Effect of a multi-domain intervention on the quality of life in older adults with major neurocognitive disorder: A pilot study.

PURPOSE: Major neurocognitive disorders (MND) have multiple negative consequences on patients' lives and on their caregivers' health. Occupational therapy and cognitive stimulation have failed to show any significant efficacy on quality of life (QoL), cognitive functioning and behavioural symptoms. Bretonneau Hospital's Day Care Unit offers personalized and structured multi-domain interventions to cognitively impaired older patients on a weekly basis, for a 3-month period. OBJECTIVES: Our objective was to determine whether a specific rehabilitation day care unit (RDCU) could influence the QoL of cognitively impaired community-dwelling elderly patients. We also aimed to better understand the characteristics of patients who had the most benefited from the RDCU. METHODS: Retrospective study based on a sample of outpatients participating in RDCU during three months. All patients underwent a cognitive (MMS), functional (IADl, ADL) and behavioral (NPI) assessment. We compared QoL using the QoL-Alzheimer's Disease (QoL-AD) scale before and after RDCU. RESULTS: Overall, we included 60 outpatients in our study (mean age 83.3±5.8; women=70%). We found a statistically significant improvement of QoL-AD scores after RDCU (31.8±4.9 to 32.9±5.2, P=0.008). Patients who benefitted the most from RDCU were older (P=0.01) and had lower baseline QoL (P=0.04). We did not find any other characteristics associated with QoL-AD score improvement in our population. CONCLUSION: RDCU showed positive effects on QoL in this uncontrolled pilot study of older adults with MND. These findings should be confirmed in a future randomized controlled trial to corroborate the potential benefits of RDCU on QoL in older cognitively impaired patients.

Chronic traumatic encephalopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repeated traumatic brain injury (TBI). This disorder is mainly observed in subjects at risk for brain traumatisms including boxers, American football and European football (soccer) players, as well as war veterans. Neuropathological findings are marked by abnormally phosphorylated tau accumulations at the depth of cerebral sulci, as well as TDP43, Aß and α-synuclein positive staining. It has been described 3 clinical variants: the behavioural/mood variant, the cognitive variant and the mixed behavioural/cognitive variant. Cerebral MRI revealed signs of diffuse atrophy with abnormal axonal findings using the diffusion tensor imaging methods. Cerebral PET tau revealed increased standardised uptake value ratio (SUVR) levels in various brain regions of CTE patients compared to controls. The place of CTE among other neurodegenerative diseases is still debated. The focus of CTE management must be on prevention. The best way to prevent CTE in athletes is to put in place strict and appropriate measures by physicians. An individual with concussion should not be allowed to play again immediately (and sometimes never) in cases of abnormal neurological symptoms or imaging abnormalities.

Interest of biological biomarkers in the diagnostic approach of neurocognitive disorders in the elderly.

Alzheimer's disease (AD) is the most common cause of major neurocognitive disorders in older adults, affecting millions of individuals worldwide and leading to irreversible cognitive decline. The main neuropathological features of AD are brain amyloid deposition and neurofibrillary tangles. The biomarkers of AD are highly accurate in detecting these pathophysiological and neuropathological changes, up to several decades before the onset of cognitive impairment. They specifically reflect the presence of abnormal proteins in the brain, and can be measured reliably in the cerebrospinal fluid of affected individuals and in plasma for research purposes. Their implementation in clinical practice, together with neuropsychological assessment and neuroimaging, strongly increases diagnostic precision. Thus, amyloid and tau biomarkers can help rule out differential diagnoses such as vascular cognitive impairment or frontotemporal lobar degeneration. They also enable earlier diagnosis and are used in research to characterize the preclinical stage of AD. The new definition of AD has highlighted the usefulness of these biomarkers, shifting the focus from symptoms to biological and brain changes in living patients. Recent longitudinal studies demonstrated the ability of these biomarkers to predict future cognitive decline, regardless of the stage of the disease. Ongoing drug trials against AD systematically require diagnostic confirmation with biomarkers. Apart from clinical research, they have been increasingly used for several years in clinical practice, in secondary and tertiary-referral memory clinics. Nevertheless, their use has been raising ethical issues, in particular in the oldest old or in patients with multimorbidity. Their interpretation in patients older than 90 years is limited by the lack of evidence. The implications of a misdiagnosis of AD should be taken into account. Besides, there may be discrepancies between the biological diagnosis and the clinical course of the disease. In the absence of clear guidelines for their utilization, we hereby discuss their potential interests and limitations in older individuals.

The ROSAS Cohort: A Prospective, Longitudinal Study of Biomarkers for Alzheimer's Disease. Strategy, Methods and Initial Results.

