[Association between the A2 allele of the HLA system and age at onset of Alzheimer's disease]. / Association entre allèle A2 du système HLA et âge de début de la maladie d'Alzheimer.

OBJECTIVE: Alzheimer is a multifactor disease occurring in a sensitive genetic territory. The e4 allele of the apolipoprotein E (APO E) is a recognised factor of risk. Some studies have suggested an association between the A2 allele of the HLA system and an earlier onset of the disease notably when it appears before the age of 64 or after the age of 75. The aim of our study was to explore this hypothesis in an independent sample of patients. METHODS: We compared the influence of the A2 allele of the HLA system on the age at onset of the disease in two groups of Caucasian patients presenting with Alzheimer's disease: early onset if the disease appeared before the age of 60 (n= 31) and late onset if it had appeared after the age of 75 (n= 44). The influence of the e4 allele of APO E was also taken into account. RESULTS: The comparison of the patients depending on the presence or not of at least one HLA-A2 allele revealed no significant difference, whatever the group of patients studied, in the age at onset of the disease. CONCLUSION: The age at onset of Alzheimer's disease was not influenced in our study by the presence of the HLA-A2 allele.

[Burden experienced by informal caregivers assisting Alzheimer's patients in the REAL.FR study]. / Charge ressentie par les aidants informels de patients atteints de la maladie d'Alzheimer au sein de l'étude REAL.FR: méthode de mesure et facteurs associés.

BACKGROUND: Most AD patients are cared for at home by informal caregivers. The effect of different kind of stressors on caregivers has been referred to as caregiver burden. OBJECTIVE: To determine (1) the level of burden of informal caregivers of Alzheimer's patients in a French national sample; (2) the factors associated with a high level of burden. METHODS: Cross-sectional study of informal caregivers of the demented elderly referred to a psychogeriatric, geriatric or neurological service. The principal caregivers of 531 patients with mild to moderate dementia attending an outpatient cognitive assessment clinic were interviewed via a structured questionnaire that focused upon caregiver-related characteristics such as whether they were living with the patients, their feelings of burden assessed by the Zarit Burden Interview and patients were examined at baseline to evaluate their cognitive, behavioral and functional limitation. RESULTS: Logistic regression analysis showed that patients' characteristics (MMSE, behavioral problems, nutritional problems), caregiver's characteristics (female gender, number of tasks involved in caregiving, cohabitation) and the provision of medical services were independently associated with a high level of burden. In this study increased caregiver burden was related independently to increased levels of patient behaviour disturbance and cognitive impairment. However, neither the illness duration nor the functional disabilities in activities of daily living affected the level of burden. This may have relevance to appropriate interventions for informal caregivers.

Instrumental activities of daily living as a potential marker of frailty: a study of 7364 community-dwelling elderly women (the EPIDOS study).

BACKGROUND: A number of clinical conditions have been shown to be associated with frailty in elderly people. We hypothesized that incapacities on the Instrumental Activities of Daily Living (IADLs) scale could make it possible to identify this population. We investigated the associations between IADL incapacities and the various known correlates of frailty in a cohort of community-dwelling elderly women. METHODS: Cross-sectional analysis was carried out on the data from 7364 women aged over 75 years (EPIDOS Study). The IADL was the dependent variable. Sociodemographic, medical, and psychological performance measures were obtained during an assessment visit. Falls in the previous 6 months and fear of falling were also ascertained. Body composition was measured by dual-energy x-ray absorptiometry. The factors associated with disability in at least one IADL were included in a logistic regression model. RESULTS: Thirty-two percent of the population studied had disability in at least one IADL item. This group was significantly older (81.7 +/- 4.1 yr vs 79.8 +/- 3.4 yr), had more frequent histories of heart disease, stroke, depression or diabetes, and was socially less active (p =.001). These associations persisted after multivariate analysis. Cognitive impairment as assessed by the Pfeiffer test (Pfeiffer score <8) was closely associated with disabilities on the IADL (OR 3.101, 95% confidence interval [CI] 2.19-4.38). Falls and fear of falling were also more frequent in the group of women with an abnormal IADL (p =.001) but only fear of falling remained significantly associated with incapacities on at least one IADL item after logistic regression (OR 1.47, 95% CI 1.28-1.69). Women with disability on at least one IADL item also had lower bone mineral density, this was independent of the other factors. CONCLUSION: Our results confirmed that women with disability on at least one IADL item are frailer because they had more associated disorders, poorer cognitive function and more frequent falls. Disabilities on this scale could be a good tool for identifying individuals at risk of frailty among elderly persons living at home and in apparent good health. This finding requires confirmation by longitudinal studies.

