Effect of age, stress and protein supply on plasma amino acids during continuous enteral nutrition; a pragmatic study in rats.

BACKGROUND & AIMS: As life expectancy increases, an increasing older population may require surgery with perioperative nutritional management. While little is known about the combined effect of age and stress on amino acid metabolism during enteral nutrition, we hypothesized that blood amino acid bioavailability may be influenced not only by the characteristics of the ingested protein but also by intestinal ageing and splanchnic sequestration of amino acids. Plasma amino acid kinetics were thus evaluated in aged and adult rats receiving continuous enteral nutrition before and after standardized surgical stress. METHODS: Sixteen 5-month-old and sixteen 21-month-old male rats were used. After a gastrostomy, the insertion of a jugular vein catheter and a one-week recovery, the animals were enterally fed with commercially available formulas containing whole milk proteins or a whey hydrolysate for 24 h before (healthy state) and 18 h after a standardized laparotomy (surgical stress). Data were analyzed by 3-factor ANOVA. RESULTS: In all rats, enteral nutrition was associated with a marked increase in plasma alanine, threonine, lysine and proline (+50 to +150 µmol/L; p < 0.001), and a decrease in glycine (≈-80 µmol/L; p < 0.01). For most amino acids, their availability depended first on the amino acid composition of each protein and second on surgical stress. Aging was only associated with higher tyrosine and threonine availability (p < 0.001). There was only limited statistical interaction between age and surgical stress. CONCLUSION: In rats, plasma amino acid availability during continuous enteral nutrition is determined by the nature of the protein source and the occurrence of stress. The effects of aging on plasma amino acid availability seem very limited. Commonly used formulas therefore appear to be as suitable for elderly patients as for adult patients.

Compliance to oral nutritional supplementation decreases the risk of hospitalisation in malnourished older adults without extra health care cost: Prospective observational cohort study.

BACKGROUND & AIMS: Malnutrition affects 5-10% of elderly people living in the community. A few studies suggest that nutritional intervention may reduce health care costs. The present study included malnourished elderly patients living at home. It aimed to compare health care costs between patients that were prescribed ONS by their general practitioner and those who were not, and to assess the effect of ONS prescription on the risk of hospitalisation. METHODS: This prospective multicentre observational study included malnourished patients ≥70 years old who lived at home. Patients were defined as malnourished if they presented with one or more of the following criteria: weight loss ≥5% in 1 month, weight loss ≥10% in 6 months, BMI <21 kg/m2, albuminemia <35 g/L or Short-Form MNA ≤ 7. Their general practitioners prescribed an ONS, or not, according to their usual practice. Health care costs were recorded during a 6-month period. Other collected data were diseases, disability, self-perception of current health status, quality of life (QoL), nutritional status, appetite and compliance to ONS. A propensity score method was used to compare costs and risk of hospitalisation to adjust for potential confounding factors and control for selection bias. RESULTS: We analysed 191 patients. At baseline, the 133 patients (70%) who were prescribed ONS were more disabled (p < 0.001) and had poorer perception of their health (p = 0.02), lower QoL (p = 0.04) and lower appetite (p < 0.001) than the 58 patients (30%) who were not prescribed ONS. At 6 months, appetite had improved more in the ONS prescription group (p = 0.001). Weight change was not different between groups. Patients prescribed ONS were more frequently hospitalised (OR 2.518, 95% CI: [1.088; 5.829] hosp; p = 0.03). Analyses of adjusted populations revealed no differences in health care costs between groups. In the ONS prescription group, we identified that health care costs were lower (p = 0.042) in patients with an energy intake from ONS ≥ 500 kcal/d (1389 ± 264 €) vs. < 500 kcal/d (3502 ± 839 €). The risk of hospitalisation was reduced 3 and 5 times when the intake from ONS was ≥30 g of protein/day or ≥500 kcal/d, respectively. CONCLUSIONS: ONS prescription in malnourished elderly patients generated no extra heath care cost. High energy and protein intake from ONS was associated with a reduced risk of hospitalisation and health care costs.

Effect of aging on the availability of amino acids from an immune-enhancing diet (IED) after a surgical stress in rats.

