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INTRODUCTION: Cerebral amyloid angiopathy (CAA) is a main cause of cognitive dysfunction in the elderly. We investigated specific cognitive profiles, cognitive function in the stage before intracerebral hemorrhage (ICH), and the association between magnetic resonance imaging (MRI) based cerebral small vessel disease (cSVD) burden in CAA because data on these topics are limited. METHODS: We included Dutch‐type hereditary CAA (D‐CAA) mutation carriers with and without ICH, patients with sporadic CAA (sCAA), and age‐matched controls. Cognition was measured with a standardized test battery. Linear regression was performed to assess the association between MRI‐cSVD burden and cognition. RESULTS: D‐CAA ICH− mutation carriers exhibited poorer global cognition and executive function compared to age‐matched controls. Patients with sCAA performed worse across all cognitive domains compared to D‐CAA ICH+ mutation carriers and age‐matched controls. MRI‐cSVD burden is associated with decreased processing speed. DISCUSSION: CAA is associated with dysfunction in multiple cognitive domains, even before ICH, with increased MRI‐cSVD burden being associated with slower processing speed. Highlights: Cognitive dysfunction is present in early disease stages of cerebral amyloid angiopathy (CAA) before the occurrence of symptomatic intracerebral hemorrhage (sICH).Presymptomatic Dutch‐type CAA (D‐CAA) mutation carriers show worse cognition than age‐matched controls.More early awareness of cognitive dysfunction in CAA before first sICH is needed.Increased cerebral small vessel disease CAA‐burden on magnetic resonance imaging is linked to a decrease in processing speed. [ABSTRACT FROM AUTHOR]

Background and Purpose: Data on health‐related quality of life (HRQoL) and mood in cerebral amyloid angiopathy (CAA), a disease characterized by stroke and cognitive decline, are limited. We aimed to investigate the impacted domains of life, value‐based HRQoL and the prevalence of depression and anxiety in patients with CAA. Methods: We conducted a cross‐sectional study of patients with sporadic (s)CAA, lobar dominant mixed CAA and hypertensive arteriopathy (mixed CAA‐HTA), or Dutch‐type hereditary (D‐)CAA, from prospective outpatient clinic cohorts. Participants completed four questionnaires: the EuroQoL 5 dimensions 5‐level questionnaire (EQ‐5D‐5L; EQ‐VAS for visual analogue scale; EQ‐Index for index rating), the Short‐Form 36 questionnaire (SF‐36), the Center for Epidemiologic Studies—Depression scale (CES‐D), and the Hospital Anxiety and Depression Scale (HADS; ‐D for depression and ‐A for anxiety subscales). The EQ‐5D‐5L assesses the domains mobility, self‐care, usual activities, pain/discomfort and anxiety/depression. The SF‐36 domains are physical functioning, social functioning, physical role limitations, emotional role limitations, mental health, vitality, bodily pain, and general health perceptions. We compared age‐ and sex‐ adjusted HRQoL (SF‐36 domain scores; EQ‐VAS; EQ‐Index) to the Dutch normative population, and estimated the prevalences of current depression (either: history of depression or current use of antidepressants, with high score on CES‐D [≥16] and/or HADS‐D [≥8]; or high score on both depression questionnaires) and anxiety (HADS‐A ≥ 8). Results: We included 179 patients: 77 with sCAA (mean age: 72 years, women: 36%), 31 with mixed CAA‐HTA (68 years, women: 29%), and 71 with D‐CAA (56 years, women: 52%, symptomatic: 35 [49%]). The SF‐36 profiles of all patient groups were similar, negatively differing from the norm in emotional role functioning, social functioning and vitality. The EQ‐VAS score of patients (mean [SD] sCAA: 76 [16], D‐CAA: 77 [15]) was similar to the norm, as was the EQ‐Index score. Fifteen patients with sCAA (23%; 95% confidence interval [CI] 13%–33%), seven with mixed CAA‐HTA (27%; 95% CI 10%–44%) and eight with D‐CAA (14%; 95% CI 5%–22%) were noted as having depression. The prevalences of anxiety and depression were equivalent. Conclusions: We found that CAA influenced emotional role functioning and aspects linked to social engagement consistently across its subtypes. One quarter of patients exhibited depressive or anxiety symptoms. Recognizing these impacted domains could enhance overall well‐being. [ABSTRACT FROM AUTHOR]

