Clinical impact of an individualised clinical pharmacy programme into the memory care pathway of older people: an observational study.

BACKGROUND: In older patients, medication exposure [i.e. polypharmacy, potentially inappropriate medications (PIMs), medications with anticholinergic and/or sedative properties] is a modifiable risk factor associated with cognitive iatrogenic risk and dementia. AIM: To assess the potential clinical impact of the implementation of an individualised clinical pharmacy programme at the initiation of the Memory care pathway in older patients with a cognitive complaint. METHOD: This prospective observational study included older patients with high-risk of adverse drug event (HR) admitted in a French geriatric university hospital to explore the cognitive complaint or the cognitive disorder between January and November 2021. Drug-related problems (DRPs) were identified during a medication review performed in HR patients, and pharmaceutical interventions (PIs) notified in the patient's hospitalisation report were collected. The clinical impact of PIs was assessed by an expert panel (geriatricians and clinical pharmacists) using the Clinical, Economic, and Organisational (CLEO) tool. RESULTS: Overall, 326 patients were eligible and 207 (63.5%) were considered as HR patients. Among HR patients, 88.9% (n = 184) were treated using at least 5 medications (polypharmacy), and 36.7% (n = 76) received at least one PIM with cognitive iatrogenic risk. During the medication review, 490 PIs were provided and their clinical impact was rated as minor for 57.3% (n = 281), moderate for 26.7% (n = 131), and major for 2.5% (n = 12). CONCLUSION: The integration of clinical pharmacist secured the Memory care pathway of older patients with a cognitive complaint by identifying an important number of DRPs and PIMs with potential cognitive iatrogenic risk.

Medication exposure of the dyad patient-caregiver in Alzheimer's disease and related dementias: a cross-sectional study.

BACKGROUND: Patients with Alzheimer's disease and related dementias and their caregivers can be defined as people with higher risk of developing medication-related problems due to aging and polypharmacy. AIM: To assess the medication exposure of patient with Alzheimer's disease and related dementias and their caregivers. METHOD: Ancillary cross-sectional study based on baseline medication data of the PHARMAID RCT. The PHARMAID study was a multi-center RCT assessing an integrated pharmaceutical care at a psychosocial program. Older outpatients with Alzheimer's disease and related dementias and their older caregivers were eligible for inclusion. Baseline medication data were used to assess the medication exposure, illustrated by the number of medications, the prevalence of potentially inappropriate medications (PIMs) using the EU(7)-PIM list and the Medication Regimen Complexity Index (MRCI). RESULTS: Seventy-three dyads were included in this ancillary study. The mean numbers (SD) of medications used by patients was 6.8 (2.6) and by caregivers was 4.7 (3.7). Overall, 60.3% of patients used at least one PIM and 47.9% of caregivers. Regarding the medication regimen complexity, the mean MRCI was 16.3(8.1) for patients and 11.3(10.5) for caregivers. CONCLUSION: The results of this study confirm the relevance of carrying out medication review with patients, but also with their caregivers who can be considered as hidden patients.

[Early management of presbycusis: recommendations from the French Society of Otorhinolaryngology and Head and Neck Surgery, the French Society of Audiology, and the French Society of Geriatrics and Gerontology]. / Recommandations de la Société française d'otorhinolaryngologie et de chirurgie de la face et du cou, la Société française d'audiologie et la Société française de gériatrie et gérontologie pour la prise en charge précoce de la presbyacousie.

