Circulating Omega-3 and Omega-6 Fatty Acids, Cognitive Decline, and Dementia in Older Adults.

BACKGROUND: Comprising nearly 35% of brain lipids, polyunsaturated fatty acids (PUFA) are essential for optimal brain function. However, the role of PUFA on cognitive health outcomes later in life is largely unknown. OBJECTIVE: We investigated prospective associations of plasma phospholipid omega-3 (ALA [18 : 3], EPA [20 : 5], DPA [22 : 5], DHA [22 : 6]) and omega-6 (LA [18 : 2], AA [20 : 4]) PUFA with cognitive decline, risk of cognitive impairment and dementia among adults aged≥65 years in the Cardiovascular Health Study. METHODS: Circulating fatty acid concentrations were measured serially at baseline (1992/1993), 6 years, and 13 years later. Cognitive decline and impairment were assessed using the 100-point Modified Mini-Mental State Examination (3MSE) up to 7 times. Clinical dementia was identified using adjudicated neuropsychological tests, and ICD-9 codes. RESULTS: Among 3,564 older adults free of stroke and dementia at baseline, cognitive function declined annually by approximately -0.5 3MSE points; 507 participants developed cognitive impairment and 499 dementia over up to 23 years of follow-up. In multivariable models, higher circulating arachidonic acid (AA) concentrations were associated with slower cognitive decline and lower dementia risk, with associations growing stronger with greater length of follow-up (hazard ratio [HR,95% CI] of dementia per interquintile range, 0.74 [0.56-0.97] at 5 years, and 0.53 [0.37-0.77] at 15 years). Circulating docosapentaenoic (DPA) concentrations were associated with slower cognitive decline and lower risk of cognitive impairment (extreme-quintile HR, 0.72 [95% CI: 0.55, 0.95]). Findings were generally null or inconsistent for other omega-3 or omega-6 PUFA. CONCLUSION: Circulating AA and DPA, but not other PUFA, are associated with slower rate of cognitive decline and lower risk of dementia or cognitive impairment later in life.

Biotinylated selenocyanates: Potent and selective cytostatic agents.

Most of the currently available cytotoxic agents for tackling cancer are devoid of selectivity, thus causing severe side-effects. This situation stimulated us to develop new antiproliferative agents with enhanced affinity towards tumour cells. We focused our attention on novel chalcogen-containing compounds (thiosemicarbazones, disulfides, selenoureas, thio- and selenocyanates), and particularly on selenium derivatives, as it has been documented that this kind of compounds might act as prodrugs releasing selenium-based reactive species on tumour cells. Particularly interesting in terms of potency and selectivity was a pharmacophore comprised by a selenocyanato-alkyl fragment connected to a p-phenylenediamine residue, where the nature of the second amino moiety (free, Boc-protected, enamine-protected) provided a wide variety of antiproliferative activities, ranging from the low micromolar to the nanomolar values. The optimized structure was in turn conjugated through a peptide linkage with biotin (vitamin B7), a cellular growth promoter, whose receptor is overexpressed in numerous cancer cells; the purpose was to develop a selective vector towards malignant cells. Such biotinylated derivative behaved as a very strong antiproliferative agent, achieving GI50 values in the low nM range for most of the tested cancer cells; moreover, it was featured with an outstanding selectivity, with GI50 > 100 µM against human fibroblasts. Mechanistic studies on the mode of inhibition of the biotinylated selenocyanate revealed (Annexin-V assay) a remarkable increase in the number of apoptotic cells compared to the control experiment; moreover, depolarization of the mitochondrial membrane was detected by flow cytometry analysis, and with fluorescent microscopy, what supports the apoptotic cell death. Prior to the apoptotic events, cytostatic effects were observed against SW1573 cells using label-free cell-living imaging; therefore, tumour cell division was prevented. Multidrug resistant cell lines exhibited a reduced sensitivity towards the biotinylated selenocyanate, probably due to its P-gp-mediated efflux. Remarkably, antiproliferative levels could be restored by co-administration with tariquidar, a P-gp inhibitor; this approach can, therefore, overcome multidrug resistance mediated by the P-gp efflux system.

Plasma antioxidants and risk of dementia in older adults.

INTRODUCTION: Plant-based diets rich in fruits and vegetables have been associated with lower risk of dementia, but the specific role of antioxidants, a key class of bioactive phytochemicals, has not been well ascertained. METHODS: We measured antioxidants in a case-cohort study nested within the Ginkgo Evaluation of Memory Study. We included 996 randomly selected participants and 521 participants who developed dementia, of which 351 were diagnosed with Alzheimer's disease (AD) during a median of 5.9 years of follow-up. We measured baseline plasma levels of retinol, α-, and γ-tocopherol; zeaxanthin and lutein (combined); beta-cryptoxanthin; cis-lycopene; trans-lycopene; α-carotene; and trans-ß-carotene by organic phase extraction followed by chromatographic analysis and related these to neurologist-adjudicated risks of all-cause dementia and AD. RESULTS: Plasma retinol, α-, and γ-tocopherol, and carotenoids were not significantly related to risk of dementia or AD. Associations were not significant upon Bonferroni correction for multiple testing and were consistent within strata of sex, age, apolipoprotein E ε4 genotype, mild cognitive impairment at baseline, and intake of multivitamin, vitamin A or ß-carotene, or vitamin E supplements. Higher trans-ß-carotene tended to be related to a higher risk of dementia (adjusted hazard ratio [HR] per 1 standard deviation [SD] higher trans-ß-carotene: 1.10; 95% confidence interval [CI]: 1.00, 1.20) and α-carotene tended to be associated with higher risk of AD only (adjusted HR per 1 SD higher α-carotene: 1.15; 95% CI: 1.02, 1.29). DISCUSSION: Plasma antioxidants were not significantly associated with risk of dementia or AD among older adults. Similar studies in younger populations are required to better understand the association between plasma antioxidants and dementia risk.