BACKGROUND & AIMS: Dietary amino acid (AA) requirements increase after a surgical stress while the systemic AA availability from the diet decreases with age, due to splanchnic sequestration. While immune-enhancing diets (IEDs) have been recommended for the nutritional management of surgical patients, the systemic bioavailability of their AA supply has not been evaluated in elderly surgical patients. This was determined in surgically-stressed IED-fed aged rats. METHODS: Thirty-four 5-month- or 21-month-old male Sprague-Dawley rats were used. After a gastrostomy and placement of a jugular vein catheter and a one-week recovery period, the animals underwent two 24 h-enteral feedings with an arginine-enriched IED (Impact®, Nestlé Health Science) before (healthy state) and 18 h after a standardized laparotomy, used as a model of surgical stress. During enteral nutrition, blood samples were repeatedly collected to measure plasma AA bioavailability (incremental areas under the curve) at 2, 5 and 24 h. Surgical stress was evaluated from urinary catecholamines and plasma protein profile. RESULTS: Whatever the age or stress situation, IED feeding was associated with decreased plasma glycine and increased alanine, proline and arginine. Aging was mainly associated with a delayed plasma AA accumulation in the first hours after the initiation of enteral nutrition. Stress was associated with higher plasma arginine increase and lower histidine, methionine, phenylalanine and tyrosine accumulation. Age and stress interactions seem limited. CONCLUSIONS: AA bioavailability from an arginine-enriched IED seems to be maintained whatever age and stress situation. Aging appears to be mainly associated with a delay in plasma AA accumulation probably related to age-associated splanchnic sequestration of AAs. Additional effects of surgical stress per se seem limited.

Are enhanced recovery programs in colorectal surgery feasible and useful in the elderly? A systematic review of the literature.

INTRODUCTION: Enhanced recovery programs (ERP) are no longer questionable in the management of patients undergoing surgery. However, there is some doubt as to their feasibility and efficacy in the elderly. Our goal was to systematically review the evidence-based literature concerning the feasibility of ERP in elderly patients undergoing colorectal surgery. MATERIAL AND METHODS: The PubMed and Cochrane Database for systematic reviews as well as the "grey" literature between 2000 and 2015 were sought. Articles were selected if they compared ERP in elderly patients to ERP in young patients (feasibility) or compared ERP to traditional post-operative management in the elderly (efficacy). RESULTS: Sixteen articles were identified according to the inclusion criteria. All showed that an ERP was feasible in the elderly although post-operative morbidity was higher compared to younger patients. Compared to traditional management, ERP was effective since it decreased (as in the young) the overall rate of complications and thus the duration of hospital stay. There were not enough data on the degree of implementation of ERP and the medico-economic aspects to come to any formal conclusions. CONCLUSION: This comprehensive systematic review of the literature showed that ERP was feasible and effective in the elderly undergoing colorectal surgery. Protocols should be adapted to the particular aspects of this population. Future research should target pre-operative evaluation and the place of pre-habilitation in geriatric ERP.

Validation of the Mini Nutritional Assessment-Short Form in a Population of Frail Elders without Disability. Analysis of the Toulouse Frailty Platform Population in 2013.

OBJECTIVE: To assess the validity of the Mini Nutritional Assessment-Short Form (MNA-SF) in elderly patients from the Toulouse Frailty Platform. PARTICIPANTS: Overall, 267 patients aged 65 and over, without severe cognitive impairment (i.e. Mini Mental Status Examination > 20 and CDR<1), no physical disability (i.e. Activities of Daily Living ≥ 5) and no active cancer history (over the past 12 months) were included in 2013. MEASUREMENTS: Receiver operating characteristic (ROC) analyses were used to assess the predictive validity of the French version of the MNA-SF for good nutritional status (defined as a full MNA score≥24/30). Analyses were conducted in the overall sample and then in subgroups of frail and pre-frail subjects according to the frailty phenotype. Optimal cut-off points were determined to obtain the best sensitivity/specificity ratio and the highest number of correctly classified subjects. RESULTS: Among 267 patients, mean age=81.5±5.8; women=67.0%; 138 (51.7%) were frail, 98 (36.7%) were pre-frail and 31 (11.6%) were robust. Given their MNA-SF scores, 201 (75.3%) had a good nutritional status, 61 (22.8%) were at risk of malnutrition and 5 (1.9%) were malnourished. In the overall sample, but also in subgroups of pre-frail or frail elders, the areas under ROC curves were 0.954, 0.948 and 0.958 respectively. The 11 points cut-off provided the best correct classification ratio (91.4%); sensitivity=94.0%, specificity=83.3%. CONCLUSION: The MNA-SF appeared to be a validated and effective tool for malnutrition screening in frail elders. Implementing this tool in clinical routine should contribute to improving the screening of malnourished frail individuals.

