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Purpose Whole brain radiation therapy (WBRT) remains a commonly used cancer treatment, although controversy exists regarding the optimal dose/fractionation to optimize intracranial tumor control and minimize resultant cognitive deficits. Methods and Materials NCCTG N107C [Alliance]/CEC.3 randomized 194 patients with brain metastases to either stereotactic radiosurgery alone or WBRT after surgical resection. Among the 92 patients receiving WBRT, sites predetermined the dose/fractionation that would be used for all patients treated at that site (either 30 Gy in 10 fractions or 37.5 Gy in 15 fractions). Analyses were performed using Kaplan-Meier estimates, log rank tests, and Fisher’s exact tests. Results Among 92 patients treated with surgical resection and adjuvant WBRT, 49 were treated with 30 Gy in 10 fractions (53%), and 43 were treated with 37.5 Gy in 15 fractions (47%). Baseline characteristics, including cognitive testing, were well balanced between groups with the exception of primary tumor type (lung cancer histology was more frequent with protracted WBRT: 72% vs 45%, P = .01), and 93% of patients completed the full course of WBRT. A more protracted WBRT dose regimen (37.5 Gy in 15 fractions) did not significantly affect time to cognitive failure (hazard ratio [HR], 0.9; 95% confidence interval [CI], 0.6-1.39; P = .66), surgical bed control (HR, 0.52 [95% CI, 0.22-1.25], P = .14), intracranial tumor control (HR, 0.56 [95% CI, 0.28-1.12], P = .09), or overall survival (HR, 0.72 [95% CI, 0.45-1.16], P = .18). Although there was no reported radionecrosis, there is a statistically significant increase in the risk of at least 1 grade ≥3 adverse event with 37.5 Gy in 15 fractions versus 30 Gy in 10 fractions (54% vs 31%, respectively, P = .03). Conclusions This post hoc analysis does not demonstrate that protracted WBRT courses reduce the risk of cognitive deficit, improve tumor control in the hypoxic surgical cavity, or otherwise improve the therapeutic ratio. Adverse events were significantly higher with the lengthened course of WBRT. For patients with brain metastases where WBRT is recommended, shorter course hypofractionated regimens remain the current standard of care.

The neurodevelopmental impact of fentanyl given to preterm newborns for pain control is still unknown. The aim of this study was to assess the neurodevelopmental impact of 2 regimens of fentanyl administration by a prospective follow-up evaluation. In our previous multicenter, double-blind, randomized controlled trial, 131 mechanically ventilated newborns (gestational age ≤32 weeks) were randomized to fentanyl (continuous infusion of fentanyl + open label boluses of fentanyl) or placebo (continuous infusion of placebo + open label boluses of fentanyl). Infant development was evaluated using Griffiths Mental Developmental Scales (Griffiths, 1996) until 24 months of corrected age by trained psychologists who were not aware of the group allocation. 106/131 infants survived at discharge; 3 died after discharge, 25 were lost to follow-up (12 in the fentanyl and 13 in the placebo group). Seventy-eight patients were evaluated at 2 years of corrected age. Children in the fentanyl group, compared with those in the placebo group, obtained significantly lower Griffiths general developmental quotient (mean [SD]: 89.95 [13.64] vs 97.18 [12.72], P = 0.024) together with the scores on the eye-hand coordination (mean [SD]: 89.09 [12.13] vs 99.19 [13.19], P = 0.002) and performance skills (mean [SD]: 79.71 [15.80] vs 90.09 [15.28], P = 0.009) scales. After adjustment for clinical confounders (gestational age, CRIB score, and sex) only eye-hand co-ordination was associated with fentanyl infusion. This study demonstrates that continuous infusion of fentanyl in very preterm infants, given at 1 mcg·kg·h during mechanical ventilation, is associated with a significant decrease in eye and hand co-ordination skills. Longer follow-up is needed to evaluate the impact on future motor, cognitive, and behavioral functions.