OBJECTIVE: The aims of the Research Of biomarkers in Alzheimer's diseaSe (ROSAS) study were to determine the biofluid and imaging biomarkers permitting an early diagnosis of Alzheimer's disease and better characterisation of cognitive and behavioural course of the pathology. This paper outlines the overall strategy, methodology of the study, baseline characteristics of the population and first longitudinal results from the ROSAS cohort. METHODS: Longitudinal prospective monocentric observational study performed at the Alzheimer's disease Research centre in Toulouse. A total of 387 patients were studied and analyzed in 3 groups: 184 patients with dementia of Alzheimer's type, 96 patients with memory disorders without dementia (Mild Cognitive Impairment) and 107 patients without abnormal memory tests (control group), and were followed up during 4 years. Patient's sociodemographic characteristics, risk factors, medical conditions, previous and current medications, neuropsychological assessment and overall cognitive status were recorded. Blood and urine samples were collected at every year, Magnetic Resonance Imaging were performed at inclusion, after one year of follow-up and at the end of the study. RESULTS: At baseline, three different groups of the cohort differed interestingly in age, level of education, and in percentage of ApoEε4 carriers whereas the history of cardiovascular and endocrine pathologies were similar among the groups. During the follow-up period (3-4 years) 42 mild cognitive impairment patients (43.8%) progressed to dementia, 7 controls progressed into mild cognitive impairment and 1 patient in the control group converted from mild cognitive impairment group to dementia of Alzheimer's type group. During the first year of follow up, the incidence of progression from mild cognitive impairment to dementia of Alzheimer's type was 12.7 per 100, during the second year 33.9 per 100 and 46.7 per 100 for the third year. CONCLUSION: This paper presents the baseline characteristics of the unique French prospective monocenter study in which the natural course of dementia of Alzheimer's type was evaluated. Future analysis of blood and urine samples collection from the ROSAS study will permit to identify possible biofluid biomarkers predicting the early stages of the dementia of Alzheimer's type and risk of progression from Mild Cognitive Impairment to Alzheimer's disease.

Validation of the Mini Nutritional Assessment-Short Form in a Population of Frail Elders without Disability. Analysis of the Toulouse Frailty Platform Population in 2013.

OBJECTIVE: To assess the validity of the Mini Nutritional Assessment-Short Form (MNA-SF) in elderly patients from the Toulouse Frailty Platform. PARTICIPANTS: Overall, 267 patients aged 65 and over, without severe cognitive impairment (i.e. Mini Mental Status Examination > 20 and CDR<1), no physical disability (i.e. Activities of Daily Living ≥ 5) and no active cancer history (over the past 12 months) were included in 2013. MEASUREMENTS: Receiver operating characteristic (ROC) analyses were used to assess the predictive validity of the French version of the MNA-SF for good nutritional status (defined as a full MNA score≥24/30). Analyses were conducted in the overall sample and then in subgroups of frail and pre-frail subjects according to the frailty phenotype. Optimal cut-off points were determined to obtain the best sensitivity/specificity ratio and the highest number of correctly classified subjects. RESULTS: Among 267 patients, mean age=81.5±5.8; women=67.0%; 138 (51.7%) were frail, 98 (36.7%) were pre-frail and 31 (11.6%) were robust. Given their MNA-SF scores, 201 (75.3%) had a good nutritional status, 61 (22.8%) were at risk of malnutrition and 5 (1.9%) were malnourished. In the overall sample, but also in subgroups of pre-frail or frail elders, the areas under ROC curves were 0.954, 0.948 and 0.958 respectively. The 11 points cut-off provided the best correct classification ratio (91.4%); sensitivity=94.0%, specificity=83.3%. CONCLUSION: The MNA-SF appeared to be a validated and effective tool for malnutrition screening in frail elders. Implementing this tool in clinical routine should contribute to improving the screening of malnourished frail individuals.

The Mini Nutritional Assessment-Short Form and mortality in nursing home residents--results from the INCUR study.

OBJECTIVES: To examine whether the Mini Nutritional Assessment-Short Form (MNA-SF) score and its individual items are predictors of mortality in a nursing home population. DESIGN: Prospective, secondary analysis from the Incidence of pNeumonia and related ConseqUences in nursing home Residents (INCUR) study with 1-year follow-up. PARTICIPANTS: A total of 773 older persons (women 74.4%) living in 13 French nursing homes. MEASUREMENTS: At baseline, nutritional status was assessed with the MNA-SF. Overall mortality rate was measured over a 12-month follow-up period after the baseline assessment visit. Cox proportional hazard models were performed to test the predictive capacity of the MNA-SF score and its single components for mortality. RESULTS: Mean age of participants was 86.2 (standard deviation, SD 7.5) years. Mean MNA-SF score was 9.8 (SD 2.4). Among participants, 198 (25.6%) presented a normal nutritional status (12-14 points), 454 (58.7%) were at risk of malnutrition (8-11 points), and 121 (15.7%) were malnourished. After one year of follow-up, 135 (17.5%) participants had died. Age, female gender, baseline weight, BMI and MNA-SF were significant predictors of mortality whereas no specific chronic disease was. The total MNA-SF score was a significant predictor of mortality (Hazard Ratio=0.83; 95% CI 0.75-0.91; p<0.001), even after adjustment for potential confounders. Four individual items: weight loss, decrease in food intake, recent stress and BMI were independent predictors of mortality. CONCLUSIONS: The MNA-SF appears to be an accurate predictor of one-year mortality in nursing home residents. Thus, this tool may be regarded not only as a nutritional screening tool, but also as an instrument for identifying the most-at-risk individuals in this population.