Blood amyloid levels and risk of dementia in the Ginkgo Evaluation of Memory Study (GEMS): A longitudinal analysis.

INTRODUCTION: Both high or low plasma amyloid levels have been associated with risk of dementia in nondemented subjects. METHODS: We examined baseline plasma ß-amyloid (Aß) levels in relationship to incident dementia during a period of 8.5 years in 2840 subjects age >75 years; 2381 were cognitively normal (CN) and 450 mild cognitive impairment. RESULTS: Increased plasma Aß1-40 and Aß1-42 levels were associated with gender (women), age, low education, creatinine levels, history of stroke, and hypertension. CN participants who developed dementia had lower levels of Aß1-42 and Aß1-42/Aß1-40 ratio compared with those who did not. Aß levels did not predict dementia in mild cognitive impairment participants. DISCUSSION: There was an inverse association between Aß1-42 and Aß1-42/Aß1-40 ratio to risk of dementia in CN participants. Cerebral and cardiovascular disease and renal function are important determinants of increased Aß levels and must be considered in evaluations of relationship of plasma Aß and subsequent risk of dementia.

HIV infection and age effects on striatal structure are additive.

The age of the HIV-infected population is increasing. Although many studies document gray matter volume (GMV) changes following HIV infection, GMV also declines with age. Findings have been inconsistent concerning interactions between HIV infection and age on brain structure. Effects of age, substance use, and inadequate viral suppression may confound identification of GMV serostatus effects using quantitative structural measures. In a cross-sectional study of HIV infection, including 97 seropositive and 84 seronegative, demographically matched participants, ages 30-70, we examined serostatus and age effects on GMV and neuropsychological measures. Ninety-eight percent of seropositive participants were currently treated with anti-retroviral therapies and all were virally suppressed. Gray, white, and CSF volumes were estimated using high-resolution T1-weighted MRI. Linear regression modeled effects of serostatus, age, education, comorbidities, and magnetic field strength on brain structure, using both a priori regions and voxel-based morphometry. Although seropositive participants exhibited significant bilateral decreases in striatal GMV, no serostatus effects were detected in the thalamus, hippocampus, or cerebellum. Age was associated with cortical, striatal, thalamic, hippocampal, and cerebellar GMV reductions. Effects of age and serostatus on striatal GMV were additive. Although no main effects of serostatus on neuropsychological performance were observed, serostatus moderated the relationship between pegboard performance and striatal volume. Both HIV infection and age were associated with reduced striatal volume. The lack of interaction of these two predictors suggests that HIV infection is associated with premature, but not accelerated, brain age. In serostatus groups matched on demographic and clinical variables, there were no observed differences in neuropsychological performance. Striatal GMV measures may be promising biomarker for use in studies of treated HIV infection.

Diabetes and Cognitive Decline in Older Adults: The Ginkgo Evaluation of Memory Study.

BACKGROUND: Previous studies have shown that individuals with diabetes exhibit accelerated cognitive decline. However, methodological limitations have limited the quality of this evidence. Heterogeneity in study design, cognitive test administration, and methods of analysis of cognitive data have made it difficult to synthesize and translate findings to practice. We analyzed longitudinal data from the Ginkgo Evaluation of Memory Study to test our hypothesis that older adults with diabetes have greater test-specific and domain-specific cognitive declines compared to older adults without diabetes. METHODS: Tests of memory, visuo-spatial construction, language, psychomotor speed, and executive function were administered. Test scores were standardized to z-scores and averaged to yield domain scores. Linear random effects models were used to compare baseline differences and changes over time in test and domain scores among individuals with and without diabetes. RESULTS: Among the 3,069 adults, aged 72-96 years, 9.3% reported diabetes. Over a median follow-up of 6.1 years, participants with diabetes exhibited greater baseline differences in a test of executive function (trail making test, Part B) and greater declines in a test of language (phonemic verbal fluency). For the composite cognitive domain scores, participants with diabetes exhibited lower baseline executive function and global cognition domain scores, but no significant differences in the rate of decline. CONCLUSIONS: Identifying cognitive domains most affected by diabetes can lead to targeted risk modification, possibly in the form of lifestyle interventions such as diet and physical activity, which we know to be beneficial for improving vascular risk factors, such as diabetes, and therefore may reduce the risk of executive dysfunction and possible dementia.

Chronotherapy versus conventional statins therapy for the treatment of hyperlipidaemia.

