The physical phenotype of frailty for risk stratification of older medical inpatients.

OBJECTIVES: To determine the usefulness of physical phenotype of frailty, cognitive impairment, and serum albumin for risk stratification of elderly medical impatients. DESIGN: Prospective, observational cohort study. SETTING: A general internal medicine unit of a university hospital in Italy. PARTICIPANTS: Inpatients with an average age of 80.8 ± 7.5 yr (N = 470). MEASUREMENTS: Frailty was defined using the Study of Osteoporotic Fractures Index, a parsimonious version of the physical phenotype (two of the following markers: weight loss, inability to rise five times from a chair, and exhaustion). Two frailty markers from non-physical dimensions were also evaluated: cognitive impairment (Mini-Cog score < 3) and low serum albumin on ward admission (< 3,5 gr/dl). Logistic regression adjusted for preadmission and admission-related confounders was used to investigate whether the physical phenotype of frailty and the two non-physical markers were associated with ward length of stay and unfavorable discharge (death plus any other ward discharge disposition different from direct return home). Areas Under the receiver operating characteristic Curve (AUCs) and Likelihood Ratios (LRs) were used for evaluation of discriminatory ability and clinical usefulness of significant predictors. RESULTS: The physical phenotype of frailty was associated with both study outcomes (p < 0.010) but the association was mainly mediated by chair standing ability. Non-physical markers were associated only with unfavourable discharge (p < 0.001). All of these predictors, either alone or in combination, had poor discriminatory ability (AUCs < 0.70) and poor clinical usefulness (+LRs near 1) for the study outcomes. CONCLUSIONS: The physical phenotype of frailty appears of limited clinical use for risk stratification of older medical inpatients. Combination with markers from non-physical dimensions does not improve its prognostic abilities.

A comparison of risk factors as predictors of cardiovascular and non-cardiovascular mortality in the elderly people--relevance of N-terminal pro-B-type natriuretic peptide and low systolic blood pressure.

BACKGROUND: Many risk factors are known to predict ischaemic events and mortality in the elderly people, but their ranking of importance remains uncertain. This study was designed to identify and compare the main predictors of total mortality (TM), cardiovascular mortality (CVM) and non-cardiovascular mortality (NCVM) in older adults. METHODS: Nine hundred and seventy-nine community resident adults aged ≥ 65 years, free of previous heart failure and cardiovascular events, participated in the study. The univariate and multivariate (Cox regression) relationships of baseline cardiovascular risk factors, treatments and laboratory data with TM, CVM and NCVM were assessed after a median follow up of 6.7 years. RESULTS: Overall, there were 104 deaths (30 because of CVM and 74 to NCVM). In multivariate analysis, the following factors remained independently associated with mortality: NT pro-B-type natriuretic peptide (NT-proBNP) upper quintile (≥ 237 pg/ml for men, ≥ 280 pg/ml for women): hazard ratio (HR) vs. the rest of the population (95% confidence interval) 2.34 (1.52-3.60), p < 0.001 for TM; HR 5.41 (2.32-12.65), p < 0.001 for CVM; systolic blood pressure lower quintile (≤ 130 mmHg): HR 3.06 (1.80-5.21), p < 0.001 for NCVM; diabetes: HR 2.46 (1.29-4.72), p = 0.007 for NCVM; erythrocyte sedimentation rate (ESR) upper decile (≥ 41 mm/h): HR 2.33 (1.16-4.69), p = 0.02 for NCVM; platelet count lower quintile (≤ 177 × 10(9) /l): HR 2.09 (1.20-3.64), p = 0.009 for NCVM; ever-smoker status: HR 2.08 (1.23-3.52), p = 0.007 for NCVM. CONCLUSIONS: In elderly community dwellers, NT-proBNP was the strongest predictor of TM and CVM, while especially low systolic blood pressure, together with diabetes, ESR, reduced platelet count and ever-smoker status, were the main predictors of NCVM.

APOE and Alzheimer disease: a major gene with semi-dominant inheritance.

Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios alone are insufficient to assess these risks. We calculated AD LTR in 7351 cases and 10 132 controls from Caucasian ancestry using Rochester (USA) incidence data. At the age of 85 the LTR of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers, consistent with semi-dominant inheritance of a moderately penetrant gene. Using PAQUID (France) incidence data, estimates were globally similar except that at age 85 the LTRs reached 68 and 35% for APOE 44 and APOE 34 female carriers, respectively. These risks are more similar to those of major genes in Mendelian diseases, such as BRCA1 in breast cancer, than those of low-risk common alleles identified by recent GWAS in complex diseases. In addition, stratification of our data by age groups clearly demonstrates that APOE4 is a risk factor not only for late-onset but for early-onset AD as well. Together, these results urge a reappraisal of the impact of APOE in Alzheimer disease.

Comparison of two frailty measures in the Conselice Study of Brain Ageing.

OBJECTIVES: Uncertainty about the definition of frailty is reflected by the development of many ways to identify frail people. We aimed to compare the validity of two frailty measures in participants of the Conselice Study of Brain Aging. DESIGN: Prospective population-based study with 4 year follow up. PARTICIPANTS/SETTING: 1,016 subjects aged 65 and over in a rural Italian population. METHODS: For each participant, a Frailty Index (FI) and a Conselice Study of Brain Aging Score (CSBAS) were determined. The FI was created from 43 deficits according to a standardized methodology; 7 variables derived from a previously validated Easy Prognostic Score comprised the CSBAS. RESULTS: The FI had characteristic properties described in other population samples, with a gamma distribution, a 99% limit of about 0.64 and higher values in women than men. CSBAS and FI were strongly correlated with each other (r = 0.72) and both correlated with age (r = 0.32, r = 0.27, respectively). Each was independently predictive of death in a multivariate model, with greater specificity and sensitivity than age alone. CONCLUSIONS: Frailty can be measured by different tools and facilitates a more direct quantification of individual vulnerability than chronological age alone. Though the Frailty Index and the Conselice Study of Brain Aging Score are underpinned by different rationales, clinical utility will continue to motivate their development.

Elevated plasma levels of alpha-1-anti-chymotrypsin in age-related cognitive decline and Alzheimer's disease: a potential therapeutic target.

alpha-1-antichymotrypsin (ACT), is an acute phase protein and a protease inhibitor produced by the liver and brain. ACT is involved in the pathogenesis of Alzheimer's disease (AD), since elevated ACT concentration was found in cerebrospinal fluid (CSF) and brain from AD. ACT has also been shown to influence amyloid deposition in vitro and in animal models of AD. In this investigation 830 healthy controls, 69 subjects with cognitive impairment and not dementia (CIND), 53 patients with severe clinical AD and 142 patients with mild AD were investigated. Plasma levels of ACT were measured with a new competitive immune enzyme linked immune-assay (ELISA). ACT levels were higher in AD patients than in CIND or controls. An age dependent increase of plasma ACT was present in both healthy elderly and CIND. Patients with mild clinical AD were followed up for two years and stratified according to the rate of clinical deterioration. CT plasma levels were elevated in AD patients that showed an accelerated rate of cognitive deterioration during the follow up; this increment being prominent in AD with the Apolipoprotein E (APOE) epsilon 4 allele. Therefore, increased peripheral ACT levels in APOE 4 positive patients appear to predict an accelerated clinical progression. Plasma ACT might be used as a surrogate marker to monitor the conversion of pre-dementia stages to AD and the progression of the disease. The development of compounds able to interfere with the ACT biological activity (protease inhibition and/or promotion of amyloid deposition) might have therapeutic relevance for the disease.

Physical activity and dementia risk in the elderly: findings from a prospective Italian study.

OBJECTIVE: To examine the effect of physical activity on risk of developing Alzheimer disease (AD) and vascular dementia (VaD) in the elderly. METHODS: Data are from a prospective population-based cohort of 749 Italian subjects aged 65 and older who, in 1999/2000, were cognitively normal at an extensive assessment for clinically overt and preclinical dementia and, in 2003/2004, underwent follow-up for incident dementia. Baseline physical activity was measured as energy expenditure on activities of different intensity (walking, stair climbing, moderate activities, vigorous activities, and total physical activity). RESULTS: Over 3.9 +/- 0.7 years of follow-up there were 86 incident dementia cases (54 AD, 27 VaD). After adjustment for sociodemographic and genetic confounders, VaD risk was significantly lower for the upper tertiles of walking (hazard ratio [HR] 0.27, 95% CI 0.12 to 0.63), moderate (HR 0.29, 95% CI 0.12 to 0.66), and total physical activity (HR 0.24, 95% 0.11 to 0.56) compared to the corresponding lowest tertile. The association persisted after accounting for vascular risk factors and overall health status. After adjustment for sociodemographic and genetic confounders, AD risk was not associated with measures of physical activity and results did not change after further adjustment for vascular risk factors and overall health and functional status. CONCLUSIONS: In this cohort, physical activity is associated with a lower risk of vascular dementia but not of Alzheimer disease. Further research is needed about the biologic mechanisms operating between physical activity and cognition.

