Caffeic acid attenuates oxidative stress,learning and memory deficit in intra-cerebroventricular streptozotocin induced experimental dementia in rats

Oxidative stress has been implicated in cognitive decline as seen during normal aging and in sporadic Alzheimer’s disease (AD). Caffeic acid, a polyphenolic compound, has been reported to possess potent antioxidant and neuroprotective properties. The role of caffeic acid in experimental dementia is not fully understood. Thus the present study was designed to investigate the therapeutic potential of caffeic acid in streptozotocin (STZ)-induced experimental dementia of Alzheimer’s type in rats. Streptozotocin (STZ) was administered intracerebroventrically (ICV) on day 1 and 3 (3 mg/kg, ICV bilaterally) in Wistar rats. Caffeic acid was administered (10, 20 and 40 mg/kg/day p.o.) 1 h following STZ infusion upto 21st day. Morris water maze and object recognition task were used to assess learning and memory in rats. Terminally, acetylcholinesterase (AChE) activity and the levels of oxido-nitrosative stress markers were determined in cortical and hippocampal brain regions of rats. STZ produced significant (p < 0.001) learning and memory impairment, oxido-nitrosative stress and cholinergic deficit in rats. Whereas, caffeic acid treatment significantly (p < 0.001) and dose dependently attenuated STZ induced behavioral and biochemical abnormalities in rats. The observed cognitive improvement following caffeic acid in STZ treated rats may be due to its antioxidant activity and restoration of cholinergic functions. Our results suggest the therapeutic potential of caffeic acid in cognitive disorders such as AD.     

Urtica dioica leaves modulates hippocampal smoothened-glioma associated oncogene-1 pathway and cognitive dysfunction in chronically stressed mice

The present study was aimed to evaluate the effect of Urtica dioica (UD) extract against chronic unpredictable stress (CUS)-induced associative memory dysfunction and attempted to explore the possible mechanism. Male Swiss albino mice (25–30 g) were divided into six groups, viz. group-I received 0.3% carboxymethyl cellulose and served as control (CTRL), group II was exposed to CUS (21 days) and received vehicle (CUS), group III was subjected to CUS and received Hypericum perforatum extract (350 mg/kg, p.o.) (CUS + HYP), group IV received Hypericum perforatum extract (350 mg/kg, p.o.) (CTRL + HYP); group V was subjected to CUS and received UD extract (50 mg/kg, p.o.) (CUS + UD), group VI received UD extract (50 mg/kg, p.o.) (CTRL + UD). CUS significantly induced body weight loss (p < 0.05) and associative memory impairment in step down task (p < 0.05) as compared to control mice. CUS significantly downregulated Smo (p < 0.05), Gli1 (p < 0.01), cyclin D1 (p < 0.05), BDNF (p < 0.01), TrKB (p < 0.01) and MAPK1 (p < 0.01) mRNA expression in hippocampus as compared to control mice. CUS significantly increased the levels of TBARS (p < 0.01) and nitric oxide (p < 0.001), and decreased catalase (p < 0.001) and total thiol (p < 0.01) in plasma resulting in oxidative stress and inflammation. Chronic UD administration significantly reverted CUS mediated body weight loss (p < 0.05) and cognitive impairment (p < 0.05). UD administration significantly decreased the levels of TBARS (p < 0.01) and nitric oxide (p < 0.05), and increased the levels of catalase (p < 0.01) and total thiol (p < 0.05) in plasma. Chronic UD administration significantly upregulated hippocampal Smo (p < 0.05), Gli1 (p < 0.001), cyclin D1 (p < 0.05), BDNF (p < 0.05), TrKB (p < 0.05) and MAPK1 (p < 0.05) in stressed mice. Further, UD extract did not reverse cyclopamine induced downregulation of Gli1 and Ptch1 mRNA in hippocampal slices. UD modulated Smo-Gli1 pathway in the hippocampus as well as exerted anti-inflammatory and antioxidant effects. UD extract might prove to be effective for stress mediated neurological disorders.     

