The free plasma amyloid Aß1-42/Aß1-40 ratio predicts conversion to dementia for subjects with mild cognitive impairment with performance equivalent to that of the total plasma Aß1-42/Aß1-40 ratio. The BALTAZAR study.

BACKGROUND AND PURPOSE: Blood-based biomarkers are a non-invasive solution to predict the risk of conversion of mild cognitive impairment (MCI) to dementia. The utility of free plasma amyloid peptides (not bound to plasma proteins and/or cells) as an early indicator of conversion to dementia is still debated, as the results of studies have been contradictory. In this context, we investigated whether plasma levels of the free amyloid peptides Aß1-42 and Aß1-40 and the free plasma Aß1-42/Aß1-40 ratio are associated with the conversion of MCI to dementia, in particular AD, over three years of follow-up in a subgroup of the BALTAZAR cohort. We also compared their predictive value to that of total plasma Aß1-42 and Aß1-40 levels and the total plasma Aß1-42/Aß1-40 ratio. METHODS: The plasma Aß1-42 and Aß1-40 peptide assay was performed using the INNO-BIA kit (Fujirebio Europe). Free amyloid levels (defined by the amyloid fraction directly accessible to antibodies of the assay) were obtained with the undiluted plasma, whereas total amyloid levels were obtained after the dilution of plasma (1/3) with a denaturing buffer. Free and total Aß1-42 and Aß1-40 levels were measured at inclusion for a subgroup of participants (N = 106) with mild cognitive impairment (MCI) from the BALTAZAR study (a large-scale longitudinal multicenter cohort with a three-year follow-up). Associations between conversion and the free/total plasma Aß1-42 and Aß1-40 levels and Aß1-42/Aß1-40 ratio were analyzed using logistic and Cox Proportional Hazards models. Demographic, clinical, cognitive (MMSE, ADL and IADL), APOE, and MRI characteristics (relative hippocampal volume) were compared using non-parametric (Mann-Whitney) or parametric (Student) tests for quantitative variables and Chi-square or Fisher exact tests for qualitative variables. RESULTS: The risk of conversion to dementia was lower for patients in the highest quartile of free plasma Aß1-42/Aß1-40 (≥ 25.8%) than those in the three lower quartiles: hazard ratio = 0.36 (95% confidence interval [0.15-0.87]), after adjustment for age, sex, education, and APOE ε4 (p-value = 0.022). This was comparable to the risk of conversion in the highest quartile of total plasma Aß1-42/Aß1-40: hazard ratio = 0.37 (95% confidence interval [0.16-0.89], p-value = 0.027). However, while patients in the highest quartile of total plasma Aß1-42/Aß1-40 showed higher MMSE scores and a higher hippocampal volume than patients in the three lowest quartiles of total plasma Aß1-42/Aß1-40, as well as normal CSF biomarker levels, the patients in the highest quartile of free plasma Aß1-42/Aß1-40 did not show any significant differences in MMSE scores, hippocampal volume, or CSF biomarker levels relative to the three lowest quartiles of free plasma Aß1-42/Aß1-40. CONCLUSION: The free plasma Aß1-42/Aß1-40 ratio is associated with a risk of conversion from MCI to dementia within three years, with performance comparable to that of the total plasma Aß1-42/Aß1-40 ratio. Threshold levels of the free and total plasma Aß1-42/Aß1-40 ratio could be determined, with a 60% lower risk of conversion for patients above the threshold than those below.

Orthostatic hypotension and orthostatic hypertension are both associated with lower cognitive function: The S.AGES cohort.