Atrial fibrillation and risk of dementia in non-demented elderly subjects with and without mild cognitive impairment (MCI).

MCI is regarded as a precursor of dementia, but not all patients with MCI actually develop dementia. As Alzheimer and vascular dementia (AD and VD, respectively) are thought to share many common etiopathogenetic mechanisms, we investigated whether the vascular risk factor atrial fibrillation affect the risk of conversion to dementia for different MCI subtypes diagnosed according to international criteria. One-hundred-eighty elderly outpatients with MCI and 431 elderly outpatients with a normal cognition were followed-up for a mean of 3 and 4 years, respectively. The risk of conversion to dementia associated with atrial fibrillation was studied in both samples using a Cox proportional-hazards model adjusted for sociodemographic and medical variables. Overall conversion rate to dementia was 10.5 (8.0-13.8) per 100 person-years in the MCI group and 2.2 (1.5-3.1) per 100 person-years in the normal cognition group. Atrial fibrillation was significantly associated with conversion to dementia (hazard ratio=HR=4.63, 95% confidence interval=Cl=1.72-12.46) in the MCI group, but not in the cognitively normal group (HR=1.10, 95% Cl=0.40-3.03). Current diagnostic criteria for MCI subtypes define heterogeneous populations, but atrial fibrillation can be useful in identifying people with increased risk of conversion to dementia.

Risk factors for dementia: data from the Conselice study of brain aging.

Among the age-related diseases, the development of cognitive impairments, in particular dementia, is the most devastating for the individual and has great social and healthcare costs. Accurate information is needed about the prevalence and incidence of cognitive disorders and the physiology of the aging brain. In particular, only scarce data are available about the relationship between aging, cognitive status and nutritional factors. In order to address these issues, we planned the Conselice Study, a longitudinal study of physiological and pathological brain aging. The center involved in the study was the municipality of Conselice, (Province of Ravenna), in the Northern-Italian Region Emilia-Romagna. A total of 1,016 subjects aged 65 years and over was enrolled at baseline. Information about cognitive status at 4-years of follow-up was collected from 940 of them. These data have been used to estimate prevalence and incidence of dementia in the elderly Italian population and to investigate the possible role of homocysteine as a predictor of dementia.

Incidence and etiology of dementia in a large elderly Italian population.

OBJECTIVE: To estimate age- and sex-specific incidence of dementia, Alzheimer disease (AD), and vascular dementia (VaD) in the Conselice Study of Brain Aging, an Italian prospective population-based study, and to assess whether poor education is a risk factor for dementia. METHODS: In 1999 to 2000, the baseline study identified a dementia-free cohort of 937 subjects aged 65 years and older who were reexamined in 2003 to 2004 using a two-phase procedure. RESULTS: Information was obtained for 91% of the subjects at risk; 115 incident cases of dementia were identified. Incidence rates per 1,000 person-years were 37.8 (95% CI = 30.0 to 47.7) for dementia, 23.8 (95% CI = 17.3 to 31.7) for AD, and 11.0 (95% CI = 7.2 to 16.9) for VaD. This translates into more than 400,000 new cases of dementia expected per year in Italy. Increasing age was an independent risk factor for both AD and VaD. Poor education was an independent risk factor for AD but not VaD. Sex did not affect dementia risk. CONCLUSIONS: In this Italian population-based cohort, incidence of dementia increased with age, and Alzheimer disease (AD) was the most frequent type of dementia. Poor education was associated with a higher risk of AD. Our incidence rates are higher than previously reported in Italy, and provide new estimates for projection of future burden of disease in Italy.

Peripheral blood markers of inflammation and functional impairment in elderly community-dwellers.

