Improving quality of life in the elderly: hearing loss treatment with cochlear implants.

BACKGROUND: Hearing loss impacts health-related quality of life and general well-being and was identified in a Lancet report as one of the largest potentially modifiable factors for the prevention of age-related dementia. There is a lack of robust data on how cochlear implant treatment in the elderly impacts quality of life. The primary objective was to measure the change in health utility following cochlear implantation in individuals aged ≥ 60 years. METHODS: This study uniquely prospectively recruited a large multinational sample of 100 older adults (mean age 71.7 (SD7.6) range 60-91 years) with severe to profound hearing loss. In a repeated-measures design, pre and post implant outcome measures were analysed using mixed-effect models. Health utility was assessed with the Health Utilities Index Mark III (HUI3). Subjects were divided into groups of 60-64, 65-74 and 75 + years. RESULTS: At 18 months post implant, the mean HUI3 score improved by 0.13 (95%CI: 0.07-0.18 p < 0.001). There was no statistically significant difference in the HUI3 between age groups (F[2,9228] = 0.53, p = 0.59). The De Jong Loneliness scale reduced by an average of 0.61 (95%CI: 0.25-0.97 p < 0.014) and the Lawton Instrumental Activities of Daily Living Scale improved on average (1.25, 95%CI: 0.85-1.65 p < 0.001). Hearing Handicap Inventory for the Elderly Screening reduced by an average of 8.7 (95%CI: 6.7-10.8, p < 0.001) from a significant to mild-moderate hearing handicap. Age was not a statistically significant factor for any of the other measures (p > 0.20). At baseline 90% of participants had no or mild depression and there was no change in mean depression scores after implant. Categories of Auditory perception scale showed that all subjects achieved a level of speech sound discrimination without lip reading post implantation (level 4) and at least 50% could use the telephone with a known speaker. CONCLUSIONS: Better hearing improved individuals' quality of life, ability to communicate verbally and their ability to function independently. They felt less lonely and less handicapped by their hearing loss. Benefits were independent of age group. Cochlear implants should be considered as a routine treatment option for those over 60 years with bilateral severe to profound hearing loss. TRIAL REGISTRATION: ClinicalTrials.gov ( http://www. CLINICALTRIALS: gov/ ), 7 March 2017, NCT03072862.

Healthy aging in elderly cochlear implant recipients: a multinational observational study.

BACKGROUND: Given an increase in the aging population and its impact on healthcare systems, policy makers for provision of health and social services are aiming to keep older adults in good health for longer, in other words towards 'healthy aging'. Our study objective is to show that rehabilitation with cochlear implant treatment in the elderly with hearing impairment improves the overall health-related quality of life and general well-being that translate into healthy aging. METHODS: The multicentre, prospective, repeated measures, single-subject, clinical observational study will accrue 100 elderly, first-time, unilateral CI recipients (≥ 60 years) and analyze changes on specific measurement tools over ca. 20 months from preimplant to postimplant. Evaluations will consist of details collected through case history and interview questionnaires by clinicians, data logging, self-report questionnaires completed by the recipients and a series of commonly used audiometric measures and geriatric assessment tools. The primary indicator of changes in overall quality of life will be the HUI-3. DISCUSSION: The protocol is designed to make use of measurement tools that have already been applied to the hearing-impaired population in order to compare effects of CI rehabilitation in adults immediately before their implantation, (pre-implant) and after gaining 1-1.5 years of experience (post-implant). The broad approach will lead to a greater understanding of how useful hearing impacts the quality of life in elderly individuals, and thus improves potentials for healthy aging. Outcomes will be described and analyzed in detail. TRIAL REGISTRATION: This research has been registered in ClinicalTrials.gov (http://www.clinicaltrials.gov/), 7 March 2017 under the n° NCT03072862 .

[The Confusion Assessment Method: Transcultural adaptation of a French version]. / Adaptation transculturelle francophone de la Confusion Assessment Method.