The main objective of most clinical trials is to estimate the effect of some treatment compared to a control condition. We define the signal‐to‐noise ratio (SNR) as the ratio of the true treatment effect to the SE of its estimate. In a previous publication in this journal, we estimated the distribution of the SNR among the clinical trials in the Cochrane Database of Systematic Reviews (CDSR). We found that the SNR is often low, which implies that the power against the true effect is also low in many trials. Here we use the fact that the CDSR is a collection of meta‐analyses to quantitatively assess the consequences. Among trials that have reached statistical significance we find considerable overoptimism of the usual unbiased estimator and under‐coverage of the associated confidence interval. Previously, we have proposed a novel shrinkage estimator to address this "winner's curse." We compare the performance of our shrinkage estimator to the usual unbiased estimator in terms of the root mean squared error, the coverage and the bias of the magnitude. We find superior performance of the shrinkage estimator both conditionally and unconditionally on statistical significance. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim was to evaluate the effect of anti‐calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies on depressive symptoms in subjects with migraine and to determine whether depressive symptoms predict treatment response. Methods: Patients with migraine treated with erenumab and fremanezumab at the Leiden Headache Centre completed daily E‐headache diaries. A control group was included. Depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Center for Epidemiological Studies Depression Scale (CES‐D) questionnaires at baseline (T0) and after 3 months (T1). First, the effect of treatment on the reduction in HADS‐D and CES‐D scores was assessed, with reduction in depression scores as the dependent variable and reduction in monthly migraine days (MMD) and treatment with anti‐CGRP medication as independent variables. Second, depression as a predictor of treatment response was investigated, using the absolute reduction in MMD as a dependent variable and age, gender, MMD, active depression, impact, stress and locus of control scores as independent variables. Results: In total, n = 108 patients were treated with erenumab, n = 90 with fremanezumab and n = 68 were without active treatment. Treatment with anti‐CGRP medication was positively associated with a reduction in the HADS‐D (β = 1.65, p = 0.01) compared to control, independent of MMD reduction. However, the same effect was not found for the CES‐D (β = 2.15, p = 0.21). Active depression predicted poorer response to erenumab (p = 0.02) but not to fremanezumab (p = 0.09). Conclusion: Anti‐CGRP (ligand or receptor) monoclonals lead to improvement of depressive symptoms in individuals with migraine, independent of migraine reduction. Depression may predict treatment response to erenumab but not to fremanezumab. [ABSTRACT FROM AUTHOR]

Introduction/Aims: In patients with traumatic radial nerve injury (RNI), the chance of spontaneous recovery must be balanced against the benefits of early surgical reconstruction. We aimed to explore the time‐specific value of needle electromyography (NEMG) to diagnose nerve lesion severity. Methods: In this retrospective diagnostic accuracy study at Leiden Nerve Center, patients at least 12 years of age with RNI caused by fractures or fracture treatment were included. The sensitivity and specificity of the patients' first NEMG examination were assessed, stratified by the timing after the nerve injury. The absence of motor unit potentials (MUPs) in muscles distal to the nerve lesion was considered a positive test result. Lesion severity was dichotomized to moderate injury (spontaneous Medical Research Council grade ≥3 recovery) or severe injury (poor spontaneous recovery or surgical confirmation of a mainly neurotmetic lesion). Results: Ninety‐five patients were included in our study. The sensitivity of NEMG to detect severe RNI was 75.0% (3 of 4) in the fourth, 66.7% (2 of 3) in the fifth, and 66.7% (2 of 3) in the sixth month after the nerve injury. The specificity in the first to the sixth month was 0.0% (0 of 1), 50.0% (2 of 4), 77.3% (17 of 22), 95.5% (21 of 22), 95.8% (23 of 24), and 100.0% (12 of 12), respectively. Discussion: The specificity of NEMG is higher than 95% and therefore clinically relevant from the fourth month after the nerve injury onward. Absence of MUPs at this time can be considered an indication to plan nerve exploration. Moreover, the presence of MUPs on NEMG does not completely exclude the necessity for surgical reconstruction. [ABSTRACT FROM AUTHOR]

