Olivier Guérin

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.

Prognosis of Alzheimer’s disease today: A two-year prospective study in 686 patients from the REAL-FR Study

The aim of the present study was to describe the long‐term evolution of Alzheimers disease (AD) in a prospective cohort of patients under treatment with a close follow‐up.

Diagnostic accuracy of a rapid urine-screening test (Multistix8SG) in cirrhotic patients with spontaneous bacterial peritonitis.

Objective To assess the diagnostic accuracy of a rapid urine-screening test (Multistix8SG) for spontaneous bacterial peritonitis (SBP) in cirrhotic patients. Methods Seventy-two consecutive patients (44 males, 28 females; mean age 61.6 years) with cirrhosis and ascites were included in the study. A diagnostic paracentesis was performed on hospital admission in all patients and 2 days after antibiotic treatment in the case of SBP (polymorphonuclear [PMN] count over 250/mm3 in ascitic fluid). Each fresh sample of ascitic fluid was also tested using the Multistix8SG urine test, and the results were scored as negative, trace or positive. Results Nine of the 72 patients had SBP and the Multistix8SG urine test was positive. After 48 h of antibiotic therapy, the PMN count of three of these nine patients was still above 250/mm3 and the Multistix8SG test remained positive. In three other patients with SBP, the PMN count dropped below 250/mm3 and the Multistix8SG test result had become negative. Two of the nine SBP patients died before 48 h, and paracentesis was not performed in the ninth case. In the other 63 patients, the PMN count in ascitic fluid was below 250/mm3; the Multistix8SG test revealed 17 trace results and 46 negative results. At the threshold of 250 PMN/mm3 in ascitic fluid, this test had a sensitivity and a specificity of 100%. Conclusion A positive Multistix8SG urine test result in ascitic fluid appears to be an indication for antibiotic treatment.

FRAILTY AND NUTRITION: SEARCHING FOR EVIDENCE

Frailty is a geriatric syndrome that predicts disability, morbidity and mortality in the elderly. Poor nutritional status is one of the main risk factors for frailty. Macronutrients and micronutrients deficiencies are associated with frailty. Recent studies suggest that improving nutritional status for macronutrients and micronutrients may reduce the risk of frailty. Specific diets such as the Mediterranean diet rich in anti-oxidants, is currently investigated in the prevention of frailty. The aim of this paper is to summarize the current body of knowledge on the relations between nutrition and frailty, and provide recommendations for future nutritional research on the field of frailty.

Characteristics of Alzheimer's disease patients with a rapid weight loss during a six-year follow-up.

BACKGROUND & AIMS Weight loss in Alzheimers disease (AD) may be either progressive or rapid, with different consequences. The aim of this study was to characterize massive weight loss (>or= 5 kg over 6 months) during a 6.5-year follow-up. METHODS 395 patients with AD (mean age 75.4 years) were included in a prospective single-centre cohort study (mean follow-up 2.5 years). A standardized gerontologic assessment was performed every six months, including nutritional, neuropsychological, functional, and caregiver burden evaluations, along with recording all intercurrent events before weight loss. RESULTS Among the 127 cases of weight loss (in 110 subjects, 27.8% of the population), we identified 60 cases of intercurrent illnesses and 88 cases of behavioral and psychological symptoms of dementia (BPSD) during the six months before weight loss. Three factors were independently associated with rapid weight loss: higher initial weight (HR=1.06, 95% CI [1.02, 1.08]), higher Prognosis Inflammatory and Nutritional Index (HR=2.16, 95% CI [1.26, 3.72]) and a higher Cohen-Mansfield agitation inventory score, reflecting BPSD (HR=1.05, 95% CI [1.01, 1.10]). Cholinesterase inhibitors appeared as protective (HR=0.33, 95% CI [0.15, 0.73]). Rapid weight loss was predictive of death at 6 months (HR=3.01, 95% CI [1.73, 5.22]). CONCLUSION BPSD play an important role in rapid weight loss and should be managed effectively. Biological assessment of malnutrition may be warranted.

Detection of activities of daily living impairment in Alzheimer's disease and mild cognitive impairment using information and communication technology

Background One of the key clinical features of Alzheimer’s disease (AD) is impairment in daily functioning. Patients with mild cognitive impairment (MCI) also commonly have mild problems performing complex tasks. Information and communication technology (ICT), particularly techniques involving imaging and video processing, is of interest in order to improve assessment. The overall aim of this study is to demonstrate that it is possible using a video monitoring system to obtain a quantifiable assessment of instrumental activities of daily living (IADLs) in AD and in MCI. Methods The aim of the study is to propose a daily activity scenario (DAS) score that detects functional impairment using ICTs in AD and MCI compared with normal control group (NC). Sixty-four participants over 65 years old were included: 16 AD matched with 10 NC for protocol 1 (P1) and 19 MCI matched with 19 NC for protocol 2 (P2). Each participant was asked to undertake a set of daily tasks in the setting of a “smart home” equipped with two video cameras and everyday objects for use in activities of daily living (8 IADLs for P1 and 11 for P2, plus 4 temporal execution constraints). The DAS score was then computed from quantitative and qualitative parameters collected from video recordings. Results In P1, the DAS score differentiated AD (DASAD,P1 = 0.47, 95% confidence interval [CI] 0.38–0.56) from NC (DASNC,P1 = 0.71, 95% CI 0.68–0.74). In P2, the DAS score differentiated MCI (DASMCI,P2 = 0.11, 95% CI 0.05–0.16) and NC (DASNC,P2 = 0.36, 95% CI 0.26–0.45). Conclusion In conclusion, this study outlines the interest of a novel tool coming from the ICT world for the assessment of functional impairment in AD and MCI. The derived DAS scores provide a pragmatic, ecological, objective measurement which may improve the prediction of future dementia, be used as an outcome measurement in clinical trials and lead to earlier therapeutic intervention.