BACKGROUND: Elevated levels of total cholesterol and low-density lipoprotein play an important role in the development of atheromas and, therefore, in cardiovascular diseases. Cholesterol biosynthesis follows a circadian rhythm and is principally produced at night (between 12:00 am and 6:00 am). The adjustment of hypolipaemic therapy to biologic rhythms is known as chronotherapy. Chronotherapy is based on the idea that medication can have different effects depending on the hour at which it is taken. Statins are one of the most widely used drugs for the prevention of cardiovascular events. In usual clinical practice, statins are administered once per day without specifying the time when they should be taken. It is unknown whether the timing of statin administration is important for clinical outcomes. OBJECTIVES: To critically evaluate and analyse the evidence available from randomised controlled trials regarding the effects of chronotherapy on the effectiveness and safety of treating hyperlipidaemia with statins. SEARCH METHODS: We searched the CENTRAL, MEDLINE, Embase, LILACS, ProQuest Health & Medical Complete, OpenSIGLE, Web of Science Conference Proceedings, and various other resources including clinical trials registers up to November 2015. We also searched the reference lists of relevant reviews for eligible studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), enrolling people with primary or secondary hyperlipidaemia. To be included, trials must have compared any chronotherapeutic lipid-lowering regimen with statins and any other statin lipid-lowering regimen not based on chronotherapy. We considered any type and dosage of statin as eligible, as long as the control and experimental arms differed only in the timing of the administration of the same statin. Quasi-randomised studies were excluded. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. We extracted the key data from studies in relation to participants, interventions, and outcomes for safety and efficacy. We calculated odds ratios (OR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI). Using the GRADE approach, we assessed the quality of the evidence and we used the GRADEpro Guideline Development Tool to import data from Review Manager to create 'Summary of findings' tables. MAIN RESULTS: This review includes eight RCTs (767 participants analysed in morning and evening arms). The trials used different lipid-lowering regimens with statins (lovastatin: two trials; simvastatin: three trials; fluvastatin: two trials; pravastatin: one trial). All trials compared the effects between morning and evening statin administration. Trial length ranged from four to 14 weeks. We found a high risk of bias in the domain of selective reporting in three trials and in the domain of incomplete outcome data in one trial of the eight trials included. None of the studies included were judged to be at low risk of bias.None of the included RCTs reported data on cardiovascular mortality, cardiovascular morbidity, incidence of cardiovascular events, or deaths from any cause. Pooled results showed no evidence of a difference in total cholesterol (MD 4.33, 95% CI -1.36 to 10.01), 514 participants, five trials, mean follow-up 9 weeks, low-quality evidence), low-density lipoprotein cholesterol (LDL-C) levels (MD 4.85 mg/dL, 95% CI -0.87 to 10.57, 473 participants, five trials, mean follow-up 9 weeks, low-quality evidence), high-density lipoprotein cholesterol (HDL-C) (MD 0.54, 95% CI -1.08 to 2.17, 514 participants, five trials, mean follow-up 9 weeks, low-quality evidence) or triglycerides (MD -8.91, 95% CI -22 to 4.17, 510 participants, five trials, mean follow-up 9 weeks, low-quality evidence) between morning and evening statin administration.With regard to safety outcomes, five trials (556 participants) reported adverse events. Pooled analysis found no differences in statins adverse events between morning and evening intake (OR 0.71, 95% CI 0.44 to 1.15, 556 participants, five trials, mean follow-up 9 weeks, low-quality evidence). AUTHORS' CONCLUSIONS: Limited and low-quality evidence suggested that there were no differences between chronomodulated treatment with statins in people with hyperlipidaemia as compared to conventional treatment with statins, in terms of clinically relevant outcomes. Studies were short term and therefore did not report on our primary outcomes, cardiovascular clinical events or death. The review did not find differences in adverse events associated with statins between both regimens. Taking statins in the evening does not have an effect on the improvement of lipid levels with respect to morning administration. Further high-quality trials with longer-term follow-up are needed to confirm the results of this review.

Inflammatory Biomarkers and Cognitive Decline: The Ginkgo Evaluation of Memory Study.

OBJECTIVES: To examine the association between inflammatory biomarkers and global cognitive function. DESIGN: Case-cohort. SETTING: Ginkgo Evaluation of Memory Study. PARTICIPANTS: Individuals aged 75 and older free of neurological or neurodegenerative conditions recruited from 2000 to 2002 (N = 1,315). MEASUREMENTS: Outcome was cognitive function assessed using the modified Mini-Mental State Examination (3MSE) every 6 months for up to 7 years. Exposures were 10 biomarkers measured at baseline: interleukin-2, -6, and -10 (general systemic inflammation); pentraxin 3 (PTX3) and serum amyloid P (SAP) (vascular inflammation); plasminogen activator inhibitor-1, adiponectin, and resistin (metabolic function); receptor for advanced glycation endproduct (oxidative stress); and endothelin-1 (endothelial function). Associations between biomarkers and 3MSE scores (stratified according to mild cognitive impairment (MCI) at baseline) were analyzed using Cox regression (outcome: 3MSE decline of ≥5 points) and mixed-model regression. Bonferroni correction was used to determine significance threshold (P < .0025). RESULTS: In individuals with baseline MCI, PTX3 was associated with a 20% greater hazard of cognitive decline (95% confidence interval = 1.07-1.35), although this association was no longer statistically significant after adjustment for apolipoprotein (APO)E ε4 allele. Adiponectin was associated with faster rate of 3MSE decline in individuals without baseline MCI in mixed-model regression, but the association was similarly attenuated after adjustment for APOE-ε4. CONCLUSION: This study did not find strong evidence of the utility of the biomarkers evaluated for identifying individuals at risk of cognitive decline. Future studies investigating the association between PTX3, SAP, and adiponectin and 3MSE scores may be useful.