Frailty and nutrition: searching for evidence.

Frailty is a geriatric syndrome that predicts disability, morbidity and mortality in the elderly. Poor nutritional status is one of the main risk factors for frailty. Macronutrients and micronutrients deficiencies are associated with frailty. Recent studies suggest that improving nutritional status for macronutrients and micronutrients may reduce the risk of frailty. Specific diets such as the Mediterranean diet rich in anti-oxidants, is currently investigated in the prevention of frailty. The aim of this paper is to summarize the current body of knowledge on the relations between nutrition and frailty, and provide recommendations for future nutritional research on the field of frailty.

Flavonoids and arterial stiffness: promising perspectives.

BACKGROUND AND AIMS: Flavonoids are a group of polyphenol compounds, ubiquitously found in plants. Great emphasis has been given to their possible benefits for cardiovascular health. These beneficial effects may be mediated by a specific action on arterial walls. Arterial stiffness is a marker of vascular aging, increasingly used in the clinical setting and assessed by pulse wave velocity. It has shown to be a robust predictor of cardiovascular events and mortality. This review aims at providing a comprehensive evaluation of available intervention and observational studies examining the relationship between flavonoid consumption and arterial stiffness. DATA SYNTHESIS: A Medline(®) literature search was performed using the keywords "arterial stiffness" and "flavonoids". As a result, 2 cross-sectional and 16 intervention studies assessing the relationship between flavonoids intake and arterial stiffness were retained. Four intervention trials reported a significant decrease of arterial stiffness after a flavonoid-based intervention, independently from blood pressure changes. The two observational studies reported significant associations between a higher flavonoid consumption and a lower arterial stiffness. In this review, isoflavones, anthocyanins and to a lesser extent cocoa flavan-3-ols appeared to be the more efficient to improve vascular function. CONCLUSIONS: Despite their heterogeneity, preliminary data seem to support an improvement of the arterial stiffness related to flavonoid intake. However, further research on absorption and dose-response effects of the specific flavonoid subclasses on arterial structure is warranted.

Geriatric syndromes increased the nutritional risk in elderly cancer patients independently from tumour site and metastatic status. The ELCAPA-05 cohort study.

BACKGROUND & AIMS: We assessed the prevalence and risk factors of malnutrition in elderly cancer patients. METHODS: We studied a prospective cohort of solid cancer patients aged ≥70 years at referral to two geriatric oncology clinics between 2007 and 2010. Nutrition was evaluated using the Mini-Nutritional Assessment (MNA) using validated cut-offs (<17: malnutrition, 17-23.5: at-risk for malnutrition). Patients with non-digestive tumours (breast, prostate, urinary tract) and with digestive (colorectal, upper digestive tract and liver) were analysed separately using multinomial logistic regression. RESULTS: Of 643 consecutive patients, 519 had available data (median age, 80; men, 48.2%; metastases, 46.3%; digestive cancer 47.8%). In non-digestive group, 13.3% had malnutrition versus 28.6% in digestive group. The link between metastasis and malnutrition was significantly higher in non-digestive group (adjusted odds ratio [ORa ], 25.25; 95%CI: 5.97-106.8) than in digestive group (ORa, 2.59; 1.08-6.24; p for heterogeneity = 0.04). Other factors independently associated with malnutrition were cognitive impairment (ORa MMMSE ≤ 24 versus > 24 in non-digestive group: 16.68; 4.89-56.90 and in digestive group: 3.93; 1.34-11.50), and depressed mood (ORa MiniGDS ≥1 versus <1 in non-digestive group: 11.11; 3.32-37.17 and in digestive group: 3.25; 1.29-8.15) and fall risk (ORa fall risk versus no fall risk in non-digestive group: 4.68; 1.77-12.37; in digestive group: 100% of malnourished patients were faller's). CONCLUSION: We highlighted, in elderly cancer patients, the high prevalence of malnutrition and that geriatrics syndromes (i.e. cognitive impairment, depressed mood and fall risk) were independent risk factors for malnutrition. Moreover, metastatic status was significantly much more strongly associated with malnutrition in non-digestive than digestive tumours.

Vitamin D supplementation in older adults: searching for specific guidelines in nursing homes.