BACKGROUND: Blood pressure (BP) postural changes, both orthostatic hypotension (OHYPO) and orthostatic hypertension (OHYPER) are common in older adults. Few studies have investigated their association with cognition, particularly for OHYPER, an emerging cardiovascular risk factor. We aimed to assess the association between OHYPO, OHYPER and cognition in non-institutionalized older subjects. METHODS: The S.AGES (Sujets ÂGES, Aged Subjects) cohort followed every 6 months for 3 years non-institutionalized subjects aged ≥65 years without dementia at inclusion, in France. OHYPO and OHYPER were respectively defined as a fall or an increase of ≥20 mmHg in systolic BP and/or ≥10 mmHg in diastolic BP after standing from a sitting position. Cognition was assessed using the Mini-Mental State Examination (MMSE). Linear mixed models were used for the analyses. RESULTS: Among the 3170 subjects included (mean age 78 years, 56% women), 209 (6.5%) had OHYPO and 226 (7.1%) had OHYPER at baseline. After adjustment for demographics, cardiovascular risk factors and disease, seated SBP/DBP and BP lowering treatment, mean MMSE was 0.52 point lower in participants with OHYPER compared to those with normal BP postural changes (ß adjusted [95% CI] = -0.52 [-0.96; -0.09], p = 0.02) and 0.50 point lower in participants with OHYPO compared to those with normal BP postural changes (ß adjusted [95% CI] = -0.50 [-0.95; -0.06], p = 0.03). Sensitivity analyses showed a dose-response relationship between OHYPO and cognition. CONCLUSION: Although the absolute differences in MMSE were small, both OHYPO and OHYPER were associated with lower cognition. Orthostatic BP measurements could help identify patients with risk of cognitive impairment. Further studies are needed to assess whether controlling orthostatic BP could be a promising interventional target in preserving cognition among older adults.

Real-Life Peak and Trough Dabigatran Plasma Measurements over Time in Hospitalized Geriatric Patients with Atrial Fibrillation.

BACKGROUND: Few geriatric patients were included in studies on direct oral anticoagulants and data on dabigatran concentration and safety are needed in this population. Our objectives were to evaluate peak and trough dabigatran plasma concentrations over time in a geriatric population and to identify factors associated with dabigatran plasma concentrations and to assess the relationship with bleeding events. METHODS: Peak and trough dabigatran plasma concentration were performed 4,8,15,30,45 days after inception of dabigatran treatment in 68 consecutive patients ≥75 years old hospitalized in a geriatric hospital with atrial fibrillation. Bleeding events were monitored for 1 year. RESULTS: Mean age was 85.8(5.1) years old and 76.5% were women. Overall, 541 dabigatran plasma measurements (270 peak, 271 trough) were performed. Mean dabigatran concentrations of the 5 sequential measurements ranged 106-146ng/mL for peak and 66-84ng/mL for trough. Renal failure was associated with high peak and trough dabigatran concentration. Inter- and intra-individual coefficients of variation were 59.5% and 44.7% for peak and 74.5% and 44.6% for trough. Participants in the lower two tertiles of dabigatran concentration at day 8 (D8) remained below the 90th percentile (243.9ng/ml) on the next measurements. Bleeding events were associated with high trough dabigatran concentrations. Trough dabigatran concentration at D8>243.9ng/mL significantly predicted bleeding. CONCLUSION: In this geriatric population, renal function and low albumin were associated with dabigatran concentrations. Despite large variability, participants in the lower two tertiles of dabigatran concentration at D8 remained below the 90th percentile on the following measurements. D8 dabigatran trough concentration≥243.9ng/mL identified patients at risk of bleeding.

Therapeutic management in ambulatory elderly patients with atrial fibrillation: the S.AGES cohort.

UNLABELLED: Few epidemiologic studies have specifically focused on very old community dwelling population with atrial fibrillation (AF). The objectives of the AF-S.AGES cohort were to describe real-life therapeutic management of non-institutionalized elderly patients with AF according to age groups, i.e., 65-79 and ≥ 80 and to determine the main factors associated with anticoagulant treatment in both groups. METHODS: Observational study (N=1072) aged ≥ 65 years old, recruited by general practitioners. Characteristics of the sample were first evaluated in the overall sample and according to age (< 80 or ≥ 80 years) and to use of anticoagulant treatment at inclusion. Logistic models were used to analyze the determinants of anticoagulant prescription among age groups. RESULTS: Mean age was 78.0 (SD=6.5) years and 42% were ≥ 80 years. Nineteen percent had paroxysmal AF, 15% persistent, 56% permanent and 10% unknown type, 77% were treated with vitamin K antagonists (VKA), 17% with antiplatelet therapy with no differences between age groups. Rate-control drugs were more frequently used than rhythm-control drugs (55% vs. 37%, p < 0.001). VKA use was associated with permanent AF, younger age and cancer in patients ≥ 80 years old and with permanent AF and preserved functional autonomy in patients < 80 years old. Hemorrhagic scores were independently associated with non-use of VKA whereas thromboembolic scores were not associated with VKA use. CONCLUSIONS: In this elderly AF outpatient population, use of anticoagulant therapy was higher even after 80 years than in previous studies suggesting that recent international guidelines are better implemented in the elderly population.

