Current developments in the radiotherapy approach to elderly and frail patients with glioblastoma multiforme.

The benefit of postoperative radiotherapy (RT) has been demonstrated in elderly patients aged 65 years or older with glioblastoma multiforme. Hypofractionated RT schedules can reduce the time and morbidity of treatment while maintaining comparable survival outcomes to lengthy conventional RT. Current international randomized clinical trials are studying the optimized hypofractionated RT regimens, hypofractionated RT in comparison with temozolomide chemotherapy and hypofractionated RT in comparison with the same RT plus temozolomide. Given the guarded prognosis of the elderly and frail patients, quality of life and side effects of treatment should be closely examined. As more than half of cancers in the world occur in developing countries, hypofractionated RT could be better utilized as a cost-effective treatment for this group of patients.

Comparison of clinical and angiographic prognostic risk scores in elderly patients presenting with acute coronary syndrome and referred for percutaneous coronary intervention.

BACKGROUND: Multiple risk prediction models have been validated in all-age patients presenting with acute coronary syndrome (ACS) and treated with percutaneous coronary intervention (PCI); however, they have not been validated specifically in the elderly. METHODS: We calculated the GRACE (Global Registry of Acute Coronary Events) score, the logistic EuroSCORE, the AMIS (Acute Myocardial Infarction Swiss registry) score, and the SYNTAX (Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) score in a consecutive series of 114 patients ≥75 years presenting with ACS and treated with PCI within 24 hours of hospital admission. Patients were stratified according to score tertiles and analysed retrospectively by comparing the lower/mid tertiles as an aggregate group with the higher tertile group. The primary endpoint was 30-day mortality. Secondary endpoints were the composite of death and major adverse cardiovascular events (MACE) at 30 days, and 1-year MACE-free survival. Model discrimination ability was assessed using the area under receiver operating characteristic curve (AUC). RESULTS: Thirty-day mortality was higher in the upper tertile compared with the aggregate lower/mid tertiles according to the logistic EuroSCORE (42% vs 5%; odds ratio [OR] = 14, 95% confidence interval [CI] = 4-48; p <0.001; AUC = 0.79), the GRACE score (40% vs 4%; OR = 17, 95% CI = 4-64; p <0.001; AUC = 0.80), the AMIS score (40% vs 4%; OR = 16, 95% CI = 4-63; p <0.001; AUC = 0.80), and the SYNTAX score (37% vs 5%; OR = 11, 95% CI = 3-37; p <0.001; AUC = 0.77). CONCLUSIONS: In elderly patients presenting with ACS and referred to PCI within 24 hours of admission, the GRACE score, the EuroSCORE, the AMIS score, and the SYNTAX score predicted 30 day mortality. The predictive value of clinical scores was improved by using them in combination.

A framework to understand the variations of PSD-95 expression in brain aging and in Alzheimer's disease.

The postsynaptic density protein PSD-95 is a major element of synapses. PSD-95 is involved in aging, Alzheimer's disease (AD) and numerous psychiatric disorders. However, contradictory data about PSD-95 expression in aging and AD have been reported. Indeed in AD versus control brains PSD-95 varies according to regions, increasing in the frontal cortex, at least in a primary stage, and decreasing in the temporal cortex. In contrast, in transgenic mouse models of aging and AD PSD-95 expression is decreased, in behaviorally aged impaired versus unimpaired rodents it can decrease or increase and finally, it is increased in rodents grown in enriched environments. Different factors explain these contradictory results in both animals and humans, among others concomitant psychiatric endophenotypes, such as depression. The possible involvement of PSD-95 in reactive and/or compensatory mechanisms during AD progression is underscored, at least before the occurrence of important synaptic elimination. Thus, in AD but not in AD transgenic mice, enhanced expression might precede the diminution commonly observed in advanced aging. A two-compartments cell model, separating events taking place in cell bodies and synapses, is presented. Overall these data suggest that AD research will progress by untangling pathological from protective events, a prerequisite for effective therapeutic strategies.

Delirium in elderly patients hospitalized in an acute care unit.