Neuronal apoptosis may not contribute to the long-term cognitive dysfunction induced by a brief exposure to 2% sevoflurane in developing rats

BackgroundSevoflurane is an inhaled anesthetic commonly used in the pediatric. Recent animal studies suggest that early exposure to high concentration of sevoflurane for a long duration can induce neuroapoptosis and later cognitive dysfunction. However, the neurodevelopmental impact induced by lower concentration and shorter exposure duration of sevoflurane is unclear. To investigate whether early exposure to 2% concentration of sevoflurane for a short duration (clinically relevant usage of sevoflurane) can also induce neuroapoptosis and later cognitive dysfunction.MethodsRat pups were subjected to control group, 2% sevoflurane for 3 h and 3% sevoflurane for 6 h. TUNEL assay and apoptotic enzyme cleaved caspase-3 measured by western blot were used for detection of neuronal apoptosis in frontal cortex and CA1 region of hippocampus 24 after sevoflurane treatment. Long-term cognitive function was evaluated by Morris water maze and passive avoidance test as the rats grew up.ResultsThe apoptotic levels in frontal cortex and CA1 region were significantly increased after rats exposed to 3% sevoflurane for 6 h (P < 0.05), but not 2% sevoflurane for 3 h (P > 0.05). Exposure to both 2% sevoflurane for 3 h and 3% sevoflurane for 6 h could cause long-term cognitive dysfunction and animals exposed to 3% sevoflurane for 6 h exhibited worse neurodevelopmental outcomes (P < 0.05).ConclusionIt was suggested that neuronal apoptosis might not contribute to long-term cognitive dysfunction induced by 2% concentration and short exposure time of sevoflurane. Our findings also suggested that the mechanisms of sevoflurane-induced neurodevelopmental impact might be various, depending on the concentration and exposure duration.     

Post-discharge outcomes after resuscitation from out-of-hospital cardiac arrest: A ROC PRIMED substudy

ImportanceAssessment of morbidity is an important component of evaluating interventions for patients with out-of-hospital cardiac arrest (OHCA).ObjectiveWe evaluated among survivors of OHCA cognition, functional status, health-related quality of life and depression as functions of patient and emergency medical services (EMS) factors.DesignProspective cohort sub-study of a randomized trial.SettingThe parent trial studied two comparisons in persons with non-traumatic OHCA treated by EMS personnel participating in the Resuscitation Outcomes Consortium.ParticipantsConsenting survivors to discharge.Main outcome measuresTelephone assessments up to 6 months after discharge included neurologic function (modified Rankin score, MRS), cognitive impairment (Adult Lifestyle and Function Mini Mental Status Examination, ALFI-MMSE), health-related quality of life (Health Utilities Index Mark 3, HUI3) and depression (Telephone Geriatric Depression Scale, T-GDS).ResultsOf 15,794 patients enrolled in the parent trial, 729 (56% of survivors) consented. About 644 respondents (88% of consented) completed ≥ 1 assessment. Likelihood of assessment was associated with baseline characteristics and study site. Most respondents had MRS ≤ 3 (82.7%), no cognitive impairment (82.7% ALFI-MMSE ≥ 17), no severe impairment in health (71.6%, HUI3 ≥ 0.7) and no depression (90.1% T-GDS ≤ 10). Outcomes did not differ by trial intervention or time from hospital discharge.Conclusions and relevanceThe majority of patients in this large cohort who survived cardiac arrest and were interviewed had no, mild or moderate health impairment. Concern about poor quality of life is not a valid reason to abandon efforts to improve an EMS system's response to cardiac arrest.     

The effectiveness of memory remediation strategies after traumatic brain injury: Systematic review and meta-analysis

BackgroundTraumatic brain injury (TBI) is a steadily rising health concern associated with significant risk of emotional, behavioral and cognitive impairments. Cognitive memory impairment is one of the most concerning outcomes after TBI, affecting a wide range of everyday activities, social interactions and employment. Several comparative and comprehensive reviews on the effects of cognitive interventions in individuals with TBI have been conducted but usually with a qualitative rather than quantitative approach. Thus, evidence synthesis of the effects of TBI interventions on memory difficulties is limited.ObjectiveIn this meta-analysis, we examined the memory-remediating effects of internal and external interventions, injury severity and the interaction of both factors for patients with TBI.MethodsData were extracted from studies published between 1980 and 2020 that used objective memory measures (computerized or pencil-and-paper), and multiple meta-analyses were conducted to compare effectiveness across these interventions. Publication bias was assessed, as was quality of evidence using the Cochrane Risk of Bias tool for randomized controlled studies. Our final meta-analysis included 16 studies of 17 interventions classified into 3 categories: internal, external and mixed.ResultsMixed interventions demonstrated the highest average effect size for memory difficulties (Morris d = 0.79). An evaluation of injury severity yielded 2 categories: mild-moderate and moderate-severe. Analyses demonstrated a homogenous medium effect size of improvement across injury severity, with moderate-severe injury with the largest average effect size (Morris d = 0.65). Further evaluation of injury severity interaction with intervention type revealed a mediating effect for both factors, demonstrating the largest effect size for mixed interventions with moderate-severe injury (Morris d = 0.81).ConclusionThis study highlights the effectiveness of memory remediation interventions on memory impairment after TBI. A wide range of interventions are more effective because they address individual variability for severity and memory deficits. The study further supports and expands existing intervention standards and guidelines.     