Electroestimulación neuromuscular intradiálisis, fuerza muscular, capacidad funcional y composición corporal / Intradialysis neuromuscular electro stimulation muscle strength, functional capacity and body composition

Introducción: La capacidad funcional disminuida y la importante atrofia muscular caracterizan a los pacientes en hemodiálisis (HD). El ejercicio físico intradiálisis y recientemente la electroestimulación neuromuscular (EMS), representan dos serias opciones terapéuticas para mejorar esta deteriorada condición física. Actualmente, no existen estudios publicados sobre el papel de la EMS y la composición corporal en los pacientes en HD. Objetivo: Analizar que efecto produce un programa de EMS sobre la fuerza muscular, capacidad funcional, parámetros nutricionales y composición corporal en nuestros pacientes en HD. Material y Métodos: Estudio unicéntrico, prospectivo de 12 semanas de duración. Los pacientes incluidos realizaron un programa adaptativo de EMS en ambos cuádriceps intradiálisis mediante el dispositivo Compex R Theta 500i. Analizamos: 1.- Parámetros nutricionales (Albumina, pre albúmina, triglicéridos, colesterol total y fracciones, ferritina y Proteína C reactiva). 2.- Datos musculares: Composición muscular cuadriceps, Fuerza extensión máxima cuádriceps (FEMQ) y handgrip (HG) brazo dominante. 3.- Test funcionales: “Sit to stand to sit” (STS10) y “six- minutes walking test” (6MWT). 4.- Composición corporal mediante biompedancia electrica (BIA). Resultados: 13 pacientes incluidos: (69.2% hombres). Edad media: 65.7 años y 33.9 meses en HD. I.Charlson medio 9.1. La principal etiología de la ERC fue la DM ( 38.5%). Al final del estudio se observó una mejoría en (*p<0.05): FEMQ* ( 11.7±7.1 vs 13.4±7.4 Kg), STS10 (39.3±15.5 vs 35.8±13.7 seg), 6MWT* (9.9%, 293.2 vs 325.2 m). En relación a la composición corporal, se observó únicamente un aumento significativo del área muscular (AMQ*: 128.6 ± 30.2 vs 144.6 ± 22.4 cm2) y una disminución del área grasa (AGQ*: 76.5 ± 26.9 vs 62.1 ± 20.1 cm2) a nivel quadricipital, sin cambios en el resto de datos analizados (% grasa abdominal, peso graso, peso magro, agua corporal total). No se objetivaron cambios relevantes en los parámetros nutricionales y de adecuación dialítica. Conclusiones: 1.- La electroestimulación neuromuscular intradialísis mejoró la fuerza muscular, la capacidad funcional y la composición muscular del cuadriceps de nuestros pacientes en HD. 2.- Nuestros resultados remarcan el carácter local de la electroes-timulación neuromuscular, dada la ausencia de cambios relevantes en el resto de los parámetros nutricionales y datos corporales analizados. 3.- No obstante, son necesarios futuros estudios mejor diseñados, de cara a discernir si la electroestimulación neuromuscular podría ser una nueva alternativa terapéutica para evitar la atrofia muscular y el deterioro progresivo de la condición física de éstos pacientes (AU)

Background: The reduced functional capacity and significant muscle atrophy characterized patients on hemodialysis. Intradialytic exercise and recently neuromuscular electrostimulation (EMS) represent two serious therapeutical options to improve the deteriorated physical condition. Until date, there are no published studies about the role of EMS and body composition in HD patients. Objectives: Analyze the effect a program of EMS on muscle strength, functional capacity, nutritional parameters and body composition in our HD patients. Methods: A 12 weeks single-center, prospective study. Patients included in the study performed an intradialysis EMS adaptive program in both quadriceps using the Compex R Theta 500i device. We analyzed: 1.- Nutritional parameters (albumin, pre-albumin, triglycerides, total cholesterol and fractions, ferritin and C-reactive protein). 2.- Muscular data: Muscular composition, Maximum length quadriceps strength (MLQS) and “hand-grip” (HG) dominant arm. 3.- Functional capacity test: “Sit to stand to sit” (STS10) and “six- minutes walking test” (6MWT). 4.- Body composition. Results: 13 HD patients included: 69.2 % men. Mean age 65.7 years and 33.9 months on HD. A significant (* p < 0,05) improvement was observed in MLQS* (11.7±7.1 vs 13.4±7.4 Kg), STS10* (39.3±15.5 vs 35.8±13.7 seg), 6MWT* (9.9%, 293.2 vs 325.2 m). There was a signi-ficant increase in the quadriceps muscular area (QMA*: 128.6 ± 30.2 vs 144.6 ± 22.4 cm2) and decrease of fat quadricipital area (FQA*: 76.5 ± 26.9 vs 62.1 ± 20.1 cm2). No significant changes were observed in nutritional parameters, body composition (body fat percentage, lean and fat mass, total body water) or dialysis adecuacy data. Conclusions: 1.- Intradialysis quadriceps EMS improved muscle strength, functional capacity and the quadriceps muscle composition in our HD patients. 2.- Our results underline the local aspects on EMS, given the absence of relevant changes on nutritional parameters and body composition. 3.- Future studies are manadatory in order to establish if EMS could be a new alternative to prevent muscle atrophy and the progressive deterioration of the physical condition of these patients (AU)

Phenolic thio- and selenosemicarbazones as multi-target drugs.

