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Bruno Vellas

Publications and source records attributed to Bruno Vellas.

At least 19 recordsLinked to original sources
PubMed2007

Predictive value of 6-month decline in ADAS-cog for survival without severe Alzheimer's disease.

BACKGROUND/AIMS: To determine the predictive value of the 6-month evolution of the ADAS-cog score in initially mild to moderate Alzheimer's disease (AD) patients on the risk of death or severe dementia (MMSE <10) within 2 years. METHODS: Cognition was assessed every 6 months using the ADAS-cog scale in the Real.fr study, a cohort of AD patients. Six classes of ADAS-cog evolution were distinguished, from the severest deterioration (decline >or=7 points) to the greatest cognitive improvement (gain >or=4 points). RESULTS: Among 536 AD patients, 53 (9.9%) had a 6-month decline of 7 points or more. This group with the severest deterioration was significantly associated with the risk of severe dementia or death at 2 years (relative risk, RR = 3.8, 95% confidence interval, CI = 2.1-6.8), even after adjustment for baseline MMSE, disability and ADAS-cog score (RR = 2.6, 95% CI = 1.4-5.0). In addition, subjects with a decline by at least 4 points were also at greater risk of severe dementia. CONCLUSION: These results confirm the value of the ADAS-cog scale as a judgement criterion in clinical trials since it is a good surrogate marker of long-term prognosis. The proportion of fast decliners on the ADAS-cog could be a helpful judgement criterion for future trials in AD.

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PubMed2007

Disease-modifying trials in Alzheimer's disease: a European task force consensus.

After symptomatic treatments, the new target for therapeutic approaches in Alzheimer's disease is the development of disease-modifying drugs. The concept of disease modification in Alzheimer's disease is controversial and the design of these trials raises many questions. Which populations should be studied? For how long? With which principal and secondary endpoints? Are surrogate markers available? Here, we present a European consensus on disease-modifying trials in Alzheimer's disease, agreed under the auspices of the European Alzheimer's Disease Consortium and based on the European perspective of the concept of disease modification, study designs, the role for biomarkers, risk benefit, and pharmacoeconomic issues.

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PubMed2006

Physical performance measures as predictors of mortality in a cohort of community-dwelling older French women.

This prospective cohort study evaluate the predictive value of physical performance measures for mortality in older French women, in particular those with a high health status. The subjects were 7,250 community-dwelling non-disabled French women aged 75 years or older, enrolled in the Epidémiologie de l'ostéoporose (EPIDOS) study. The short physical performance battery (SPPB), including walking speed, repeated chair stands, and balance tests, was administered and handgrip strength was measured. Anthropometric measurements, physical function, cognitive performance, sensory status, smoking, medical history, medication use, subjective self-assessment of health status, and physical activity level were assessed at the baseline visit. During a mean follow-up of 3.8 years, 754 (10.4%) participants died. Complementary analysis was performed on the 2,157 non-disabled healthiest participants (no disease at baseline). The SPPB and handgrip strength distinguished a gradient of risk for mortality from a low to high functional spectrum. Risk of death was 2.04-fold higher in poor (SPPB 0-6) than in good (SPPB 10-12) performers and 1.56-fold higher in participants with lower tertile grip strength. Walking speed alone also distinguished a gradient of mortality risk. After adjustment for confounders, low SPPB, grip strength score and slow walking speed remained significantly associated with death. In the non-disabled healthiest women, no physical performance measure predicted death. In community-dwelling elderly French women, physical performance measures significantly and independently predicted mortality. Increased risk of death was partly explained by baseline health status and was absent in the healthiest elderly.

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PubMed2006

Outcome of Alzheimer's disease: potential impact of cholinesterase inhibitors.

