Diseases and aging: patterns of morbidity with age; relationship between aging and age-associated diseases.

Patterns of morbidity with age can be schematically represented in three situations: 1) as a progressive illness, such as Alzheimer's disease, leading to a relatively rapid functional decline. 2) as a catastrophic event, such as a stroke or hip fracture, leading to a decline in function with improvement after rehabilitation. 3) as normal aging with gradual progressive functional decline. Results from the New Mexico Aging Process Study provide some unique insights about the consequences of the effects of aging on the nutritional status of healthy elderly people. Between 1979 and 1989, anthropometric and biochemical markers as well as dietary intakes remained relatively constant in this healthy elderly population. Thus, the aging process alone may have little or no important consequences on the nutritional status of healthy elderly individuals. However, the adaptation of pancreatic and intestinal function to undernutrition and refeeding can be perturbed in these individuals.

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.

Risk factors for hip fracture. MEDOS study: results of the Toulouse Centre.

The development of preventive strategies for hip fractures requires better identification of risk factors. The MEDOS study was designed to study prospectively the incidence of hip fracture in 14 centres from six countries and characterise risk factors. At one centre (Toulouse), data were gathered from questionnaires completed by 386 cases of hip fracture aged over 50 years and 848 age- and sex-matched controls over a 12-month period. Of the 935 variables of the MEDOS questionnaire, 235, grouped into 56 items, were statistically analysed. Odds ratios (and 95% confidence intervals) were estimated for each variable from a multiple stepwise logistic regression model. The population comprised 19.2% men and 80.8% women, with a mean age of 80 +/- 8.8 years; 80% were living in an urban area and 76% with their family. Of the 17 significant variables, moderate excess weight and a high nutritional intake of calcium were associated with a decreased risk of hip fracture. Loss of autonomy, a higher height than normal (> 1SD), and a history of previous fractures significantly increased the risk of fracture. Interestingly, all these variables accounted for only 18% of the risk of hip fracture.

Tolerance and biological activity of pentosan polysulfate after intramuscular or subcutaneous administration for ten days in human volunteers.

This study reports on the tolerance and the pharmacological activity of pentosan polysulfate (PPS) administered to healthy volunteers for 10 days. Three groups of 10 subjects received either one daily injections of 100 mg of PPS by I. M. route (group I), or two daily injection of 50 mg of PPS by I. M. or S. C. route (groups II and III, respectively). In each group two random subjects received a placebo for the 10 days; on day 0, each subject was injected by a placebo. Clinical tolerance was checked by a daily physical examination; biological tolerance was assessed comparing the results of the main biochemical and haematological constants measured before starting the treatment (day 0) and 12 or 24 h after the end of the treatment (day 11). The pharmacological activity was measured on serial samples taken before treatment and between 1 and 6 h after the drug injection on days 1, 3 and 10; the results were compared to those obtained on day 0. Clinical tolerance was good. The biological side effects concern the transaminase levels and the platelet counts. An increase above the upper normal limit was observed in 18/24 and 3/24 for alanine and aspartic transaminase respectively. The mean platelet reduction ranged between 24 and 34% according to the groups. The drug injection induced a slight Quick time (PT) prolongation, no significant alteration of factors II, VII-X, V levels and of thrombin clotting time. The activated partial thromboplastin time (APTT) was significantly prolonged and there was a weak but significant circulating anti-Xa activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Disability, psychosocial factors and mortality among the elderly in a rural French population.

The purpose of this work is to identify risk markers of mortality in a cohort of 645 people aged 60 and over. The study was carried out in rural areas in south west France. Data were collected by questionnaire in 1982. Mortality was determined 4 years later; 111 deaths were registered. The analysis of age-adjusted odds ratios (OR) showed strong relationships between mortality and disability (OR = 7.75), compared health (OR = 3.94), self-rated health (OR = 2.47), home comfort (OR = 0.52), physical activity (OR = 0.32), sociability (OR = 0.43) and two subjective well-being items: the feeling of uselessness (OR = 3.51), and the lack of projects for the future (OR = 2.35). By contrast, no significant association was observed with reported morbidity and social support. Two multivariate analyses were performed: the first on longevity using Cox's regression model, the second on mortality using a linear discriminant analysis. The results of these analyses were translated into a simple set of 8 independent risk markers for the identification of a "high risk group" of mortality within 4 years. The sensitivity of this mortality risk indicator was 73% and its specificity 77%.