INTRODUCTION: Presbycusis is the physiological decrease in hearing due to advancing age and begins well before the sixth decade. These recommendations recall the principles of early diagnosis of presbycusis and the means of optimal rehabilitation as soon as the first symptoms appear. MATERIAL AND METHODS: The recommendations are based on a systematic analysis of the literature carried out by a multidisciplinary group of doctors and audioprosthetists from all over France. They are graded A, B, C or expert opinion according to decreasing level of scientific evidence. RESULTS: The diagnosis of presbycusis is more difficult at the beginning of its evolution but a certain number of tools are available for its early diagnosis and its management in face-to-face or even distance learning. CONCLUSION: In case of a clinical profile suggestive of presbycusis in a young subject, especially if there are several family cases, it is recommended to propose a genetic investigation. It is recommended to perform free-field speech audiometry in noise to measure intelligibility in an environment as close as possible to reality. Questionnaires can be used in addition to audiometry to best assess the patient's disability. It is recommended that hearing rehabilitation with a hearing aid or cochlear implant may slow or prevent cognitive decline. Combined auditory and cognitive rehabilitation should be offered regardless of the time elapsed since the fitting. It is recommended to integrate programs accessible via smartphones, tablets or the Internet, integrating different training domains in addition to face-to-face sessions.

Potentially inappropriate medications and anticholinergic and sedative burden in older community-dwelling patients with advanced chronic kidney disease

Objective: Regarding older patients, multiple chronic conditions lead to the intake of multiple medications, involving a higher risk of adverse drug events. In older patients with advanced chronic kidney disease, the medication exposure was poorly explored. The aim of this study was to describe the use of potentially inappropriate medications and medications with anticholinergic and sedative properties in older community-dwelling patients with advanced chronic kidney disease. Methods: An observational study was conducted in a geriatric day-care unit. All patients aged over 65 years with advanced chronic kidney disease, defined by estimated glomerular filtration rate < 20 mL/min/1.73 m2 or estimated glomerular filtration rate > 20 mL/min/1.73 m2 with rapid progression, and referred by nephrologist for pretransplant comprehensive geriatric assessment, were included in the study. Potentially inappropriate medications were identified using the EU(7)-PIM list, and he anticholinergic and sedative drug exposure was measured using the Drug Burden Index. Results: Overall, 139 patients were included in the study (mean age 74.4 ± 3.3 years, 32.4% females, 61.9% on dialysis). Potentially inappropriate medications were used by 74.1% (103/139) of patients and were mainly represented by proton pump inhibitors, alpha-1-blockers and central antihypertensive drugs. Regarding anticholinergic and / or sedative medications, 79.9% (111/139) of older patients were exposed. Conclusion: In older community-dwelling patients with advanced chronic kidney disease, the prevalence of potentially inappropriate medication exposure and anticholinergic and sedative exposure was high. Interventions focusing on deprescription of these inappropriate medications should be conducted in this specific population.

Objectif: Chez le patient âgé, la polypathologie est souvent associée à la prise de plusieurs médicaments, impliquant un risque élevé d'iatrogénie médicamenteuse. L'exposition médicamenteuse a été peu explorée chez les patients âgés atteints d'insuffisance rénale chronique. L'objectif de cette étude est de décrire l'exposition aux médicaments potentiellement inappropriés et aux médicaments présentant des propriétés anticholinergiques et sédatives chez ces patients. Méthodes: Il s'agit d'une étude observationnelle conduite au sein d'un hôpital de jour gériatrique. Tous les patients âgés de plus de 65 ans avec une maladie rénale chronique avancée, définie par un débit de filtration glomérulaire estimé inférieur à 20 mL/min/1,73 m² ou supérieur à 20 mL/min/1,73 m² avec une progression rapide, et adressés par un néphrologue pour la réalisation d'une évaluation gériatrique standardisée pré-transplantation rénale, ont été inclus dans l'étude. Les médicaments potentiellement inappropriés ont été identifiés à partir de la liste EU(7)-PIM, et l'exposition aux médicaments anticholinergiques et sédatifs a été mesurée à partir du Drug Burden Index. Résultats: Un total de 139 patients a été inclus dans l'étude (74,4 ± 3,3 ans, 32,4 % de femmes, 61,9 % dialysés). Des médicaments potentiellement inappropriés ont été retrouvés chez 74,1 % (103/139) des patients. Ils étaient principalement représentés par les inhibiteurs de la pompe à protons, les alpha-1-bloquants et les antihypertenseurs centraux. Concernant les médicaments anticholinergiques et/ou sédatifs, 79,9 % (111/139) des patients âgés étaient exposés. Conclusion: L'étude montre que la prévalence de l'exposition aux médicaments potentiellement inappropriés et aux médicaments anticholinergiques et/ou sédatifs est élevée chez les patients âgés atteints de maladie rénale chronique avancée. Des interventions portant sur la déprescription de ces médicaments devraient être menées auprès de cette population spécifique.