BACKGROUND: The prevalence of vitamin D insufficiency is very high in the nursing home (NH) population. Paradoxically, vitamin D insufficiency is rarely treated despite of strong clinical evidence and recommendations for supplementation. This review aims at reporting the current knowledge of vitamin D supplementation in NH and proposing recommendations adapted to the specificities of this institutional setting. DESIGN: Current literature on vitamin D supplementation for NH residents was narratively presented and discussed by the French Group of Geriatrics and Nutrition. RESULT: Vitamin D supplementation is a safe and well-tolerated treatment. Most residents in NH have vitamin D insufficiency, and would benefit from vitamin D supplement. However, only few residents are actually treated. Current specific and personalized protocols for vitamin D supplementation may not be practical for use in NH settings (e.g., assessment of serum vitamin D concentrations before and after supplementation). Therefore, our group proposes a model of intervention based on the systematic supplementation of vitamin D (1,000 IU/day) since the patient's admission to the NH and throughout his/her stay without the need of a preliminary evaluation of the baseline levels. Calcium should be prescribed only in case of poor dietary calcium intake. CONCLUSION: A population-based rather than individual-based approach may probably improve the management of vitamin D insufficiency in the older population living in NH, without increasing the risks of adverse health problems. The clinical relevance and cost effectiveness of this proposal should be assessed under NH real-world conditions to establish its feasibility.

Arginine plus proline supplementation elicits metabolic adaptation that favors wound healing in diabetic rats.

Diabetic patients with wounds are at risk of protein malnutrition, have low arginine plasma levels, and suffer from delayed wound healing. We sought to determine the efficacy of arginine plus proline supplementation on protein and amino acid metabolism and on wound repair in a model of diabetic rats. Eighteen 11-wk-old Zucker diabetic fatty fa/fa male rats underwent a 7-cm abdominal skin incision with implantation of sponges and daily excision of full-thickness round sections of dorsal skin for 5 days. They were randomized to be fed with either a standard formula (S group, Clinutren Iso), a high-protein and arginine (ARG) plus proline (PRO)-enriched formula (ARG+PRO group, Clinutren Repair), or an isonitrogenous isoenergetic control formula (IC group). Nitrogen balance was calculated daily. The rats were euthanized on day 5, and plasma glucose, insulin, amino acids, skin epithelialization, and angiogenesis were measured. In macrophages, we assessed inducible nitric oxide synthase (iNOS) and arginase expression, production of nitric oxide (NO) and amino acid metabolism. Both the ARG+PRO and IC groups showed improved nitrogen balance. ARG plus PRO supplementation increased proline and branched-chain amino acid plasma concentrations and improved angiogenesis. Arginase and iNOS expressions in macrophages were reduced, together with NO and citrulline production. In diabetic rats, ARG plus PRO supplementation improves wound angiogenesis and favors whole body protein metabolism. Low macrophage iNOS expression at day 5 may reflect a low inflammatory state in the wounds, favoring wound closure.

Catalase rs769214 SNP in elderly malnutrition and during renutrition: is glucagon to blame?

Impaired glucose tolerance is common during aging. The transcription factor PAX6 is involved in glucose homeostasis. Computational promoter sequence analysis of the catalase gene highlighted a putative PAX6 binding site on the rs769214 polymorphism A allele. Creation of this binding site has been suggested to explain renutrition inefficiency in malnourished elderly patients. Our aim was to evaluate the link between the rs769214 polymorphism of the catalase gene and glucose homeostasis in malnourished elderly patients at inclusion and during renutrition. Thirty-three malnourished elderly Caucasian inpatients were recruited. Nutritional and inflammatory statuses were assessed and a multiplex adipokine analysis was conducted at inclusion and discharge from the Geriatric Nutritional Care Unit at Charles-Foix Hospital (Ivry-sur-Seine, France). Serum glucagon, PAI-1, and TNF-α levels were significantly lower in the A-allele carriers at inclusion. During renutrition, A-allele carriers exhibited increased serum glucagon, PAI-1, and TNF-α variation. After renutrition, levels of these parameters were similar for A-allele carriers and G-allele carriers. A logistic ordinal multivariate regression analysis linked only variation of glucagon to rs769214 SNP. These results support a role for catalase SNP in the efficiency of renutrition in malnourished elderly patients via the modulation of glucagon secretion, probably involving PAX6.