We use information derived from over 40K trials in the Cochrane Collaboration database of systematic reviews (CDSR) to compute the replication probability, or predictive power of an experiment given its observed (two‐sided) P$$ P $$‐value. We find that an exact replication of a marginally significant result with P=.05$$ P=.05 $$ has less than 30% chance of again reaching significance. Moreover, the replication of a result with P=.005$$ P=.005 $$ still has only 50% chance of significance. We also compute the probability that the direction (sign) of the estimated effect is correct, which is closely related to the type S error of Gelman and Tuerlinckx. We find that if an estimated effect has P=.05$$ P=.05 $$, there is a 93% probability that its sign is correct. If P=.005$$ P=.005 $$, then that probability is 99%. Finally, we compute the required sample size for a replication study to achieve some specified power conditional on the p$$ p $$‐value of the original study. We find that the replication of a result with P=.05$$ P=.05 $$ requires a sample size more than 16 times larger than the original study to achieve 80% power, while P=.005$$ P=.005 $$ requires at least 3.5 times larger sample size. These findings confirm that failure to replicate the statistical significance of a trial does not necessarily indicate that the original result was a fluke. [ABSTRACT FROM AUTHOR]

Background and purpose: Medication overuse headache is a prevalent disorder, with a strong biobehavioural component. Hence, behavioural interventions might effectuate reduction of the overused medication. We assessed in a double‐blind manner the efficacy of a behavioural intervention during medication withdrawal therapy. Methods: In this concealed, double‐blind, randomized controlled trial in medication overuse headache, conducted at the Leiden University Medical Centre, we compared the effect of maximal versus minimal behavioural intervention by a headache nurse during withdrawal therapy. Maximal intervention consisted of an intensive contact schedule, comprising education, motivational interviewing, and value‐based activity planning during 12 weeks of withdrawal therapy. Minimal intervention consisted of a short contact only. Patients were unaware of the existence of these treatment arms, as the trial was concealed in another trial investigating botulinum toxin A. Endpoints were successful withdrawal and monthly days of acute medication use after the withdrawal period. Results: We enrolled 179 patients (90 maximal, 89 minimal intervention). At Week 12, most patients achieved withdrawal in both groups (82/90 [93%] maximal intervention vs. 75/89 [86%] minimal intervention, odds ratio = 2.44, 95% confidence interval [CI] = 0.83–7.23, p = 0.107). At Week 24, patients in the maximal intervention group had fewer medication days (mean difference = −2.23, 95% CI = −3.76 to −0.70, p = 0.005). This difference receded over time. Change in monthly migraine days did not differ between groups (−6.75 vs. −6.22). Conclusions: This trial suggests modest benefit of behavioural intervention by a headache nurse during withdrawal therapy for medication overuse headache, to reduce acute medication use during and shortly after intervention, but extension seems warranted for a prolonged effect [ABSTRACT FROM AUTHOR]

Introduction/Aims: Duchenne and Becker muscular dystrophies (DMD and BMD, respectively) are characterized by fat replacement of different skeletal muscles in a specific temporal order. Given the structural role of dystrophin in skeletal muscle mechanics, muscle architecture could be important in the progressive pathophysiology of muscle degeneration. Therefore, the aim of this study was to assess the role of muscle architecture in the progression of fat replacement in DMD and BMD. Methods: We assessed the association between literature‐based leg muscle architectural characteristics and muscle fat fraction from 22 DMD and 24 BMD patients. Dixon‐based magnetic resonance imaging estimates of fat fractions at baseline and 12 (only DMD) and 24 months were related to fiber length and physiological cross‐sectional area (PCSA) using age‐controlled linear mixed modeling. Results: DMD and BMD muscles with long fibers and BMD muscles with large PCSAs were associated with increased fat fraction. The effect of fiber length was stronger in muscles with larger PCSA. Discussion: Muscle architecture may explain the pathophysiology of muscle degeneration in dystrophinopathies, in which proximal muscles with a larger mass (fiber length × PCSA) are more susceptible, confirming the clinical observation of a temporal proximal‐to‐distal progression. These results give more insight into the mechanical role in the pathophysiology of muscular dystrophies. Ultimately, this new information can be used to help support the selection of current and the development of future therapies. [ABSTRACT FROM AUTHOR]