Introduction: Delirium is frequent in hospitalized older people, with incidence rate up to 40% in acute care. Delirium is associated with several adverse consequences, including increased mortality and institutionalization. This study aims to investigate the prevalence, incidence, and consequences of delirium in patients hospitalized in an acute care unit for elderly (ACE unit). Methods: Over a 3 months period, every patient (N = 93, mean age 84.1 ± 7.8 years, 66/93(71%) women) admitted to a 28-bed ACE unit were systematically assessed for delirium. Trained nurses used the Confusion Assessment Method (CAM) instrument to determine the presence of delirium at admission and on each subsequent day over patients' stay. Delirium prevalence rate was defined as the proportion of patients with a positive CAM within 24 hours of admission to the ACE unit. Delirium incidence rate was defined as the proportion of patients with a negative CAM at admission whose CAM became positive at least once during their stay. This evaluation was part of a functional assessment, including Basic Activities of Daily Life (Katz BADL, from 0 to 6, higher score indicating better function). Delirium prevention interventions and specific treatment was provided if needed. Results: Overall,25/93(27%)patients had delirium during their stay. Prevalence of delirium at admission was 10/93 (11%), with an incidence of 15/83(18%). Compared with non-delirious patients, those with delirium were more frequently men (10/25(40%) vs 17/68(25%), p <.001) and had reduced functional status at admission(BADL 2.0 ± 1.9 vs 3.6 ± 2.1, p = .004). They tended to be older (86.0 ± 6.7 vs 83.3 ± 8.1 years, p = .110). At discharge, delirium was associated with reduced functional status (BADL 2.0 ± 2.1 vs 4.3 ± 1.9, p <.001), lower rate of home discharge (6/20(30%) vs 28/65 (43%), p = .009) and increased mortality (5/25 (20%) vs 3/68 (5%), p <.001). On average, patients with delirium stayed 5.7 days longer (17.0 ± 9.8 vs 11.31 ± 6.3, p = .011). Conclusion: Delirium occurred in almost a third of these older patients, even though its incidence was relatively low in this frail population. Despite specific management, delirium remained associated with higher risk for adverse outcomes at discharge. These results suggest that early preventive interventions, implemented as soon as possible after hospital admission, might be needed in similar population to achieve better outcomes. Effectiveness of such interventions will be evaluated in future studies.

Analysis of glial acidic fibrillary protein in the human entorhinal cortex during aging and in Alzheimer's disease.

Glial fibrillary acidic protein, GFAP, is a major intermediate filament protein of glial cells and major cytoskeletal structure in astrocytes. The entorhinal cortex has a key role in memory function and is one of the first brain areas to reveal hallmark structures of Alzheimer's disease and therefore provides an ideal tissue to investigate incipient neurodegenerative changes. Here we have analyzed age- and disease-related occurrence and composition of GFAP in the human entorhinal cortex by using one- and two-dimensional electrophoresis, Western blots and immunocytochemistry combined with confocal microscopy. A novel monoclonal antibody, GF-02, was characterized that mainly reacted with intact GFAP molecules and indicated that more acidic and soluble GFAP forms were also more susceptible to degradation. GFAP and vimentin increased with aging and in Alzheimer's disease (AD). Two-dimensional electrophoresis and Western blots revealed a complex GFAP pattern, both in aging and AD with different modification and degradation forms. Immunohistochemistry indicated that reactive astrocytes mainly accumulated in relation to neurofibrillary tangles and senile plaques in deeper entorhinal cortex layers. GFAP may be used as an additional but not exclusive diagnostic tool in the evaluation of neurodegenerative diseases because its levels change with age and respond to senile plaque and tangle formation.

Healthcare utilization of elderly persons hospitalized after a noninjurious fall in a Swiss academic medical center.

OBJECTIVES: To determine the risk of hospital readmission, nursing home admission, and death, as well as health services utilization over a 6-month follow-up, in community-dwelling elderly persons hospitalized after a noninjurious fall. DESIGN: Prospective cohort study with 6-month follow-up. SETTING: Swiss academic medical center. PARTICIPANTS: Six hundred ninety persons aged 75 and older hospitalized through the emergency department. MEASUREMENTS: Data on demographics and medical, physical, social, and mental status were collected upon admission. Follow-up data were collected from the state centralized billing system (hospital and nursing home admission) and proxies (death). RESULTS: Seventy patients (10%) were hospitalized after a noninjurious fall. Fallers had shorter hospital stays (median 4 vs 8 days, P<.001) and were more frequently discharged to rehabilitation or respite care than nonfallers. During follow-up, fallers were more likely to be institutionalized (adjusted hazard ratio=1.82, 95% confidence interval=1.03-3.19, P=.04) independent of comorbidity and functional and mental status. Overall institutional costs (averaged per day of follow-up) were similar for both groups ($138.5 vs $148.7, P=.66), but fallers had lower hospital costs and significantly higher rehabilitation and long-term care costs ($55.5 vs $24.1, P<.001), even after adjustment for comorbidity, living situation, and functional and cognitive status. CONCLUSION: Elderly patients hospitalized after a noninjurious fall were twice as likely to be institutionalized as those admitted for other medical conditions and had higher intermediate and long-term care services utilization during follow-up, independent of functional and health status. These results provide direction for interventions needed to delay or prevent institutionalization and reduce subsequent costs.