Factores predictores del deterioro cognitivo en personas mayores de 60 años

ObjectiveTo determine the relationship of depressive symptoms, sleep hygiene, nutritional status and gait speed with cognitive impairment in people over 60 years.MethodCross-sectional, correlational design with a non-probability convenience sampling. The population was made up of people over 60 years of age belonging to recreational stays in an urban area of Tamaulipas, Mexico. Criterion measures included three neuropsychological tests (Stroop Test, Trail Making Test and Digit Span Subtest) the Geriatric Depression Scale, Pittsburgh Sleep Quality Index, Mini Nutritional Assessment and the Short Physical Performance Battery.ResultsThe final sample was of 108 participants. Regarding the influence of risk factors to predict cognitive impairment a significant model was observed (F = 12.914, gl = 4, P ≥ .001), showing a variance explained of 33.4%, where depressive symptoms (β = .205, P = .048), sleep (β = –.322, P = .001), nutritional status (β = –.336, P = .001) and gait speed (β = .244, P = .004) were associated with cognitive impairment.ConclusionsHigh levels of depressive symptoms, prolonged sleep duration, a malnutrition status and a slow gait speed predict cognitive impairment of the people over 60 years, this provides knowledge for the implementation of interventions aimed at preventing the risk factors that predict cognitive decline in order to delay its appearance.     

Neurocognitive outcomes following successful resuscitation from cardiac arrest

IntroductionCardiac arrest commonly results in varying degrees of cognitive injury. Standard outcome measures used in the cardiac arrest cohort do not rigorously evaluate for these injury patterns. We examined the utility of the Computerized Assessment for Mild Cognitive Injury (CAMCI) in cardiac arrest (CA) survivors. We hypothesized that cognitive deficits would be more severe in patients who were comatose on hospital arrival.MethodsProspective cohort of CA survivors at a single tertiary care facility where participants received neurocognitive testing using CAMCI. CAMCI results were subdivided into memory, attention, and executive functions. Scores between subjects who were initially comatose and were not comatose following resuscitation were compared using the Mann–Whitney test.ResultsOf 72 subjects included, the majority (N = 44) were initially comatose following resuscitation with mean age of 54 (±14) years. The majority experienced a good neurologic outcome based on Cerebral Performance Category (N = 47; 66%) and Modified Rankin Scale (N = 38; 53%). Time from resuscitation to CAMCI testing was not associated with total CAMCI score in this cohort (Pearson's r² value −0.1941, p = 0.20). Initially comatose and not comatose subjects did not differ in their CAMCI overall scores (p = 0.33), or in any subtest areas. The not comatose cohort had 1 subtest for which there was a Moderate Risk for mild cognitive impairment (Nonverbal Accuracy), and 2 for which there was a Moderately Low Risk (Verbal Accuracy and Executive Accuracy). The Comatose cohort had 4 subtests, which were deemed Moderately Low Risk for cognitive impairment (Verbal Accuracy, Attention Accuracy, Executive Accuracy and Nonverbal Accuracy).ConclusionsIn-hospital CAMCI testing suggests memory, attention and executive impairment are commonly in patients following resuscitation from cardiac arrest. Outcome evaluations should test for deficits in memory, attention, and executive function.     