INTRODUCTION: The Confusion Assessment Method (CAM) is a validated key tool in clinical practice and research programs to diagnose delirium and assess its severity. There is no validated French version of the CAM training manual and coding guide (Inouye SK). The aim of this study was to establish a consensual French version of the CAM and its manual. METHODS: Cross-cultural adaptation to achieve equivalence between the original version and a French adapted version of the CAM manual. RESULTS: A rigorous process was conducted including control of cultural adequacy of the tool's components, double forward and back translations, reconciliation, expert committee review (including bilingual translators with different nationalities, a linguist, highly qualified clinicians, methodologists) and pretesting. A consensual French version of the CAM was achieved. CONCLUSION: Implementation of the CAM French version in daily clinical practice will enable optimal diagnosis of delirium diagnosis and enhance communication between health professionals in French speaking countries. Validity and psychometric properties are being tested in a French multicenter cohort, opening up new perspectives for improved quality of care and research programs in French speaking countries.

French Society of ENT (SFORL) guidelines. Indications for cochlear implantation in adults.

The authors present the guidelines of the French Society of ENT and Head and Neck Surgery (SFORL) regarding indications for cochlear implantation in adults. After a literature review by a multidisciplinary workgroup, guidelines were drawn up based on retrieved articles and group-members' experience, then read over by an independent reading group to edit the final version. Guidelines were graded A, B, C or "expert opinion" according to decreasing level of evidence. There is no upper age limit to cochlear implantation in the absence of proven dementia and if autonomy is at least partial. Bilateral implantation may be proposed if unilateral implantation fails to provide sufficiently good spatial localization, speech perception in noise and quality of life, and should be preceded by binaural hearing assessment. Rehabilitation by acoustic and electrical stimulation may be proposed when low-frequency hearing persists. Quality of life should be assessed before and after implantation.

Guidelines (short version) of the French Society of Otorhinolaryngology (SFORL) on pediatric cochlear implant indications.

OBJECTIVES: The authors present the guidelines of the French Society of Otorhinolaryngology - Head and Neck Surgery (Société française d'oto-rhino-laryngologie et de chirurgie de la face et du cou - SFORL) on the indications for cochlear implantation in children. METHODS: A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence. RESULTS: The SFORL recommends that children with bilateral severe/profound hearing loss be offered bilateral cochlear implantation, with surgery before 12months of age. In sequential bilateral cochlear implantation in children with severe/profound hearing loss, it is recommended to reduce the interval between the two implants, preferably to less than 18months. The SFORL recommends encouraging children with unilateral cochlear implants to wear contralateral hearing aids when residual hearing is present, and recommends assessing perception with hearing-in-noise tests. It is recommended that the surgical technique should try to preserve the residual functional structures of the inner ear as much as possible.

International publications from the French geriatric teams: evolution in the course of last 22 years.

BACKGROUND: Bibliometry is a widely used method assessing the activity of research. AIM: Assess research activity of the French geriatric teams by bibliometry for the last 22 years and replaced it in the evolution of the French geriatrics. METHODS: Data were collected via MEDLINE through Internet PubMed. Publications from French geriatrics teams were identified using search of relevant terms for geriatrics in the field Affiliation from 1985 to 2006. Citations and abstracts were analyzed before including the publication in the study. RESULTS: We identified 692 articles published by French geriatric teams. Among them, 295 were English articles and 166 were reviews of the literature. Throughout these twenty-two years, the number of publications was consequentially increased. Nutrition and dementia-psychogeriatrics were the themes most often mentioned. The total of these publications impact factors (IF) is 753 points over the last twenty-two years, rating from 45 points between 1985 and 1989 to 330 points between 2000 and 2004. The mean score of the impact factors by publication remains relatively stable, but the number of publications having an impact factor superior to 3 increases in the course of this time interval. CONCLUSION: This bibliometric investigation points out the growing interest of the French geriatrics in clinical research, mostly oriented toward nutrition and dementia in the elderly.

Practical guidelines for the diagnosis and management of weight loss in Alzheimer's disease: a consensus from appropriateness ratings of a large expert panel.