A series of isosteric phenolic thio- and selenosemicarbazones have been obtained by condensation of naturally-occurring phenolic aldehydes and thio(seleno)semicarbazides. Title compounds were designed as potential multi-target drugs, and a series of structure-activity relationships could be established upon their in vitro assays: antioxidant activity, α-glucosidase inhibition and antiproliferative activity against six human tumor cell lines: A549 (non-small cell lung), HBL-100 (breast), HeLa (cervix), SW1573 (non-small cell lung), T-47D (breast) and WiDr (colon). For the antiradical activity, selenium atom and 2 or 3 phenolic hydroxyl groups proved to be essential motifs; remarkably, the compound with the most potent activity, with a trihydroxyphenyl scaffold (EC50 = 4.87 ± 1.57 µM) was found to be stronger than natural hydroxytyrosol, a potent antioxidant present in olive oil (EC50 = 13.80 ± 1.41 µM). Furthermore, one of the thiosemicarbazones was found to be a strong non-competitive inhibitor of α-glucosidase (Ki = 9.6 ± 1.6 µM), with an 8-fold increase in activity compared to acarbose (Ki = 77.9 ± 11.4 µM), marketed for the treatment of type-2 diabetes. Most of the synthesized compounds also exhibited relevant antiproliferative activities; in particular, seleno derivatives showed GI50 values lower than 6.0 µM for all the tested cell lines; N-naphthyl mono- and dihydroxylated derivatives behaved as more potent antiproliferative agents than 5-fluorouracil or cisplatin.

Resultado de un programa adaptado de ejercicio físico en pacientes ancianos en hemodiálisis / Effects of an adapted physical activity program in elderly haemodialysis patients

Introducción: Los pacientes ancianos constituyen un grupo en continuo crecimiento en los programas de hemodiálisis. Éstos se caracterizan por su elevada complejidad, dependencia y comorbilidad asociada. Múltiples beneficios del ejercicio físico en los pacientes en hemodiálisis han sido descritos; si bien no han sido completamente evaluados en la población anciana en hemodiálisis. Objetivos: Analizar el efecto de un programa adaptado de ejercicio físico intradiálisis sobre la fuerza muscular, la capacidad funcional, la sintomatología depresiva y la calidad de vida en nuestros pacientes ancianos (>75 años) en hemodiálisis. Material y métodos: Estudio prospectivo de 12 semanas de duración. 11 pacientes incluidos (36.4% hombres). Edad media 83.9 años y 37.2 meses en hemodiá- lisis. Charlson medio: 9.7. Principal etiología: Diabetes Mellitus (45.5%), No filiada (27.3%), hipertensión (9.1%). Los pacientes incluidos realizaron un programa de ejercicio físico adaptado mediante pelotas medicinales, pesas, bandas elásticas y cicloergómetros en las primeras dos horas de hemodiálisis. Analizamos: 1.-Parámetros bioquímicos. 2. Datos musculares: Fuerza extensión máxima cuádriceps y hand-grip. 3.-Tests Test funcionales: “Sit to stand to sit" y “six-minutes walking test”. 4.- Sintomatología depresiva: Inventario Beck. 5.-Calidad de Vida: EuroQol-5D. Resultados: De forma global, se observó una mejoría en las pruebas realizadas (*p<0.05): Fuerza extensión máxima del cuádriceps (10.5 ± 7.6 vs 12.9 ± 10 kg), hand-grip* (16.6 ± 8.7 vs 18.2 ± 8.9 kg), Sit to stand to sit 10* (29.9 ± 10.6 vs 25 ± 7.8 seg), six-minutes walking test* (22.6%, 234.4 vs 286.8 m), inventario de Beck* (14.4 ± 11.5 vs 11.7 ± 10.8) y EuroQol-5D (49.1 ± 19.1 vs 59.5 ± 20.3, p=0.064) al finalizar el estudio. Del mismo modo, no observamos cambios relevantes en los datos bioquímicos y antropométricos durante el estudio. Conclusiones: 1.-El programa adaptado de ejercicio físico intradiálisis mejoró la fuerza muscular, la capacidad funcional y la calidad de vida de nuestros pacientes ancianos en hemodiálisis. 2.- Aún en población anciana, nuestros resultados realzan los beneficios del ejercicio físico en los pacientes en hemodiálisis. 3.-Ante un paciente anciano en hemodiálisis, merece la pena considerar la realización de ejercicio físico adaptado intradiálisis como una parte más del cuidado integral en hemodiálisis (AU)

Introduction: Elderly patients are a group continuously growing in haemodialysis programs. They are characterized by their high complexity, dependency and associated comorbidity. Multiple benefits of physical activities in haemodialysis patients have been described; although they have not been fully evaluated in the elderly haemodialysis population. Objectives: To analyse the effect of an intradialytic adapted physical activity program on muscle strength, functional capacity, depressive symptoms and quality of life in our elderly patients (> 75 years) on haemodialysis. Methods: A prospective study of 12 weeks. 11 patients were included (36.4% male). Mean age of 83.9 years and haemodialysis vintage of 37.2 months. Mean Charlson index of 9.7. Main aetiologies: Diabetes Mellitus (45.5%), Not drafted (27.3%), hypertension (9.1%). Included patients performed a tailored physical exercise program using medicine balls, weights, elastic bands and ergometer in the first two hours of dialysis. We analyse: 1.-Biochemical parameters. 2.-Muscular Data: Maximum quadriceps extension strength and maximum handgrip strength. 3.-Functional tests: “Sit to stand to sit" and “six-minutes walking test”. 4.-Depressive symptomatology: Beck Depression Inventory. 5.-Quality of Life: EuroQol-5D. Results: Overall, an improvement was observed in tests (*p<0.05): Maximum quadriceps extension strength (10.5 ± 7.6 vs. 12.9 ±10 kg), hand-grip* (16.6 ± 8.7 vs. 18.2 ± 8.9 kg) Sit to stand to sit 10* (29.9 ± 10.6 vs. 25 ± 7.8 sec), Six-minute walking test* (22.6%, 234.4 vs. 286.8 m), Beck Depression Inventory* (14.4 ± 11.5 vs. 11.7 ± 10.8) and EuroQol-5D (49.1 ± 19.1 vs. 59.5 ± 20.3, p = 0.064) at study end. Similarly, we observed no significant changes in biochemical and anthropometric data during the study. Conclusions: 1. Intradialytic adapted physical activity program improved muscle strength, functional capacity and quality of life in elderly haemodialysis patients. 2. Our results highlight the benefits of exercise in elderly haemodialysis patients. 3. It is worth considering conducting intradialytic adapted physical exercises as just another part of comprehensive care in haemodialysis (AU)