Automatic segmentation of white matter hyperintensities: validation and comparison with state-of-the-art methods on both Multiple Sclerosis and elderly subjects.

Different types of white matter hyperintensities (WMH) can be observed through MRI in the brain and spinal cord, especially Multiple Sclerosis (MS) lesions for patients suffering from MS and age-related WMH for subjects with cognitive disorders and/or elderly people. To better diagnose and monitor the disease progression, the quantitative evaluation of WMH load has proven to be useful for clinical routine and trials. Since manual delineation for WMH segmentation is highly time-consuming and suffers from intra and inter observer variability, several methods have been proposed to automatically segment either MS lesions or age-related WMH, but none is validated on both WMH types. Here, we aim at proposing the White matter Hyperintensities Automatic Segmentation Algorithm adapted to 3D T2-FLAIR datasets (WHASA-3D), a fast and robust automatic segmentation tool designed to be implemented in clinical practice for the detection of both MS lesions and age-related WMH in the brain, using both 3D T1-weighted and T2-FLAIR images. In order to increase its robustness for MS lesions, WHASA-3D expands the original WHASA method, which relies on the coupling of non-linear diffusion framework and watershed parcellation, where regions considered as WMH are selected based on intensity and location characteristics, and finally refined with geodesic dilation. The previous validation was performed on 2D T2-FLAIR and subjects with cognitive disorders and elderly subjects. 60 subjects from a heterogeneous database of dementia patients, multiple sclerosis patients and elderly subjects with multiple MRI scanners and a wide range of lesion loads were used to evaluate WHASA and WHASA-3D through volume and spatial agreement in comparison with consensus reference segmentations. In addition, a direct comparison on the MS database with six available supervised and unsupervised state-of-the-art WMH segmentation methods (LST-LGA and LPA, Lesion-TOADS, lesionBrain, BIANCA and nicMSlesions) with default and optimised settings (when feasible) was conducted. WHASA-3D confirmed an improved performance with respect to WHASA, achieving a better spatial overlap (Dice) (0.67 vs 0.63), a reduced absolute volume error (AVE) (3.11 vs 6.2 mL) and an increased volume agreement (intraclass correlation coefficient, ICC) (0.96 vs 0.78). Compared to available state-of-the-art algorithms on the MS database, WHASA-3D outperformed both unsupervised and supervised methods when used with their default settings, showing the highest volume agreement (ICC = 0.95) as well as the highest average Dice (0.58). Optimising and/or retraining LST-LGA, BIANCA and nicMSlesions, using a subset of the MS database as training set, resulted in improved performances on the remaining testing set (average Dice: LST-LGA default/optimized = 0.41/0.51, BIANCA default/optimized = 0.22/0.39, nicMSlesions default/optimized = 0.17/0.63, WHASA-3D = 0.58). Evaluation and comparison results suggest that WHASA-3D is a reliable and easy-to-use method for the automated segmentation of white matter hyperintensities, for both MS lesions and age-related WMH. Further validation on larger datasets would be useful to confirm these first findings.

Pretransplant Comprehensive Geriatric Assessment in Older Patients with Advanced Chronic Kidney Disease.