The "significance filter" refers to focusing exclusively on statistically significant results. Since frequentist properties such as unbiasedness and coverage are valid only before the data have been observed, there are no guarantees if we condition on significance. In fact, the significance filter leads to overestimation of the magnitude of the parameter, which has been called the "winner's curse." It can also lead to undercoverage of the confidence interval. Moreover, these problems become more severe if the power is low. These issues clearly deserve our attention. They have been studied mostly through empirical observation and simulation, while there are relatively few mathematical results. Here we study them both from the frequentist and the Bayesian perspective. We prove that the relative bias of the magnitude is a decreasing function of the power and that the usual confidence interval undercovers when the power is less than 50%. We conclude that it is important to apply the appropriate amount of shrinkage to counter the winner's curse. [ABSTRACT FROM AUTHOR]

Background: Meralgia paresthetica is a mononeuropathy of the lateral femoral cutaneous nerve. A common therapy is injection with corticosteroids. The goal of this study was to analyze the effect of injection with methylprednisolone/lidocaine vs placebo.Methods: After randomization, 10 patients received a nerve stimulator-guided injection with methylprednisolone/lidocaine, and 10 patients received saline. The primary outcome measure was pain (visual analogue scale, VAS).Results: In the placebo group, there was a significant pain reduction (baseline VAS, 6.8; VAS week 12, 4.3; P = .014). The VAS score in the methylprednisolone group did not show a significant reduction (baseline VAS, 7.4; VAS week 12, 4.8; P = .053). There was no significant difference in pain reduction between the groups.Conclusions: We found no objective evidence for benefit from nerve stimulator-guided injection with corticosteroids in meralgia paresthetica, although this study is limited by a small sample size. Future placebo-controlled studies using ultrasound-guided injection are warranted. [ABSTRACT FROM AUTHOR]

Background: Cluster headache attacks follow a striking circadian rhythm with an intriguing influence of sleep. We aim to investigate differences in sleep quality, chronotype, and the ability to alter individual sleep rhythms in episodic and chronic cluster headache patients vs controls. Methods: Cluster headache patients and non‐headache controls from the Dutch Leiden University Cluster headache neuro‐Analysis program aged 18 and above completed web‐based questionnaires in a cross‐sectional study. Results: A total of 478 episodic, 147 chronic cluster headache patients and 367 controls participated. Chronic cluster headache patients had more often early chronotypes than controls, as measured by mid‐sleep phase (P =.021 adjusted B −15.85 minutes CI −29.30; −2.40). Compared to controls, chronic cluster headache participants were less able to alter their sleep rhythms (P <.001 adjusted B −1.65 CI −2.55; 0.74), while episodic cluster headache participants reported more difficulty in coping with reduced sleep (P =.025 adjusted B 0.75 CI 0.09; 1.40). Sleep quality was reduced in both types of cluster headache compared to controls ("poor sleepers": 71.4% (105/147) in chronic and 48.3% (235/367) in episodic cluster headache vs 25.6% (94/367) in controls; both P <.001; episodic adjusted B −1.71 CI 0.10; 0.32; chronic adjusted B −0.93 CI 0.24; 0.65). Conclusion: Sleep quality is decreased in both episodic and chronic cluster headache, most likely caused by cluster headache attacks that strike during the night. Episodic cluster headache patients report more difficulty in coping with reduced sleep, while chronic patients are less able to alter their sleep rhythm. Although not directly proven, cluster headache patients will likely benefit from a structured, regular daily schedule. [ABSTRACT FROM AUTHOR]