Amyloid, neurodegeneration, and small vessel disease as predictors of dementia in the oldest-old.

OBJECTIVE: To examine the association between brain structural changes and ß-amyloid deposition, and incident dementia in 183 elderly subjects without dementia (mean age 85.5 years) 2 years later. METHODS: Subjects had a brain structural MRI scan and a PET scan with (11)C-labeled Pittsburgh compound B (PiB) in 2009, and were evaluated clinically in 2011. RESULTS: At baseline evaluation, of the 183 participants (146 cognitively normal [CN]); 37 mild cognitive impairment [MCI]), 139 (76%) were PiB+, had small hippocampal volume (<25th percentile), or had high white matter lesion (WML) volume (>75th percentile). Two years later, 111 (61%) were classified as CN, 51 (28%) as MCI, and 21 (11%) as dementia. At baseline, 51% of the CN participants and 67.5% of the MCI cases were PiB+. Thirty percent of the CN and 51% of the MCI cases had small hippocampi, and 24% of the CN and 40.5% of the MCI cases had abnormal WMLs. Of the 21 participants who progressed to dementia, 20 (95%) had at least one imaging abnormality. Only 3 (14%) were only PiB+, 1 (5%) had only small hippocampi, 1 (5%) had only WMLs, 1 (5%) was biomarker negative, and the other 16 had various pairs of imaging abnormalities. Continuous variables of PiB retention, left and right hippocampal volume, and WML volume were independent predictors of dementia in a logistic regression analysis controlling for age, sex, education level, and Mini-Mental State Examination scores. CONCLUSIONS: The prevalence of ß-amyloid deposition, neurodegeneration (i.e., hippocampal atrophy), and small vessel disease (WMLs) is high in CN older individuals and in MCI. A combination of 2 or 3 of these factors is a powerful predictor of short-term incidence of dementia.

Phenolic compounds and antioxidant capacity of virgin olive oil.

The characterisation of virgin olive oil from Arbequina, Carrasqueña, Corniche, Manzanilla Cacereña, Morisca, Picual, and Verdial de Badajoz varieties according to the individual phenolic compounds at different ripening stage was carried out. In all olive oil varieties studied, secoiridoid derivatives were most abundant, followed by phenolic alcohols, flavonoids and phenolic acids. The secoiridoid derivatives of hydroxytyrosol were the most important complex phenols for Picual and Carrasqueña, whereas the tyrosol derivatives were the major ones found in Manzanilla Cacereña, and Verdial de Badajoz. For secoiridoid derivatives of hydroxytyrosol and tyrosol, Arbequina was the oil variety showing the lowest concentration. Tyrosol, hydroxytyrosol, vanillic acid, p-cumaric acid, luteolin, and apigenin levels were greater in early harvested samples in almost all oils analysed. Antioxidant activity measurements (antiradical, lipid peroxide inhibition, H2O2 and NO scavenging) were also accomplished for the seven varieties in the first ripening stage.

Pulse wave velocity is associated with ß-amyloid deposition in the brains of very elderly adults.

OBJECTIVE: To determine arterial stiffness and ß-amyloid (Aß) deposition in the brain of dementia-free older adults. METHODS: We studied a cohort of 91 dementia-free participants aged 83-96 years. In 2009, participants completed brain MRI and PET imaging using Pittsburgh compound B (PiB; a marker of amyloid plaques in human brain). In 2011, we measured resting blood pressure (BP), mean arterial pressure (MAP), and arterial stiffness by pulse wave velocity (PWV) in the central, peripheral, and mixed (e.g., brachial ankle PWV [baPWV]) vascular beds, using a noninvasive and automated waveform analyzer. RESULTS: A total of 44/91 subjects were Aß-positive on PET scan. Aß deposition was associated with mixed PWV, systolic BP, and MAP. One SD increase in baPWV resulted in a 2-fold increase in the odds of being Aß-positive (p = 0.007). High white matter hyperintensity (WMH) burden was associated with increased central PWV, systolic BP, and MAP. Compared to Aß-negative individuals with low WMH burden, each SD increase in PWV was associated with a 2-fold to 4-fold increase in the odds of being Aß-positive and having high WMH. CONCLUSIONS: Arterial stiffness was associated with Aß plaque deposition in the brain, independent of BP and APOE ε4 allele. The associations differed by type of brain abnormality and vascular bed measured (e.g., WMH with central stiffness and Aß deposition and mixed stiffness). Arterial stiffness was highest in individuals with both high Aß deposition and WMH, which has been suggested to be a "double hit" contributing to the development of symptomatic dementia.