BACKGROUND: In older patients with advanced chronic kidney disease (CKD), the decision of kidney transplantation (KT) is a challenge for nephrologists. The use of comprehensive geriatric assessment (CGA) is increasingly gaining interest into the process of decision-making about treatment modality choice for CKD. The aim of this study was to assess the prevalence of geriatric impairment and frailty in older dialysis and nondialysis patients with advanced CKD using a pretransplant CGA model and to identify geriatric impairments influencing the geriatricians' recommendations for KT. METHODS: An observational study was conducted with retrospective data from July 2017 to January 2020. Patients aged ≥65 years with advanced CKD, treated or not with dialysis, and referred by the nephrologist were included in the study. The CGA assessed comorbidity burden, cognition, mood, nutritional status, (instrumental) activities of daily living, physical function, frailty, and polypharmacy. Geriatric impairments influencing the geriatricians' recommendations for KT were identified using univariate and multivariate logistic regressions. RESULTS: 156 patients were included (74.2 ± 3.5 years and 62.2% on dialysis). Geriatric conditions were highly prevalent in both dialysis and nondialysis groups. The rate of geriatric impairments was higher in dialysis patients regarding comorbidity burden, symptoms of depression, physical function, autonomy, and frailty. Geriatrician's recommendations for KT were as follows: favorable (79.5%) versus not favorable or multidisciplinary discussion needed with nephrologists (20.5%). Dependence for Instrumental Activities of Daily Living (IADL) (odds ratio [OR] = 3.01 and 95% confidence interval [CI] = 1.30-7.31), physical functions (OR = 2.91 and 95% CI = 1.08-7.87), and frailty (OR = 2.66 and 95% CI = 1.07-6.65) were found to be independent geriatric impairments influencing geriatrician's recommendations for KT. CONCLUSIONS: Understanding the burden of geriatric impairment provides an opportunity to direct KT decision-making and to guide interventions to prevent functional decline and preserve quality of life.

Investigating the association between cancer and the risk of dementia: Results from the Memento cohort.

INTRODUCTION: Studies on the association of cancer and risk of dementia are inconclusive due to result heterogeneity and concerns of survivor bias and unmeasured confounding. METHODS: This study uses data from the Memento cohort, a French multicenter cohort following persons with either mild or isolated cognitive complaints for a median of 5 years. Illness-death models (IDMs) were used to estimate transition-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cancer in relation to dementia from time since study entry. RESULTS: The analytical sample (N = 2258) excluded 65 individuals without follow-up information. At the end of follow-up, 286 individuals were diagnosed with dementia, 166 with incident cancer, and 95 died. Incident cancer was associated with a reduced risk of dementia (HR = 0.58, 95% CI = 0.35-0.97), with a corresponding E-value of 2.84 (lower CI = 1.21). DISCUSSION: This study supports a protective relationship between incident cancer and dementia, encouraging further investigations to understand potential underlying mechanisms.

Exposure to Anticholinergic and Sedative Drugs and Healthcare Costs in Older Patients with Neurocognitive Disorders.

BACKGROUND: Literature supports an increasing number of older patients living with neurocognitive disorders alongside with their annual worldwide costs. Therapeutic management of behavioral and psychological symptoms includes the use of anticholinergic and sedative drugs for which significant exposure is negatively associated with clinical outcomes. OBJECTIVE: The aim of this study was to assess the healthcare costs differences related to an increase in the exposure to anticholinergic and sedative drugs in older patients with neurocognitive disorder. METHODS: A longitudinal study was conducted during 3 years on 1,604 participants of the MEMORA cohort linked with both regional public health insurance and hospital discharge databases between 2012 and 2017. Direct medical and non-medical costs were included. Exposure to anticholinergic and sedative drugs was measured by the drug burden index (DBI). RESULTS: Costs difference associated with a DBI≥0.5 were + 338€ (p < 0.001). After adjustment on comorbidities, NCD stage, cognitive impairment, functional limitation, polypharmacy, and sociodemographic characteristics, a DBI≥0.5 was found to be an independent predictor of an increase of total healthcare costs by 22%(p < 0.001). CONCLUSION: Anticholinergic and sedative drugs have a substantial economic burden among older patients with neurocognitive disorder. More studies are required to assess the clinical and economic impact of an efficient strategy based on the reduction of the exposure to anticholinergic and sedative drugs and the promotion of non-pharmacological interventions.

Consensus of experts from the French Society of Geriatrics and Gerontology on the management of heart failure in very old subjects.