Postoperative Cognitive Dysfunction (POCD) and Inflammatory Markers in Elderly Patients

Introduction: Particularly in elderly patients, the brain responds to a systemic inflammatory response with an increased production of inflammatory mediators. This has hypothetically been linked to the development of postoperative cognitive dysfunction (POCD). Methods: We investigated 31 patients aged >65 yrs undergoing elective major surgery under standardized general anaesthesia (thiopental, sevoflurane, fentanyl, atracurium). Cognitive function was measured preoperatively and 7 days postoperatively using the extended version of the Consortium to Establish a Registry for Alzheimer's Disease - Neuropsychological Assessment Battery (CERAD-NAB, validated German version) for which we developed a diagnostic cut-off in healthy elderly volunteers. Systemic C-reactive protein (CRP) and interleukin 6 (IL-6) were measured preoperatively, 2 days postoperatively, and 7 days postoperatively. Values for CRP, IL-6, operative characteristics and hospital length of stay in patients with POCD and without POCD were compared using the Mann- Whitney U test and are shown as median [range]. Results: Fourteen patients (45%) developed POCD. Values for CRP were not statistically different in patients with POCD and without POCD but tended to be higher in patients with POCD 2 days postoperatively. Patients with POCD had significantly higher IL-6 values on postoperative days 2 and 7 (table 1). These patients also had a significantly longer duration of anaesthesia (305 [195-620] vs.190 [150-560] min, p = 0.034), larger intraoperative blood loss (425 [0-1600] vs. 100 [0-1500] ml, p = 0.018) and longer hospital stays (15 [8-45] vs. 8 [4-40] days, p = 0.008). Table 1 POCD (n = 14) No POCD (n = 17) p value CRP (mg/dl) preop. 4.0 [1.0-245] 4.2 [0.3-36.2] 0.6 2 days postop. 223 [20-318] 98 [4.5-384] 0.07 7 days postop. 58 [15-147] 44 [11-148] 0.2 IL-6 (U/ml) preop. 2[2-28.1] 2 [2-7.3] 0.8 2 days postop. 56 [17-315] 20 [2-123] 0.009 7 days postop. 9[2-77] 4 [2-16] 0.03 Interpretation: In this small group of patients, high IL-6 values postoperatively were associated with POCD supporting a role for systemic inflammation in the development of POCD. In patients with POCD, duration of anaesthesia was significantly longer, and intraoperative blood losses were larger. These risk factors will need to be confirmed in a larger group of patients. The difference in length of stay may be indicative of postoperative complications, which have been linked to POCD earlier.

Impact of brain aging and neurodegeneration on cognition: evidence from MRI.

PURPOSE OF REVIEW: We present an overview of recent concepts in mechanisms underlying cognitive decline associated with brain aging and neurodegeneration from the perspective of MRI. RECENT FINDINGS: Recent findings challenge the established link between neuroimaging biomarkers of neurodegeneration and age-related or disease-related cognitive decline. Amyloid burden, white matter hyperintensities and local patterns of brain atrophy seem to have differential impact on cognition, particularly on episodic and working memory - the most vulnerable domains in 'normal aging' and Alzheimer's disease. Studies suggesting that imaging biomarkers of neurodegeneration are independent of amyloid-β give rise to new hypothesis regarding the pathological cascade in Alzheimer's disease. Findings in patients with autosomal-dominant Alzheimer's disease confirm the notion of differential temporal trajectory of amyloid deposition and brain atrophy to add another layer of complexity on the basic mechanisms of cognitive aging and neurodegeneration. Finally, the concept of cognitive reserve in 'supernormal aging' is questioned by evidence for the preservation of neurochemical, structural and functional brain integrity in old age rather than recruitment of 'reserves' for maintaining cognitive abilities. SUMMARY: Recent advances in clinical neuroscience, brain imaging and genetics challenge pathophysiological hypothesis of neurodegeneration and cognitive aging dominating the field in the last decade and call for reconsidering the choice of therapeutic window for early intervention.

Polyarthrite rhumatoïde du sujet agé: présentation clinique et prise en charge [Late-onset rheumatoid arthritis: clinical presentation and management]

Onset of rheumatoid arthritis in an elderly patient is common, in fact more common than in younger subject. If the reality of true differences in clinical presentation between younger and older subjects remained discussed, the central point remains that the prognosis is not better in older patients. Finally, conventional disease-modifying antirheumatic drugs (DMARD) and biological treatments are as efficient and safe than in younger patients, and the same strict management objectives used for younger subjects must be applied in the elderly.