Scurvy in hospitalized elderly patients.

OBJECTIVES: The aim of this study was to systematically screen hospitalized elderly patients for clinical symptoms of scurvy and to confirm the diagnosis with biological measures. SETTINGS: Geriatric acute care ward. MEASUREMENTS: Scurvy symptoms (one or more among perifollicular hyperkeratosis, petechiae or bruises, haemorrhagic features caused by venous puncture, severe gingivitis). We compared associated diseases, nutritional status, need for assistance for feeding, serum albumin, transthyretin, B9 and B12 vitamins, iron status and Serum Ascorbic Acid Level (SAAL) and outcome (in-hospital mortality) between scurvy and scurvy free patients. RESULTS: 18 patients with clinical symptoms of scurvy (scurvy group) were identified out of 145 consecutive patients (12%). They were compared to 23 consecutive control patients with no clinical symptoms of scurvy (scurvy-free group). SAAL was significantly lower (1.09 +/- 1.06 vs 4.87 +/- 4.2 mg x L-1, p < .001) and vitamin C deficiency more frequent (94 vs 30 %, p < .001) in the scurvy group. Moreover, in scurvy group, coronary heart disease (39 vs 9 %, p=.028), need for assistance for feeding (56 vs 13 %, p=.006) and in-hospital deaths (44 vs 9 %, p=.012) were more frequent. CONCLUSION: Ninety-four percent of patients with clinical symptoms of scurvy had vitamin C deficiency. Our results suggest that in hospitalized elderly patients, clinical symptoms allow scurvy diagnosis. Scurvy could be a frequent disease in elderly patients admitted to acute geriatric ward.

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.

Levels of plasma insulin-like growth factor I (IGF I), IGF II, IGF binding proteins, type 1 IGF receptor and growth hormone binding protein in community-dwelling elderly subjects with no malnutrition and no inflammation.

Plasma samples from community-dwelling subjects aged 65 to 92 presenting no malnutrition and no inflammation (as assessed by albumin, transthyretin, CRP, and orosomucoid levels and BMI) were compared to those of healthy controls aged 20 to 65 to determine the effect of aging on the IGF system. Concentrations of IGF I, IGF II and IGFBP3 significantly decreased, and those of GHBP slightly increased with age from 20 to 92 years (n=327 r=-0.64 p<0.0001; n=45 r=-0.44 p<0.003; n=91 r=-0.23 p<0.03 and n=61 r=0.26; p<0.05 respectively). Western immunoblotting showed that the proteolysis of IGFBP3 was not significantly different in elderly and younger subjects. The affinity of the IGF type 1 receptor for IGF I was moderately lower (Ki=0.56 0.2 vs 0.33 0.1, nM respectively; p<0.005) and the number of binding sites was moderately higher (10.4 1.5 vs 8.1 1.9 binding sites/cell, respectively; p<0.03) in the elderly than in the younger adults. Our results suggest that the age-related decline in plasma levels of IGF I, IGF II and IGFBP3 occurs independently from malnutrition and inflammation processes. GHBP plasma levels, which reflect the number of GH receptors at the level of the liver, do not decline in our malnutrition-free elderly population, and thus are not involved in the decline of IGF I plasma levels with age. In the elderly, affinity and number of type 1 IGF receptor were close to those of younger subjects; the decline in IGF I plasma levels may account for the small rise in the number of type 1 IGF receptors binding sites per cell.

IGF-I, IGF-I-binding proteins and GH-binding protein in malnourished elderly patients with inflammation receiving refeeding therapy.