The prevalence of heart failure increases with age. In France, the 1-year mortality rate is 35% in subjects aged 80-89 years with heart failure, and 50% after the age of 90 years. In octogenarians, heart failure is associated with high rates of cardiovascular and non-cardiovascular events, and is one of the main causes of hospitalization and disability. The prevalence of frailty increases in elderly subjects with heart failure, and the co-occurrence of heart failure and frailty increases the risk of mortality in patients with heart failure. In the elderly, the presence of frailty must be evaluated using a comprehensive geriatric assessment to manage geriatric syndromes, such as cognitive disorders, malnutrition, falls, depression, polypharmacy, disability and social isolation. The objective of heart failure therapy in octogenarians is to reduce symptoms, mortality and hospitalizations, but also to improve quality of life. In the absence of specific studies involving very old subjects, most recommendations are extrapolated from evidence-based data from younger populations. Overall, the epidemiological studies in patients with heart failure aged>80 years highlight the underprescription of recommended drugs. This underprescription may be related to comorbidity, a fear of side-effects and the lack of specific recommendations for drug prescription in heart failure with preserved ejection fraction, which is common in this very old population. The benefit/risk ratio related to heart failure treatment and comorbidity should be carefully weighed and reassessed on a regular basis. Consideration of disease prognosis according to factors that predict mortality can help to better define the care plan and promote palliative and supportive care when needed.

Medication exposure and frailty in older community-dwelling patients: a cross-sectional study.

Objective To investigate the association between the medication exposure, measured by the polypharmacy/excessive polypharmacy and the anticholinergic and/or sedative drug exposure, on frailty status among French older community-dwelling patients. Setting day-care unit in France (Lyon), with retrospective data from July, 2017 to March, 2018. Method This monocentric cross-sectional study included community-dwelling patients aged 65 years and over and admitted at the day-care unit for a geriatric evaluation. Frailty was assessed according to the frailty phenotype, described by Fried et al. Polypharmacy and excessive polypharmacy were defined as the concomitant use of 5-9 and 10 or more drugs, respectively. The cumulative anticholinergic and sedative exposure was measured using the drug burden index (DBI). The DBI score was presented in 4 differentiated scores: a null score (DBI = 0), a combined score (anticholinergic and sedative score), an anticholinergic score, and a sedative score. The association between medication and frailty was assessed by logistic regression models controlled for multiple potential confounders. Main outcome measure Association between medication exposure (polypharmacy, anticholinergic and sedative exposure) and frailty. Results In this study, 403 patients were included: 44.7% were frail and 40.7% were pre-frail. Polypharmacy and excessive polypharmacy affected 44.7% and 17.1% of the population respectively. The mean DBI was 0.33 ± 0.43, with 16.4% of patients with only sedative exposure, 9.7% with only anticholinergic exposure and 33.0% with both exposures. After adjustment, polypharmacy and excessive polypharmacy were associated with frailty with adjusted odds ratios (95% confidence interval) of 2.18 (1.03-4.22) and 2.72 (1.01-7.37) respectively. The cumulative exposure to anticholinergic and sedative drugs (combined score) was significantly associated to an increased risk for frailty with adjusted odds ratios (95% confidence interval) of 3.54 (1.47-8.57). Conclusion The study showed that polypharmacy and cumulative anticholinergic and sedative exposure are associated with frailty. Further research should address the potential benefit of collaborative medication review for preventing medication-associated frailty.

Multimorbidity in Elderly Persons According to the Year of Diagnosis of Human Immunodeficiency Virus Infection: A Cross-sectional Dat'AIDS Cohort Study.