Nutritional risk factors for institutional placement in Alzheimer's disease after one year follow-up.

Amongst factors associated with the institutional placement of elderly people with dementia, there has been little study of those related to malnutrition. We followed a cohort of 318 individuals with Alzheimer's disease (AD). Patients, who were all living at home at the start of the study were recruited from the outpatient service of a hospital unit specialising in AD. After one year, 20% of the patients had moved into institutional care. Multivariate analysis showed that a Mini nutritional Assessment score (MNA) of less than 25.5 (median score of the sample) and overeating behavioural problems (p=0.006) were risk factors for institutional placement. Nutritional problems are reversible and patients with a low MNA score could benefit from a thorough geriatric assessment, in order to slow or prevent institutional placement.

Descriptive analysis of emergency hospital admissions of patients with Alzheimer disease.

The aim of this project was to study the underlying reasons for emergency hospital admission of patients with dementia of the Alzheimer type (DAT) and their characteristics. This prospective 4-month study identified 118 patients with DAT, most of whom were referred to the two emergency departments of the Toulouse University Hospital. The two main reasons for admission were behavioral problems (26.3%) and falls (18.6%). Patients were generally at an advanced stage of the disease process and had substantial evidence of poor nutritional status and loss of activities of daily living ability. About one third of patients had already been admitted to the hospital for the same reasons in the preceding months. Psychotropic drugs predominated (71%) among the current medications taken by the patients and were mainly anxiolytics and neuroleptics. Finally, the discharge report indicated that medications were a contributing factor in the disorders of 25% of patients. We believe that improved information for caregivers and early management and treatment are essential to respond adequately to the problems raised by this population.

Relationships between nutritional markers and the mini-nutritional assessment in 155 older persons.

OBJECTIVE: To investigate the relationships between nutritional status measured by a comprehensive nutritional assessment including anthropometric measurements, nutritional biological markers, evaluation of dietary intake, and the Mini-Nutritional Assessment (MNA) nutrition screening tool. DESIGN: A prospective study. PARTICIPANTS: One hundred fifty-five older subjects (53 men and 102 women; mean age = 78 years; range = 56-97 years). These participants were hospitalized in a geriatric evaluation unit (n = 105) or free living in the community (n = 50). MEASUREMENT: Weight, height, knee height, midarm and calf circumferences, triceps and subscapular skinfolds, albumin, transthyretin (prealbumin), transferrin, ceruloplasmin, C-reactive protein, alpha1-acid glycoprotein, cholesterol, vitamins A, D, E, B1, B2, B6, B12, folate, copper, zinc, a 3 day food record combined with a food-frequency questionnaire; the MNA nutritional screening. RESULTS: The MNA scores have been found to be significantly correlated to nutritional intake (P < .05 for energy, carbohydrates, fiber, calcium, vitamin D, iron, vitamin B6, and vitamin C), anthropometric and biological nutritional parameters (P < .001 for albumin, transthyretin, transferrin, cholesterol, retinol, alpha-tocopherol, 25-OH cholecalciferol zinc). An MNA score between 17 and 23.5 can identify those persons with mild malnutrition in which nutrition intervention may be effective. CONCLUSIONS: The MNA is a practical, noninvasive, and cost-effective instrument allowing for rapid nutritional evaluation and effective intervention in frail older persons.

[Falls, frailty and osteoporosis in the elderly: a public health problem]. / Chutes, fragilité et ostéoporose chez la personne âgée: un problème de santé publique.

INTRODUCTION: Elderly people can be subdivided into three groups: healthy elderly persons (65-70% of the population), elderly subjects with diseases (about 5%) and frail old people. Frailty represents "age-related physiologic vulnerability resulting from impaired homeotasic stock and a reduced capacity of the organism to withstand stress". It could lead elderly subjects to pathological, barely reversible, ageing. CURRENT KNOWLEDGE AND KEY POINTS: One of the main objective of geriatricians is to develop useful screening tools to identify people at high risk, thus allowing them to benefit from preventive interventions as early as possible. It has been suggested that the decline in homeostatic stock involves numerous physiological systems. Those at the core of frailty would be neuromuscular changes resulting in sarcopenia, neuroendocrine dysregulation, and immune disorders. A recent study has shown that increased levels of interleukin 6 is a risk factor for frailty. FUTURE PROSPECTS AND PROJECTS: Work in progress aimed at identification of at-risk patients should: lead to early detection; draw attention on underestimated fields such as the nutritional status, sarcopenia, or gait disorders; promote the development of the standardized gerontological evaluation in order to identify the different components of frailty; and promote the development of non-pharmacological programmes including physical training, nutritional managing, and optimal social life.