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.

Postprandial cholecystokinin secretion in elderly with protein-energy undernutrition.

OBJECTIVE: Malnutrition is currently observed in aged people, and cholecystokinin is an important peripheral satiety signal. The aim of this study was to examine the effect of aging and protein-energy malnutrition on postprandial cholecystokinin (CCK) release. DESIGN: Non-randomized, cross-sectional comparison by age group. SETTING: Gastroenterology section of a teaching hospital. PARTICIPANTS: Twenty-one human volunteers divided into three groups: young healthy subjects (Group 1: mean 29 years, n = 7), aged healthy subjects (Group 2, mean 80 years, n = 7), and aged subjects with an important degree of malnutrition (Group 3, mean 84.6 years, n = 7). INTERVENTION: Each subject ingested a standardized liquid meal after an overnight fast. MAIN OUTCOME MEASURES: Plasma cholecystokinin was measured using a sensitive bioassay before and after the ingestion of the liquid meal. RESULTS: Basal cholecystokinin levels were similar (0.9 to 1 pM equivalent CCK-8) in the three groups. Postprandial levels were significantly increased over basal (P less than 0.05). The maximal cholecystokinin value was lower in Group 1 (3.5 +/- 0.8 pM equivalent CCK-8) and Group 2 (3.3 +/- 0.77 pM equivalent CCK-8) than in Group 3 (8.3 +/- 2 pM equivalent CCK-8) (P less than 0.05). Integrated plasma cholecystokinin was also similar in Group 1 (171 +/- 38 pM.60 min), (P less than 0.05). CONCLUSION: The increase of postprandial maximal levels of cholecystokinin is more related to malnutrition than to aging.

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.

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.

Predictive value of life events, psychosocial factors and self-rated health on disability in an elderly rural French population.

Increasing evidence suggests that exposure to stressful life events and a variety of psychosocial factors are related to different health outcomes in the elderly. Our purpose is to study the predictive value of each of these items on the ability deterioration of a panel of 645 rural adults, aged 60 and over, living at home and followed for 4 years (1982-1986). This survey was carried out in five rural areas of Haute-Garonne (South-West France). Data were collected from the elderly themselves by questionnaire in 1982 and 1986. An indicator of ability evolution (1982-1986) was constructed for all those surviving and reviewed in 1986. Our study concerned 470 elderly people. Ability deterioration was 55.3% (260 elderly people). The analysis of age-adjusted relative risks (RR) of ability deterioration showed a significant impact of economic level (RR = 2.3), self-rated health (RR = 2.2) and reported morbidity (RR = 2.2). Among the psychosocial factors, we noted the predictive role of a lack of project for the future (RR = 1.7) and mostly of a feeling of uselessness (RR = 9.8), but also of non-participation in association activities for people aged less than 75. All these relationships remain significant after adjustment according to reported morbidity. In contrast, no significant effect was found for social support and life events which occurred during the follow-up period. Logistic discriminant analysis and segmentation analysis were performed. They confirmed the independence of the predictive roles played by age, economic level, reported morbidity and the feeling of uselessness. These results, discussed with bibliographic data, should give a better knowledge of the processes which underlie pathological ageing.

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.

Relationship between malnutrition and falls in the elderly.

Due to the multifactorial nature of falls in the elderly population, it is difficult to determine causal relationships for risk factors for falls. In some cases, other risk factors may play a role. For example, the association between poor nutrition status and falls has not been studied extensively. The association of commonly demonstrated nutritional deficiencies in the elderly with factors such as balance, gait, and mobility may lead to new insights into causes of falls in the elderly not previously established. In this article, we review how malnutrition can be a risk factor for falls, how falls can induce malnutrition, and the possible relationship between mobility and nutrition in the elderly.

Life expectancy, comorbidity, and quality of life. A framework of reference for medical decisions.

The treatment of cancer in the elderly can benefit from increasingly sophisticated methods that measure a patient's quality of life. These measures are both general and cancer specific and herald a new and enlightened approach to patient care. The care of the older patient must be seen in light of what is known about life expectancy, the outcome of treatment, an awareness of comorbidity, and the importance of informed consent and respect for the values and preferences of the individual patient. This article reviews the growing literature on quality of life research in cancer patients.

Changes in dietary intakes with age.