Robot services for elderly with cognitive impairment: testing usability of graphical user interfaces.

BACKGROUND: Socially assistive robotics for elderly care is a growing field. However, although robotics has the potential to support elderly in daily tasks by offering specific services, the development of usable interfaces is still a challenge. Since several factors such as age or disease-related changes in perceptual or cognitive abilities and familiarity with computer technologies influence technology use they must be considered when designing interfaces for these users. OBJECTIVE: This paper presents findings from usability testing of two different services provided by a social assistive robot intended for elderly with cognitive impairment: a grocery shopping list and an agenda application. The main goal of this study is to identify the usability problems of the robot interface for target end-users as well as to isolate the human factors that affect the use of the technology by elderly. METHODS: Socio-demographic characteristics and computer experience were examined as factors that could have an influence on task performance. A group of 11 elderly persons with Mild Cognitive Impairment and a group of 11 cognitively healthy elderly individuals took part in this study. Performance measures (task completion time and number of errors) were collected. RESULTS: Cognitive profile, age and computer experience were found to impact task performance. Participants with cognitive impairment achieved the tasks committing more errors than cognitively healthy elderly. Instead younger participants and those with previous computer experience were faster at completing the tasks confirming previous findings in the literature. CONCLUSIONS: The overall results suggested that interfaces and contents of the services assessed were usable by older adults with cognitive impairment. However, some usability problems were identified and should be addressed to better meet the needs and capacities of target end-users.

Capacity to consent to biomedical research's evaluation among older cognitively impaired patients. A study to validate the University of California Brief Assessment of Capacity to Consent questionnaire in French among older cognitively impaired patients.

CONTEXT: Some studies have highlighted the difficulty for physicians to evaluate patient's ability to consent to bio-medical research in the elderly population. The University of California Brief Assessment of Capacity to Consent (UBACC) is a rapid questionnaire to assess the ability to consent, previously validated among schizophrenic patients. OBJECTIVE: To evaluate the accuracy of the UBACC scale, French version, to determine the capacity to consent to biomedical studies of older people with normal cognition, mild cognitive impairment (MCI) or Alzheimer Disease (AD). DESIGN: A prospective validation study between September 2008 to November 2011. SETTING: A Memory clinic. PATIENTS: We included 61 subjects in a memory clinic who had already consented to participate to a biomedical research and had signed a consent form. Those subjects, who had memory impairment, had a comprehensive neuro-psychological (including Mini Mental State Examination (MMSE)/30), clinical, biological assessment and brain imagery during day-care hospital. They were classified as MCI or AD patients. Control group included patients' caregivers without memory complaints and a normal comprehensive neuro-psychological assessment. INTERVENTION AND MEASUREMENTS: The consent form was once again explained to the subjects by a physician who subjectively evaluated if subjects had understood the study. Then, the 10 questions of the French version of the UBACC scale (max score 20) were asked to the participants. This scale evaluates the understanding of the study's aim, risks and benefits. A comparison was made between subjective assessment and the UBACC score. RESULTS: The physician considered that 18/61 patients (2 MCI and 16 AD) had not understood. These ones had a lower UBACC score (Score/20 (SD) [range]: 7.56 (3.03) [0-12] versus 17.72 (2.68) [13-28], p<0.001), a lower MMSE (Score/ 30 (SD): 21.1 (5.9) versus 27.3 (2.9); p<0.001) and were older (age (years old) 80.8 versus 76.6. p<0.0001) compared to those who had understood. Moreover, all the patients who had not understood had an UBACC score ≤ 12. The administration time was accurate in this population (<10 minutes). CONCLUSION: The UBACC scale, in its French version, was accurate to assess capacity to consent in an older, cognitively impaired population.