BACKGROUND: Alzheimer's disease is fast becoming a major public health concern with serious economic consequences. The cholinesterase inhibitors (CEIs) offer some benefit in the symptomatic treatment of the disease. This study aims to investigate the effect of CEIs on three clinically relevant domains (rapid cognitive decline, institutionalization, and weight loss) in patients with Alzheimer's disease. METHODS: A prospective observational study was performed in which a population of 455 Alzheimer's disease patients were recruited and followed up for at least 1 year between 1994 and 2002. Patients were reevaluated at 6 monthly intervals using standardized neurocognitive and geriatric evaluations in addition to complete clinical examination, standard paraclinical investigations, and recording of treatment received. RESULTS: The risk of rapid cognitive deterioration was significantly decreased in patients taking CEIs for at least 1 year compared to untreated patients (odds ratio [OR]=0.56, 95% confidence interval [CI], 0.34-0.93; p=.025). The potential benefit of CEI use was also found on institutionalization (OR=0.2, 95% CI, 0.08-0.48; p<.001) and weight loss (OR=0.56, 95% CI, 0.32-0.97; p=.039) after 1 year of follow-up. CONCLUSION: The special interest of this study is that all patients were recruited and followed in the same center with the same management care plan and the same medical team. This follow-up offers us a unique opportunity to compare the 1-year evolution of the disease in clinical practice before and after the marketing of CEIs and allows us to demonstrate a clinically significant improvement in patient outcome over time.

Age Factors↗
PubMed2006

Strontium ranelate reduces the risk of vertebral and nonvertebral fractures in women eighty years of age and older.

UNLABELLED: Strontium ranelate produces an early and sustained reduction of both vertebral and nonvertebral fractures in patients > or = 80 years of age. INTRODUCTION: About 25-30% of the population burden of all fragility fractures in the community arise from women > or = 80 years of age, because this population is at high risk for all types of fracture, particularly nonvertebral fractures. Despite this, evidence that therapies reduce the risk of both vertebral and nonvertebral fractures in this group is lacking. The aim of this study was to determine whether strontium ranelate, an agent that reduces the risk of vertebral and nonvertebral fractures in postmenopausal women >50 years of age, also reduces fractures in the elderly. MATERIALS AND METHODS: An analysis based on preplanned pooling of data from two international, phase III, randomized, placebo-controlled, double-blind studies (the Spinal Osteoporosis Therapeutic Intervention [SOTI] and TReatment Of Peripheral OSteoporosis [TROPOS]) included 1488 women between 80 and 100 years of age followed for 3 years. Yearly spinal X-rays were performed in 895 patients. Only radiographically confirmed nonvertebral fractures were included. RESULTS: Baseline characteristics did not differ in placebo and treatment arms. In the intent-to-treat analysis, the risk of vertebral, nonvertebral, and clinical (symptomatic vertebral and nonvertebral) fractures was reduced within 1 year by 59% (p = 0.002), 41% (p = 0.027), and 37% (p = 0.012), respectively. At the end of 3 years, vertebral, nonvertebral, and clinical fracture risks were reduced by 32% (p = 0.013), 31% (p = 0.011), and 22% (p = 0.040), respectively. The medication was well tolerated, and the safety profile was similar to that in younger patients. CONCLUSIONS: Treatment with strontium ranelate safely reduces the risk of vertebral and nonvertebral fractures in women with osteoporosis > or = 80 years of age. Even in the oldest old, it is not too late to reduce fracture risk.

Age Factors↗
PubMed2006

Diabetes, hyperglycemia, and inflammation in older individuals: the health, aging and body composition study.

OBJECTIVE: The objective of this study was to assess the association of inflammation with hyperglycemia (impaired fasting glucose [IFG]/impaired glucose tolerance [IGT]) and diabetes in older individuals. RESEARCH DESIGN AND METHODS: Baseline data from the Health, Aging and Body Composition study included 3,075 well-functioning black and white participants, aged 70-79 years. RESULTS: Of the participants, 24% had diabetes and 29% had IFG/IGT at baseline. C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels (P < 0.001) were significantly higher among diabetic participants and those with IFG/IGT. Odds of elevated IL-6 and TNF-alpha (>75th percentile) were, respectively, 1.95 (95% CI 1.56-2.44) and 1.88 (1.51-2.35) for diabetic participants and 1.51 (1.21-1.87) and 1.14 (0.92-1.42) for those with IFG/IGT after adjustment for age, sex, race, smoking, alcohol intake, education, and study site. Odds ratios for elevated CRP were 2.90 (2.13-3.95) and 1.45 (1.03-2.04) for diabetic women and men and 1.33 (1.07-1.69) for those with IFG/IGT regardless of sex. After adjustment for obesity, fat distribution, and inflammation-related conditions, IL-6 remained significantly related to both diabetes and IFG/IGT. CRP in women and TNF-alpha in both sexes were significantly related to diabetes, respectively, whereas risk estimates for IFG/IGT were decreased by adjustment for adiposity. Among diabetic participants, higher levels of HbA(1c) were associated with higher levels of all three markers of inflammation, but only CRP remained significant after full adjustment. CONCLUSIONS: Our findings show that dysglycemia is associated with inflammation, and this relationship, although consistent in diabetic individuals, also extends to those with IFG/IGT.

