Prédiction des issues défavorables des hospitalisations gériatriques

This research project was undertaken to assess the relative contribution of cognitive, functional and nutritional status, comorbidities and biomarkers predicting adverse outcomes in the hospitalized elderly. In older people, dementia is frequently associated with adverse health outcomes (poor functional and nutritional status; higher rates of institutionalization and of readmission; and lower survival rates). The relative weight of dementia of varying type and severity as predictors of adverse health outcomes after other risk factors taken into account remains unclear. In this context, we performed, since 2004, a prospective clinico-biological study aiming to investigate the relationship among clinical and specific biological markers and adverse health outcomes in a population of very old, acutely ill patients discharged from a geriatric hospital. We assessed the extent to which a clinical or a biological marker was of greater added prognostic value than other markers of risk for the adverse outcomes. The studied adverse outcomes were death in hospital, greater length of stay, institutionalization and increase formal home care need after discharge; 1-year risk of rehospitalization, institutionalization and death; and long-term mortality after 5-years of follow-up. The studied clinical markers were cognitive diagnosis (various etiologies and severity of dementia), functional and nutritional status, comorbidities and the studied biomarker was leukocytes telomere length. As few comorbidity indices are valid and reliable in the elderly and were rarely compared, first we compared the performance, relevance and ability of six widely used comorbidity indices (comorbid Charlson index, cumulative illness rating scale (CIRS), index of coexistent diseases (ICED), Kaplan scale, geriatrics index of comorbidity (GIC) and chronic disease score (CDS) to predict the adverse outcomes. As there is evidence of association between telomere length and aging but data investigating the association between telomere length and dementia remained scarce; first, we determined whether telomere length may contribute to the diagnosis of AD and whether they allow to discriminate AD from other dementias; secondly, we assessed whether telomere length alone is associated to the studied adverse outcomes or when combined to the clinical markers provided an additional predictive value. In our cohort of 449 very old inpatients (mean age = 85yrs), we were able to demonstrate, that: - Demented patients, non-demented patients and patients with mild cognitive impairment (MCI) had similar levels of comorbidity, but demented patients had a poorer functional and nutritional status. Till now, demented patients have been reported to be healthier than other old people and these findings could be a consequence of inaccurate symptoms reporting, delaying diagnosis; or may reflect a failure on the part of screening strategies to investigate thoroughly and to diagnose disease in these patients. - Comorbidity scores performed differently predicting the studied adverse outcomes and, according to our results, the CIRS and the GIC are those that we recommend to use in the elderly for clinical and research purposes. The GIC was the most accurate predictor of death during hospitalization, the risk of death being 30 times higher; followed by the CIRS. The CIRS was the strongest predictor of a prolonged hospital stay and institutionalization. Concerning 1-year risk, the GIC and the CIRS were the best predictors for mortality and for readmission. The GIC was the only significant predictor of institutionalization. The CIRS was the strongest risk predictor of 5 years survival after hospital discharge, followed by the GIC. - Dementia predicted only institutionalisation immediately after discharge; whereas higher comorbidity score predicted death in hospital or longer hospital stay, regardless of cognitive status. Functional status was the best predictor of greater home care needs. Regarding the 5-year risk of mortality, the univariate model showed that being older, male and having vascular and severe dementia, higher comorbidity and functional disability were predictive of shorter survival. However, in the full multivariate model adjusted for age and sex, the effect of dementia type or severity completely disappeared when all the variables were added. In multivariate analysis, the best predictor of long-term mortality was higher comorbidity score, followed by functional status. - Telomere length could not be used to distinguish between demented and non demented patients, regardless of the type of dementia, or to predict dementia or MCI conversion. No significant difference in telomere length was observed between cognitively normal patients, demented patients and patients with MCI. Similarly, no significant differences in telomere length were found between patients with different etiologies or severities of dementia. In addition, the combination of telomere length and ApoE polymorphism did not confer a significantly higher dementia risk than ApoEε4 alone. - Telomere length and change in cognitive status (from normal to MCI or dementia, or from MCI to dementia) were not associated after two years of follow-up. Telomere length is not associated with 5-year survival beyond the impact of other risk factors of mortality like comorbidity, functional, nutritional and cognitive status

Is it possible to treat vascular dementia?