Background: Parkinsonian syndromes are characterized by a wide spectrum of non-motor symptoms. A few studies explored cognitive deficits and neuropsychiatric symptoms in atypical parkinsonism compared to Parkinson’s disease (PD). The study was performed to identify cognitive and neuropsychiatric differences between PD, multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) and to evaluate the influence of clinical features, depressive symptomatology and apathy on cognitive performances in the three groups. Methods: Fifty-five PD, 44 MSA and 42 PSP patients underwent cognitive tests assessing attention, language, memory, visuospatial and executive functions as well as scales assessing depression and apathy. Out of these patients, 20 PD, 20 MSA and 20 PSP patients were selected to be matched for age, education and global cognitive status. Within each whole patients group, correlational analysis was performed between clinical, behavioural and cognitive parameters. Results: The main difference among the groups matched was on cognitive tests exploring verbal learning, executive and linguistic functions. The PSP group was more impaired than the PD and MSA groups on cognitive tests assessing executive functions. On the other hand, MSA group obtained similar cognitive performance to the PD group. As to behavioural symptoms, in whole PSP and MSA groups, apathy and depression were more severe than in PD group, while apathy (but not depression) were more severe in the PSP group as compared to the MSA group. Conclusions: The present study underlined the pervasiveness of cognitive deficits, apathy and depressive symptoms in PSP, whereas little cognitive differences were found between PD and MSA. The findings indirectly supported a dysfunction of prefronto-subcortical circuitries (i.e., dorsolateral prefrontal and limbic circuits) in PSP and PD. Cognitive similarities between MSA and PD reinforced the pivotal role of altered basal ganglia and corresponding frontal deafferentation in the occurrence of the cognitive deficits.

The cooccurrence of Marfan syndrome and psychiatric disorders has been reported for many years. Furthermore, neuropsychological deficits have been shown to be associated with Marfan syndrome. The aim of the present article is to summarize findings from the sparse studies and case reports available. The results hold clinical and therapeutic implications and suggest that psychological and neuropsychological domains in Marfan syndrome patients should be carefully assessed. In particular, some patients may require specific rehabilitation programs. On this basis, a multidisciplinary approach to Marfan syndrome treatment seems mandatory.

Background: Defining reliable markers of conversion to dementia could be the first step in order to identify appropriate treatment strategies for mild cognitive impairment (MCI) patients. Objective: To develop a tool able to predict the risk of progression from MCI to Alzheimer's disease (AD). Methods: 406 MCI patients were included and followed for a one-year period. Demographic characteristics, vascular risk factors, extent of cerebrovascular lesions, markers of carotid atherosclerosis investigated with an ultrasonographic assessment (plaque index and intima-media thickness) and cerebrovascular reactivity to apnea (breath-holding index) were considered as potential predictors of conversion. Results: 106 (26%) MCI patients showed a conversion to AD. Plaque index, intima-media thickness, and breath-holding index were relevant predictors of conversion (p = 0.042; p = 0.003; p < 0.001, multivariate logistic regression analysis). A simplified scoring system was devised based on the magnitude of the estimated multinomial logistic regression β coefficient results. A total score was calculated as the sum of each predictive factor which resulted in a 0-5 range. The optimal cut-off score was ≥3 (sensitivity, 23.6%, 95% CI 15.9%-32.8%; specificity, 97.7%, 95% CI 95.3%-99.1%; positive likelihood ratio, 10.1, 95% CI 4.5%-22.7%; negative likelihood ratio, 0.78, 95% CI 0.70%-0.87%). The AUC was 0.71 (95% CI, 0.65-0.77). Conclusions: Our findings show the possibility to obtain a predictive indicator of the risk of conversion from MCI to dementia by considering the presence of both atherosclerotic changes in the carotid district and impairment of cerebral hemodynamics. Such an approach may allow us to formulate a correct prognosis in more than 70% of patients with amnesic MCI.

