[Oncogeriatric assessment: The first step in personalizing cancer treatment in the elderly]. / L'évaluation oncogériatrique : la première étape de la personnalisation du traitement du cancer du sujet âgé.

With aging worldwide population and the high incidence of cancer in the population of people over 75 years old, there is a need for oncologists and geriatricians to strengthen their collaboration to improve elderly patients care. Complexity of cancer and aging issues must be considered simultaneously to establish a personalized care plan. Thus, the G8 is a screening tool that allows to identify patients who should benefit from a geriatric assessment, which is a key step in the management process. This specific evaluation offers a multidisciplinary approach to functional, psychological, nutritional, cognitive and social status and has demonstrated its prognostic value in terms of choice of treatment but also in terms of patient survival. In nearly 20% of cases, the geriatric assessment leads to a change in the choice of treatment, and at one year the initial care plan is not carried out in a quarter of cases. The presence of malnutrition and functional impairment leading to dependence on basic activities of daily living had a significant impact on this change in therapeutic choice. Survival is not only impacted by malnutrition and functional impairment but also by the presence of severe comorbidities and thymic and neurocognitive impairment. The patient's choice must remain at the center of the elaboration of the care plan with the oncologists and geriatricians in order to propose the most appropriate treatment for his or her situation.

[Clinical presentation and performance of urine dipstick for diagnosis of urinary infection in geriatric population]. / Présentation clinique et performance de la bandelette urinaire pour le diagnostic d'infection urinaire en population gériatrique.

BACKGROUND: Urinary tract infections (UTI) are the second cause of community-acquired bacterial infections in the elderly. Distinguishing symptomatic UTI from asymptomatic bacteriuria is problematic, as older adults are less likely to present with localized urinary symptoms. We evaluated characteristics of patients presenting UTI among elderly with sepsis. Moreover, we aimed to evaluate the sensibility and specificity of urine dipstick tests in the diagnosis of UTI in geriatric population. PATIENTS AND METHOD: We led a prospective, monocentric, observational study between April 2017 and January 2018. We included patients hospitalized in geriatric wards, who were prescribed urine culture for UTI symptoms or/and infection without primary sites for which a urine culture was prescribed. Dipstick urinalyses were performed for all patients. Clinical and biological characteristics of all patients were compared according to the final diagnosis of UTI. Moreover, results of dipstick tests were evaluated for the diagnosis of UTI in this population. RESULTS: Among 165 patients, 67 (40.6 %) had a UTI and 98 (59.4 %) had another diagnosis. These two groups were comparable for age and daily-living activities. In the UTI group, the proportion of women was higher than in the other group (P<0.05), and mean MMSE score was lower (P<0.05). Positive urine dipstick test for leukocytes and/or nitrites had high sensitivity (92 %), but low specificity (50 %). Negative predictive value of this test was high (91 %). CONCLUSION: For suspicion of UTI among elderly, few criteria are specific. Negative dipstick tests can suggest an absence of UTI due to its high negative predictive value.

[Ethic reflexion in the care of elderly people with cancer]. / Réflexion éthique dans le cadre de la prise en charge des patients âgés atteints de cancer.

Medical ethics is concerned with practices of care, their purposes, their feasibility. It raises questions about taking care of elderly patients with cancer. The decision criteria of exploration in search of cancer or treatment of confirmed cancer are numerous. Some are medical criteria (benefit on survival, polypathology, impact on the body, the prognosis associated with comorbidities), others are more subjective (quality of life, difficulty of patient's information, longer hospitalisation, ageism). Age appears to be the first lock, the second is cognitive disorders. Overexpenditure of current assumptions seems necessary to improve the care of elderly patients with cancer. Especially since many publications indicate that cancer treatments are generally well supported and beneficial to advanced ages.

Persistent apathy in Alzheimer's disease as an independent factor of rapid functional decline: the REAL longitudinal cohort study.

OBJECTIVE: To determine the role of persistent apathy in rapid loss of autonomy in Instrumental Activities of Daily Living (IADL) in women with Alzheimer s disease (AD), taking into account the grade of cognitive decline. METHODS: The study was conducted on 272 women from the French REAL cohort. At inclusion patients had a Mini-Mental State Examination (MMSE) score between 10-26. A rapid functional decline was defined as a yearly drop of 4 points or more on the 14-point IADL Lawton scale. Persistent apathy was defined as a frequency score equal to 3 or 4 on the Neuro-Psychiatric Inventory at the three consecutive 6-monthly assessments. RESULTS: 27.6% of women had rapid functional decline in 1 year and 22.1% of them had persistent apathy. A logistic regression analysis showed that, in addition to cognitive decline, persistent apathy plays a role in rapid functional decline in 1 year. For example, for a 3-point decline in MMSE in 1 year, the probability of a rapid loss in IADL is 0.45 for women with persistent apathy compared with 0.28 for those without persistent apathy. CONCLUSIONS: In this study, a rapid loss in IADL score was partly explained by persistent apathy.