The cross-sectional association of functional impairment with several peripheral blood inflammatory markers (increased C-reactive protein (CRP), fibrinogen and leucocyte count, decreased cholesterol and albumin) was studied in 739 elderly community-dwellers. Functional measures included Tinetti test for gait and balance, and basic and Instrumental Activities of Daily Living. When considering each marker individually, only increased CRP was inversely associated with all functional measures independently of demographics, lifestyle, and comorbidity (P < 0.05). When considering the sum of positive markers, having more than one marker was also inversely associated with all functional measures (P < 0.05), but no clear gradient of impairment was found across increasing numbers of markers. When considering specific combinations of markers, having both increased CRP and at least another positive marker had a stronger association with functional impairment (P < 0.01 for all measures) than increased CRP alone (P > 0.05), or other positive markers alone or in combination (P < 0.05). In conclusion, in elderly individuals, peripheral blood markers of inflammation are associated with functional impairment independently of potential confounders. A specific combination of CRP with other markers provides a better correlate of functional impairment than both individual markers or a simple count of positive markers.

Common polymorphisms in methylenetetrahydrofolate reductase (MTHFR): relationships with plasma homocysteine concentrations and cognitive status in elderly northern italian subjects.

Hyperhomocysteinemia may be a risk factor for cognitive impairment. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in homocysteine (Hcy) metabolism. Both the MTHFR 677C-->T and the 1298A-->C polymorphisms are associated with mild hyperhomocysteinemia, particularly in conditions of low folate status. The prevalence of these MTHFR polymorphisms and their relationships with plasma total Hcy (tHcy), serum folate and cognitive function was evaluated in 194 elderly Italian individuals: 122 healthy controls (73.8 +/- 7.1 years of age), 24 cognitively- impaired- not-demented individuals (78.6 +/- 9.3 years), and 48 subjects with Alzheimer dementia (AD = 26), vascular dementia (VD =22; 85.5 +/- 7.0 years). Twenty-one percent of all subjects were homozygous for 677C-->T and 7 % for 1298A-->C polymorphism. No significant relationship was found betweenMTHFR polymorphisms and age, cognitive status and type of dementia. Plasma tHcy did not differ significantly by MTHFR genotypes, but, subjects of all genotypes with low serum folate (<12 nmole/l) had higher plasma tHcy (p < 0.001), than subjects with high serum folate (>= 12 nmole/l). The study suggests that 677C-->T and 1298A-->C polymorphisms are common in the Northern Italian population, but do not significantly affect plasma tHcy levels of elderly individuals, even under conditions of low folate status. The lack of association of age and cognitive function with MTHFR genotypes argues against a negative selection for these polymorphisms.

Homocysteine and cognitive performance in healthy elderly subjects.

Hyperhomocysteinemia is a risk factor for dementia but only scanty data exist about its relationship to specific cognitive abilities during normal aging. We recruited 62 healthy and cognitively normal subjects of age 65-91 years from the Conselice Study of brain aging. The following neuropsychological tests were applied (i) The mental deterioration battery(MDB) consisting of 7 parts: the Rey's 15 words immediate and delayed recall, word fluency, sentence construction, Raven's progressive matrices '47, immediate visual memory, freehand copying of drawings and copying drawings with landmarks. (ii) The Prose memory test. (iii) The Corsi block-tapping task. (iv) The mini mental state examination(MMSE) scores. We measured plasma total homocysteine (tHcy), serum folate, vitamin B12 and plasma vitamin B6. Multivariate-adjusted linear regression analysis showed statistically significant negative association of plasma tHcy with scores at MMSE (b= -0.01 2,p < 0.001) and word fluency (b = -0.009, p = 0.021). A non-significant trend towards a negative association was also found for sentence construction (b = -0.006, p = 0.076). One can conclude that in healthy elderly subjects, increased plasma tHcy is correlated to poorer performance at a specific measure of language abilities being compromised in both vascular and Alzheimer's dementia. The study suggests that plasma tHcy could be an early marker of cognitive impairment.

Immediate effectiveness of the "new identity" reality orientation therapy (ROT) for people with dementia in a geriatric day hospital.

Techniques of reality orientation in dementia are widely used around the world and indifferent settings. Nevertheless, after the controversies for adverse effects and frustration,by the new millennium "a new era" is coming on where cognitive rehabilitation "has come of age" and a series of positive results appeared until the fulfillment in the global and person-centered approach. This renewed technique may no more be based only on cognitive psychology but it is necessary to apply a more complete psychosocial approach taking into account also emotional, behavioral and functional domains of the globally considered person. The aims of our study are: (1) To assess the global efficacy on cognitive and affective functions. (2) To detect cognitive subsystems more sensible to our three-phase stimulation program. We studied 34 outpatients, 13 men and 21 women, age range 67-88 years, referred to our Expertise Center, all but one affected by mild cognitive impairment(MCI), suffering from mild dementia (clinical dementia rating, CDR <1). After 20 sessions of formal and complementary activities, a comprehensive improvement of cognition, language,memory and affective functions was observed. Semantic fluency improved with high statistically significant difference. The immediate recall, free or cued, appeared more sensible to stimulation than the delayed one. A correlation between a mini mental state examination (MMSE) low basal score and higher performance after the program was also obtained.