Introduction: It is unknown how fluctuations in muscle weakness affect activity limitations in myasthenia gravis patients and how the severity of these limitations compares with published data on other neuromuscular disorders (NMD).Methods: In this study we analyzed ACTIVLIM (acronym of "ACTIVity LIMitations") and quantitative myasthenia gravis (QMG) scores. We assessed the impact of QMG and other clinical variables on ACTIVLIM, using B coefficients.Results: The mean ACTIVLIM score in 118 MG patients was 3.3. There was a correlation between QMG and ACTIVLIM (B coefficient = -0.206, P < 0.001) and between changes in both scores (B coefficient = -0.175, P = 0.002). Men and patients without another autoimmune disease had a better ACTIVLIM score (B coefficient = 0.785, P = 0.015 and B coefficient = 0.998, P = 0.008, respectively).Conclusions: The ACTIVLIM score in MG is higher than in other NMD. Fluctuations in QMG correlated significantly with changes in ACTIVLIM. Muscle Nerve 56: 64-70, 2017. [ABSTRACT FROM AUTHOR]

Objective To identify a learning curve and monitor operator performance for fetoscopic laser surgery for twin-to-twin transfusion syndrome using cumulative sum analysis. Design Retrospective cohort study. Setting National tertiary referral center for invasive fetal therapy. Population A total of 340 consecutive monochorionic pregnancies with twin-to-twin transfusion syndrome treated with fetoscopic laser coagulation between August 2000 and December 2010. Methods A learning curve was generated using learning curve cumulative sum analysis and cumulative sum methodology to assess changes in double survival across the case sequence. Laser surgery was initially performed by two operators, joined by a third and fourth operator after 1 and 2 years, respectively. Main outcome measures Individual operator performance, double perinatal survival at 4 weeks. Results Overall survival of both twins occurred in 59% (201/340), median gestational age at birth was 32.0 weeks. Cumulative sum graphs showed that level of competence for double survival for the operators was reached after 26, 25, 26, and 35 procedures, respectively. Two operators kept their competence level and continued to improve after completing the initial learning process; two others went out of control at one point in time, according to the cumulative sum boundaries. A difference in learning effect was associated with number of procedures performed annually and previous experience with other ultrasound-guided invasive procedures. Conclusions This study shows that all operators reached a level of competence after at least 25 fetoscopic laser procedures and confirms the value of using the cumulative sum method both for learning curve assessment and for ongoing quality control. [ABSTRACT FROM AUTHOR]

Motor disturbances can be present in both manifest and premanifest Huntington's disease (HD). We aimed to investigate the role of motor functioning on executive functioning to better understand the progression of cognitive dysfunction in HD. Forty patients with manifest HD, 21 patients with premanifest HD, and a group of 28 controls were tested twice with a 1-year interval. For the Symbol Digit Modalities Test and the Figure Fluency Test, extra conditions were designed to measure motor involvement. Subtraction of this motor score from the original test score resulted in isolation of the cognitive component. Groups were compared on motor, cognitive, and original test scores using multilevel regression analysis. Manifest patients had lower baseline scores of 0.53 standard deviations (SD) on the original Symbol Digit Modalities Test (P = 0.03) and 0.71 SD on the motor isolation part (P = 0.006), and they showed a deterioration of 0.47 SD over 1 year of follow-up on the original Symbol Digit Modalities Test (P = 0.001) compared with controls. Premanifest patients had lower baseline scores of 0.67 SD on the Symbol Digit Modalities motor part (P = 0.008) and deterioration of 0.48 SD on the original (P = 0.001) and cognitive isolation (P = 0.02) parts. Secondary analyses revealed that the premanifest deterioration resulted from the close-to-predicted-onset group. Motor disturbances have a negative influence on performance on the Symbol Digit Modalities Test. Isolation of the cognitive component of this test revealed cognitive deterioration in the premanifest group only, caused by deteriorating scores for patients who were close to their predicted clinical disease onset. The Figure Fluency Test did not prove sensitive to cognitive change. © 2014 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Aim Treatment decisions in obstetric brachial plexus lesions are often based on clinical paralysis of elbow flexion at 3 months of age, when electromyography (EMG) is misleading because motor unit potentials (MUPs) occur in clinically paralytic muscles. We investigated whether EMG at 1 week or 1 month identifies infants with flexion paralysis at 3 months, allowing early referral. Method Forty-eight infants (27 females, 21 males) were prospectively studied. The presence or absence of flexion paralysis at around 1 week (median 9d; range 5-17d), 1 month (median 31d; range 24-53d), and 3 months of age (median 87d; range 77-106d) was noted for clinical (shoulder external rotation, elbow flexion, extension, and supination) and EMG parameters (denervation activity, MUPs and polyphasic MUPs in the deltoid, biceps, and triceps muscles). Results At 1 month, the absence of biceps MUPs had a sensitivity of 95% for later flexion paralysis, and absence of deltoid MUPs had a sensitivity of 100% for flexion paralysis; the false-positive rates for the same findings were 21% and 33% respectively. EMG at 3 months was highly misleading as MUPs were seen in 19 of 20 clinically paralytic biceps muscles. Interpretation EMG at 1 month can identify severe cases of flexion paralysis for early referral EMG of the biceps at 3 months is highly misleading; the discrepancy between the EMG and clinical testing may be due to abnormal axonal branching and aberrant central motor control. [ABSTRACT FROM AUTHOR]