Building research in diet and cognition: The BRIDGE randomized controlled trial

Obesity has been linked to cognitive impairment, cognitive decline and dementia. Given that 38.5% of U.S. adults 60 years and older are obese and these numbers are rapidly increasing, strategies to decouple obesity from cognitive decline are needed. Innovative lifestyle strategies that may postpone the onset of subclinical symptoms or even arrest the transition to overt dementia in at-risk individuals are critically needed. Poor diet is central to the development of obesity and diet may affect cognition. Adherence to a Mediterranean Diet (MedDiet) is associated with reduced risk of cognitive impairment and dementia. Furthermore, weight loss through caloric restriction improves cognitive function. This paper describes the Building Research in Diet and CoGnition (BRIDGE) study, a randomized trial examining the effect of the MedDiet, with and without weight loss, on cognitive functioning in obese older adults. Obese (BMI ≥ 30 and ≤ 50 kg/m²) older adults (≥ 55 years) (n = 180) will be randomized in a 2:2:1 allocation scheme to: Typical Diet Control; MedDiet alone, without weight loss; or MedDiet lifestyle intervention to promote weight loss and weight loss maintenance. Both MedDiet intervention groups will meet for one individual session and 27 group sessions over an 8-month period. Individuals in the control group will not receive instruction on changing lifestyle habits. Outcomes will be assessed at baseline, 8 and 14 months. The primary outcome is cognitive functioning; secondary outcomes will include changes in body weight, diet, cardiovascular, metabolic, and inflammatory biomarkers.     

Minor Cognitive Impairments in Cancer Patients Magnify the Effect of Caregiver Preferences on End-of-Life Care

ContextCognitive impairment commonly affects cancer patients.ObjectivesTo examine whether minor cognitive impairment in patients with advanced cancer is associated with the intensity of end-of-life (EOL) care or modifies the influence of patient and caregiver preferences on the intensity of EOL care.MethodsData were derived from structured interviews with 221 advanced cancer patient-caregiver dyads in the Coping with Cancer Study, a multisite, longitudinal cohort study. Deficits in patients' cognitive function were identified using the Short Portable Mental Status Questionnaire (SPMSQ). Patients and caregivers reported preferences regarding life-extending vs. symptom-directed care. Information regarding EOL care was obtained from postmortem interviews with caregivers. Logistic regression analyses modeled main and interactive effects of patients' cognitive impairment and patients' and caregivers' treatment preferences on intensive EOL care.ResultsCognitive impairment was associated with less intensive EOL care (odds ratio [OR] = 0.56; 95% confidence interval [CI]: 0.34–0.91). Patients and caregivers had poor agreement regarding preferences for life-extending vs. symptom-directed care (Φ = 0.10; χ² = 2.32, df = 1, P = 0.13). Patient preference for life-extending care predicted intensive EOL care irrespective of cognitive status (adjusted odds ratio [AOR] = 2.11; 95% CI: 1.04–4.28). For patients with no errors on the SPMSQ, caregiver preference for life-extending care was unrelated to intensive EOL care (AOR = 0.40; 95% CI: 0.09–1.77). However, the association between caregiver preference for life-extending care and intensive EOL care increased by nearly a factor of seven for every error on the SPMSQ (interaction AOR = 6.90; 95% CI: 1.40–34.12).ConclusionCognitive impairment in patients with advanced cancer is associated with less intensive EOL care. Caregivers' influence on intensive EOL care dramatically increases with minor declines in patients' cognitive function.     

The Mental Activity and eXercise (MAX) trial: Effects on physical function and quality of life among older adults with cognitive complaints

BackgroundOlder adults with cognitive complaints are vulnerable to dementia, physical impairments, and poor quality of life. Exercise and mental activity may improve physical function and health-related quality of life (HRQOL) but combinations have not been investigated systematically. The Mental Activity and eXercise (MAX) trial found that mental activity plus exercise over 12 weeks improved cognitive function (primary outcome) in sedentary older adults with cognitive complaints.ObjectiveTo investigate the effects of combinations of two mental activity and exercise programs on physical function and HRQOL (secondary outcomes).MethodsParticipants (n = 126, age 73 ± 6 years, 65% women) were randomized to 12 weeks of exercise (aerobic exercise or stretching/toning, 3 × 60 min/week) plus mental activity (computer-based cognitive training or educational DVDs, 3 × 60 min/week) using a factorial design. Assessments included the Senior Fitness Test (physical function), Short Form-12 physical and mental sub-scales (HRQOL), and CHAMPS questionnaire (physical activity).ResultsThere were no differences between groups at baseline (p > 0.05). We observed improvements over time in most physical function measures [chair stands (p-for-time = 0.001), arm curls (p-for-time < 0.001), step test (p-for-time = 0.003), sit & reach (p-for-time = 0.01), and back scratch (p-for-time = 0.04)] and in physical HRQOL (p-for-time = 0.04). There were no differences in change between groups (group 1 time p > 0.05). Changes in most physical function measures and physical HRQOL correlated with physical activity changes.ConclusionCombined mental activity and exercise interventions of various types can improve both physical function and physical HRQOL among sedentary older adults with cognitive complaints. Exercise control group design should be carefully considered as even light exercise may induce benefits in vulnerable older adults.     