[Assessment of antihypertensive monotherapies effectiveness by home blood pressure self-measurement in hypertensive patients]. / Évaluation par l'automesure au domicile de l'efficacité de monothérapies antihypertensives chez des hypertendus traités en France.

OBJECTIVE: To evaluate the blood pressure (BP) control and the efficacy of antihypertensive monotherapy using home BP self-measurement in a French population of treated hypertensive subjects in 2007 2009 and 2010. METHODS: The French League Against Hypertension Surveys (FLAHS) are conducted among a representative sample of individuals aged 35 years and older living in France. For the 2007, 2009 and 2010 surveys, a sample of 1467 subjects who owned a BP self-measurement device and performed three consecutive morning BP measurements were included. Among the 60% of subjects who reported taking at least one antihypertensive drug, we analyzed subjects treated with one of the following antihypertensive monotherapy, i.e., beta-blocker (BB), ACE inhibitors, calcium channel blocker (CCB) and angiotensin receptor blockers (ARB). RESULTS: Among treated hypertensive subjects (n=886), 66% (n=586) had home BP below the 140/90mmHg threshold and 50% (n=449) below 135/85mmHg. Three hundred two subjects were treated with a single antihypertensive drug, 33% had ARB, 25% BB, 19% CCB and 13% ACE inhibitors. Age (years) for each treatment group is different (P<0.01) CCB (72.1±9.3), BB (65.6±9.8), ARB (68.6±8.9) and ACEI (67.3±10.2). The mean systolic/diastolic BP (mmHg) is not comparable between monotherapy 130.7/76.1 (ARB), 130.7/78.7 (BB), 134.0/75.2 (CCB) and 139.1/80.3 (ACEI) for ARB, BB, CCB and ACE inhibitors respectively. Compared to ACE inhibitors, BP was significantly lower with ARB (P<0.01). The proportion of subjects with a BP below 140/90mmHg was 73% for ARB, 52% for BB, 68% for CCB and 47% for ACE with a statistical significance (P=0.03) for ARB vs. ACEI and CCB vs. ACEI. CONCLUSION: Among subjects treated for hypertension who owned a BP self-measurement device, 50 to 66% had a controlled BP (depending on the threshold used). It is observed differences between antihypertensive efficacy of monotherapy with a larger number of patients controlled with ARB or CCB.

DAD-6: A 6-ltem version of the Disability Assessment for Dementia scale which may differentiate Alzheimer's disease and mild cognitive impairment from controls.

BACKGROUND: The need to detect early changes in instrumental activities of daily life led us to modify the Disability Assessment for Dementia Scale (DAD) by focusing on executive components of 6 instrumental items (DAD-6). AIM: To evaluate the relevance of the DAD-6 for detecting early impairment in a nondemented population. METHODS: The DAD-6 was administered to informants of 84 patients: 31 with mild dementia (MD), 53 with mild cognitive impairment (MCI) and 55 healthy controls. RESULTS: DAD-6 scores gradually decreased with increasing severity of the cognitive status [18 in healthy controls vs. 15.1 ± 3.2 in MCI versus 9.6 ± 3.5 in MD, p < 0.0001). Receiver-operating characteristic curve analyses yielded an optimal cut score of 14 to distinguish MCI from MD with a sensitivity of 0.83 (95% confidence interval 0.74-0.92) and a specificity of 0.84 (0.71-0.94), and a cut score of 15 to distinguish single-domain MCI from multi-domain MCI with a sensitivity of 0.96 (0.90-0.99) and a specificity of 0.54 (0.33-0.75). CONCLUSION: The DAD-6 reliably detects early loss of autonomy due to cognitive impairment.