Abstract— Elevated systolic blood pressure (SBP) correlates to cognitive decline and incident dementia. The effects of heart rate (HR), visit to visit HR variation, and visit to visit SBP variation are less well established. Patients without preexisting cognitive dysfunction (N=24 593) were evaluated according to mean SBP, SBP visit to visit variation (coefficient of variation [standard deviation/mean×100%], CV), mean HR, and visit to visit HR variation (HR-CV) in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease. Cognitive function was assessed with mini mental state examination. Cognitive dysfunction (fall in mini mental state examination ≤24 points), important cognitive decline (drop of ≥5 points), and cognitive deterioration (drop of >1 point per year or decline to < 24 points) were assessed. SBP and HR were measured over 10.7±2.2 (mean±SD) visits. Mean SBP, mean HR, and SBP-CV were associated with cognitive decline, dysfunction, and deterioration (all P P =0.0030) and mean HR ( P =0.0008) remained predictors for cognitive dysfunction (odds ratios [95% confidence intervals], 1.32 [1.10–1.58] for 5th versus 1st quintile of SBP-CV and 1.40 [1.18–1.66] for 5th versus 1st quintile of mean HR). Similar effects were observed for cognitive decline and deterioration. SBP-CV and mean HR showed additive effects. In conclusion, SBP-CV and mean HR are independent predictors of cognitive decline and cognitive dysfunction in patients at high CV risk. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT 00153101.

Objective The study aimed to explore premorbid academic and social functioning in patients with schizophrenia, and its associations with the severity of negative symptoms and neurocognitive impairment. Method Premorbid adjustment (PA) in patients with schizophrenia was compared to early adjustment in unaffected first-degree relatives and healthy controls. Its associations with psychopathology, cognition, and real-life functioning were investigated. The associations of PA with primary negative symptoms and their two factors were explored. Results We found an impairment of academic and social PA in patients (P ≤ 0.000001) and an impairment of academic aspects of early adjustment in relatives (P ≤ 0.01). Patients with poor PA showed greater severity of negative symptoms (limited to avolition after excluding the effect of depression/parkinsonism), working memory, social cognition, and real-life functioning (P ≤ 0.01 to ≤0.000001). Worse academic and social PA were associated with greater severity of psychopathology, cognitive impairment, and real-life functioning impairment (P ≤ 0.000001). Regression analyses showed that worse PA in the academic domain was mainly associated to the impairment of working memory, whereas worse PA in the social domain to avolition (P ≤ 0.000001). Conclusion Our findings suggest that poor early adjustment may represent a marker of vulnerability to schizophrenia and highlight the need for preventive/early interventions based on psychosocial and/or cognitive programs.

Objective: In a driving simulation, we investigated the efficacy of galvanic cutaneous stimulation (GCS) provided during curves or intermittently during the whole circuit to mitigate simulator syndrome (SS). Background: The literature on how GCS decreases SS, although scarce, has demonstrated the effectiveness of this technique. Stimulation with this and similar techniques has usually been provided in curves or continuously during the whole circuit but never intermittently. This stimulation method could generate a continued activation of processes related to GCS mitigating SS. Method: Fifteen drivers (8 men; mean age = 25.5 years) participated in this experiment. We compared the total scores of the Simulator Sickness Questionnaire (SSQ) across three stimulation conditions: (a) curve GCS condition, whereby GCS was provided in curves; (b) intermittent GCS condition, whereby GCS was provided intermittently during the whole circuit; and (c) no-stimulation condition, whereby no stimulation was provided (baseline condition). Results: The experimental outcomes revealed that GCS decreased SS in both the curve and intermittent stimulation conditions. Conclusion: We provide evidence that GCS is an effective countermeasure to decrease SS. It could be applied indifferently in curves or intermittently during the whole circuit. Application: For future interventions, we recommend the use of GCS to mitigate SS with similar intermittent stimulation programs. These programs have a crucial advantage as they are easily integrated into the simulator setup without the necessity of generating a complicated experimental design to stimulate during the curves.