BACKGROUND: Weight loss is a frequent condition in Alzheimer's disease patients and is responsible for complications and impaired quality of life. Practical guidelines for the diagnosis and management of weight loss in Alzheimer's disease are lacking. AIM: To elaborate practical guidelines for the diagnosis and management of weight loss in Alzheimer's disease. METHODS: Following a literature review, a set of statements about weight loss in Alzheimer's disease were proposed to a 23-member nationwide expert panel drawn from French geriatricians selected by the organisation committee. Statements were discussed and modified with the experts during a meeting and modified according to their remarks. By the means of a postal questionnaire each expert was then asked to rate each statement on a 9-point appropriateness scale, 1 being highly inappropriate and 9 highly appropriate. Analysis was based on the median and the range of the ratings. To avoid the influence of extreme or atypical opinions, the two ratings the furthest from the median were excluded from analysis for each statement. Agreement/disagreement about the statements was determined using the RAND/UCLA methodology. RESULTS: Of the 23 statements selected by the expert panel and submitted for rating, 17 obtained the agreement of the expert panel. Practical guidelines were produced from these 17 statements. CONCLUSION: These expert panel ratings, based on the best evidence currently available, provide comprehensive guidelines to appropriately diagnose, manage and prevent weight loss in Alzheimer's disease.

IANA (International Academy on Nutrition and Aging) Expert Group: weight loss and Alzheimer's disease.

Weight loss, together with psychological and behavioural symptoms and problems of mobility, is one of the principal manifestations of Alzheimer's disease (AD). Weight loss may be associated with protein and energy malnutrition leading to severe complications (alteration of the immune system, muscular atrophy, loss of independence). Various explanations have been proposed such as atrophy of the mesial temporal cortex, biological disturbances, or feeding behaviours; however, none has been proven. Prevention of weight loss in AD is a major issue. It requires regular follow-up and must be an integral part of the care plan. The aim of this article is to review the present state of scientific knowledge on weight loss associated with AD. We will consider four points: the natural history of weight loss, its known etiological factors, its consequences and the various management options.

[Repetitive transcranial magnetic stimulation: A potential therapy for cognitive disorders?] / La stimulation magnétique transcrânienne répétée : une piste thérapeutique pour les maladies neurocognitives ?

Considering the limited effectiveness of drugs treatments in cognitive disorders, the emergence of noninvasive techniques to modify brain function is very interesting. Among these techniques, repetitive transcranial magnetic stimulation (rTMS) can modulate cortical excitability and have potential therapeutic effects on cognition and behaviour. These effects are due to physiological modifications in the stimulated cortical tissue and their associated circuits, which depend on the parameters of stimulation. The objective of this article is to specify current knowledge and efficacy of rTMS in cognitive disorders. Previous studies found very encouraging results with significant improvement of higher brain functions. Nevertheless, these few studies have limits: a few patients were enrolled, the lack of control of the mechanisms of action by brain imaging, insufficiently formalized technique and variability of cognitive tests. It is therefore necessary to perform more studies, which identify statistical significant improvement and to specify underlying mechanisms of action and the parameters of use of the rTMS to offer rTMS as a routine therapy for cognitive dysfunction.

Bleeding risk of antiplatelet drugs compared with oral anticoagulants in older patients with atrial fibrillation: a systematic review and meta-analysis.

Essentials Hemorrhagic risk of antiplatelet drugs is generally thought to be lower than anticoagulants. We systematically reviewed trials comparing antiplatelet and anticoagulant drugs in older patients. Overall, the risk of major bleeding was similar with antiplatelet and with anticoagulant drugs. In elderly patients, risks and benefits of antiplatelet drugs should be carefully weighted. SUMMARY: Background The hemorrhagic risk of antiplatelet drugs in older patients could be higher than is usually assumed. Objective To compare the bleeding risk of antiplatelet drugs and oral anticoagulants in elderly patients. Methods We carried out a systematic review and meta-analysis. We searched PubMed, EMBASE and the Cochrane Library up to January 2016 for randomized and non-randomized controlled trials (RCTs) and parallel cohorts comparing antiplatelet drugs and oral anticoagulants in patients aged 65 years or older. Two independent authors assessed studies for inclusion. The pooled relative risk (RR) of major bleeding was estimated using a random model. Results Seven RCTs (4550 patients) and four cohort studies (38 649 patients) met the inclusion criteria. The risk of major bleeding when on aspirin or clopidogrel was equal to that when on warfarin in RCTs (RR, 1.01; 95% confidence interval (95% CI), 0.69-1.48; moderate-quality evidence), lower than when on warfarin in non-randomized cohort studies (RR, 0.87; 95% CI, 0.77-0.99; low-quality evidence) and not different when all studies were combined (RR, 0.86; 95% CI, 0.73-1.01). Bleeding of any severity (RR, 0.70; 95% CI, 0.57-0.86) and intracranial bleeding (RR, 0.46; 95% CI, 0.30-0.73) were less frequent with antiplatelet drugs than with warfarin. All-cause mortality was similar (RR, 0.99). Subgroup analysis suggested that major bleeding might be higher with warfarin than with aspirin in patients over 80 years old. Conclusion Elderly patients treated with aspirin or clopidogrel suffer less any-severity bleeding but have a risk of major bleeding similar to that of oral anticoagulants, with the exception of intracranial bleeding.