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PubMed2005

[Treatment of Alzheimer's disease].

Alzheimer's disease (AD) is a neurodegenerative disorder with a decline in memory and cognitive abilities. During the past 20 years, research on AD has increased the knowledge of the physiopathological mechanisms leading to the disease. The major hallmarks of AD are amyloid plaques and neurofibrillary tangles, associated with a prevalent and early cholinergic deficit and an excitotoxicity with inflammation. These pathological mechanisms represent current and future therapeutic targets. cholinesterase inhibitors were the first therapeutic class that has consistently shown a clinical efficacy and safety in patients with mild to moderate ad. more recently glutamate receptor antagonists have been shown effective in the management of patients with moderate to severe AD. These two therapeutic classes could improve cognitive functions, slow the progression of the cognitive decline, prevent some behavioural changes and delay institutionalisation. However, AD represents a problem of public health and preventive and curative strategies have to be proposed.

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PubMed2005

Grouping for behavioral and psychological symptoms in dementia: clinical and biological aspects. Consensus paper of the European Alzheimer disease consortium.

Behavioral and psychological symptoms of dementia (BPSD), constitute a major clinical component of Alzheimer's disease (AD). There is a growing interest in BPSD as they are responsible for a large share of the suffering of patients and caregivers, and they strongly determine the patient's lifestyle and management. Better detection and understanding of these symptoms is essential to provide appropriate management. This article is a consensus produced by the behavioral group of the European Alzheimer's Disease Consortium (EADC). The aim of this article is to present clinical description and biological correlates of the major behavioral and psychological symptomatology in AD. BPSD is not a unitary concept. Instead, it should be divided into several symptoms or more likely: groups of symptoms, each possibly reflecting a different prevalence, course over time, biological correlate and psychosocial determinants. There is some clinical evidence for clusters within groups of BPSD. Biological studies indicate that patients with AD and BPSD are associated with variations in the pathological features (atrophy, brain perfusion/metabolism, histopathology) when compared to people with AD without BPSD. An individually tailored approach taking all these aspects into account is warranted as it may offer more, and better, pharmacological and non-pharmacological treatment opportunities.

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PubMed2005

Efficacy and safety of donepezil in patients with more severe Alzheimer's disease: a subgroup analysis from a randomized, placebo-controlled trial.

BACKGROUND: There have been very limited investigations of cholinesterase inhibitor therapy in more advanced stages of Alzheimer's disease (AD). The efficacy and safety of donepezil were evaluated in post hoc analyses of a subgroup of patients with more severe AD (standardized Mini-Mental State Examination [sMMSE] score 5-12) within a randomized, placebo-controlled trial in moderate to severe AD (MSAD study). Additional analyses examined whether donepezil's treatment effects were consistent across the full range of baseline AD severity studied (sMMSE score 5-17). METHODS: Patients with moderate to severe AD (n = 290) who were living in the community or in assisted living facilities received donepezil or placebo for 24 weeks; n = 145 in the more severe AD subgroup. The primary outcome measure was the Clinician's Interview-Based Impression of Change (CIBIC-plus) with secondary outcomes including the sMMSE, Severe Impairment Battery, Neuropsychiatric Inventory, and Disability Assessment for Dementia. Analysis of Variance and Analysis of Covariance models tested for treatment x disease severity interaction in the full MSAD study sample. RESULTS: CIBIC-plus scores for donepezil patients were significantly improved compared with placebo for each time-point, with a 0.70 mean treatment difference at Week 24 last observation carried forward (LOCF; p = 0.0002). Significant differences favoring donepezil were noted at Week 24 LOCF for all secondary measures. There were no treatment x severity interactions for any of the efficacy measures. CONCLUSIONS: In this analysis, donepezil had significant benefits over placebo on global, cognitive, functional, and behavioral measures in a subgroup of patients with more severe AD. Furthermore, the treatment effects of donepezil were not driven by a particular stratum within the moderate to severe dementia range.