Plasma homocysteine and inflammation in elderly patients with cardiovascular disease and dementia.

Increased levels of plasma total homocysteine (tHcy) may play a role in both cardiovascular diseases (CVD) and old-age dementias via enhancement of vascular inflammation. However, the association between plasma tHcy and serum C-reactive protein (sCRP), taken as a marker of low-grade inflammation, is still uncertain. We investigated this association in normal aging, CVD, and dementia, and examined whether it was modified by the presence of two major comorbid diseases of older age: chronic obstructive pulmonary disease (CPOD) and peptic ulcer (PU). Six hundred-twenty-seven individuals aged > or = 65 yr (74+/-7 yr) were selected for this study: 373 healthy controls; 160 patients with CVD but no evidence of comorbid diseases (CVD+/comorbidity-); 46 patients with CVD and concurrent CPOD and/or PU (CVD+/comorbidity+); and 48 patients with dementia. A positive association between plasma tHcy and serum CRP, independent of several confounders (socio-demographic status, known tHcy and sCRP determinants, inflammation markers, traditional vascular risk factors), was found for CVD+/comorbidity+ (p=0.001; not affected by dementia type) and dementia (p=0.001; not affected by dementia type), but not for CVD+/comorbidity- and controls. The results suggest that the association between plasma tHcy and sCRP is more an aspecific reflection of poor health than a specific correlate of vascular inflammation.

The clock-drawing test in elderly Italian community dwellers: associations with sociodemographic status and risk factors for vascular cognitive impairment.

To evaluate whether performance in the clock-drawing test (CDT) is associated with sociodemographic status and risk factors for cognitive impairment, we examined 744 Italian community dwellers aged > or =65 (73 +/- 6) years scoring > or =24 on the MMSE. CDT was scored by two different methods, the Sunderland and the Wolf-Klein methods. Sociodemographic, lifestyle, clinical and biochemical variables were also recorded. For both scoring methods, lower CDT scores were associated with age, poor education, increased serum C-reactive protein and history of cancer. Associations of lower CDT scores with increased serum glucose and history of cerebrovascular disease were also found for the method with the highest sensitivity to cognitive impairment. This study shows that in elderly community dwellers, CDT may be not totally free from sociodemographic biases, and that it is associated with risk factors for cognitive impairment and frailty.

[Clinical and functional results after restorative proctocolectomy with ileal J reservoir in the treatment of ulcerative colitis]. / Risultati clinici e funzionali dopo proctocolectomia restaurativa con serbatoio ileale a J nel trattamento della colite ulcerosa.

PURPOSE: Restorative proctocolectomy is the procedure of choice in the treatment of ulcerative colitis. The operation is successful in removing all diseased mucosa while preserving a normal bowel function and a good quality of life for the patient. In this article are presented the clinical and functional results obtained in 28 patients, 19 males (68%) and 9 females (32%) after stapled restorative proctocolectomy with ileal J pouch-anal anastomosis. RESULTS: There were no perioperative deaths. The overall morbidity rate was 31%. Six patients (21%) presented pelvic abscess; 2 (7%) pelvic hematoma, 4 patients (14%) ileo-anal anastomotic stricture, 1 patient (3.6%) pouch-vagina fistula, three patients (11%) intestinal obstruction and 7 (25%) pouchitis. All patients were able to evacuate their pouches spontaneously. The mean bowel movements were 6-9/24 hours at the first postoperative month and 3-5/24 hours at the sixth month. Infrequent nocturnal seepage occurred in 6 patients (21%). Stool consistency returned to normal within 3-6 months. The mean pouch capacity was 210 cc. The mean resting pressure was diminished in 11 patients (39%), the men and maximal squeeze pressures were improved in 9 (32%); the ileo-rectal-anal inhibitory reflex was normal in 5 patients (18%), not defined in 12 (43%). Impotence or impaired bladder function was not present. CONCLUSION: The use of staplers in the surgical technique of restorative proctocolectomy with J shaped ileo-anal pouch is associated with low morbidity and better long-term results. The procedure requires a good selection of patients, a correct surgical timing, a very carefully technique and a low pre and postoperative treatment with steroids.