[Anticoagulation use in older patients with atrial fibrillation in a cardio-geriatric unit]. / Utilisation des anticoagulants chez les patients âgés atteints de fibrillation atriale dans un service de cardiogériatrie.

OBJECTIVE: Older people with atrial fibrillation (AF) have an increased embolic risk but they are less frequently treated with anticoagulants. We wanted to assess our current practice in a specialized service. PATIENTS AND METHODS: Prospective observational study including all patients older than 75 years admitted during 3 months in a cardio-geriatric unit. Patients' embolic risk (CHADS2 score), hemorrhagic risk (HAS-BLED score), anti-thrombotic treatment at arrival and any modification afterwards, were analyzed. RESULTS: Thirty-four patients were included (mean age: 85 years). AF was known in 28 patients, of whom 20 were under anticoagulant therapy at their admission (10 fluindione, 9 warfarine, 1 dabigatran), 4 received aspirin and 4 no anti-thrombotic treatment. Only the treatment of one of these patients was modified, replacing aspirin by warfarin. AF was newly diagnosed in 6 patients, of whom anticoagulation were initiated in 4 patients (3 warfarine, 1 fluindione). Finally, 9 patients (26%) left the hospital without anticoagulant treatment. Reasons given by their attending doctors were: advanced dementia (4 patients), estimated excessive hemorrhagic risk (4), and estimated low embolic risk (1). There was a clear trend to initiate anticoagulation more frequently in patients with a newly diagnosed AF (P=0.09) CONCLUSIONS: A substantial proportion of older patients with AF do not receive anticoagulant therapy, even after having been admitted to a specialized service. Advanced dementia and hemorrhagic risk are the reasons most frequently given for that.

Relation between endothelial cell apoptosis and blood flow direction in human atherosclerotic plaques.

BACKGROUND: Blood flow characteristics influence endothelial cell apoptosis. However, little is known about the occurrence of endothelial cell apoptosis in human atherosclerosis and its relation to blood flow. METHODS AND RESULTS: A total of 42 human carotid atherosclerotic plaques were retrieved by endarterectomy; they were examined in the longitudinal axial direction. Plaques were included in this study when upstream and downstream parts were clearly visible, occlusion was absent, and immunostaining for luminal endothelium was present all along the plaque. Using these criteria, 13 plaques were processed for further immunohistochemical studies (using anti-CD31, anti-Ki-67, and anti-splicing factor antibodies) and in situ detection of apoptosis (terminal dUTP nick end-labeling and ligase assay). Eight plaques showed > or =1 apoptotic endothelial cell at the luminal surface. Quantitative analysis of endothelial cell apoptosis in these plaques showed a systematic preferential occurrence of apoptosis in the downstream parts of plaques, where low flow and low shear stress prevail, in comparison with the upstream parts (18.8+/-3.3% versus 2.7+/-1.2%, respectively, P<0.001). Endothelial cell apoptosis was barely detectable in plaque microvessels. CONCLUSIONS: Our results suggest that in vivo local shear stress influences luminal endothelial cell apoptosis and may be a major determinant of plaque erosion and thrombosis.

Wrist Actigraphy: A Simple Way to Record Motor Activity in Elderly Patients with Dementia and Apathy or Aberrant Motor Behavior.

INTRODUCTION: In dementia, behavioral psychological symptoms are frequent and variable. OBJECTIVE: To assess the value of wrist actigraphy as a measure of disorder in motor behavior especially apathy, aberrant motor behavior, agitation and anxiety. METHODS: Cross sectional observational study of consecutive patients older than 75 years admitted to an intermediate care unit of a geriatric hospital ward during a two-year period. Psycho behavioral symptoms and cognitive status were assessed using the NPI scale and MMSE and diagnosis of dementia was done using DSMIV criteria. A wrist actigraph was worn for 10 days to record motor activity, sleep time and number of periods of sleep. RESULTS: 183 patients were included. Among patients with dementia, a significant decrease in motor activity was recorded in those with apathy from 9h to 12h and 18h to 21h (p <0.05) and in those with anxiety from 21h to 24h (p <0.05). Aberrant motor behavior in dementia was associated with a significant increase in motor activity from 21h to 24h (p <0.01). Agitation was not associated with a significant differences in motor activity. CONCLUSIONS: Wrist actigraphy can be used to record motor activity in elderly patients with dementia especially in those with apathy and aberrant motor behavior.