Randomized controlled trials of primary and secondary prevention of vascular dementia demonstrate real effects on the cause or progression of disease (disease-modifying treatment). These strategies lead to a reduction in all cerebrovascular risk factors, in particular hypertension. Such treatment may prevent dementia by reducing stroke and possibly by other mechanisms that remain undetermined,such as those involved in neurodegeneration and cell death. Curative treatment of vascular dementia, particularly given recent studies on cholinesterase inhibitors (rivastigmine, donepezil and galantamine) and memantine, is still ineffective. There is insufficient evidence to support widespread use of these drugs in vascular dementia. Particular considerations should be taken into account in clinical trials. Vascular dementia is a heterogeneous disease with different subtypes and mechanisms.Therefore, well-designed, adequately powered trials accounting for this heterogeneity, with better clinical definitions and an assessment and detection of cognitive and global changes specific to vascular dementia, are needed

Management of mixed dementia

Alzheimer's disease (AD) and vascular dementia (VaD) are the most common causes of dementia in the elderly. Although AD can be diagnosed with a considerable degree of accuracy, the distinction between isolated AD, VaD and mixed dementia (MD) [when both pathologies coexist in the same patient] remains a controversial issue and one of the most difficult diagnostic challenges. MD represents a very common pathology, especially in the elderly, as reported in neuropathological studies. Accurate diagnosis of MD is of crucial significance for epidemiological purposes and for preventive and therapeutic strategies. Until recently, pharmacological studies have generally focused on pure disease, either AD or VaD, and have provided few data on the best therapeutic approach to MD. There is only one original randomized clinical trial on (acetyl)cholinesterase inhibitor therapy (GAL-INT-6, galantamine) for MD; the other studies are post hoc analyses of AD trial subgroups (AD2000, donepezil) or of VaD trial subgroups (VantagE, rivastigmine). Cholinesterase inhibitors have reproducible beneficial effects on cognitive and functional outcomes in patients with MD. These benefits are of a similar magnitude to those previously reported for the treatment of AD. It is likely that the beneficial effects of memantine (an NMDA receptor antagonist) in AD may also apply to MD, but randomized controlled trials are still lacking. Treatment of cardiovascular risk factors, especially hypertension, may protect brain function and should be included in prevention strategies for MD

Les démences mixtes. Point de vue neuropathologique

Alzheimer's disease (AD) and vascular dementia (VaD) are the most frequent causes of dementia in the elderly. Although AD can be diagnosed with a very high degree of accuracy, the distinction between pure AD, VaD and mixed dementia (MD), where both pathologies co-exist in the same patient, remains a controversial issue and one of the most difficult diagnostic challenges. MD represents a very frequent pathology, especially in the elderly, as underlined by the neuropathological studies. However, the respective importance of degenerative and vascular lesions, their interaction in the genesis of dementia and the mere existence of mixed dementia are still debated. Accurate diagnosis of MD is of crucial significance for epidemiologic purposes and for preventive and therapeutic strategies. Until recently, pharmacological studies have generally focused on pure diseases, either AD or VaD, and have provided little data on the best therapeutic approach to MD. This review will provide an overview of neuropathological aspects of MD in the elderly, which appears to be one of the most common forms of dementia

The Association Between the Body Mass Index and 4-Year All-Cause Mortality in Older Hospitalized Patients

BACKGROUND: Association between body mass index (BMI) and long-term mortality is poorly studied in older hospitalized populations. METHODS: The researchers prospectively studied the impact of the BMI, comorbidities, and malnutrition on long-term mortality in 444 patients (mean age 85.3+/-6.7 years; 74.0% women) receiving geriatric inpatient care. All-cause mortality was determined using simple and multiple Cox proportional hazard models. RESULTS: Higher BMI was associated with a higher prevalence of diabetes, hypertension, and heart failure, but with a lower prevalence of malignancies. Four-year all-cause mortality was inversely associated with a BMI greater than or equal to 30kg/m(2) (hazard ratio = 0.59, p = .037) and positively associated with age, male gender, several individual comorbidities, and the global disease load determined by the Cumulative Illness Rating scale. The inverse association between a BMI greater than or equal to 30 and mortality remained significant after adjustment for age, gender, smoking, individual comorbidities (including heart failure and malignancies), Cumulative Illness Rating scale scores, and malnutrition parameters (hazard ratio = 0.52, p = .015). One-year mortality was associated with the Cumulative Illness Rating scale score but not with BMI categories. There were no survival differences between patients in low (<20.0) and intermediate (20.0-24.9 and 25.0-29.9) BMI categories. CONCLUSIONS: A BMI greater than or equal to 30 is associated with better long-term survival in hospitalized older patients, even after extensive adjustment for comorbidities, malnutrition, and smoking. Conversely, a low BMI (<20-25) is not associated with excess mortality, likely due to the overriding impact of multiple comorbidities. The researchers' observations have important implications for the mortality risk stratification in older high-risk patients

Est-il possible de réduire les inégalités de santé au grand âge?