The SCOPA-Cognition is a reliable and valid test to evaluate cognitive functioning in Parkinson's disease and is widely used in clinical and research settings. Recently, the Movement Disorder Society introduced criteria for Parkinson's disease dementia. The objective of the present study was to use these criteria to determine SCOPA-Cognition cutoffs for maximum accuracy, screening, and diagnosing of Parkinson's disease dementia. A total of 282 patients with Parkinson's disease were assessed with the SCOPA-Cognition and the Movement Disorder Society's Parkinson's disease dementia criteria. From the 275 patients with a complete assessment of the dementia criteria, 12% (n = 32) fulfilled the criteria. Data from 268 patients with complete assessments of both the dementia criteria and the SCOPA-Cognition were used to determine cutoffs for maximum accuracy, screening, and diagnosing of Parkinson's disease dementia. The area under the curve was 0.91 (95% confidence interval, 0.85-0.97), showing a strong association between the dementia criteria and the SCOPA-Cognition. The cutoff for maximum accuracy was 22/23, based on the highest sum of sensitivity (0.80) and specificity (0.87), with positive and negative predictive values of 0.43 and 0.97, respectively. The optimal screening cutoff was 24/25, and the optimal diagnostic cutoff was 17/18. Using the recently published Parkinson's disease dementia criteria as a reference, the current study presents SCOPA-Cognition cutoffs for maximum accuracy, screening, and diagnosing of Parkinson's disease dementia. The availability of SCOPA-Cognition cutoffs for Parkinson's disease dementia may contribute to the scale's usefulness and promote its further use in both clinical and research settings. © 2011 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Aim: We assessed the influence of system messages (SyMs) on oxygen saturation (SpO2 ) and heart rate measurements after birth to see whether clinical decision-making changed if clinicians included SyM data., Methods: The heart rate and SpO2 of term infants were recorded using Masimo pulse oximeters. Differences in means and standard deviations (SD) were calculated. Permutation corrected the nonrandom distribution and intersubject variation. SpO2 and heart rate centile charts were computed with, and without, SyMs., Results: Pulse oximetry measurements from 117 neonates provided 28 477 data points. SyMs occurred in 46% of measurements. Low signal quality accounted for 99.9% of SyMs. The mean SpO2 was lower with SyMs (p < 0.001), while the SpO2 SD was similar to data without SyMs. The SpO2 centile charts were approximately 2% lower with SyMs included, but they were not more dispersed. Mean heart rate was lower (p < 0.001) and more dispersed (p < 0.001) when a SyM occurred. The heart rate centile charts were lower, with increased variability, when SyMs were included., Conclusion: A SyM occurred frequently during pulse oximetry in term infants after birth. SpO2 measurements with low signal quality proved reliable for monitoring an infant's clinical condition. However, heart rate could be underestimated by low signal quality measurements., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Earlier research has found cross-sectional attentional control deficits in manifest Huntington's disease (HD) using neuropsychological testing combined with simultaneous P300 registration. In the current pilot-study, we investigate attentional control in pre-manifest and manifest HD over a 3-year follow-up period., Method: Five manifest HD (MHD), 9 pre-manifest HD (PMHD), and 12 control subjects were included. Sustained Attention to Response task (SART) and P300 registration resulted in number of errors, reaction time (RT), and P300 amplitude and latency. RT change patterns surrounding No-go trials were also investigated. Within-subject differences were tested using paired-samples t-tests and between-group results with ANCOVA on delta scores (follow-up--baseline scores)., Results: Manifest HD made more errors and were slower than controls and PMHD. Longitudinally, MHD showed an overall RT increase and a specific slowing on trials preceding a correct No-go trial (within-group effects). The latter was also seen in PMHD. P300 latency prolongation was found for controls on No-go and for MHD on Go trials. On specific trials surrounding both correct and incorrect No-go trials, MHD became significantly slower over time than controls and PMHD (between-group effects)., Conclusions: Over 3-years, MHD subjects became slower on the SART and showed a prolongation of P300 latency on specific SART trials. Specific slowing of performance over time was also seen in PMHD, suggestive of compensatory mechanisms in this group., (© 2013 The British Psychological Society.)