Effect of two French nurses' strikes on mortality in a geriatric hospital.

PURPOSE: To study the influence of the 1988 French nurses' strikes on mortality in a geriatric hospital. MATERIALS AND METHODS: Two nurses' strikes affected the Charles Foix Hospital near Paris from June 29 to July 31 and from September 17 to October 22, 1988. Mortality was studied in nine geriatric wards of this hospital, including two rehabilitation units comprising 187 beds, and seven long-term care units comprising 1,132 beds. Monthly mortality rates were calculated from the hospital's administrative registers and expressed as deaths per 1,000 patient-days. These rates were calculated in each of the aforementioned nine units for the 36 months preceding the first strike (control period) and for the 12 months following it (study period). RESULTS: Over the control period, monthly mortality was significantly higher in rehabilitation units than in long-term care units (2.46 +/- 1.21 versus 0.83 +/- 0.47, p less than 0.001), but mortality rates among rehabilitation units, as well as among long-term care units, were comparable. Also, during the control period, large seasonal fluctuations in monthly mortality rates were observed in both rehabilitation units and long-term care units (peak in winter and nadir in summer). These rates tended to decrease from year to year in rehabilitation units but not in long-term care units. A statistical model based on time-series analysis of the control period data was used to calculate the expected monthly mortality rates for the study period in rehabilitation units and in long-term care units, respectively. Three of the 12 actual monthly mortality rates exceeded the upper limit of the 95% confidence interval of the 12 expected monthly mortality rates, in the units where the more severe care disruption occurred. A detailed analysis of discharge summaries of these units failed to identify a possible link between some of these deaths and a possible absence of care. CONCLUSIONS: The nurses' strikes did not induce a clear-cut increase in mortality in this population of elderly patients. However, we cannot exclude the possibility that these strikes had some negative effects on health. Our results fail to provide answers to the difficult ethical problems created by such stoppages.

Osler's maneuver: absence of usefulness for the detection of pseudohypertension in an elderly population.

PURPOSE: To investigate the prevalence and clinical relevance of Osler's maneuver for detecting pseudohypertension in the elderly. PATIENTS AND METHODS: Osler's maneuver was performed by one investigator in 205 consecutive inpatients of a French geriatric hospital (40 men and 165 women; mean age 84.2 +/- 6.2 years). In 12 Osler-positive and 12 Osler-negative patients matched for age, sex, and presence of hypertension, the blood pressure values measured directly at the radial artery were compared to those measured indirectly with a standard mercury sphygmomanometer. Aortic and upper limb pulse wave velocities (PWV) were also measured in these 24 patients. RESULTS: Twenty-three of 205 patients (11%) were Osler-positive. Age, sex ratio, and prevalence of hypertension or other cardiovascular diseases did not differ significantly in Osler-positive and Osler-negative patients. Systolic blood pressure (SBP), measured by standard mercury sphygmomanometer, was significantly greater in Osler-positive than Osler-negative patients (157 +/- 37 versus 132 +/- 28 mm Hg; P < 0.01). Diastolic blood pressure (DBP) did not differ significantly (78 +/- 18 versus 74 +/- 14 mm Hg). Interobserver agreement concerning Osler's sign, studied in 40 patients, was good (kappa = 0.72). In 12 Osler-positive and 12 Osler-negative patients, the mean differences between SBP obtained by cuff-manual indirect blood pressure and direct measurements were -3.71 +/- 22.85 mm Hg and -8.59 +/- 14.40 mm Hg (P = NS). For DBP, these differences were 18.40 +/- 15.72 and 12.01 +/- 5.80 mm Hg (P = NS). The differences between the indirect and direct blood pressure measurements were significantly correlated to upper limb PWV, but not aortic PWV, for both SBP and DBP. Pseudohypertension, defined as the indirect measurement overestimation of SBP or DBP by 10 mm Hg or more, was found in 15 of the 24 patients (63%). In these patients, upper limb PWV was significantly greater than in those with no pseudohypertension (7.0 +/- 2.2 versus 5.4 +/- 1.3 m/s; P < 0.05). CONCLUSION: The Osler-positive maneuver is frequently found in elderly hospital inpatients, but its ability to detect pseudohypertension in clinical practice is poor. Measurement of upper limb PWV might be a more appropriate way of screening for this condition.