A Pilot Cluster-Randomized Trial of a 20-Week Tai Chi Program in Elders With Cognitive Impairment and Osteoarthritic Knee: Effects on Pain and Other Health Outcomes

ContextBecause Tai Chi (TC) is beneficial to elders without cognitive impairment (CI), it also may benefit elders with CI. But elders with CI have generally been excluded from TC studies because many measurement tools require verbal reports that some elders with CI are unable to provide.ObjectivesTo test the efficacy of a TC program in improving pain and other health outcomes in community-dwelling elders with knee osteoarthritis (OA) and CI.MethodsThis pilot cluster-randomized trial was conducted between January 2008 and June 2010 (ClinicalTrials.gov Identifier: NCT01528566). The TC group attended Sun style TC classes, three sessions a week for 20 weeks; the control group attended classes providing health and cultural information for the same length of time. Measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, physical function and stiffness subscales; the Get Up and Go test; the Sit-to-Stand test; and the Mini-Mental State Examination (MMSE), administered at baseline, every four weeks during the intervention and at the end of the study (post-test).ResultsEight sites participated in either the TC group (four sites, 28 participants) or control group (four sites, 27 participants). The WOMAC pain (P = 0.006) and stiffness scores (P = 0.010) differed significantly between the two groups at post-test, whereas differences between the two groups in the WOMAC physical function score (P = 0.071) and the MMSE (P = 0.096) showed borderline significance at the post-test. WOMAC pain (P = 0.001), physical function (P = 0.021), and stiffness (P ≤ 0.001) scores improved significantly more over time in the TC group than in controls. No adverse events were found in either group.ConclusionPracticing TC can be efficacious in reducing pain and stiffness in elders with knee OA and CI.     

Celecoxib and omega-3 fatty acids alone and in combination with risperidone affect the behavior and brain biochemistry in amphetamine-induced model of schizophrenia

The implications of oxidative stress and neuro-inflammation in the pathogenesis of schizophrenia have been elucidated. Despite their effectiveness against positive symptoms of schizophrenia, antipsychotics have limited effectiveness against negative and cognitive symptoms and are associated with remarkable adverse effects. The use of celecoxib or omega-3 in schizophrenia may have beneficial effects. This study aimed to evaluate the possible efficacies of celecoxib, omega-3 or the combination of celecoxib + risperidone and omega-3+ risperidone compared to risperidone on the behavior and brain biochemistry in rats. In the present study, an amphetamine-induced model of schizophrenia in adult male rats was used to evaluate the effects of celecoxib, omega-3, celecoxib + risperidone and omega-3+ risperidone on the behavior of animals and on brain lipid peroxidation or tumor necrosis factor-alpha. In the water maze task, celecoxib, omega-3, celecoxib + risperidone, omega-3+ risperidone significantly decreased the latency time compared to amphetamine-treated group. Celecoxib, omega-3, celecoxib + risperidone, omega–3 + risperidone also significantly reversed the decreased spontaneous alternation induced by amphetamine in the Y-maze task. In the social interaction task, groups treated with celecoxib, omega-3, celecoxib + risperidone, omega-3+ risperidone spent less time to recognize foreign animals than animals in the amphetamine-treated group. Increased brain MDA and TNF-α levels due to amphetamine were significantly reduced in groups treated with celecoxib + risperidone or omega-3+ risperidone. The present findings showed that celecoxib or omega-3 can attenuate amphetamine- induced behavioral impairment and these effects may be associated with their ability to decrease lipid peroxidation and cytokine release. Celecoxib or omega-3 may be promising candidates as adjuvant therapy for schizophrenia.     