[Geriatric intervention team in an academic orthopedic surgery department: activity at the Ambroise-Paré Hospital in Boulogne, France]. / L'équipe d'intervention gériatrique dans un service de chirurgie orthopédique adulte: Bilan de la première année d'activité à l'hôpital Ambroise-Paré de Boulogne.

To respond to increasing demand resulting from population aging, a geriatric intervention team was created at the Ambroise-Paré hospital in February 2004. The main activity of the team is to improve medical and social care of elderly patients who are regularly frail with multiple morbid conditions and taking multiple medications. During the first year of activity, 23% of requests came from the orthopedic surgery department which annually cares for 720 patients aged over 75 years. Physicians and nurses from this department need to adapt their practices to the specific features of geriatric care. The geriatric intervention team provides advice, support, and suggestions as well as professional training.

Predictive factors of rate of loss of autonomy in Alzheimer's disease patients. A prospective study of the REAL.FR Cohort.

Alzheimer's disease is characterised by a progressive loss of autonomy in activities of daily living. Many patients lose this autonomy rapidly with dramatic consequences for the patients and their relatives, and for health and social services. The aim of this study was to determine, in a large French cohort of community-living Alzheimer patients (REAL.FR), the factors underpinning different rates of loss of autonomy. Six hundred and eighty seven patients were recruited to this French cohort. Autonomy in activities of daily living was estimated with the IADL scale (Lawton). Patients were divided into three groups according to loss of autonomy during the first one-year follow-up period. Patients with a decrease in the IADL score had worse ADAS-cog score (Alzheimer's Disease Assessment Scale, cognitive subscale), Mini-Mental State Examination (MMSE), and Clinical Dementia Rating Scale scores. Up to a point, a marked decrease in the IADL score was less frequent among patients with a better ADAS-cog score (p < 0.10, bilateral test). At one-year evaluation, patients with a marked decline in autonomy were characterised by a greater decrease in Mini-Mental State score, faster progression of behavioural disturbance, and more hospitalisations. Further prospective studies, using established models, are needed to isolate the factors associated with a high rate of loss of autonomy in activities of daily living in Alzheimer patients.

Does food restriction increase life span in lean rats?

The effect of food restriction on survival of lean animals was investigated using WAG/Rij rats. In this strain, body weight of males and females fed ad libitum reached a plateau of 350 g and 220 g, respectively, at the age of 10 months. Their spontaneous food intake was 15 g per 24 h in males and 10 g in females, values which were 50 to 40 % lower than that reported for most strain of laboratory rats. A 30 % food restriction was initiated at the age of 10 months in both gender, and also at 20 months in males. In females, reduction in caloric intake had no effect on mean survival until 30 months, but change the slope of the survival curve in the last part of life. As a result, mean and maximal life span were increased by 10 %. In males, when reduction in food intake was initiated at 10 months, the survival curve of the restricted animals was shift to the right, also corresponding to a 10 % increase in mean and maximal survival, without change in the slope of mortality curve. When started at 20 months, diet restriction has no significant effect on survival of male rats. It was concluded that food restriction initiated in adults is mostly efficient to increase survival in rodents with large spontaneous food intake, but have a minor effect on lean strain, although it has beneficial effect on several aging processes.

[Diagnosis of dementia]. / Démarche diagnostique devant un syndrome démentiel.

PURPOSE: The high prevalence of dementia, particularly of Alzheimer's disease, the increase of their incidence with age, and the population aging make this group of diseases a major problem for public health. Nevertheless, diagnosis is difficult because it depends on evolution of disturbances that patients often cannot precisely relate, on complex neuropsychological explorations, and on pathological examination difficult to obtain. Today in France, geriatricians are fully implicated in the diagnosis of dementia and all the physicians who give care to elderly, should lead easily a diagnosis of dementia. CURRENT KNOWLEDGE AND KEY POINTS: In February 2000 ANAES (French governmental agency for accreditation and evaluation of health system) published recommendations called "practical recommendations for the diagnosis of Alzheimer's disease". These recommendations allow physicians to standardize their practices and consist of a rigorous clinical history and examination, a neuropsychological analysis, standard investigations and application of diagnostic criteria already widely diffused and used. FUTURE PROSPECTS AND PROJECTS: Deepening of knowledge, in particular in the domains of neuropsychology and functional cerebral imagery, should allow physicians to diagnose early dementia. These early diagnosis should allow to initiate a multidisciplinary, preventive and effective care for patients. Specific drugs, that will be available, will be intended mostly for patients with early diagnosis, ideally at a pre-dementia state.