Reliability of sampling urine from disposable diapers in elderly incontinent women.

OBJECTIVE: To assess the reliability for biochemical and microbiological analysis of urine collection from disposable diapers in elderly women with severe urinary incontinence. DESIGN: Cross-sectional comparison of two methods of collection. PATIENTS AND MEASUREMENTS: Urine was sampled from 52 women inpatients (aged 68-98 years) in a geriatric hospital ward by pressing a diaper which the patient had worn for 3 hours. Just after this collection, another sample was obtained by retrograde catheterization. Both samples were analyzed for sodium, potassium, chloride, proteins, urea, creatinine, calcium, and phosphate and for cell counts, the presence of bacteria, and bacteria culture. RESULTS: For all the biochemical parameters, the urinary concentrations obtained by the two methods were strongly and significantly correlated. The following differences (mean and range, in mmol/L) were found between the values obtained by the two methods: sodium: 6.05 (-26 to 27), potassium: (-16 to 14), chloride: -1.13 (-24 to 23), urea: 6.85 (-33 to 37), creatinine: 0.24 (-0.95 to 1.45), calcium: -0.22 (-1.27 to 1.70), and phosphate: 2.17 (-2.5 to 13.4). For diagnosis of urinary tract infection, agreement between the two methods was good (kappa = 0.84), and bacteriological agreement was obtained in 25 out of 28 cases (89%). However, for diagnosis of microscopic hematuria, agreement was poor (kappa = 0.50), probably due to the overestimation of the true urinary red cell count in the samples collected by catheterization. CONCLUSION: For routine microbiological and biochemical analysis, urine extraction from disposable diapers is a simple and reasonably reliable method of sampling urine from elderly women with severe incontinence.

Variability of blood pressure response to orthostatism and reproducibility of the diagnosis of orthostatic hypotension in elderly subjects.

BACKGROUND: Orthostatic hypotension (OH) is a major problem in the elderly population. Its diagnosis is based on measurement of the blood pressure (BP) response to orthostatism (BPRO). This study investigates the within-day and day-to-day variability of the BPRO and the reproducibility of the diagnosis of OH in this population. METHODS: BP was measured in the supine position and after 1 and 2 minutes of orthostatism in 53 consecutive elderly patients (43 women and 10 men aged 83.7 +/- 9.5 years) of an intermediate care geriatric ward. BPRO was assessed 4 times on the same day (8-9 AM, 10-11 AM, 1-2 PM, and 5-6 PM) and twice more on another day of the same week (8-9 AM and 1-2 PM). RESULTS: There were significant within-day differences between the four orthostatic changes in systolic BP (OCs, supine minus standing systolic BP) after 1 minute or 2 minutes (p < .05). Day-to-day differences between the OCs measured at the same times were not significant. OH defined as an OCs of 20 mm Hg or more at 1 or 2 minutes of orthostatism, was found in ten cases (19%) in the initial set of measurements on the first day. A cumulative diagnosis of OH after the six BPRO tests was found in 23 cases (43%). The reproducibility of the diagnosis of OH was mild or poor (all kappa values were below 0.47). CONCLUSIONS: BPRO exhibits significant within-day variability in elderly patients. Within-day and day-to-day reproducibility of the diagnosis of OH, based on conventional criteria, were found to be poor.

Age and gender effects on cardiomyocyte apoptosis in the normal human heart.