The bodily decline that occurs with advancing age strongly impacts on the prospects for future health and life expectancy. Despite the profound role of age in disease etiology, knowledge about the molecular mechanisms driving the process of aging in humans is limited. Here, we used an integrative network-based approach for combining multiple large-scale expression studies in blood (2539 individuals) with protein-protein Interaction (PPI) data for the detection of consistently coexpressed PPI modules that may reflect key processes that change throughout the course of normative aging. Module detection followed by a meta-analysis on chronological age identified fifteen consistently coexpressed PPI modules associated with chronological age, including a highly significant module (P = 3.5 × 10(-38)) enriched for 'T-cell activation' marking age-associated shifts in lymphocyte blood cell counts (R(2) = 0.603; P = 1.9 × 10(-10)). Adjusting the analysis in the compendium for the 'T-cell activation' module showed five consistently coexpressed PPI modules that robustly associated with chronological age and included modules enriched for 'Translational elongation', 'Cytolysis' and 'DNA metabolic process'. In an independent study of 3535 individuals, four of five modules consistently associated with chronological age, underpinning the robustness of the approach. We found three of five modules to be significantly enriched with aging-related genes, as defined by the GenAge database, and association with prospective survival at high ages for one of the modules including ASF1A. The hereby-detected age-associated and consistently coexpressed PPI modules therefore may provide a molecular basis for future research into mechanisms underlying human aging., (© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Background: Patients with type 1 diabetes have altered sleep characteristics and are thought to have deficits in sustained attention. We compared the sustained attention to response task (SART) of patients with type 1 diabetes to that of healthy controls, and related results with sleep characteristics and disease-related factors., Methods: SART was applied in 122 patients and 109 controls. Glucoregulation was assessed by HbA1c values and a questionnaire assessing glycaemic history. Clinical parameters were obtained from medical charts. Polyneuropathy was assessed by neurological examination and quantitative sensory testing. Sleep characteristics were assessed with sleep questionnaires. Anxiety and depression scores were assessed by the Hospital Anxiety and Depression Scale., Results: The SART reaction time (RT) was significantly longer than in controls (327 ± 5 vs. 285 ± 3 ms, p < 0.001), although there were no significant differences in error scores. Repeated measurement analyses showed that diabetes per se was associated with prolonged RT (p < 0.001) and more commission errors (p = 0.010). None of the sleep-related and diabetes-related factors were significantly associated with these SART parameters., Conclusions: Patients with type 1 diabetes had impaired sustained attention, which was associated with diabetes per se but not with disturbed sleep characteristics., (Copyright © 2013 John Wiley & Sons, Ltd.)