Role of behavioural disturbance in the loss of autonomy for activities of daily living in Alzheimer patients.

BACKGROUND: Cognitive impairment is associated with functional impairment in patients with Alzheimer's disease (AD). Behavioural disturbance is very common in these patients. Nevertheless, there has been very little research into the relations between behavioural disturbance and functional status in AD. The purpose of this study is to investigate the relationship between behavioural disturbance and functional status after taking account of cognitive impairment. MATERIAL AND METHODS: 579 patients were prospectively evaluated at 16 French hospitals, all referents for AD, and were diagnosed with possible or probable AD. These patients were assessed with NeuroPsychiatric Inventory (NPI), cognitive subscales of the Alzheimer's Disease Assessment Scale (ADAS-cog), Clinical Dementia Rating scale (CDR) and Instrumental Activities of Daily Living scale (IADL). RESULTS: The number of men with available data for IADL total score was too small to make any analysis. 'Group A' gathered 256 women for whom the relation between autonomy for Activities of Daily Living (ADL) and the other variables were determined. 'Group B', pooled 85 women for whom relations found were verified. Linear regression was used for the analysis. With age, cognitive impairment allows us to explain best (38%) the loss of autonomy for ADL. CONCLUSION: The role of behavioural disturbances in the loss of autonomy for ADL was not determinant in our study, whereas cognitive impairment and age were better able to determine the loss of autonomy for ADL. Further study is needed to explain the decline of functional status in AD patients.

Urea transporter expression in aging kidney and brain during dehydration.

Aging is commonly associated with defective urine-concentrating ability. The present study examined how the kidney and the brain of senescent (30-mo-old) female WAG/Rij rats respond to dehydration induced by 2 days of water deprivation in terms of urea transporter (UT) regulation. In euhydrated situation, senescent rats exhibited similar vasopressin plasma level but lower urine osmolality and papillary urea concentration and markedly reduced kidney UT-A1, UT-A3, and UT-B1 abundances compared with adult (10-mo-old) rats. Senescent rats responded to dehydration similarly to adult rats by a sixfold increase in vasopressin plasma level. Their papillary urea concentration was doubled, without, however, attaining that of dehydrated adult rats. Such an enhanced papillary urea sequestration occurred with a great fall of both UT-A1 and UT-A3 abundances in the tip of inner medulla and an increased UT-A1 abundance in the base of inner medulla. UT-A2 and UT-B1 were unchanged. These data suggest that the inability of control and thirsted senescent rats to concentrate urine as much as their younger counterparts derives from lower papillary urea concentration. In aging brain, UT-B1 abundance was increased twofold together with a fourfold increase in aquaporin-4 abundance. Dehydration did not alter the abundance of these transporters.

[Clinical features of ambulatory patients over 80 years of age followed for Alzheimer's disease. French prospective multicenter study REAL.FR]. / Caractéristiques cliniques des patients ambulatoires âgés de plus de 80 ans suivis pour une maladie d'Alzheimer. Etude française multicentrique prospective REAL.FR.

PURPOSE: Twice out off three, patients with Alzheimer's disease (AD) are aged 80 and older. Very old patients are more frail, have social precariousness and have often polypathology. Few data are available about these elderly patients. The aim of our study was to analyse characteristics of AD patients aged 80 and older. MATERIAL AND METHODS: This is a prospective, multicentric French study (REAL.FR) of a cohort of ambulatory AD patients, with Mini-Mental State values between 10 and 26. Clinical and social data at inclusion of patients aged 80 and older and patients younger were compared. RESULTS: Six hundred eighty nine patients (488 women, 201 men) were included between April 2000 and June 2002. The mean age was 77.8 +/- 6.9 years. Two hundred sixty four patients (38%) were aged 80 and older. Those patients were more dependant for Activities of Daily Living (ADL) than younger patients (ADL score of Katz: 5.2 +/- 1.07 et 5.6 +/- 0.74 respectively; p < 0.001 and IADL (Instrumental Activities of Daily Living) score of Lawton: 7.3 +/- 3.57 et 9.3 +/- 1.57 respectively; p < 0.001). Duration of evolution of the disease were comparable between older and younger patients. CONCLUSION: In our cohort, AD patients aged 80 and older had a weakest autonomy for the ADL than younger patients with the same stage of the disease. Results has implications on care. Following the cohort will permit to specify evolution of data.