A simple clinical tool to inform the decision-making process to refer elderly incident dialysis patients for kidney transplant evaluation

Patients over the age of 70 constitute the fastest growing segment of the ESKD population worldwide, but most of them are not considered candidates for kidney transplantation (KT). We have developed a simple clinical screening score to identify incident elderly dialysis patients over 70 years with an acceptable long-term prognosis to identify those patients most suitable for KT evaluation. From the French national prospective registry, a logistic regression was used to develop a risk score of mortality within 3 years in a derivation cohort (years 2002-06) and validated in a separate cohort (years 2007-08). Of the 9305 patients in the derivation cohort, the points assigned for the score were: male (1pt); age (75-80); 2pts), (80-85; 5pts), 85 and over (9pts); diabetes (2pts); intermittent hemodialysis (2pt); peripheral vascular disease stage III-IV (5pts); congestive heart failure stages I-II (2pts), III-IV (4pts); dysrhythmia (2pts); chronic respiratory disease (2pts); active malignancy (5pts); severe behavioral disorder (6pts); cardiovascular disease (1pt); mobility (needs assistance for transfers (4pt), totally dependent (9pts)); BMI (21-25; 1pt), BMI (<21; 3pts); and temporary central vascular catheter (3pts). In the 7947 patient validation cohort, the probability of patients being alive within 3 years was around 70% for the lowest risk score quintile (0-6 pts) representing about 20% of incident patients. Thus, our tool identified a subgroup of patients to help nephrologists select individuals who, despite their age, could be suitable candidates for KT evaluation.

Vitamin D supplementation in older adults: Searching for specific guidelines in nursing homes

BackgroundThe prevalence of vitamin D insufficiency is very high in the nursing home (NH) population. Paradoxically, vitamin D insufficiency is rarely treated despite of strong clinical evidence and recommendations for supplementation. This review aims at reporting the current knowledge of vitamin D supplementation in NH and proposing recommendations adapted to the specificities of this institutional setting.DesignCurrent literature on vitamin D supplementation for NH residents was narratively presented and discussed by the French Group of Geriatrics and Nutrition.ResultVitamin D supplementation is a safe and well-tolerated treatment. Most residents in NH have vitamin D insufficiency, and would benefit from vitamin D supplement. However, only few residents are actually treated. Current specific and personalized protocols for vitamin D supplementation may not be practical for use in NH settings (e.g., assessment of serum vitamin D concentrations before and after supplementation). Therefore, our group proposes a model of intervention based on the systematic supplementation of vitamin D (1,000 IU/day) since the patient’s admission to the NH and throughout his/her stay without the need of a preliminary evaluation of the baseline levels. Calcium should be prescribed only in case of poor dietary calcium intake.ConclusionA population-based rather than individual-based approach may probably improve the management of vitamin D insufficiency in the older population living in NH, without increasing the risks of adverse health problems. The clinical relevance and cost effectiveness of this proposal should be assessed under NH real-world conditions to establish its feasibility.

EGFR Targeting in Hormone-Refractory Prostate Cancer: Current Appraisal and Prospects for Treatment.

The incidence of prostate cancer increases with age and because of its high prevalence this disease has become a major public health concern. Despite advances in our understanding of the biological mechanisms responsible for the development of this cancer, the transition to the hormone refractory stage (HRPC) and metastatic progression pose real problems of clinical management. Currently, docetaxel chemotherapy has been shown to have a slight but significant impact on survival, though the gain in median survival is still less than three months. Research is therefore continuing to improve treatment outcomes. The progression of prostate cancer is accompanied by the overexpression of EGFR (epidermal growth factor receptor) in a very large majority of cases, suggesting that this may play a mechanistic role. Unfortunately, although preclinical findings seem to be promising for therapies targeting the EGFR in HRPC, current clinical results are disappointing. These results should however encourage us to look for different ways of using anti-EGFR agents or combining them with other targeted therapies.

Telomeric impact of conventional chemotherapy

The increased level of chromosome instability in cancer cells, leading to aneuploidy and gross chromosomal rearrangements, is not only a driving force for oncogenesis but also can be the Achille’s heel of the disease since many chemotherapies (CT) kill cells by inducing a non-tolerable rate of DNA damage. A wealth of published evidence showed that telomere stability can be more affected than the bulk of the genome by several conventional antineoplasic drugs. These results raise the interesting possibility that CT with genotoxic drugs preferentially target telomeres. In agreement with this view, accelerated shortening of telomere length has been described in blood lineage cells following high-dose CT (stem cell transplantation) or non-myeloablative CT. However, almost nothing is known on the consequences of this shortening in terms of telomere stability, senescence and on the development of second cancers or post-treatment aging-like syndromes in cancer survivors (cognitive defect, fertility impairment, etc.). In this article, we propose: (1) telomeres of cancer cells are preferential genomic targets of chemotherapies altering chromosome maintenance; (2) telomere functional parameters can be a surrogate marker of chemotherapy sensitivity and toxicity; (3) the use of anti-telomere molecule could greatly enhance the sensitivity to standards chemotherapies.