OBJECTIVE: To investigate the mechanisms determining the success or failure of refeeding therapy in malnourished elderly patients with inflammation by studying changes in plasma IGF-I, GH-binding protein (GHBP) and IGF-binding protein (IGFBP) levels and IGFBP-3 proteolysis. DESIGN AND METHODS: We studied 15 severely malnourished hospitalized elderly patients. Weight, food intake, plasma albumin, transthyretin, C-reactive protein (CRP), orosomucoid, interleukin-6 (IL-6), IGF-I, intact and proteolytically degraded IGFBP-3 and GHBP levels were determined on admission and during refeeding therapy designed to increase food intake to 40 kcal/kg body weight per day (15% protein). RESULTS: Plasma IGF-I, IGFBP-3 and GHBP levels were significantly low for age on admission in all malnourished elderly patients. They increased in nine patients as nutritional status improved (albuminemia >30 g/l; transthyretinemia >200 mg/l or weight gain >5% of initial body weight) and levels of inflammation markers decreased (group 1). In contrast, plasma IGF-I, IGFBP-3 and GHBP levels remained low in six patients in whom nutritional status failed to improve and levels of inflammation markers increased (group 2). IGF-I showed greater variations than IGFBP-3 or GHBP with respect to nutritional status. High plasma CRP and IL-6 levels were associated with high levels of IGFBP-3 proteolysis. CONCLUSION: Efficient refeeding therapy was associated with a significant increase in IGF-I plasma levels. In patients with severe and persistent inflammation, high levels of proteolysis of IGFBP-3 may have contributed to the low plasma IGF-I levels, persistence of hypercatabolism and lack of improvement in nutritional status.

Orosomucoid: a mortality risk factor in elderly people living in the community?

AIM: We explored the value of variables relating to inflammation and nutrition as a prognostic factors for mortality in an elderly community-dwelling population. METHODS: We measured plasma levels of orosomucoid, C-reactive protein (CRP), albumin, and transthyretin, and the body mass index (BMI) of 245 subjects aged 65 to 95 living in the community (PAQUID study). The risk of death was analyzed two, four and six years after blood sampling by use of the Cox proportional hazards model with delayed entry. A survival curve was generated by the Kaplan-Meier method. RESULTS: Multivariate analysis--including sex, BMI, and plasma levels of albumin, transthyretin orosomucoid and CRP levels--showed that orosomucoid in the highest quartile (>0.88 g/L) was the strongest predictor of mortality two years after blood sampling [relative risk (RR)=7.4; 95% interval confidence (IC) 2.2-24.6; P<0.1]; the association remained significant four and six years after blood sampling [RR=2.5; 95%IC 1.2-5.2 and RR=1.9; 95%IC 1.0-3.4 respectively, P<0.05]. Orosomucoid levels above 1 g/L (the most accurate threshold for prediction of mortality) were associated with a strong increase in the risk of death two years [RR=12.3; 95%IC 4.3-35.0; P<0.001], four years [RR=6.9; 95%IC 3.3-14.7; P<0.001], and six years [RR=4.4; 95%IC 2.3-8.5; P<0.001) after blood sampling. CONCLUSION: These results further underline the association between systemic inflammation and mortality. They may help us to identify of high-risk subpopulations of elderly subjects so we can employ prevention strategies.

Plasma insulin-like growth factor I levels in the elderly: relation to plasma dehydroepiandrosterone sulfate levels, nutritional status, health and mortality.

BACKGROUND: Insulin-like growth factor I (IGF-I) has beneficial metabolic effects. Because plasma IGF-I levels have been reported to be enhanced by dehydroepiandrosterone (DHEA) administration, it has been suggested that the IGF-I may be implicated in some of the reported associations between low DHEA sulfate (DHEAS) levels and impaired health measures in elderly subjects. The nutritional status, which also regulates plasma IGF-I levels, is also an important determinant of health outcome. OBJECTIVE: We sought to investigate the associations between plasma IGF-I levels and plasma DHEAS levels, nutritional status, health, and mortality in the elderly. METHODS: In 256 community-dwelling subjects aged 65-101 years, enrolled in the Paquid study, a health questionnaire was used to acertain their functional disabilities, any history of medical disorders, self-perceived health, depressive symptoms, and their cognitive function. Biological measurements included levels of plasma IGF-I, albumin, transthyretin, and DHEAS. Mortality data were available for 6 years following blood sampling. RESULTS: In this elderly population with no impairment in nutritional status, the plasma IGF-I levels decreased significantly with age (p = 0.02). The plasma IGF-I levels correlated positively with those of transthyretin (p = 0.0001). IGF-I also correlated with DHEAS (p = 0.04), but the correlation did not remain significant after adjustment for age. As opposed to SDHEA, the plasma IGF-I levels did not correlate with the results from the health questionnaire. The baseline IGF-I values in the highest tertile were associated with a higher risk of short-term mortality than those in the lowest tertile (RR = 8.4 at 2 years, p = 0.007). CONCLUSIONS: Our results suggest that IGF-I is not connected with the association between low plasma DHEAS levels and the impaired results from the health questionnaire. The relationship between plasma IGF-I highest levels and mortality should be further explored.