Objective and background The interplay between motor and cognitive functions during performance of concurrent tasks is not fully understood but is known to vary depending on task characteristics and across clinical populations. Our controlled study examined how a concurrent digit span task affected a motor stability and motor overflow task in patients with multiple sclerosis (MS). Method We asked 22 patients with MS and 22 matched controls to exert force on a transducer using 1 index finger at a time. We measured their motor stability (accuracy of voluntary force production) and motor overflow (involuntary force produced by the opposite, inactive finger). During half of the trials, the participants concurrently performed a digit span task. Results Overall, the patients with MS had more motor overflow and less motor stability than the controls; these measures correlated with the patients' disease severity. Adding the concurrent task affected motor stability; this relationship varied with the required level of exerted force. Motor overflow was lower during trials with the concurrent task. The concurrent task affected patients and controls similarly for both motor stability and overflow. Conclusions This study demonstrates preserved motor function in a concurrent-task paradigm in patients with MS, and sheds further light on the relationship between attention and motor function in both the patients and controls. This research may help to inform rehabilitation for everyday life situations in which patients routinely perform cognitive and motor tasks simultaneously.

Background and purpose: Cognitive impairment is common in Parkinson's disease (PD), even in the early stages. We aimed to assess the relationship between insulin-like growth factor-1 (IGF-1) and cognitive functions in early, drug-naïve patients with PD. Methods: Serum IGF-1 was measured in 65 early, drug-naïve patients with PD that underwent a complete neuropsychological battery at baseline and after 2years. Linear regression analysis was used to evaluate the relationships between neuropsychological scores and IGF-1. Repeated-measures anova was applied to assess changes in neuropsychological variables over time. Results: At baseline, IGF-1 levels were related to phonological fluency. At follow-up, IGF-1 levels were associated with the Rey auditory verbal learning test (RAVLT) - immediate and delayed recall, Frontal Assessment Battery, verbal span and Benton judgement of the line orientation test. Patients with low IGF-1 levels at baseline showed a significantly faster decline of performances than patients with high IGF-1 levels on immediate and delayed recall of the RAVLT and interference task of the Stroop test. Conclusions: Low serum IGF-1 levels are related to poor performance on executive tasks in early, drug-naïve patients with PD, and may predict poor performance on attention/executive and verbal memory tasks after a 2-year follow-up. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Background: The contribution of monocyte activation in the development of HIV-associated neurocognitive disorders is not completely understood. This study aimed to explore the predictive value of peripheral monocyte/macrophage (M/M) phenotypes on the evolution of cognitive performance in a population of virologically suppressed HIV-infected patients. Setting: Prospective, observational, longitudinal study. Methods: HIV-1-infected patients with HIV-RNA 12 months underwent neuropsychological examination at baseline and after 1 year. Cognitive performance was evaluated using Z-transformed scores, and neurocognitive impairment (NCI) was defined according to Frascati criteria. Peripheral M/M phenotypes (classic CD14 ++ CD16 -, intermediate CD14 ++ CD16 +, and nonclassic CD14 + CD16 ++) and specific surface activation markers (eg, CD163, CD11b, and CD38) were evaluated using flow cytometry at baseline. Predictive value of peripheral M/M phenotypes on the evolution of cognitive performance over 1-year follow-up was also evaluated. Results: Overall, 54 patients [85.2% men, median age 50 years (range 27-60 years), 27.8% hepatitis C virus coinfected, 48.1% with past AIDS-defining events, median nadir CD4 83 cells/L (range 1-334), median baseline CD4 547 cells/L (range 136-1652)] were enrolled. Proportion of patients with NCI was low, accounting for 13% at baseline and 16.5% after 1 year (P = 0.687). Memory was the only single domain in which decreased performance after 1 year was observed (-0.25 Z-score, P = 0.025). In patients with significant decrease (≥0.5 SD) in memory performance (n = 20), significantly lower CD14 ++ CD16 + CD163 + (% CD14 ++ CD16 +) (P = 0.038) and higher CD14 + CD38 + (% CD14 +) (P = 0.030) levels were observed. Conclusions: In virologically suppressed HIV-infected patients, the evolution of memory performance could be linked to the expression of certain peripheral activated M/M phenotypes. Such associations should be verified in larger populations over the long term.