BACKGROUND: We assessed prevalence of multimorbidity (MM) according to year of human immunodeficiency virus (HIV) diagnosis in elderly people living with HIV (PLWH). METHODS: This was a cross-sectional study of MM in PLWH aged ≥70 years from the Dat'AIDS French multicenter cohort. MM was defined as at least 3 coexistent morbidities of high blood pressure, diabetes mellitus, osteoporosis, non-AIDS cancer, chronic renal failure, cardiovascular and cerebrovascular disease, obesity, undernutrition, or hypercholesterolemia. Logistic regression models evaluated the association between MM and calendar periods of HIV diagnosis (1983-1996, 1997-2006, and 2007-2018). The secondary analysis evaluated MM as a continuous outcome, and a sensitivity analysis excluded PLWH with nadir CD4 count <200 cells/µL. RESULTS: Between January 2017 and September 2018, 2476 PLWH were included. Median age was 73 years, 75% were men, median CD4 count was 578 cells/µL, and 94% had controlled viremia. MM prevalence was 71%. HBP and hypercholesterolemia were the most prevalent comorbidities. After adjustment for age, gender, smoking status, hepatitis C and hepatitis B virus coinfection, group of exposure, nadir CD4 count, CD4:CD8 ratio, and last CD4 level, calendar period of diagnosis was not associated with MM (P = .169). MM was associated with older age, CD4/CD8 ratio <0.8, and nadir CD4 count <200 cells/µL. Similar results were found with secondary and sensitivity analyses. CONCLUSIONS: MM prevalence was high and increased with age, low CD4/CD8 ratio, and nadir CD4 count <200 cells/µL but was not associated with calendar periods of HIV diagnosis. Known duration of HIV diagnosis does not seem to be a criterion for selecting elderly PLWH at risk of MM.

A multi-center, randomized, controlled trial to assess the efficacy of optimization of drug prescribing in an elderly population, at 18 months of follow-up, in the evolution of functional autonomy: the OPTIM study protocol.

BACKGROUND: Pharmacotherapy is necessary for the management of many diseases which number increased with aging. However, potentially inappropriate prescriptions and polymedication increases iatrogenic risks and can lead to adverse events. To limit the consequences of potentially harmful prescriptions, optimization of drug prescribing is a major stake of improving quality and safety of care in the elderly. The purpose of the OPTIM study is to study the impact of the optimization of drug prescribing on the evolution of functional autonomy at 18 months of follow-up. METHODS: A multicenter, open-label, Randomized Controlled Trial was designed to assess the impact of an optimization program of drug prescribing consisting in a clinical medication review by a pharmacist, in collaboration with specialist physician of the geriatric/memory center and the referent physician, on the evolution of functional autonomy level, measured during 18 months of follow-up. The study will include 302 elderly outpatients visiting geriatric and memory centers, randomly distributed in one of the two parallel groups. One group will benefit of the intervention, while the other will be considered as control group. The effect of the intervention on evolution of the level of autonomy function, defined with repeated measures, will be estimated in a generalized linear mixed model. The intervention will be considered significant if the interaction between time and the study group is significant. Secondary analysis will be conducted to assess the impact of the intervention on secondary clinical outcomes. DISCUSSION: The "OPTIM" program should enable optimization of drug prescribing in elderly patients and therefore slow or prevent progression to loss of functional autonomy. It should also help to strengthen collaboration between the hospital team of geriatric/neurologist, the pharmacist and the private practice who are all involved in caring for the patient's health. The benefits for the patient are thus optimizing its medical management by linking health professionals met during his care pathway. In addition, pharmaceutical recommendations sent to referent physicians should help raise awareness of the prescription of drugs in these patients. TRIAL REGISTRATION NUMBER CLINICALTRIALS: NCT02740764.

There is no correlation between peripheral inflammation and cognitive status at diagnosis in Alzheimer's disease.