Resultados de un programa de ejercicio físico combinado con electroestimulación neuromuscular en pacientes en hemodiálisis / Exercise training program combined with leg electroestimulation in patients on hemodialysis: a prospective study

Los pacientes en hemodiálisis presentan una importante disminución de la condición física y la capacidad funcional. Ampliamente son conocidos los numerosos beneficios del ejercicio físico en los pacientes con insuficiencia renal en éstos aspectos. Hasta la fecha, existe mínima experiencia con la electroestimulación neuromuscular en los pacientes en hemodiálisis. Objetivos: 1. Analizar el efecto de un programa de entrenamiento físico intradiálisis combinado con electroestimulación neuromuscular sobre la fuerza muscular y la capacidad funcional en nuestros pacientes en hemodiálisis. 2. Analizar la seguridad, eficacia y tolerancia de la electroestimulación neuromuscular en nuestros pacientes en hemodiálisis. Métodos: Los pacientes en hemodiálisis realizaron un programa completo de entrenamiento físico mediante balones medicinales, pesas, bandas elásticas y cicloergómetros combinado con electroestimulación neuromuscular en las primeras dos horas de hemodiálisis durante 12 semanas en un estudio prospectivo unicéntrico. La electroestimulación se realizó en ambos cuádriceps usando el Compex ® Theta 500i. Principales datos analizados: 1. Fuerza extensión máxima cuádriceps (FEMQ) y “handgrip” brazo dominante (HG). 2. Test funcionales:“Sit to stand to sit” (STS10) y “six-minutes walking test” (6MWT). 3. Escala Visual Analógica (EVA) y cuestionario propio de electroestimulación neuromuscular (QE). Resultados: 11 pacientes incluidos (55% mujeres). Edad media 67.6 años y 62.3 meses en hemodiálisis. Se observó una mejoría significativa (*p<0.05) en la FEMQ*(13.7±8.1 vs 16.2±10.9kg), HG*(23.8±15.9 vs 25.1±15.9kg), STS10*(24.6±13.4 vs 20.1±10.1 seg) y 6MWT*(21%,332.6 vs 402.7 m). No observamos dolor muscular, rampas, hormigueos o calambres musculares relevantes en el cuestionario propio de electroestimulación. El grado medio de satisfacción (EVA) fue 9.4 puntos. Conclusiones: 1. El programa de entrenamiento físico intradiálisis combinado con electroestimulación neuromuscular mejoró la fuerza muscular y la capacidad funcional en nuestros pacientes en hemodiálisis. 2. La electroestimulación neuromuscular intradiálisis de ambos cuádriceps resultó segura, efectiva y bien tolerada en nuestros pacientes en hemodiálsis. 3. Éstos resultados constituyen una novedosa alternativa terapéutica relacionada con los beneficios del ejercicio físico en los pacientes en hemodiálisis (AU)

Patients on hemodialysis (HD) have a decreased physical and functional capacity. There is proven evidence about the benefits of exercise training on functional capacity in HD. Untildate, minimal experience with electroestimulation (ETEM) in HD patient sis reported. Objectives: 1. Analize the effect of intradialysis training program combined with electroestimulation on muscular strenght and functional capacity in our HD patients. 2. Analize the safety, efficacy and tolerance of ETEM in our HD patients. Methods: HD patients were enrolled into an exercise training program combined with ETEM in the first two hours of HD session during a 12 weeks single-center prospective study. ETEM included physical training using balls, weights, elastic bands and cycle ergometer. Leg electroestimulation were performed using the Compex® Theta 500i device in both quadriceps muscles. Most relevant analized data: 1. Maximum length quadriceps strength (MLQS) and “hand-grip (HG) dominant arm. 2. Functional capacity tests: “Sit to stand to sit” (STS10) and “six-minutes walking test” (6MWT). 3. Visual analogic scale (VAS) and our own satisfaction electroestimulation questionnaire (SEQ) was completed. Results: 11 HD patients included: 55%women.Mean age 67.6 years and 62.3 months on HD.A significant (*p<0.05) improvement was observed in MLQS* (13.7±8.1 vs 16.2±10.9kg), HG*(23.8±15.9 vs 25.1±15.9kg), STS10*(24.6±13.4 vs 20.1±10.1 sec) and 6MWT* (21%, 332.6 vs 402.7 m). No relevant muscular pain, cramps, tingles or pricks were related in the SEQ. The VAS satisfaction degree was 9.4 points. Conclusions: 1. Intradialysis training program combined with quadriceps electroestimulation improved muscular strenght and functional capacity in our HD patients. 2. Intradialysis quadriceps electroestimulation was safe, effective and well tolerated in our HD patients. 3. These results represents a wide therapeutic possibility related to the benefits of exercise training for HD patients(AU)

Cognitive trajectories associated with ß-amyloid deposition in the oldest-old without dementia.