Frailty and Pain: Two Related Conditions.

Frailty is a multidimensional syndrome, involving functional, nutritional, biological and psychological aspects. This condition, defined as a decreased resistance to internal and external stressors, is predictive of adverse health outcomes, including disability and mortality. Importantly, the frailty syndrome is usually considered a reversible condition, thus amenable of specific preventive interventions. Persistent pain in older adults is very common and has multiple determinants. This symptom represents a determinant of accelerated aging. In the present paper, we discuss available evidence examining the association between these two conditions. Despite the high prevalence of these two conditions and their shared underlying mechanisms, our search only retrieved few relevant studies. Most of them reported a relationship between pain (or analgesics consumption) and different operational definitions of frailty. Pain may represent a relevant risk factor as well as a potential target for interventions against the frailty syndrome, but further studies are needed.

Flavonoids and arterial stiffness: promising perspectives.

BACKGROUND AND AIMS: Flavonoids are a group of polyphenol compounds, ubiquitously found in plants. Great emphasis has been given to their possible benefits for cardiovascular health. These beneficial effects may be mediated by a specific action on arterial walls. Arterial stiffness is a marker of vascular aging, increasingly used in the clinical setting and assessed by pulse wave velocity. It has shown to be a robust predictor of cardiovascular events and mortality. This review aims at providing a comprehensive evaluation of available intervention and observational studies examining the relationship between flavonoid consumption and arterial stiffness. DATA SYNTHESIS: A Medline(®) literature search was performed using the keywords "arterial stiffness" and "flavonoids". As a result, 2 cross-sectional and 16 intervention studies assessing the relationship between flavonoids intake and arterial stiffness were retained. Four intervention trials reported a significant decrease of arterial stiffness after a flavonoid-based intervention, independently from blood pressure changes. The two observational studies reported significant associations between a higher flavonoid consumption and a lower arterial stiffness. In this review, isoflavones, anthocyanins and to a lesser extent cocoa flavan-3-ols appeared to be the more efficient to improve vascular function. CONCLUSIONS: Despite their heterogeneity, preliminary data seem to support an improvement of the arterial stiffness related to flavonoid intake. However, further research on absorption and dose-response effects of the specific flavonoid subclasses on arterial structure is warranted.

Electrode catheter ablation of resistant ventricular tachycardia in arrhythmogenic right ventricular dysplasia: experience of 13 patients with a mean follow-up of 45 months.

Electrode catheter ablation (fulguration) is a new technique for the treatment of ventricular tachycardia resistant to medical treatment. It proved effective in our hands in a series of 65 cases of ventricular tachycardia of varied origin. This paper reports the early results in a subgroup of 13 patients suffering from arrhythmogenic right ventricular dysplasia in whom shocks ranging from 160 to 280J, single or multiple, in one or up to three sessions were delivered. In the 11 patients surviving the DC ablation procedure single or multiple monomorphic sustained VT was brought under control. However, four patients (36%) required therapeutic antiarrhythmic treatment following the fulguration therapy. During the learning phase one case of death was related to poor catheter selection and the other to poor protocol. The post-mortem study of the effect of shocks depends on the anatomical structure to which the shocks have been delivered.

[Efficacy criteria in the fulguration of the bundle of His]. / Critères d'efficacité dans la fulguration du faisceau de His.

The authors have endeavoured to determine which of the parameters commonly used for His bundle ablation are likely to predict that ablation will be effective in altering the atrioventricular (AV) conduction system durability. His bundle ablation was performed in 18 patients (9 men, 9 women; mean age 47 years) presenting with supraventricular tachycardia refractory to all medical treatments. A total of 29 shocks were delivered with an Odam fulgurator, using a distal electrode connected to the positive pole of a selected catheter. Fifteen shocks were effective, resulting in a complete and permanent AV block (group I); the remaining 14 shocks failed to modify permanently the AV conduction system (group II). The parameters which differed between these two groups were the amplitude and the stability of the His bundle potential, the energy per kg bodyweight delivered with the shock and the possibility to shock the potential with the greatest amplitude in case of instability. A discriminant linear analysis showed that 3 interrelated criteria could be used to classify 83% of the shocks into one or the other group. In order of importance these criteria were: (1) amplitude of the His bundle potential; (2)energy delivered per kg bodyweight, and (3) stability of the potential. The corresponding discriminant values for successful results were more than 300 mV for parameter 1, more than 3 J/kg bodyweight for parameter 2 and very good stability of His bundle potential.