Objective: Cognitive deficits are common in Parkinson’s disease (PD) since the early stages and many patients eventually develop dementia. Yet, occurrence of dementia in PD is unpredictable. Evidence supports the hypothesis that insulin-like growth factor-1 (IGF-1) is involved in cognitive deficits. Our aim was to evaluate the relationship between serum IGF-1 levels and neuropsychological scores in a large cohort of drug-naïve PD patients during the earliest stages of the disease. Methods: Serum IGF-1 levels were determined in 405 early, drug-naïve PD patients and 191 healthy controls (HC) enrolled in the Parkinson’s Progression Markers Initiative (PPMI). The association between serum IGF-1 levels and neuropsychological scores was evaluated with linear regression analysis. Results: IGF-1 levels were similar in PD and HC. In PD patients the lowest IGF-1 quartile was a predictor of lower performances at the Semantic Fluency task (β = -3.46, 95%CI: -5.87 to -1.01, p = 0.005), the Symbol Digit Modalities Score (β = -2.09, 95%CI: -4.02 to -0.15, p = 0.034), and Hopkins Verbal Learning Test Retention (β = -0.05, 95%CI: -0.09 to -0.009, p = 0.019). Conclusions: Lower serum IGF-1 levels are associated to poor performances in cognitive tasks assessing executive function, attention and verbal memory in a large cohort of early PD patients. Follow-up studies are warranted to assess if IGF-1 is related to the development of dementia in PD.

International audience; OBJECTIVE: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry.METHODS: We assessed a cohort of participants at risk with RESULTS: Of 12,190 participants, 657 (5.38%) with CONCLUSIONS: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling.CLINICALTRIALSGOV IDENTIFIER: NCT01590589.

Background The discrepancy between subjective and objective severity of depressive syndromes has been proposed as a predictor of treatment outcome and suicidal risk in depression, and is associated with depressive cognitive distortions. A recent study reported that evening-type depressed patients showed higher depressive cognitions than morning-type patients. Therefore, it can be hypothesized that genetic factors affecting evening preference, such as carrying of the CLOCK rs1801260*C allele, may influence the discrepancy. Method We tested this hypothesis in 132 patients affected by a major depressive episode in the course of bipolar disorder. The severity of depression was evaluated using self-rated (Beck Depression Inventory: BDI) and observer-rated (Hamilton Depression Rating Scale: HDRS) measures. The BDI-HDRS discrepancy score was calculated and the effects of the rs1801260 polymorphism on this score and on depressive cognitive distortions, as measured on the Cognitions Questionnaire, were examined. Results The rs1801260*C carriers showed higher BDI-HDRS discrepancy scores than T/T homozygotes. Mediation analysis using bootstrapping procedures revealed that the dimension of depressive cognition “hopelessness” fully mediates the association between the rs1801260 polymorphism and the BDI-HDRS discrepancy. Limitations Many gene polymorphisms other than CLOCK rs1801260 may also influence the BDI-HDRS discrepancy and depressive cognitive distortions. Conclusion Our current results suggest that factors affecting the biological clock can influence the “non-clock” psychopathological features of mood disorders.

The relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and serum ACE activity, as well as amnestic mild cognitive impairment (aMCI), was investigated. The study recruited 90 aMCI patients and 90 matched healthy controls. All subjects underwent an extensive assessment of cognitive function. The ACE gene I/D genotype was determined by polymerase chain reaction. Serum ACE activity was measured using a spectrophotometric technique. The scores obtained by the aMCI patients on the neuropsychological tests were significantly lower than those of the control subjects (all p0.01). The genotype (χ(2)=11.510) and allele (χ(2)=6.945) frequencies of the ACE gene were significantly different between the aMCI and the control groups (all p0.01). The DD genotype (23%) and D-allele (57%) frequencies in the aMCI patients were higher than those in the controls (16% vs. 43%). ACE genotype was correlated with delayed recall in Auditory Verbal Memory Test, delayed recall in Complex Figure Test, Category Fluency Test, and Symbol Digit Modalities Test in all subjects, in which the carriers of the DD and DI genotypes obtained lower scores than those of the II genotype (p0.05). A significant difference in the serum ACE level was observed among the three genotypes (DDDIII) in both the aMCI and the control groups (all p0.01). D-allele may be a genetic risk factor for the development of aMCI to Alzheimer's disease. A high serum ACE level possibly plays an important role in the incidence of aMCI.

Previous studies on the association between poststroke cognitive impairment and quality of life (QoL) have shown divergent results. In this study, we investigated the relationships between cognitive functioning and various QoL domains at 1 year poststroke. This was a cross-sectional study, examining 92 patients at 1 year poststroke. Cognitive functioning was measured with a neuropsychological test battery covering language, attention and psychomotor function, memory, visuoperception, and neglect. QoL domains were functional independence (Barthel Index), social participation (Frenchay Activities Index), depressive mood (Center for Epidemiological Studies Depression Scale), and life satisfaction (Life Satisfaction Questionnaire). Bivariate and multivariate relationships between cognitive and QoL variables were analyzed, the latter both with and without controlling for demographic variables and motor impairment. The prevalence of cognitive impairments varied between 19.3% (neglect) and 72% (attention and psychomotor function). Correlations between cognitive functioning and QoL were strongest for social participation (0.41-0.60, P

Blast-related head injuries are one of the most prevalent injuries among military personnel deployed in service of Operation Iraqi Freedom. Although several studies have evaluated symptoms after blast injury in military personnel, few studies compared them to nonblast injuries or measured symptoms within the acute stage after traumatic brain injury (TBI). Knowledge of acute symptoms will help deployed clinicians make important decisions regarding recommendations for treatment and return to duty. Furthermore, differences more apparent during the acute stage might suggest important predictors of the long-term trajectory of recovery. This study evaluated concussive, psychological, and cognitive symptoms in military personnel and civilian contractors (N = 82) diagnosed with mild TBI (mTBI) at a combat support hospital in Iraq. Participants completed a clinical interview, the Automated Neuropsychological Assessment Metric (ANAM), PTSD Checklist-Military Version (PCL-M), Behavioral Health Measure (BHM), and Insomnia Severity Index (ISI) within 72 hr of injury. Results suggest that there are few differences in concussive symptoms, psychological symptoms, and neurocognitive performance between blast and nonblast mTBIs, although clinically significant impairment in cognitive reaction time for both blast and nonblast groups is observed. Reductions in ANAM accuracy were related to duration of loss of consciousness, not injury mechanism. (JINS, 2011, 17, 000–000)

Introduction After minor head injury (MHI), post-concussive symptoms commonly occur. The purpose of this study was to correlate the severity of post-concussive symptoms in MHI patients with MRI measures of microstructural brain injury, namely mean diffusivity (MD) and fractional anisotropy (FA), as well as the presence of microhaemorrhages. Methods Twenty MHI patients and 12 healthy controls were scanned at 3 T using diffusion tensor imaging (DTI) and high-resolution gradient recalled echo (HRGRE) T2*-weighted sequences. One patient was excluded from the analysis because of bilateral subdural haematomas. DTI data were preprocessed using Tract Based Spatial Statistics. The resulting MD and FA images were correlated with the severity of post-concussive symptoms evaluated with the Rivermead Postconcussion Symptoms Questionnaire. The number and location of microhaemorrhages were assessed on the HRGRE T2*-weighted images. Results Comparing patients with controls, there were no differences in MD. FA was decreased in the right temporal subcortical white matter. MD was increased in association with the severity of post-concussive symptoms in the inferior fronto-occipital fasciculus (IFO), the inferior longitudinal fasciculus and the superior longitudinal fasciculus. FA was reduced in association with the severity of post-concussive symptoms in the uncinate fasciculus, the IFO, the internal capsule and the corpus callosum, as well as in the parietal and frontal subcortical white matter. Microhaemorrhages were observed in one patient only. Conclusions The severity of post-concussive symptoms after MHI was significantly correlated with a reduction of white matter integrity, providing evidence of microstructural brain injury as a neuropathological substrate of the post-concussion syndrome.