The involvement of nitric oxide in the physiopathology of hepatoportal sclerosis

Background and aimHepatoportal sclerosis (HPS) is a clinical syndrome of unspecified etiology depicted by enlarged spleen and portal hypertension in the lack of other chronic liver disease findings, hematological disorders or any infectious disease in the liver. Nitric oxide (NO) molecule has many important functions in human body including phagocytosis in macrophages, neural transmission and endothelial relaxation. Although there is no data in literature that depicts the role of NO in HPS pathogenesis, this study was conducted in order to evaluate the potential role of NO in patients with HPS.Patients and methodsThe study participants included 24 HPS patients and 20 healthy controls. The median age of HPS and control patients was 41.2 ± 13.9 and 46.5 ± 12.4 years, respectively. NO was predicted as nitric oxide metabolites (NOx) by Griess reaction after transformation of nitrate to nitrite by nitrate reductase using the commercially obtainable Nitric Oxide Assay Kit.ResultsSerum NOx levels were 2.69 ± 2.98 μmol/L and 0.85 ± 1.05 μmol/L for the HPS patients and controls, respectively. Serum NO levels were significantly higher in patients with HPS compared to the control group (p < 0.001). ROC curve analysis suggested that the optimum NOx cut-off point for HPS was 1.305 with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 83.3%, 90 %, 90.9 %, and 81.8% respectively.ConclusionCirculating NO concentration was notably higher in patients with HPS in comparison to the control group. Our study verified that an elevated level of NO might have a role in the pathogenesis of HPS.     

Ursolic acid regulates aging process through enhancing of metabolic sensor proteins level

We previously reported that Ursolic Acid (UA) ameliorates skeletal muscle performance through satellite cells proliferation and cellular energy status. In studying the potential role of the hypothalamus in aging, we developed a strategy to pursue UA effects on the hypothalamus anti-aging proteins such as; SIRT1, SIRT6, PGC-1β and α-Klotho.In this study, we used a model of aging animals (C57BL/6). UA dissolved in Corn oil (20 mg/ml) and then administrated (200 mg/Kg i.p injection) to mice, twice daily for 7 days. After treatment times, the mice perfused and the hypothalamus isolated for preparing of tissue to Immunofluorescence microscopy.The data illustrated that UA significantly increased SIRT1 (∼3.5 ± 0.3 folds) and SIRT-6 (∼1.5 ± 0.2 folds) proteins overexpression (P< 0.001). In addition, our results showed that UA enhanced α-Klotho (∼3.3 ± 0.3) and PGC-1β (∼2.6 ± 0.2 folds) proteins levels (P < 0. 01). In this study, data were analyzed using SPSS 16 (ANOVA test).To the best of our knowledge, it seems that UA through enhancing of anti-aging biomarkers (SIRT1 and SIRT6) and PGC-1β in hypothalamus regulates aging-process and attenuates mitochondrial-related diseases. In regard to the key role of α-Klotho in aging, our data indicate that UA may be on the horizon to forestall diseases of aging.     

Dual-task as a predictor of falls in older people with mild cognitive impairment and mild Alzheimer's disease: a prospective cohort study

Background

A dual-task tool with a challenging and daily secondary task, which involves executive functions, could facilitate the screening for risk of falls in older people with mild cognitive impairment or mild Alzheimer's disease.

HDL 2 Particles are associated with hyperglycaemia,lower PON1 activity and oxidative stress in type 2 diabetes mellitus patients

ObjectivesIn this study we examined the relationship of oxidative stress and hyperglycaemia to antioxidative capacity of high-density cholesterol (HDL-C) particles in type 2 diabetes mellitus (DM).Design and methodsOxidative stress status parameters (superoxide anion (O₂^?), superoxide dismutase (SOD) activity and paraoxonase (PON1) status were assessed in 114 patients with type 2 DM and 91 healthy subjects. HDL particle diameters were determined by non-denaturing polyacrylamide gradient (3–31%) gel electrophoresis.ResultsPatients had significantly higher concentrations of oxidative stress parameter O₂^?(p < 0.001) and antioxidative defence, SOD activity (p < 0.001). Paraoxonase activity was significantly lower in diabetics (p < 0.001). The PON1₁₉₂ phenotype distribution among study groups was not significantly different. HDL 3 phenotype was significantly prevalent among patients (p < 0.001). Paraoxonase activity was significantly lower in patients with predominantly HDL 2 particles than in controls.ConclusionsThe results of our current study indicate that the diabetic HDL 2 phenotype is associated with hyperglycaemia, lower PON1 activity and elevated oxidative stress.     

