ischaemic strokes, 1 myocardial infarction, 1 acute interstitial nephropathy). In 7 patients (18%; 95% CI: 6-30), a minor complication occurred (5 transient ischaemic attacks, 1 transient confusional state, 1 non-disabling ischaemic stroke). CONCLUSION: CAS cannot be considered as a routine procedure and should be restricted to high-risk patients unfit for surgery.

[Peripheral haemosiderosis of the central nervous system]. / Hémosidérose marginale du névraxe.

We report 2 cases of patients with hemosiderosis of the central nervous system. The diagnosis was made in 1999 in a stroke unit. The patients had both deafness, but their clinical presentation was different, due to heterogeneous features of this pathology. Hemosiderosis of the central nervous system is due to chronic subarachnoidal hemorrhage. Magnetic resonance imaging is extremely sensitive to the presence of hemosiderin and is the investigation of choice enabling diagnosis and sometimes bleeding source (50 p. cent). The interest of our observations concerned the source of bleeding. In the first patient, diagnostic work-up was negative. For the second one, the deposition of hemosiderin was explained by 3 possible sources. If a bleeding source can be identified, surgery is the optimal treatment. Copper chelation, like Trientine can be used, but there is no evidence-based for using this treatment.

Relationship between leuko-araiosis and blood pressure variability in the elderly.

Although leuko-araiosis is a common finding on computed tomographic (CT) scans of the brain, its pathogenesis remains uncertain. To investigate the association between blood pressure (BP) disturbances and leuko-araiosis, we retrospectively reviewed CT scans and 24-hour ambulatory blood pressure monitorings of 79 elderly patients (57 women and 22 men; mean age: 83.3 +/- 6.4 years). Of the 79 patients, 50 were demented (30 had Alzheimer's disease and 18 vascular dementia) and 29 were not demented. The leuko-araiosis score (LA score) was determined by using Rezek's scale. To evaluate short-term variation of BP, we determined (1) the variability of systolic and diastolic BPs (SBP, DBP; within-subject standard deviation of all readings over a 24-hour period), (2) the coefficient of variability (variability of BP/mean BP) and (3) the maximal variation of BP (difference between the maximum and minimum 24-hour BPs). Higher LA scores were associated with higher SBPs in 24-hour, diurnal and nocturnal periods, higher maximal variation of SBP, greater variability of SBP during 24-hour, diurnal and nocturnal periods and greater coefficient of variability of SBP during sleep. Our study suggests that elevations and short-term variations of SBP may contribute to the pathogenesis of white matter lesions in elderly persons.

Successes and setbacks of the falls consultation: report on the first 150 patients.

OBJECTIVE: We report the results of a Falls Consultation. DESIGN: Data concerning the first 150 patients are reported. Each patient was assessed by a geriatrician, a neurologist, and a physiatrist, who visited him or her at home, and was reassessed by the same geriatrician 6 mo later. RESULTS: Of the 150 patients, 135 patients completed the initial evaluation. Most of them were frequent fallers. The population was very heterogeneous regarding the health status and the degree of disability. In most cases, falls were the result of several interacting factors. The most frequent recommendations from the staff were physical therapy, environmental changes, and medication changes. Over the following 6 mo, approximately one out of four patients had experienced new falls. However, the risk of falling was significantly reduced (5.3 +/- 7.3 falls in 6 mo before vs. 0.8 +/- 1.6 falls in 6 mo after the intervention). The Activities of Daily Living score was a predictor of recurrent falls, hospitalization, and institutionalization. CONCLUSION: Our results show that a multidisciplinary falls consultation can be efficient in reducing the risk of falls in nonselected elderly fallers but suggest that differential strategies are needed to manage adequately the more vigorous and the frail old person as well.

Increase in endogenous brain superoxide dismutase as a potential mechanism of lipopolysaccharide-induced brain ischemic tolerance.