BACKGROUND: Animal studies have suggested that apoptosis could play a significant role in the myocardial aging process. Although no information is available in humans, the paradigm that cardiomyocyte apoptosis is increased in the aged human heart has been widely propagated. Moreover, it is unknown whether gender differences may influence cardiomyocyte apoptosis. METHODS: Cardiomyocyte apoptosis was compared between subjects ranging in age from 21 to 93 years (22 men and 19 women), free of any cardiovascular disease, who died of either violent or natural causes. Strict inclusion and exclusion criteria were used to ensure that the selected hearts accurately represented normal aging. RESULTS: Apoptosis was detected using the TdT-mediated dUTP digoxigenin nick end labeling (TUNEL) technique (controls for TUNEL included negative staining for splicing factor SC-35 and for Ki-67 antigen). The percentage of cardiomyocyte death ranged from 0% to 0.0437%, with no correlation with the age of the subject (p =.85). However, the percentage of apoptosis was threefold higher in men than in women (0.0133% +/- 0.0030% vs 0.0042% +/- 0.0008%, respectively; p <.01). CONCLUSIONS: Our results in humans do not support the hypothesis that aging influences the percentage of cardiomyocyte apoptosis. However, gender appears to be an important determinant of the occurrence of apoptosis.

Diabetic neuropathy in elderly patients. What can be done?

The prevalence of diabetes mellitus increases markedly with age. Furthermore, advancing age is a strong risk factor for diabetic neuropathy, independent of the duration of diabetes mellitus and glycaemic control. Several biological changes occurring during the aging process may account for the facilitating effect of age on diabetic neuropathy. These include an increase in the production of advanced glycosylation end-products (AGEs), a defect in the polyol pathway, nerve vascular alterations and impaired resistance to oxidative stress. The clinical diagnosis of diabetic neuropathy is often difficult in elderly patients. The relationship between symptoms and neuropathy and that between neuropathy and diabetes mellitus are more difficult to ascertain in elderly patients due to age-related changes in the peripheral and autonomic nervous system and associated diseases frequently encountered in this population. Diagnosis of diabetic neuropathy is based on nerve conduction studies, vibratory perception threshold determination and assessment of autonomic function. For most of these tests, reference values are markedly influenced by age and their interpretation should use carefully age-adjusted reference intervals. Identification of peripheral diabetic neuropathy indicates a high risk of foot complications, such as ulcers and gangrene, often resulting in amputation, whereas cardiovascular autonomic neuropathy is associated with an increased risk of postural hypotension and coronary events. All these risks increase markedly with aging. Therapeutic trials in elderly patients with diabetic neuropathy are lacking. Treatment of diabetic neuropathy consists of achievement of better glycaemic control and treatment of symptoms related to neuropathy. Specific treatments capable of preventing or curing neuropathy are under investigation. The interesting results obtained with aldose reductase inhibitors in animal studies contrast with disappointing results in patients with diabetes mellitus. Other metabolic approaches, like antioxidants and gamma-linolenic acid, seem promising. Clinical complications of diabetic neuropathy in the elderly are often severe. Early detection is required, since at the present time a preventive approach is the most effective way to avoid or postpone debilitating complications. More research is needed to make effective curative treatments of diabetic neuropathy available.

Changes in the renin-angiotensin-aldosterone axis in later life.

The renin-angiotensin-aldosterone system (RAAS) is one of the main systems involved in the regulation of blood pressure and sodium homeostasis. In animal experiments and in humans, the plasma renin activity and aldosterone levels are reduced with aging. The age-related differences in plasma renin activity and aldosterone are more pronounced in stimulated conditions (when sitting in an upright position, when salt intake is restricted and when plasma volume is depleted) than under basal conditions. Age-related alterations of the kidney (glomerulosclerosis, decreased number of functional nephrons) might account for the age-related differences in the active to inactive plasma renin ratio. In the same way, a diminished synthesis of angiotensinogen by the liver could contribute to the decrease in the activity of the RAAS in aging. This is partially compensated for by increases in the density of angiotensin II receptors reported in elderly patients. Furthermore, aging is associated with a reduced adrenal responsiveness to angiotensin II, contributing to lower production of aldosterone and alterations of sodium homeostasis. Estradiol and progesterone help stimulate the secretion of renin. Reduced levels of these hormones at menopause also lead to reduced plasma renin activity. In relation to these findings, several studies have shown that reductions in blood pressure, induced by short or long term treatment with angiotensin converting enzyme (ACE) inhibitors, were more pronounced in old than young hypertensive patients. An insertion/deletion polymorphism in the ACE gene has been described; the genotype deletion/deletion of this gene has been reported to be closely associated with longevity. This result was unexpected since the same deletion polymorphism was also shown to represent a potent risk factor for myocardial infarction.