Factors affecting exercise program adherence in patients with acute hip fracture and impact on one-year survival

ObjectiveTo study the adherence of an Early Inpatient Exercise Program in patients with acute hip fracture, identify variables associated with its performance, and its association to one-year survival.MethodsObservational longitudinal study of a cohort of 509 patients, admitted consecutively with a hip fracture in La Paz University Hospital (Madrid, Spain). Data included sociodemographic variables, pre-fracture physical functioning, cognitive impairment, comorbidities, measure of exercise adherence (pre-surgery exercise, post-surgery exercise, and rehabilitation sessions) and vital status at follow-up. One year after the fracture, either patients or relatives were contacted by telephone to ascertain their vital status. Data were analyzed using logistic regressions and multivariate Cox proportional hazards regression.ResultsThree quarters of patients (76.0%) were able to comply with the Early Inpatient Exercise Program. Factors associated with adherence were: living at home (Odds Ratio (OR) = 3.39; 95% Confidence Interval (CI): 2.03, 5.64), absence of pre-fracture disability (OR = 3.78; 95% CI: 2.21, 6.47), absence of pre-fracture cognitive impairment (OR = 2.36; 95% CI: 1.36, 4.07) and comorbidities (OR = 1.66; 95% CI: 1.03, 2.67). Early Inpatient Exercise Program adherence was associated with one-year survival (HR = 1.62; 95% CI: 1.06, 2.49).ConclusionsThe adherence with an Early Inpatient Exercise Program is high and is associated with 1-year survival. It is important to make a stronger effort to encourage participation in Early Inpatient Exercise Program in the 24% currently non-compliant, and in those with cognitive and physical impairments.     

A sex comparison of reactive knee stiffness regulation strategies under cognitive loads

BackgroundSex differences may exist in cognitive faculties and neuromuscular strategies for maintaining joint stability. The purpose of this study was to assess whether preparatory and reactive knee stiffening strategies are affected differently in males and females exposed to sex-biased cognitive loads.Methods20 male and 20 female volunteers were tested for knee joint stiffness and quadriceps and hamstring muscle activation patterns throughout a rapid eccentric knee extension perturbation. Participants were tested under 3 cognitive loads (Benton's Judgment of Line Orientation; Symbol Digit modalities Test; and Serial 7's) and a control condition. Apparent knee joint stiffness and muscle activation amplitude and timing were quantified throughout the perturbation across the 4 conditions.FindingsReactive knee stiffness values were significantly less during the cognitive tasks compared to the control condition (Judgment of Line Orientation = 0.034 Nm/deg/kg, Symbol Digit Modalities Test = 0.037 Nm/deg/kg, Serial 7's = 0.037 Nm/deg/kg, control = 0.048 Nm/deg/kg). Females had greater normalized total apparent stiffness than males. The quadriceps muscles had faster and greater activation than the hamstring muscles; however, no group differences were observed. No overall differences in muscle activation (magnitude and timing) were found between the cognitive loading tasks.InterpretationCognitive loading may decrease the ability of healthy individuals to reactively stiffen their knee joint and appears to interfere with the normal stiffness regulation strategies. This may elucidate an extrinsic risk factor for non-contact knee ligament injury.     

Identification of amyloid plaques in retinas from Alzheimer's patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model

Noninvasive monitoring of β-amyloid (Aβ) plaques, the neuropathological hallmarks of Alzheimer's disease (AD), is critical for AD diagnosis and prognosis. Current visualization of Aβ plaques in brains of live patients and animal models is limited in specificity and resolution. The retina as an extension of the brain presents an appealing target for a live, noninvasive optical imaging of AD if disease pathology is manifested there. We identified retinal Aβ plaques in postmortem eyes from AD patients (n = 8) and in suspected early stage cases (n = 5), consistent with brain pathology and clinical reports; plaques were undetectable in age-matched non-AD individuals (n = 5). In APP_SWE/PS1_?E9 transgenic mice (AD-Tg; n = 18) but not in non-Tg wt mice (n = 10), retinal Aβ plaques were detected following systemic administration of curcumin, a safe plaque-labeling fluorochrome. Moreover, retinal plaques were detectable earlier than in the brain and accumulated with disease progression. An immune-based therapy effective in reducing brain plaques, significantly reduced retinal Aβ plaque burden in immunized versus non-immunized AD mice (n = 4 mice per group). In live AD-Tg mice (n = 24), systemic administration of curcumin allowed noninvasive optical imaging of retinal Aβ plaques in vivo with high resolution and specificity; plaques were undetectable in non-Tg wt mice (n = 11). Our discovery of Aβ specific plaques in retinas from AD patients, and the ability to noninvasively detect individual retinal plaques in live AD mice establish the basis for developing high-resolution optical imaging for early AD diagnosis, prognosis assessment and response to therapies.