BACKGROUND: Besides the neurofibrillary tangles and amyloid plaques, an inflammatory process is involved at central and peripheral levels in Alzheimer's disease (AD). We aimed to determine whether peripheral inflammatory parameter levels, in plasma and in peripheral blood mononuclear cells (PBMCs), could be correlated with the cognitive status at the time of AD diagnosis. METHODS: Patients were included at diagnosis with MMSE score between 16 and 25 and were naive of symptomatic treatment for AD. C-reactive protein >10 mg/L and any acute or chronic inflammation were considered as exclusion criteria. Cognitive assessment also included the ADAScog scale. Plasma interleukins (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α and the chemokine ligand 5 (CCL5) were measured using Luminex(®) X-MAP(®) technology. A subgroup of patients also underwent measures of these parameters in extracellular and intracellular compartments of PBMCs (ancillary study). RESULTS: One hundred and nine patients were included; mean age 79.4 ± 6.8 years with 37 patients in the ancillary study. The mean values of IL-1ß, TNF-α, IL-6 and CCL5 values were 1.49, 7.18, 3.09 and 69,615.81 pg/mL, respectively. No correlation between plasma cytokines or chemokine levels and cognitive scores was found. In PBMCs, the levels of cytokines were detectable but did not either show any correlation with cognitive scores. CONCLUSION: Our data indicate that at diagnosis, peripheral levels of cytokines and CCL5 display low values without any correlation with the cognitive status. Further results of our study will show if these circulating markers are related to the progression of AD.

Risk of Alzheimer's disease biological misdiagnosis linked to cerebrospinal collection tubes.

Tau proteins and amyloid-ß (Aß) peptides are the current recognized cerebrospinal fluid (CSF) biomarkers used as an aid in the diagnosis of Alzheimer's disease (AD). However, there is no consensus on their clinical use due to non-qualified cut-off values, probably related to the observed high pre-analytical and analytical variability. Standardized pre-analytical protocols have therefore been proposed. Importantly, these recommend the use of polypropylene collection/sampling tubes while, to date, no broad comparison of these types of tubes has been conducted. In this study, we first compared, as part of a real clinical workflow, the impact of four different collection tubes on the CSF concentration of Aß peptides (Aß42, Aß40) and total (hTau) and phosphorylated (P-Tau181P) tau proteins measured using routine ELISA kits. We then extended this study to 11 polypropylene tubes used by different clinical laboratories, and investigated their plastic polymer composition using differential scanning calorimetry and Fourier Transformed Infrared spectroscopy. Significant concentration variations linked solely to the use of different types of tubes were observed. This was particularly marked for Aß peptides, with >50% disparity occurring in less than five minutes. Polymer composition analysis revealed that most polypropylene tubes were in fact copolymers with at least polyethylene. There was no clear correlation between tube composition and pre-analytical behavior. Our results show that the use of polypropylene tubes does not guarantee satisfactory pre-analytical behavior. They also point to collection/sampling tubes being a major pre-analytical source of variability that could impact the significance of AD biological diagnosis.

Impact of chronic Helicobacter pylori infection on Alzheimer's disease: preliminary results.

Recent case-control studies reported an association between H. pylori infection and Alzheimer's disease (AD). Our aim was to compare cognitive impairment, neuroinflammation, and cerebrovascular lesion load in a group of AD patients according to their H. pylori status. For the 53 AD patients included, we assessed: clinical data (vascular comorbidities and cognitive assessment), biological data (especially fibrinogen, homocysteine levels, apolipoprotein E4 genotype; cerebrospinal fluid [CSF] total tau protein [Tau], phospho-tau(181) protein [pTau(181)]), and amyloid beta peptide levels, serum/CSF-cytokines (interleukin [IL]-1ß, IL-6, IL-8, tumor necrosis factor [TNF]-α) and pepsinogen I/pepsinogen II (PgI/PgII) ratio, and cerebrovascular lesion load (magnetic resonance imaging [MRI] fluid-attenuated inversion recovery [FLAIR] with the Fazekas and Schmidt scale). H. pylori infection was diagnosed by enzyme-linked immunosorbent assay (ELISA) and immunoblot test. H. pylori infection was associated with a decreased Mini Mental State Examination (MMS) (p = 0.024), and higher CSF pTau(181) (p = 0.014) and tau (p = 0.021) levels. A decreased PgI/II ratio (i.e., an increased gastric atrophy) was associated with the infection (p = 0.005). Homocysteine levels were positively correlated to Fazekas score (r = 0.34; p = 0.032) and to H. pylori immunoglobulin (Ig)G levels (r = 0.44; p = 0.001). Higher CSF cytokine levels (IL-8, p = 0.003; TNF-α, p = 0.019) were associated with the infection, but systemic inflammation results were controversial. Finally, in multivariate analysis, a lower MMSE score (odds ratio [OR], 0.83 [0.72-0.97]; p = 0.017), plasma IL-1ß level (OR, 0.31 [0.11-0.87]; p = 0.025), an increased gastric atrophy, i.e., a lower PgI/PgII ratio (OR, 0.63 [0.43-0.93]; p = 0.020) were still associated with the infection. AD patients infected by H. pylori tended to be more cognitively impaired. Studies are needed to attest to the impact of H. pylori infection on AD course, especially on cerebrovascular lesions and neuroinflammation.