Increased adrenergic contractility and decreased mRNA expression of NOS III in aging rat urinary bladders.

Our objective was to study age-related changes in adrenergic contractility and gene expression profile in the rat urinary bladder. Young (3-month old), adult (10-month old) and senescent (30-month old) male WAG/Rij rats were used. Gene expression profile in the rat urinary bladder was defined using Atlas microarray technology. In vitro contractile responses induced by KCl, phenylephrine (PHE) and norepinephrine (NE) were compared in isolated urinary bladders dissected from young, adult and senescent rats. Among a total of 1176 genes present on the arrays, 15 genes showed an increase in expression and 10 genes a decrease with age. Four genes related to nerve growth factor were upregulated whereas NOS type III was downregulated in aging rats. Intrinsic contractility of isolated rat urinary bladders was not changed between adult and aging rats as judged by the response curves to KCl. In contrast, an age-related increase in the maximal contractile responses to NE, but not PHE, was noticed (13 +/- 1, 48 +/- 2% and 59 +/- 2% at 3, 10 and 30 months, respectively). The alpha1D-adrenoceptor antagonist BMY7378 antagonized NE-induced contractions with low potency in both groups suggesting the involvement of the alpha1A-adrenoceptor subtype. This was confirmed by microarray, which demonstrated mRNA expression for the alpha1A-adrenoceptor subtype only. These results suggest that aging of the urinary bladder is associated with an increase in the maximal contractile response to NE which could be due to NO shortage resulting from downregulation of urothelial NOS III.

[Determination of regimen fluindione needed for anticoagulation in the elderly]. / Schéma simple d'adaptation posologique de la fluindione chez les patients âgés.

INTRODUCTION: There is no validated method to predict the daily maintenance dosage of oral anticoagulation treatment by fluindione in the elderly patients. The aim of our prospective study was to look for a relation between INR at day 2 after a fixed dosage of fluindione and the daily maintenance dosage of fluindione necessary to obtain an INR value between 2 and 3. PATIENTS AND METHODS: Ten milligrams of fluindione were administered on first and second day of treatment. INR was determined the third day. RESULTS: From this value, we were able to determine the daily dosage of fluindione (+/- 5mg) that maintained a steady state INR value between 2 and 3. CONCLUSION: In these very elderly patients, there was a relation between INR at the third day after a fixed dosage of fluindione and the daily maintenance dosage of fluindione necessary to obtain an INR value between 2 and 3.

Cellular signaling, AGE accumulation and gene expression in hepatocytes of lean aging rats fed ad libitum or food-restricted.

The effects of food restriction on liver glucagon and vasopressin V1a receptors, on AGE accumulation and on gene expression were investigated in 10- and 30-month-old WAG/Rij female rats fed ad libitum or chronically food-restricted by 30%. The age-related increase in glucagon and vasopressin V1a receptor density, as well as the rise in glucagon-induced cAMP generation was prevented by the restriction. AGE accumulation, characteristic of the aging process, was normalized in food-restricted animals. Gene expression determined with rat Atlas cDNA Expression Arrays containing 1176 cDNA indicates that a few genes exhibited a greater than twofold change in mRNA ratios with age. Most down-regulated genes were related to oxidative metabolism of lipids, and most of the up-regulated genes were concerned with the cell cycle and transcription factors. Chronic food restriction partially prevents these changes in gene expression and induces up- and down-regulation of several mRNAs which are not modified with age in ad libitum fed rats.

Food restriction prevents age-related polyuria by vasopressin-dependent recruitment of aquaporin-2.

The mechanisms underlying the prevention of age-related polyuria by chronic food restriction were investigated in female WAG/Rij rats. The decreased osmolality of renal papilla observed in senescent rats was not corrected by food restriction. A reduced urea content in the inner medulla of senescent rats, fed ad libitum or food-restricted, was suggested by the marked decrease in expression of UT-A1 and UT-B1 urea transporters. Aquaporin-2 (AQP2) downregulation in the inner medulla of senescent rats was partially prevented by food restriction. Both AQP2 and the phosphorylated form of AQP2 (p-AQP2), the presence of which was diffuse within the cytoplasm of collecting duct principal cells in normally fed senescent rats, were preferentially targeted at the apical region of the cells in food-restricted senescent animals. Plasma vasopressin (AVP) was similar in 10- and 30-mo-old rats fed ad libitum, but was doubled in food-restricted 30-mo-old rats. This study indicates that 1) kidney aging is associated with a marked decrease in AQP2, UT-A1, and UT-B1 expression in the inner medulla and a reduced papillary osmolality; and 2) the prevention of age-related polyuria by chronic food restriction occurs through an improved recruitment of AQP2 and p-AQP2 to the apical membrane in inner medulla principal cells, permitted by increased plasma AVP concentration.