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PubMed2005

The need for a consensus in the use of assessment tools for Alzheimer's disease: the Feasibility Study (assessment tools for dementia in Alzheimer Centres across Europe), a European Alzheimer's Disease Consortium's (EADC) survey.

AIMS: To ensure that all Alzheimer centres across Europe are capable of using a similar method of data collection. Information about the patient assessment tools used by each participating centre was obtained and normal clinical practice in each EADC centre was documented by collecting data from routine new patient consultation. METHODS: Twenty new consecutive patients with objective memory impairment were recruited in each Alzheimer centre over 6 months. Each patient consultation was carried out according to routine clinical practice. Patient data were recorded using the anonymous patient protocol (demographic, diagnosis, MMSE score, patient assessment scales, and most prominent behavioural problem). Information about neuropsychological assessment tools used in each centre was take to account to harmonise research practice for future multicentre collaboration. RESULTS: Seven hundred and four patients from 36 memory clinics in 13 countries across Europe participated in the study. [M:F ratio 0.67. Mean age 75.4 SD 9.3 (51-102) Mean MMSE 21 SD 6 (0-30)] Five hundred and fifty-five patients had a clinical diagnosis of dementia [Alzheimer's disease (68.5%), vascular dementia (10.3%), frontal lobe dementia (5.6%), Lewy body dementia (4.1%), mixed dementia (5.6%)]. Duration of symptoms: 0-6 months 6.5%; 6-12 months 16.1%; 1-2 years 30.5%; 2-5 years 46.9%. Assessment scales used: Clinical Dementia Rating (CDR) 48.9%, Reisberg's Global Deterioration Scale (GDS) 38.6%, ADL/IADL (Lawton and Brody, 1969) 37.5%, Neuropsychological Inventory (NPI) 28.6%, Geriatric Depression Scale 22%, ADL (Katz et al., 1963) 19.2%, ADAS-Cog 14.9%, Cornell Scale for Depression 12.9%, Grober and Bushke Selective Reminding Test 11.5%, ADCS/ADL 7.7%. 64.8% of the patients experienced behavioural symptoms: apathy 13.6%; anxiety 12.8%; dysphoria 9.9%; irritability 7.8%; agitation 5.5%; hallucinations 3.6%; delusions 3.6%, sleep disorder 2.4%; desinhibition 2%. CONCLUSIONS: The most common type of cognitive decline was Alzheimer's disease followed by mild cognitive impairment and vascular dementia. CDR, GDS Reisberg, and ADL/IADL were used widely (40-50%). The NPI, geriatric depression scale and ADL (Katz, 1963) were only used in 20% of the centres. We verified large differences in the tools use in the EADC centres to evaluate patients with dementia across Europe. There is a need for a consensus in the use of assessment tools for dementia in Alzheimer's centres in Europe.

Age Distribution↗
PubMed2005

A SPECT study of wandering behavior in Alzheimer's disease.

BACKGROUND: Among behavior disturbance during Alzheimer's disease (AD), wandering is one of the most common. Different psychological processes have been suggested to explain the wandering behavior. The aim of this study was to examine whether wandering during AD was associated with cerebral perfusion patterns measured by (99 m)Tc-labeled bicisate (ECD) brain SPECT. METHODS: We compared SPECT scans of 13 AD subjects with wandering behavior (sex ratio M/F, 4/9; age, 73.1 years, SD 7.4; Mini Mental Status Examination score, median 20 interquartile range [16-23]), 13 AD subjects without wandering behavior (matched for age [ +/- 2 years], sex and MMSE score [ +/- 2 points]) and 13 healthy controls (matched for age [ +/- 2 years] and sex) without cognitive impairment. Wandering was defined on the Neuro-Psychiatric Inventory. Score of leukoaraiosis, assessed with the scale of Blennow and number of lacuna infarction were compared on CT scan. SPECT imaging was compared using statistical parametric mapping (SPM 2). RESULTS: There were no significant differences between the groups in term of educational level and CT scan analysis. SPECT imaging was consistent with the diagnosis of AD in both wanderers and AD subjects without wandering behavior. Despite similar clinical dementia severity, wanderers had more severely reduced regional cerebral blood flow (rCBF) in the left parietal-temporal lobe than AD subjects without wandering behavior. CONCLUSION: Wandering behavior could be facilitated by a specific patterns of cerebral blood flow. Wandering, as a physical activity, could also enhance the recruitment of the cortical network.