A low dose (0.5 mg/kg) of lipopolysaccharide (LPS), administered 72 hours before 60-minute middle cerebral artery occlusion, induced a delayed neuroprotection proven by the significant decrease (-35%) of brain infarct volume in comparison with control, whereas infarct volumes remained unchanged in rats treated 12, 24, or 168 hours before ischemia. This delayed neuroprotective effect of LPS was induced only with low doses (0.25 to 1 mg/kg), whereas this effect disappeared with a higher dose (2 mg/kg). The delayed neuroprotection of LPS was induced in the cortical part of the infarcted zone, not in the subcortical part. The beneficial effect of LPS on consequences of middle cerebral artery occlusion was suppressed by dexamethasone (3 mg/kg) and indomethacin (3 mg/ kg) administered 1 hour before LPS, whereas both drugs had no direct effect on infarct volume by themselves, suggesting that activation of inflammatory pathway is involved in the development of LPS-induced brain ischemic tolerance. Preadministration of cycloheximide, an inhibitor of protein synthesis, also blocked LPS-induced brain ischemic tolerance suggesting that a protein synthesis is also necessary as a mediating mechanism. Superoxide dismutase (SOD) could be one of the synthesized proteins because lipopolysaccharide increased SOD brain activity 72 hours, but not 12 hours, after its administration, which paralleled the development of brain ischemic tolerance. In contrast, catalase brain activity remained unchanged after LPS administration. The LPS-induced delayed increase in SOD brain content was suppressed by a previous administration of indomethacin. These data suggest that the delayed neuroprotective effect of low doses of LPS is mediated by an increased synthesis of brain SOD that could be triggered by activation of inflammatory pathway.

Differential role of nitric oxide pathway and heat shock protein in preconditioning and lipopolysaccharide-induced brain ischemic tolerance.

The purposes of this study were to investigate the role of nitric oxide (NO), nitric oxide synthase (NOS), and 70 kDa heat shock protein in brain ischemic tolerance induced by ischemic preconditioning and lipopolysaccharide. Focal cerebral ischemia was induced in rats by intraluminal middle cerebral artery occlusion. Infarct volume was significantly reduced (1) in rats subjected to 3 min ischemia 72 h prior to 60 min ischemia; (2) in rats administered lipopolysaccharide (0.5 mg/kg; i.p.) 72 h prior to 60 min ischemia compared with controls. The beneficial effect of ischemic preconditioning was unchanged despite prior administration of nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor. Conversely, the protective effect of lipopolysaccharide was nullified by L-NAME. Using immunohistochemical techniques, we observed that (1) ischemic preconditioning but not lipopolysaccharide induces the expression of 70 kDa heat shock protein in cerebral cortex and (2) lipopolysaccharide induces early increased expression of endothelial NOS in cerebral blood vessels. The results suggest that (1) endothelium-derived NO plays a role of a trigger in the brain tolerance induced by lipopolysaccharide, and (2) 70 kDa heat shock protein is involved in the protection afforded by ischemic preconditioning but not by lipopolysaccharide.

Susceptibility to provoked cerebral infarction is not increased in a rat model of pharmacologically-induced hypertension despite endothelial dysfunction.

An increase in susceptibility to provoked stroke has been described in a genetically-determined rat model of hypertension. We investigated whether the susceptibility to provoked cerebral ischaemia was also increased in a rat model of pharmacologically-induced hypertension with endothelial dysfunction. Chronic inhibition of nitric oxide synthase induced by N(omega)-nitro-L-arginine methyl ester (L-NAME) administration (50 or 75 mg.kg(-1) x day(-1)) in drinking water for 6 weeks caused a sustained hypertension, comparable in the two groups. Endothelium-dependent relaxation induced by acetylcholine or A23187 was significantly, and dose-dependently, impaired in rats receiving L-NAME, as proven by a decrease in maximal relaxation and increase of EC50, as compared to control. Endothelium-independent relaxation induced by sodium nitroprusside was not different in the three groups. Aortic media area was significantly, and dose-dependently, increased following chronic nitric oxide inhibition. Cerebral infarct volumes were not increased in L-NAME-treated groups independently of the level of endothelial dysfunction induced by chronic L-NAME administration. These data demonstrate that susceptibility to cerebral infarction was not increased in a non-genetically determined hypertension model in spite of the development of endothelial dysfunction and vascular structure alterations.