The aim of this study was to describe changes in dietary intakes with age in subjects aging normally within the Toulouse study. Daily caloric intakes were constant in both sexes and in the three age classes considered. Energy distributions among the meals were rather clearly modified in men: the contribution of breakfast and afternoon snacks increased while those of lunch and dinner decreased. Observations among women were less consistent but the contribution of dinner also decreased with age (from 33.3 to 30.7%). This decreased contribution from dinner was due to a change in its nutrient composition (fewer lipids and more carbohydrates) which change the nutrient constitution of the entire daily diet, and also from a change in structure (reduced contribution by the main dish and increased role of desserts). These results pose questions concerning the reasons behind this change (loss of appetite, more pronounced taste for sweets?) and requires additional study.

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.

Nutrition and successful aging: a study of 520 elderly persons from the Toulouse and New-Mexico Aging Process Study.

Epidemiological studies of aging are usually confronted with the presence of numerous pathologies or environmental factors which make it difficult to identify the effects of aging individually. One way of reducing the variability among individuals is to use well defined criteria to select the study population. This is the choice that was made for the New Mexico and Toulouse Aging Process Studies, which were particularly turned towards successful aging. In this study we have sought to explain the diversity of states of health of the subjects of these two studies by means of an aging classification exploring the medical history, balance and walking, and the cognitive functions. This reveals that the poorer health of certain subjects (about 10% and 30% of the populations of Toulouse and Albuquerque respectively) is slightly associated with changes in eating behaviour relative to subjects who age successfully. We have, however observed a decrease in vitamin E intake in Toulouse associated with a reduction of lipids in the food. But the poorer state of health is predominantly explained by advancing age and the occurrence of pathological states. This study confirms that aging was generally successful in the two populations studied.

A prospective study of changes on nutritional patterns 6 months before and 18 months after retirement.

To present results from a two year prospective study on diet, 6 months before and 18 months after retirement. The studied population exhibited an increase in social and physical activities over time after retirement. A significant decrease in weight was found in men 18 months after retirement. Retired individuals reported taking more time for breakfast. 45.5% of retired individuals, compared to 25.5% before retirement, took more than 30 minutes for lunch than before retirement. The amount of dietary nutrients consumed remained the same before and after retirement. However, retired individuals ate out more often, and had guests more frequently. Nutrients' distribution is similar before and after retirement. Given a life expectancy of more than 20 years after retirement, it is necessary to initiate nutritional intervention.

Assessment of the effectiveness of drug therapies on nutritional status in the elderly: "concerning a randomised, double-blind clinical study of the activity of pancreatic extracts and a placebo during the renutrition of elderly subjects suffering from protein caloric undernutrition".

AIMS: to study, versus placebo, the value of administering pancreatic extracts in elderly subjects suffering from denutrition. METHODS: 52 subjects over 70 years of age, living in the Toulouse region of France, were included in this study. Each subject was required to present with an impaired nutritional status of their food intake, anthropometric and laboratory markers. RESULTS: among the 52 patients included in the study, 26 received the placebo and 26 received a pancreatic extract (Créon 12,000). 88% of these patients were women and 12% were men, the mean age of patients was 87+/-6 years. The groups were comparable at entry into the study. Nutritional intake increased in the two groups. There was a non-significant increase in body weight in the treated group when compared with the placebo group. DISCUSSION: we think that in the future, it would be preferable to conduct studies in convalescent subjects, reducing the frequency of nutritional assessments (food intake on D0 and D90, to reduce interference with the patient's habits.

[Disabilities during aging: descriptive approach and risk factors. 4-year longitudinal study of an aged rural population]. / Les incapacités au cours du vieillissement: approche descriptive et facteurs de risque. Enquête longitudinale sur 4 ans dans une population rurale âgée.

A longitudinal survey has been conducted from 1982 to 1986 in a rural population of 645 persons aged 60 and over. The aim of this study is to analyse the evolution of disabilities in this population and the main risk factors. The incidence of disabilities within 4 years is more important in the oldest birth-cohort groups and this result suggests a cumulative effect of the ageing process and chronic diseases. Indeed, the assessment of predictive factors shows that age and reported morbidity are related to the incidence of disabilities, but two other factors are strongly related to the loss of functional abilities after age adjustment: socioeconomic status and the feeling of uselessness. We conclude that disability in the elderly is not an inevitable consequence of the physiological ageing process and that a preventive approach should be based on a multidimensional concept: physical, social and psychological.