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PubMed2005

Different modes of weight loss in Alzheimer disease: a prospective study of 395 patients.

BACKGROUND: Alzheimer disease is often accompanied and worsened by malnutrition. Patterns of weight loss can differ by the patients concerned and by the outcome and interventions required. OBJECTIVE: Our aim was to describe and analyze 2 modes of weight loss (progressive and severe) in the course of Alzheimer disease. DESIGN: This was a prospective study of 395 patients with Alzheimer disease, who had a mean age of 75.4 y. A standardized gerontologic evaluation was conducted at 6 mo and 1 y, including assessments of nutrition, neuropsychology, function, and caregiver burden. RESULTS: We investigated 2 modes of weight loss. The first, progressive loss (4% in 1 y), affected 33.4% of subjects. Disease severity was a risk factor [odds ratio (OR): 7.2; 95% CI: 1.4, 38.2 for a Reisberg score > or = 5], whereas treatment with cholinesterase inhibitors at baseline decreased this risk (OR: 0.33; 95% CI: 0.14, 0.79). The second mode of weight loss, a severe loss of > or =5 kg in 6 mo, affected 10.2% of subjects. The existence of an acute phase reaction was a risk factor (OR: 2.4; 95% CI: 1.2, 4.8), as was an intercurrent event, such as hospitalization, acute disease, institutionalization, and change of living arrangements (OR: 6.8; 95% CI: 1.2, 39.9). CONCLUSION: During the follow-up of patients with Alzheimer disease, risk factors for these 2 modes of weight loss should be sought to identify patients who would benefit from a nutritional intervention. Our findings lead us to advocate follow-up, which involves an assessment of functional, nutritional, and neuropsychologic status every 6 mo.

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PubMed2005

Cognitive impairment and composition of drinking water in women: findings of the EPIDOS Study.

BACKGROUND: The concentration of aluminum or silica in drinking water may be a potential environmental risk factor for Alzheimer disease (AD). OBJECTIVES: The objective was to investigate at baseline the potential association between the composition of drinking water and the level of cognitive function in women taking part in the Epidemiology of Osteoporosis (EPIDOS) Study and to determine during follow-up the effects of the composition of drinking water on the risk of AD. DESIGN: Women aged >/=75 y (n = 7598) were recruited between 1992 and 1994 in 5 geographic areas of France. The participants from one center (n = 1462) were followed for </=7 y; during this time, an active search for incident cases of AD was conducted. The initial questionnaire comprised a food consumption survey with specific questions about the daily consumption of tap and mineral water. The evaluation of cognitive function was based on the Short Portable Mental Status Questionnaire. During follow-up, the diagnosis of dementia was made by a geriatrician and a neurologist. RESULTS: A low silica concentration was associated with low cognitive performance at baseline. Compared with the nondemented subjects, the women with a diagnosis of AD during follow-up were older at inclusion, had a lower financial status and educational level, had a poorer perception of their own health, and had a more difficult time performing activities of daily living. A multivariate analysis including potential confounding factors showed that women with AD appeared to have been exposed to lower amounts of silica at baseline. CONCLUSIONS: Silica in drinking water may reduce the risk of developing AD in elderly women. The results corroborate those of another epidemiologic study carried out in France. The potential effect of silica needs to be confirmed in additional investigations.

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PubMed2005

Early onset effects of galantamine treatment on attention in patients with Alzheimer's disease.