Factors associated with emergence of pristinamycin-resistant Staphylococcus aureus in a dermatology department: a case-control study.

BACKGROUND: Pristinamycin is used for the treatment of Staphylococcus aureus skin infection. Staphylococcus aureus pristinamycin resistance is usually low. The frequency of pristinamycin-resistant S. aureus (PRSA) increased in the Caen University Hospital dermatology department from 1% in 1998 to >11% in 1999-2002. OBJECTIVES: This study aimed to identify the factors associated with PRSA acquisition. METHODS: Incidences of PRSA and pristinamycin consumption were calculated for the dermatology department and for the rest of the hospital from 1997 to 2007. Individual factors of PRSA acquisition in the dermatology department from 2000 to 2001 were analysed in a retrospective case-control study including 23 cases of PRSA skin colonization or infection and 46 controls with pristinamycin-susceptible S. aureus. Clonal relatedness of isolates was analysed by pulsed-field gel electrophoresis and pristinamycin resistance genes were detected by polymerase chain reaction. Conditional logistic regression was performed to analyse the relationship between pristinamycin resistance and epidemiological and microbiological data. RESULTS: PRSA frequency and pristinamycin consumption were significantly higher in the dermatology department than in other hospital departments. Two epidemic clones of two and six isolates were found for periods of 1 and 2 months, respectively. Thirteen of the 23 PRSA isolates (57%), including all isolates of the two epidemic clones, were found 48 h after the hospitalization or later. PRSA was associated with pristinamycin use during the previous year [odds ratio (OR) 5.60, 95% confidence interval (CI) 1.41-22.22], cumulative use of antibiotics exceeding 1 week during the previous year (OR 4.63, 95% CI 1.47-14.54) and methicillin resistance (OR 6.35, 95% CI 1.38-29.15). CONCLUSIONS: Results suggest that antimicrobial selective pressure and microbial cross-transmission are involved in PRSA acquisition.

Risk factors for progressive supranuclear palsy: a case-control study in France.

BACKGROUND: The risk factors of progressive supranuclear palsy (PSP), a rare but severe Parkinsonian syndrome, are poorly known. OBJECTIVE: To study the risk factors of PSP in a case control study among French patients. METHOD: The study was conducted between April 2000 and December 2003. Cases were in- or outpatients of five large hospitals and fulfilled the Golbe criteria. Controls were relatives of patients from the same hospitals, free of Parkinsonian syndrome and dementia, and matched to cases for age, gender and living area. Data on demographic characteristics, occupation history, diet habits, anti-inflammatory drugs use, alcohol consumption, smoking habits, gardening and leisure activities, and exposure to pesticides were collected through a face-to-face questionnaire. A conditional logistic regression was used to analyse matched data and estimate OR. RESULTS: 79 cases and 79 controls were included. Only a few comparisons were significant. Cases reached a lower education attainment than controls (odds ratio (OR) = 2.6 (1.3 to 5.3), p = 0.01). Analysis of diet habits did not show any major difference although cases ate meat or poultry more frequently. Conversely, controls ate fruits more frequently than did cases. No association was found between PSP and occupation, use of pesticides, gardening, alcohol consumption, smoking habits and anti-inflammatory agent use. CONCLUSION: In this case-control study, we did not find any strong environmental risk factors for PSP.

Prevalence and risk factors of the whole spectrum of sexually transmitted diseases in male incoming prisoners in France.

Sexually transmitted diseases (STD) are a public health issue in prison. As inmates are eventually released, it is also a community concern. There are very few data on the entire spectrum of STDs, particularly condyloma among prisoners. To determine the prevalence of all STDs: infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus (HSV), Chlamydia trachomatis, Neisseria gonorrhoea, syphilis, and condyloma among entering inmates. A cross-sectional study was conducted in France from November 2000 to June 2003. Male adults entering a prison remand center in Caen had a medical consultation and physical examination including external genital organs and perianal area for condyloma and herpes infection, a urethral swab for Chlamydia trachomatis and Neisseria gonorrhoea detection, and a blood sample for HBV, HCV, HIV, and syphilis serology. Five hundred and ninety-seven inmates agreed to participate in the study. Sixteen percent had at least one STD: 4.0% had condyloma, 4.0% chlamydia infection, and 4.9% were positive for HCV antibodies. Two had early syphilis and 1 had acute HBV, but no HIV infection, neither genital herpes nor gonorrhea. The analysis of the STD risk behaviors did not show any difference between the infected and uninfected participants, except that HCV-positive participants were more likely to be intravenous drug users. Results suggest that a systematic screening of all STDs should be at least proposed to every entering inmate since no demographic or sexual characteristics are consistently associated with STDs.