Personality traits influence clinical outcome in day hospital-treated elderly depressed patients

OBJECTIVES: Although personality traits are considered significant predictors of both physical and mental health, their specific impact on treatment outcome in elderly patients with depression remains largely unexplored. Impact of personality traits on the evolution of depressive symptoms, quality of life, and perception of clinical progress was assessed in a psychotherapeutic community. DESIGN: A prospective longitudinal study was conducted in 62 elderly outpatients. SETTING: Day hospital treatment as usual combined group and individual therapies, pharmacological treatment, as well as family and network meetings. PARTICIPANTS: Patients presented with major depression or a depressive episode of bipolar disease. MEASUREMENTS: The Geriatric Depression Scale, the Short Form Survey, and the Therapeutic Community Assessment scale were administrated at admission, 3, 6, 12 months, and at discharge. Personality was evaluated with the NEO Five-Factor Personality Inventory. RESULTS: Outcome revealed reduced depression and improved mental quality of life and clinical progress. Higher Geriatric Depression Scale scores were found in individuals with higher levels of Neuroticism (and its Vulnerability facet). Better self-perception of clinical progress was observed in individuals with lower levels of the Depressiveness and Modesty facets and higher openness to action. Improvement in quality of life was predicted by high Positive emotions facet. All these associations remained significant after controlling for age, gender, and treatment length. CONCLUSION: Personality traits may predict clinical outcome in psychotherapeutic hospital day care for elderly patients with depression.

Interventions aiming at balance confidence improvement in older adults: an updated review.

BACKGROUND: Loss of balance confidence is a frequent condition that affects 20-75% of community-dwelling older persons. Although a recent fall is a common trigger, loss of balance confidence also appears independent of previous experience with falls. Maintaining or improving balance confidence is important to avoid unnecessary, self-imposed restrictions of activity and subsequent disability. Holding another person's hand or using an assistive device while walking are simple interventions that are used naturally to address poor balance confidence in daily life. However, more complex interventions have also been developed and tested to achieve more sustained improvement in balance confidence. OBJECTIVES: This review describes interventions that have been tested to improve balance confidence in older community-dwelling persons. METHODS: Based on 2 recent systematic reviews, an additional search for literature was performed to update current information on interventions aiming at balance confidence improvement. Interventions were classified as those directly aimed at increasing balance confidence or not, and further stratified into those using monofactorial or multifactorial approaches. RESULTS: A total of 46 randomized controlled trials were identified. Five of the 8 interventions that directly targeted balance confidence showed benefits. Among those, multicomponent behavioral group interventions provided the most robust evidence of benefits in improving balance confidence and in decreasing activity avoidance. Among interventions not directly aiming at balance confidence improvement (11/21 studies with benefits), exercise (including tai chi) appears as the most promising monofactorial intervention. Nine of the 17 multifactorial fall prevention programs showed an effect on balance confidence, exercise being a main component in 7 of these 9 studies. Interventions that targeted elderly persons reporting poor balance confidence and/or those at risk for falls seemed more likely to be beneficial. CONCLUSIONS: Positive and sometimes sustained improvement in balance confidence can be achieved by various interventions among community-dwelling elderly persons. The effect of these interventions on activity restriction associated with poor balance confidence have been less well studied, but some studies also suggest potential benefits.

Energy and nutrient intake of Swiss women aged 75-87 years.

OBJECTIVE: Reliable data about the nutrient intake of elderly noninstitutionalized women in Switzerland is lacking. The aim of this study was to assess the energy and nutrient intake in this specific population. SUBJECTS: The 401 subjects were randomly selected women of mean age of 80.4 years (range 75-87) recruited from the Swiss SEMOF (Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk) cohort study. A validated food frequency questionnaire (FFQ) was submitted to the 401 subjects to assess dietary intake. RESULTS: The FFQ showed a mean daily energy intake of 1544 kcal (+/-447.7). Protein intake was 65.2 g (+/-19.9), that is 1.03 g kg(-1) body weight per day. The mean daily intake for energy, fat, carbohydrate, calcium, magnesium, vitamin C, D and E were below the RNI. However, protein, phosphorus, potassium, iron and vitamin B6 were above the RNI. CONCLUSION: The mean nutrient intake of these free living Swiss elderly women was low compared with standards. Energy dense foods rich in carbohydrate, magnesium, calcium, vitamin D and E as well as regular sunshine exposure is recommended in order to optimise dietary intake.