[Alzheimer's disease: from pathology to preventive methods?]. / Maladie d'Alzheimer: de la pathogénie vers des mesures préventives?

INTRODUCTION: Sporadic Alzheimer's disease is the most frequent form of dementia and appears to be associated with increasing age and certain genetic and environmental factors. Some studies have recently been published on potential protective factors. CURRENT KNOWLEDGE AND KEY POINTS: Several genes appear to be involved; one of the most common is the ApoE4 allele on chromosome 19. The physiopathology is not elucidated, but recent studies have shown a protective effect for NSAIDs, estrogen, nutritional factors (vitamins E, B6 and B12) as well as some biochemical amino acids (homocysteine). FUTURE PROSPECTS AND PROJECTS: Interventional studies are now in progress and some preventive approaches will soon be available.

Weight loss in Alzheimer disease.

BACKGROUND: Epidemiologic studies have shown that weight loss is commonly associated with Alzheimer disease (AD) and is a manifestation of the disease itself. The etiology of weight loss in AD appears multifactorial. Hypotheses to explain the weight loss have been suggested (eg, atrophy of the mesial temporal cortex, biological disturbances, and higher energy expenditure); however, none have been proven. OBJECTIVE: In the first part of this article, we describe weight loss in AD (epidemiologic data and hypotheses to explain weight loss and anorexia in AD). In the second part we report the results of a longitudinal study of the changes in nutritional variables in a cohort of patients with a probable diagnosis of AD. DESIGN: We followed subjects with AD (based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association) who were recruited from the Alzheimer's Disease Center in Toulouse. All subject underwent a nutritional, neuropsychologic, and functional evaluation. The Zarit scales were used to assess caregiver burden and caregiver reactions to the patients' behavioral and autonomic disorders. RESULTS: We showed that only results of the Burden Interview and the Memory and Behavior Problems Checklist, which explored caregiver burden, predicted weight loss in AD. It is possible that caregivers who consider themselves overburdened by the disease process are not willing to invest adequate resources to allow AD patients to properly nourish themselves. CONCLUSION: Nutritional education programs for the caregivers of AD patients seem to be the best way to prevent weight loss and improve the nutritional status of these patients.

Alzheimer disease: protective factors.

Approximately 6-8% of all persons aged >65 y have Alzheimer disease and the prevalence of the disease is increasing. Any intervention strategy aimed at decreasing risks or delaying the onset of the disease will therefore have a substantial effect on health care costs. Nutrition seems to be one of the factors that may play a protective role in Alzheimer disease. Many studies suggest that oxidative stress and the accumulation of free radicals are involved in the pathophysiology of the disease. Several studies have shown the existence of a correlation between cognitive skills and the serum concentrations of folate, vitamin B-12, vitamin B-6, and, more recently, homocysteine. However, nutritional factors have to be studied not alone but with the other factors related to Alzheimer disease: genetics, estrogen, antiinflammatory drug use, and socioeconomic variables. The objective of this article was to review recent studies in this field.

Nutritional support and aging in preoperative nutrition.

In the past 20 years, an increased interest geriatric nutrition has induced researchers to document the distribution and magnitude of nutritional problems in the elderly population. It has been observed that the prevalence of malnutrition is greatly affected by the general health status and autonomy of the elderly. Among free-living healthy elderly persons, the prevalence of protein-caloric undernutrition is low. As health and functional capacities deteriorate with age, however, the prevalence increases dramatically to 30-65% of those in home care, nursing homes or in hospital. Formal nutritional assessment has typically been absent from most published programmes of geriatric evaluation and comprehensive geriatric assessment. This is frequently because of the lack of a specific validated tool to assess nutritional status in older persons and, at least partly, to explain this phenomenon. The Mini Nutritional Assessment was developed and validated on large representative samples of elderly persons to address these specific issues. Recent experimental studies have shown that advanced malnutrition is much more difficult to treat in the elderly than in younger adults. Trials of nutritional support using oral supplements or enteral tube feeding have shown improved outcome in those identified as malnourished on admission to hospital.