Analysis of prospective data collected between 1984 and 2008 by the CERN medical team (European Centre of Nuclear Research, Geneva) concerning 2040 former employees who were retired or had died stimulated our interest on the impact of inequalities in socioeconomic conditions, employment, lifestyle and classical risk factors on health and life expectancy. Such inequalities explain differences in life expectancy, potentially reaching several decades, between rich and poor countries (France vs Swaziland), but also within a given country (USA), a given city (Glasgow) or even a given enterprise (CERN) where all employees have the same level of healthcare insurance and access to treatment. Classical cardiovascular and neurovascular risk factors (smoking, arterial hypertension and lipid disorders) interact with socioeconomic status, intelligence, education, emotions and job responsibility/complexity, precipitating or preventing cardiovascular events. The same is true of dementia, for which midlife risk factors (obesity, arterial hypertension and hypercholesterolemia) should be considered in the psychosocioeconomic context, which influences cognitive reserves and thus affects the risk and severity of dementia in old age. Thus, in addition to lifestyle and classical risk factors, socioeconomic status appears as a major health determinant, by imposing behaviors and habits and by determining access to healthcare

Rôle de la réserve cérébrale en pathologie cognitive

The "Brain Reserve" hypothesis was raised after the analysis of the results of the first longitudinal surveys comparing in nuns the neuropsychological aging process and the post mortem brain pathological findings. Numerous discordances were discovered: a) Persons with high education, high IQ and complex working responsibilities could benefit of a healthy cognition until death while their neuro-pathological brain findings were concordant with the International pathological criteria of Alzheimer disease and b) Moreover the same persons with a high brain reserve suffering from Alzheimer Disease have late, atypical symptoms and signs of the disease explaining a delayed diagnosis. In these patients the progress of the disease is always quick and severe

Mixed dementia: epidemiology, diagnosis, and treatment

Alzheimer's disease (AD) and vascular dementia (VaD) are the most frequent causes of dementia in older people. Although AD can be diagnosed with a considerable degree of accuracy, the distinction between isolated AD, VaD, and mixed dementia (MD), where both pathologies coexist in the same patient, remains a controversial issue and one of the most difficult diagnostic challenges. Although MD represents a very frequent pathology, especially in older people, as reported in neuropathological studies, the respective importance of degenerative and vascular lesions, their interaction in the genesis of dementia, and the mere existence of MD are still debated. Accurate diagnosis of MD is of crucial significance for epidemiological purposes and for preventive and therapeutic strategies. Until recently, pharmacological studies have generally focused on pure disease, AD or VaD, and have provided little information on the best therapeutic approach to MD. This article provides an overview of MD in older people. A retrospective review of the recent literature on prevalence, incidence, course, risk factors, diagnosis, and treatment of MD was performed. The article also emphasizes the need for further studies, including neuropsychological and functional evaluations, and neuroimaging and clinicopathological correlations to develop a better understanding of MD, which appears to be one of the most common forms of dementia

Démences vasculaires et démences mixtes

The concept of vascular dementia has evolved over the past century to include multiple underlying pathophysiological mechanisms. Neuroimaging techniques offer new and better ways to identify the presence of cerebrovascular pathology, although they do not improve our ability to link these changes to the onset of clinical cognitive impairment. Clinical criteria for vascular dementia have also evolved but they remain imperfect. Most epidemiological studies define mixed dementia as the coexistence of Alzheimer's disease and vascular dementia. Clinicopathologic correlations show a clear association between the concomitant presence of vascular and Alzheimer lesions and the severity of cognitive impairment in mixed dementia and provide strong support for the validity of the mixed dementia concept. Mixed dementia is a very frequent disease that remains underdiagnosed, especially in the elderly. The diagnosis of vascular and mixed dementia remains a clinical challenge and cannot be improved without further studies of clinicopathological correlations and functional neuroimaging. Preventive therapeutic interventions include control of vascular risk factors and especially treatment of hypertension

Syndrome confusionnel du sujet âgé : les difficultés d'un diagnostic facile

Confusion is a frequent psychiatric and behavioural manifestation of diffuse cerebral injury found in elderly patients that are severely ill or stressed. The hyperactive form is often recognised because of the psychomotor agitation. However, the hypoactive form is most frequent and has a worse prognosis. Despite, it is often under-recognised. Among contributing factors, anticholinergic agents and drug interactions are significant. Identification and treatment of the underlying cause of delirium is essential with a focus on non pharmacological approach. Antipsychotic agents are reserved for severe forms and where non pharmacological intervention fracases