Glucagon and vasopressin V1a receptor signaling in hepatocytes from aging rats.

Glucose tolerance is reduced with age. The relationship between this change in glucose homeostasis and signaling of glucagon and vasopressin V1a receptors was investigated in hepatocytes isolated from 10- and 30-month-old female WAG/Rij rats. Binding capacity of hepatocytes for 125I glucagon and 3H vasopressin increased 2- and 1.8-fold, respectively, between 10 and 30 months. Intracellular cAMP accumulation induced by glucagon was 40% greater in hepatocytes of aging rats than of adults, although EC(50) were similar in the two groups. Conversely, phosphodiesterases activity and nucleotides leakage out of the cells were unchanged with age. The rise in intracellular calcium consecutive to the stimulation of V1a receptor was comparable in adult and senescent animals. Finally, glucose release by hepatocyte suspensions was greater in senescent than in adult animals in absence as in presence of glucagon. These experiments suggest that increase in glucagon receptor expression and cAMP generation would contribute to the impaired glucose tolerance characteristic of the aging process.

Downregulation of aquaporin-2 and -3 in aging kidney is independent of V(2) vasopressin receptor.

The mechanisms underlying age-related polyuria were investigated in 10- and 30-mo-old female WAG/Rij rats. Urinary volume and osmolality were 3.9 +/- 0.3 ml/24 h and 2,511 +/- 54 mosmol/kgH(2)O in adult rats and 12.8 +/- 0.8 ml/24 h and 1,042 +/- 44 mosmol/kgH(2)O in senescent animals. Vasopressin V(2) receptor mRNA did not significantly differ between 10 and 30 mo, and [(3)H]vasopressin binding sites in membrane papilla were reduced by 30%. The cAMP content of the papilla was unchanged with age, whereas papillary osmolality was significantly lowered in senescent animals. The expression of aquaporin-1 (AQP1) and -4 was mostly unaltered from 10 to 30 mo. In contrast, aquaporin-2 (AQP2) and -3 (AQP3) expression was downregulated by 80 and 50%, respectively, and AQP2 was markedly redistributed into the intracellular compartment, in inner medulla of senescent animals, but not in renal cortex. These results indicate that age-related polyuria is associated with a downregulation of AQP2 and AQP3 expression in the medullary collecting duct, which is independent of vasopressin-mediated cAMP accumulation.

[Kidney aging: cellular mechanisms of problems of hydration equilibrium]. / Vieillissement rénal: mécanismes cellulaires des troubles de l'équilibre hydrique.

The ability to control body hydration is frequently impaired with age. This mainly results from changes in thirst and from loss of renal concentrating ability. The cellular mechanisms responsible for this functional renal failure have been extensively studied in different experimental models. Although the loss of nephrons sometimes observed with age impairs the ability of the kidney to retain water, a similar defect was reported in animals free of glomerulosclerosis, indicating that the reduction in the number of nephrons was not the only cause. Because age-related polyuria has also been demonstrated in rats with unchanged secretion of vasopressin, renal changes in water reabsorption was hypothesized. Such alterations have been searched along the whole length of the nephron. Neither the single nephron filtration rate nor proximal or early distal flow rates were modified in senescent animals where water reabsorption in the collecting duct was reduced. The affinity and the density of the V2 receptors were mainly constant in most experimental models of ageing. In contrast, intracellular cAMP accumulation following vasopressin stimulation was reduced in the oldest animals. The expression of aquaporins in luminal and basolateral membranes of the collecting duct epithelial cells was altered. The amount of basolateral aquaporin 3 and 4 was respectively decreased by 50 per cent and unchanged in renal papilla. In addition, the expression of aquaporin 2, which is rate limiting for the osmotic permeability of the collecting duct, was reduced by 50 per cent in the outer medulla and by 80 per cent in the inner medulla of the senescent animals. This drop in aquaporin 2 expression in the distal part of the nephron could be the main cause for the fall in concentrating ability of the kidney and the age-related impaired control of hydration.