Immunosuppressive therapy is more effective than interferon in neuromyelitis optica.

To determine long-term treatment (LTT) of neuromyelitis optica (NMO), we retrospectively reviewed therapies of 26 patients with NMO followed in five French neurological departments. To assess LTT efficacy, the probability of relapse free after LTT was analysed. Patients were divided into two groups according to the first treatment receiving interferon beta (IFN Group, seven patients) or immunosuppressants (IS Group, 19 patients). The probability of relapse was significantly lower in the IS Group (P =0.0007). From our results, interferon beta is not recommended, and one of the best current therapeutic options for NMO appears to be immunosuppressants.

Factors predicting improvement in motor disability in writer's cramp treated with botulinum toxin.

OBJECTIVE: To identify factors predicting improvement in motor disability in writer's cramp treated with botulinum toxin (BTX). METHODS: 47 patients with writer's cramp were treated with BTX and were evaluated by the same neurologists at initial referral, after each BTX injection, and when the effect of BTX was maximal at the time of the study. Patients and examiners simultaneously and independently rated the efficacy of BTX injections. Self assessment was a global clinical impression of the impact of treatment on writing quality, writing speed, writing errors, and legibility of handwriting; for objective assessment, the examiners used the Burke-Fahn-Marsden (BFM) scale. RESULTS: On the BFM scale, there was a significant improvement (p<0.0001) in both severity and disability scores. Patients with a pronation/flexion pattern of dystonia showed the best and the most sustained improvement. Primary writing tremor was little improved. There was a correlation between the self assessment score and the Burke-Fahn-Marsden score. Benefit was maintained over time CONCLUSIONS: These results have implications for the identification of patients most likely to benefit from BTX injections.

Association of polymorphisms in the Tau and Saitohin genes with Parkinson's disease.

BACKGROUND: The Saitohin gene has recently been identified in intron 9 of the Tau gene. Because an association between Parkinson's disease and Tau has been described, Saitohin represents a candidate gene for Parkinson's disease. OBJECTIVE: To test these two genes for their association with Parkinson's disease in a large community based case-control study. RESULTS: Cases (n = 208) were more often homozygotes for the Tau H1 haplotype than controls (n = 483; odds ratio (OR) = 1.71 (95% confidence interval, 1.20 to 2.43); p = 0.003), and the saitohin Q allele was in complete linkage disequilibrium with the H1 haplotype. This association was stronger among cases with Parkinson's disease onset below 65 years (< or =65 years: OR = 2.52 (1.49 to 4.25); p<0.001) than among those with older onset (>65 years: OR = 1.20 (0.73 to 1.98); p<0.47). CONCLUSIONS: The data suggest that there is a functional polymorphism at this locus involved in Parkinson's disease.

[Movement disorders and botulinum toxin in neurology]. / Mouvements anormaux et toxine botulique en neurologie.

Botulinum toxin has been a useful treatment in many movement disorders and more recently in other non-neurological motor dysfunctions for more than 15 years. Here, we review the various indications in neurology, mainly in the field of movement disorders. From 1973 to 2002, we searched the Medline database on this topic. We selected the most useful and relevant papers, with a special interest in dystonia. We summarized the results in the main indications (spasmodic torticollis, bleparospasm, hemifacial spasm) and in other manifestations such as writer's cramp, oromandibular dystonia, tremor, tics and myoclonus. We discuss the data of literature and compare them with the experience of the French movement disorders groups.