Radioguided surgery for gastrinoma: a case report.

AIMS AND BACKGROUND: Gastrinomas are the most common neuroendocrine tumors of the duodenopancreatic region. Surgical resection is the primary type of radical treatment. METHODS AND STUDY DESIGN: At the Institute of General, Gastrointestinal and Breast Surgery we treated a patient with a duodenal gastrinoma that was diagnosed and localized by means of selective celiac-mesenteric angiography and labelled octreotide scintigraphy. Surgery was performed using a radioguided technique; in this way we easily detected the small tumor and discovered another tracer-uptaking lesion that turned out to be a metastatic lymph node. RESULTS: Surgical resection is the ideal treatment for sporadic gastrinoma: it improves quality of life, prolongs survival, and reduces the incidence of metastases, with a modest percentage of complications and practically zero mortality. Meanwhile, medical treatment is being reevaluated, particularly in the case of metastatic disease or polyendocrine MEN1 syndrome. A fundamental aspect in the management of gastrinomas is tumor localization. Endoscopic ultrasonography and labeled octreotide scintigraphy (Ostreoscan) proved to be more effective than the usual imaging modalities. Intraoperative ultrasonography gastroscopy for duodenal transillumination and repeated measurement of blood gastrin levels should be performed intraoperatively in the surgical treatment of gastrinomas. CONCLUSIONS: The clinical application of radioguided surgery for tracer-uptaking endocrine tumors is still controversial. In our case the decision to use this method was influenced by the fear that the patient's obesity and the effects of previous surgery could hamper the identification of the small tumor.

Coeliac disease in patients with autoimmune thyroiditis.

BACKGROUND AND AIMS: The close association between coeliac disease and autoimmunity prompted us to perform an antibody screening for gluten-sensitive enteropathy in patients with autoimmune thyroid dysfunction. METHODS: Sera from 220 patients with autoimmune thyroiditis, 50 euthyroid subjects with thyroid nodules and 250 blood donors were tested for IgA anti-tissue transglutaminase (anti-tTG) and antiendomysial antibodies (EmA). RESULTS: IgA anti-tTG was positive in 7 patients with autoimmune thyroiditis, whereas IgA EmA was found only in 6 of them. Duodenal biopsy confirmed coeliac disease diagnosis disclosing marked and mild villous atrophy in 6 and 1 of them, respectively. All but 2 of the 7 coeliacs did not show any sign of malabsorption. All euthyroid controls were negative for IgA antibodies, whereas 1 blood donor, positive for both IgA anti-tTG and EmA, was found to be coeliac. The prevalence of coeliac disease in patients with autoimmune thyroiditis (3.2%) was significantly higher than that found in blood donors (0.4%) (p = 0.022, Fisher's exact test). CONCLUSIONS: Antibody screening for coeliac disease should be included in the work-up of patients with autoimmune thyroiditis. Either IgA anti-tTG or EmA may be used, even though the former seems to be slightly more sensitive than the latter.

Different IL-8 production by T and NK lymphocytes in elderly subjects.

A gradual decline in the functional activity of the immune system is described with advancing age. The adaptive immune system seems the most severely affected, but some age-associated modifications also occurs in NK cells. Several studies investigated the age related changes of cytokine production, while little is known about chemokines, whose importance in regulating immune-response becomes even more evident. In this study we investigated whether the ability of T lymphocytes and NK cells to produce IL-8, either spontaneously or after activation, respectively with anti-CD3 monoclonal antibody or interleukin 2 (IL-2) was affected by age. We demonstrated that: (a) T lymphocytes and NK cells spontaneously produced detectable amounts of IL-8; (b) anti-CD3 stimulation of T lymphocytes significantly increased IL-8 production and the increment was more evident in the nonagenarian subjects; (c) similarly, IL-2 stimulation of NK cells rose the production of IL-8 but the amount produced by the old was lower than the one produced by the young group. Because of the co-stimulatory role of chemokines on NK responses and given the demonstrated importance of NK cells in defence against viral infections, the decreased production of IL-8 can be involved in the defective functional activity of NK cells from old subjects.