Impact of a multifaceted program to prevent postoperative delirium in the elderly: the CONFUCIUS stepped wedge protocol.

BACKGROUND: Postoperative delirium is common in the elderly and is associated with a significant increase in mortality, complications, length of hospital stay and admission in long care facility. Although several interventions have proved their effectiveness to prevent it, the Cochrane advises an assessment of multifaceted intervention using rigorous methodology based on randomized study design. Our purpose is to present the methodology and expected results of the CONFUCIUS trial, which aims to measure the impact of a multifaceted program on the prevention of postoperative delirium in elderly. METHOD/DESIGN: Study design is a stepped wedge cluster randomized trial within 3 surgical wards of three French university hospitals. All patients aged 75 and older, and admitted for scheduled surgery will be included. The multifaceted program will be conducted by mobile geriatric team, including geriatric preoperative consultation, training of the surgical staff and implementation of the Hospital Elder Life Program, and morbidity and mortality conference related to delirium cases. The primary outcome is based on postoperative delirium rate within 7 days after surgery. This program is planned to be implemented along four successive time periods within all the surgical wards. Each one will be affected successively to the control arm and to the intervention arm of the trial and the order of program introduction within each surgical ward will be randomly assigned. Based on a 20% reduction of postoperative delirium rate (ICC = 0.25, α = 0.05, ß = 0.1), three hundred sixty patients will be included i.e. thirty patients per service and per time period. Endpoints comparison between intervention and control arms of the trial will be performed by considering the cluster and time effects. DISCUSSION: Better prevention of delirium is expected from the multifaceted program, including a decrease of postoperative delirium, and its consequences (mortality, morbidity, postoperative complications and length of hospital stay) among elderly patients. This study should allow better diagnosis of delirium and strengthen the collaboration between surgical and mobile geriatric teams. Should the program have a substantial impact on the prevention of postoperative delirium in elderly, it could be extended to other facilities. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01316965.

Human lateral geniculate nucleus and visual cortex respond to screen flicker.

The first electrophysiological study of the human lateral geniculate nucleus (LGN), optic radiation, striate, and extrastriate visual areas is presented in the context of presurgical evaluation of three epileptic patients (Patients 1, 2, and 3). Visual-evoked potentials to pattern reversal and face presentation were recorded with depth intracranial electrodes implanted stereotactically. For Patient 1, electrode anatomical registration, structural magnetic resonance imaging, and electrophysiological responses confirmed the location of two contacts in the geniculate body and one in the optic radiation. The first responses peaked approximately 40 milliseconds in the LGN in Patient 1 and 60 milliseconds in the V1/V2 complex in Patients 2 and 3. Moreover, steady state visual-evoked potentials evoked by the unperceived but commonly experienced video-screen flicker were recorded in the LGN, optic radiation, and V1/V2 visual areas. This study provides topographic and temporal propagation characteristics of steady state visual-evoked potentials along human visual pathways. We discuss the possible relationship between the oscillating signal recorded in subcortical and cortical areas and the electroencephalogram abnormalities observed in patients suffering from photosensitive epilepsy, particularly video-game epilepsy. The consequences of high temporal frequency visual stimuli delivered by ubiquitous video screens on epilepsy, headaches, and eyestrain must be considered.