OBJECTIVE: To determine whether a high prevalence (55%) of Aß deposition in a cohort of individuals remaining dementia-free into their 9th and 10th decades is associated with cognitive decline prior to imaging. METHODS: A total of 194 participants (mean age 85.5 years, range 82-95) who completed the Ginkgo Evaluation of Memory Study (GEMS) and remained dementia-free subsequently completed Pittsburgh compound B-PET imaging. We examined cross-sectional associations between Aß status and performance on a broad neuropsychological test battery completed at GEMS entry 7-9 years prior to neuroimaging. We also longitudinally examined cognition over annual evaluations using linear mixed models. RESULTS: At GEMS screening (2000-2002), participants who were Aß-positive in 2009 had lower performance on the Stroop test (p < 0.01) and Raven's Progressive Matrices (p = 0.05), with trend level difference for Block Design (p = 0.07). Longitudinal analyses showed significant slope differences for immediate and delayed recall of the Rey-Osterrieth figure, semantic fluency, and Trail-Making Test parts A and B, indicating greater performance decline prior to neuroimaging for Aß-positive relative to Aß-negative participants (ps < 0.05). CONCLUSIONS: Highly prevalent Aß deposition in oldest-older adults is associated with cognitive decline in visual memory, semantic fluency, and psychomotor speed beginning 7-9 years prior to neuroimaging. Mean differences in nonmemory domains, primarily executive functions, between Aß-status groups may be detectable 7-9 years before neuroimaging.

High antioxidant activity mixture of extruded whole quality protein maize and common bean flours for production of a nutraceutical beverage elaborated with a traditional Mexican formulation.

The objective of this study was to determine the best combination of extrusion process variables for the production of whole quality protein maize (EQPMF) and common bean (ECBF) flours to prepare a high antioxidant activity mixture (EQPMF + ECBF) suitable to produce a nutraceutical beverage with high acceptability elaborated with a traditional Mexican formulation. Processing conditions were obtained from a factorial combination of barrel temperature (BT = 120-170 °C) and screw speed (SS = 120-200 rpm). Response surface methodology was applied to obtain maximum values for antioxidant activity (A ( ox ) A) of the flour mixture (EQPMF + ECBF) and acceptability (A) of the nutraceutical beverage. The best combinations of extrusion process variables for EQPMF and ECBF to prepare an optimized mixture (60%EQPMF + 40%ECBF) were BT = 98 °C/SS = 218 rpm and BT = 105 °C/SS = 83 rpm, respectively. The optimized mixture had A ( ox ) A = 14,320 µmol Trolox equivalent (TE)/100 g sample dry weight (dw) and a calculated protein efficiency ratio (C-PER) of 2.17. A 200 ml portion of a beverage prepared with 25 g of the optimized flour mixture had A ( ox ) A = 3,222 µmol TE, and A = 89 (level of satisfaction "I like it extremely"). This nutraceutical beverage could be used as an alternative to beverages with low nutritional/nutraceutical value, such as those prepared with water, simple sugars, artificial flavoring and colorants, which are widely offered in the market.

Does Ginkgo biloba reduce the risk of cardiovascular events?

BACKGROUND: Cardiovascular disease (CVD) was a preplanned secondary outcome of the Ginkgo Evaluation of Memory Study. The trial previously reported that Ginkgo biloba had no effect on the primary outcome, incident dementia. METHODS AND RESULTS: The double-blind trial randomly assigned 3069 participants over 75 years of age to 120 mg of G biloba EGb 761 twice daily or placebo. Mean follow-up was 6.1 years. The identification and classification of CVD was based on methods used in the Cardiovascular Health Study. Differences in time to event between G biloba and placebo were evaluated using Cox proportional hazards regression adjusted for age and sex. There were 355 deaths in the study, 87 due to coronary heart disease with no differences between G biloba and placebo. There were no differences in incident myocardial infarction (n=164), angina pectoris (n=207), or stroke (151) between G biloba and placebo. There were 24 hemorrhagic strokes, 16 on G biloba and 8 on placebo (not significant). There were only 35 peripheral vascular disease events, 12 (0.8%) on G biloba and 23 (1.5%) on placebo (P=0.04, exact test). Most of the peripheral vascular disease cases had either vascular surgery or amputation. CONCLUSIONS: There was no evidence that G biloba reduced total or CVD mortality or CVD events. There were more peripheral vascular disease events in the placebo arm. G biloba cannot be recommended for preventing CVD. Further clinical trials of peripheral vascular disease outcomes might be indicated. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00010803.

Effect of Ginkgo biloba on blood pressure and incidence of hypertension in elderly men and women.

BACKGROUND: Accumulating evidence suggests that Ginkgo biloba is cardioprotective, in part, through its vasodilatory and antihypertensive properties. However, definitive data on its blood pressure (BP)-lowering effects in humans is lacking. METHODS: We determined the effects of G. biloba extract (240 mg/day) on BP and incident hypertension in 3,069 participants (mean age, 79 years; 46% female; 96% white) from the Ginkgo Evaluation of Memory (GEM) study. We also examined whether the treatment effects are modified by baseline hypertension status. RESULTS: At baseline, 54% of the study participants were hypertensive, 28% were prehypertensive, and 17% were normotensive. Over a median follow-up of 6.1 years, there were similar changes in BP and pulse pressure (PP) in the G. biloba and placebo groups. Although baseline hypertension status did not modify the antihypertensive effects of G. biloba, it did influence the changes in BP variables observed during follow-up, with decreases in hypertensives, increases in normotensives, and no changes in prehypertensives. Among participants who were not on antihypertensive medications at baseline, there was no difference between treatment groups in medication use over time, as the odds ratio (95% confidence interval (CI)) for being a never-user in the G. biloba group was 0.75 (0.48-1.16). The rate of incident hypertension also did not differ between participants assigned to G. biloba vs. placebo (hazard ratio (HR), 0.99, 95% CI, 0.84-1.15). CONCLUSIONS: Our data indicate that G. biloba does not reduce BP or the incidence of hypertension in elderly men and women.