INTRODUCTION: Exploratory pilot studies and knowledge of its mode of action suggested that galantamine, a cholinesterase inhibitor and modulator of nicotinic receptors, can improve attention. This study was designed to test the effects of galantamine on attention in patients with mild-to-moderate Alzheimer's disease (AD) and to see how changes in attention affected their caregivers. METHODS: This was an open-label, multicentre study. Patients received galantamine (up to 24 mg/day) for 12 weeks. Attention was assessed after 1, 4, 8 and 12 weeks using computerized tests including Choice Reaction Time (CRT), and caregiver, physician and patient ratings. RESULTS: Data were available from 373 patients (mean age 75 years, mean baseline MMSE score 21). Attention as measured by CRT improved significantly from baseline to study endpoint (p < 0.001), improvements were observed after 1 week and statistical significance was maintained from 8 weeks. Physicians rated 67% of patients as globally improved and 5% as worsened. Caregivers reported improved attention in 57% of patients and worsening in 6%; 62% of patients considered they had improved and 3% considered themselves to be worse. Caregiver stress, time spent caring for patients and patients' interactions with others all improved from baseline to endpoint. Galantamine was generally well tolerated; the most common adverse events were gastrointestinal. CONCLUSION: Previous controlled trials have demonstrated that galantamine has a positive effect on cognition, activities of daily living, behaviour and global condition, but this is the first study to suggest that galantamine may specifically improve attention (according to both objective and subjective measures) in patients with AD. These effects may be a consequence of galantamine's potentiating action at nicotinic receptors.

Adult↗
PubMed2004

[Physical restraint in old people's homes. Evaluation of skills following specific training].

AIM: The use of physical restraint in elderly patients is sometimes necessary but not without risk. We studied the prevalence and modalities of physical restraint in elderly patients in 6 old people's homes in the urban area of Toulouse, and emphasized the need for better use by the nursing staff of physical restraint in such patients with a specific training course. METHODS: Other than the prevalence of restraint, we also examined the modalities of its use in elderly patients. We studied the respect of the Anaes (Agence nationale d'accréditation et d'évaluation en santé) guidelines regarding the use of restraint in such patients, before and after an intervention that associated first a collective training course of all the staff in the old people's homes, and then specific individual training by a visiting practitioner. The information concerning the number of patients in whom restraint was used was obtained from the manager of the home or from the head nurse and was then checked by the investigator. RESULTS: The prevalence of restraint was of 22.2% (n=110 patients) at the start of the study, 15.9% following training sessions (at 6 months) and 15.5% at the end of the study (at 9 months). Skills improved regarding the benefit/risk assessment, the installation of the person restrained and the regular removal of the restraint during the day. CONCLUSION: Our strategy helped to underline this problem for the staff. The Anaes guidelines are too strict to be applied in old people's homes. One of the key points in improved management would be the presence of a coordinating physician and nurse in all the institutions caring for the elderly.

Accreditation↗
PubMed2004

Rehabilitation outcome of elderly patients with hip fracture and cognitive impairment.

PURPOSE: To assess the association between cognitive status and functional gain during a rehabilitation programme for elderly patients with hip fracture. METHOD: Prospective study in a hospital geriatric rehabilitation unit. Sixty-one consecutive patients were studied: 28 with cognitive impairment (age 87.6 +/- 7.2 years, Mini Mental State Examination (MMSE) score 11.25 +/- 5.9), 23 with possible cognitive impairment (age 83.9 +/- 6.8 years, MMSE 22.65 +/- 1.6) and 10 without cognitive impairment (age 77.6 +/- 7.4 years, MMSE 29.5 +/- 0.9). Cognitive status was assessed with the MMSE and admission and discharge functional status with the Functional Independence Measure (FIM). Functional gain was calculated by absolute FIM gain (admission FIM minus discharge FIM), relative (to maximum potential) FIM gain with the Montebello Rehabilitation Factor Score (MRFS) and analysis of covariance of the FIM (ANCOVA). RESULTS: Patients without cognitive impairment had significantly higher admission FIM and discharge FIM. Cognitive status was not significantly associated with absolute functional gain. The adjusted (age, gender, sensory impairment, nutritional status, comorbidity and treatment) MRFS score of cognitively impaired patients was significantly lower (p < 0.03). However, the functional gain related to baseline functional status (ANCOVA) was not significantly different between the groups. CONCLUSIONS: In spite of cognitive impairment, elderly patients with hip fracture can benefit from participation in rehabilitation programmes.

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