[Alzheimer's disease and nutrition]. / Maladie d'Alzheimer et nutrition.

Weight loss is a nutritional problem commonly associated with Alzheimer disease. Two types of weight loss have been described. A severe weight loss correlated with a decrease in daily caloric intake and with increased difficulties in performing the activities of daily living. A slowly progressive but clinically significant loss, not associated with either a decrease in caloric intake or an inflammatory syndrome. It is difficult to explain this type of weight loss as subjects have adequate caloric intakes. Several hypothesis are however considered as increased energy requirements (which can result from increased energy expenditure, from increased metabolic disorder, or from increased growth hormone secretion), or mesial temporal cortex atrophy. But, at the present time, no study can give a proper explanation. Vitamin deficiencies, specially vitamin B6, B12 and folates, high homocysteine level, antioxidants deficiencies (especially, vitamin E deficiency), iron, counter, and phenol derived could also influence the memory capacities and have an effect upon cognitive impairment, as reported in epidemiological studies. The prevention of nutritional deficiencies in patients with Alzheimer's disease, could be one of the strategies to improve the caregiver and the patients quality of life.

Influence of age on rectal tone and sensitivity to distension in healthy subjects.

Hypersensitivity to rectal distension is frequently observed in patients with irritable bowel syndrome (IBS). However, few data are available about the influence of age on rectal sensory thresholds and tone. The aim of this study was to measure rectal sensory thresholds and tone with a barostat in 12 healthy subjects (aged 86 +/- 4 years, eight females, four males) as compared with 12 young healthy male controls (26 +/- 1 years). Isobaric phasic distensions were performed in the fasted state (increment of 4 mmHg, steps of 5 min, interval of 5 min). Rectal tone changes were then measured as changes in volume of the barostat bag, the pressure being kept constant. After a baseline recording of 1 h, a 1000-kcal meal was served and the tone recorded until return to baseline. Rectal sensory thresholds were significantly higher in aged subjects. First sensation, sensation of urge to defaecate and sensation of pain were triggered at 21.1 +/- 3.2 mmHg, 30.4 +/- 5.4 mmHg and 40.5 +/- 5.0 mmHg, respectively, in aged subjects, vs 13.3 +/- 4.6 mmHg (P < 0.05), 20.7 +/- 1.0 mmHg (P < 0.001) 31.3 +/- 1.7 mmHg (P < 0.001) in controls. Rectal compliance was not significantly different between the two groups. Mean barostat bag volume was 104 +/- 13 mL in fasting aged subjects and 125 +/- 23 mL in controls (NS). After the meal, the barostat bag volume decreased by 69 +/- 11% during 85 +/- 17 min in aged subjects and 75 +/- 14% during 89 +/- 15 min in young controls (NS). Rectal sensory thresholds triggered by distension are increased in aged healthy subjects while compliance and tone are not different. Age should be considered as a confounding factor when studying rectal sensitivity and further studies in aged patients with IBS should include a group of control subjects within the same range of age as studied patients.

The Mini Nutritional Assessment (MNA) and its use in grading the nutritional state of elderly patients.

The Mini Nutritional Assessment (MNA) has recently been designed and validated to provide a single, rapid assessment of nutritional status in elderly patients in outpatient clinics, hospitals, and nursing homes. It has been translated into several languages and validated in many clinics around the world. The MNA test is composed of simple measurements and brief questions that can be completed in about 10 min. Discriminant analysis was used to compare the findings of the MNA with the nutritional status determined by physicians, using the standard extensive nutritional assessment including complete anthropometric, clinical biochemistry, and dietary parameters. The sum of the MNA score distinguishes between elderly patients with: 1) adequate nutritional status, MNA > or = 24; 2) protein-calorie malnutrition, MNA < 17; 3) at risk of malnutrition, MNA between 17 and 23.5. With this scoring, sensitivity was found to be 96%, specificity 98%, and predictive value 97%. The MNA scale was also found to be predictive of mortality and hospital cost. Most important it is possible to identify people at risk for malnutrition, scores between 17 and 23.5, before severe changes in weight or albumin levels occur. These individuals are more likely to have a decrease in caloric intake that can be easily corrected by nutritional intervention.