Background and purpose: Frontotemporal dementia (FTD) is the second most common neurodegenerative dementia in the young age after Alzheimer disease. Recent improvement in diagnostic assessment suggests that it is more common than previously, although with a great heterogeneity in clinical presentation. The different clinical patterns related to age of disease onset in behavioural variant FTD (bvFTD) have been fairly studied. Aim of the study was to evaluate whether age at disease onset modulate the heterogeneity of either cognitive impairment or behavioural disturbances in patients affected by bvFTD. Methods: One hundred and thirty-four patients with bvFTD entered the study. Age at onset and demographic characteristics were carefully recorded. Each patient underwent a wide neuropsychological and behavioural standardized assessment, as well as a brain SPECT perfusion imaging study. Results: Behavioural variant FTD were subdivided into four groups according to the age at onset. The four quartile groups did not differ for demographic characteristics and family history for dementia. Global cognitive impairment as well as analysis of the different cognitive domains and behavioural patterns were comparable. Conclusions: These findings provide evidence that the clinical heterogeneity of bvFTD is not explained by age at disease onset. Further studies are needed.

Routine screening of cognitive function during a course of electroconvulsive therapy (ECT) is recommended in several guidelines. However, there is little evidence regarding which measures are practical, change early in treatment, and are likely to predict longer term cognitive problems. We aimed to investigate the practicality of early formal cognitive screening in routine clinical practice of ECT.Thirty-three patients aged 25 to 84 years were recruited from 2 ECT clinics. Assessment consisted of the Rey Verbal Learning Test (RAVLT), The Short Form of the Colombia University Autobiographical Memory Interview, Digit Span Forwards and Backwards, and Modified Mini-Mental State Examination (3MSE) and was conducted at baseline, between the third and the fourth treatment of ECT and 2 months after the last treatment. Analysis examined which measures changed after 3 treatments and whether this correlated with change at the 2 month follow-up.After 3 treatments, there was a significant reduction in immediate (F1,27 = 14; P = 0.001) and 30-minute delayed (F1,25 = 34; P0.001) recall of the RAVLT. There was also a significant reduction in autobiographical memory score but no significant change in digit span or 3MSE. There was no correlation between reductions in scores on the RAVLT and The Short Form of the Colombia University Autobiographical Memory Interview, after 3 treatments and reductions at 2 month follow-up.This small pilot study suggests that significant changes in memory function can be detected as early as after 3 treatments of ECT and that such monitoring can be done in routine clinical practice. There was, however, no evidence that these changes correlated with longer term changes.

Aim Children with cognitive impairment experience pain more frequently than healthy children and are more likely to require venipuncture or intravenous cannulation for various procedures. They are frequently unable to report pain and often receive poor pain assessment and management. This study assessed the effectiveness of physical analgesia during vascular access in children with cognitive impairments. Methods We conducted a prospective randomised controlled study at a tertiary-level children's hospital in Italy from April to May 2015 to assess whether a cooling vibration device called Buzzy decreased pain during venipuncture and intravenous cannulation in children with cognitive impairment. None of the children had verbal skills and the main cognitive impairments were cerebral palsy, epileptic encephalopathy and genetic syndromes. Results We tested 70 children with a median age of nine years: 34 in the Buzzy group and 36 in the no-intervention group. Parents were trained in the use of the Noncommunicating Children's Pain Checklist – postoperative version scale, and they reported no or mild procedural pain in 32 cases (91.4%) in the Buzzy group and in 22 cases (61.1%) in the no-intervention group (p = 0.003). Conclusion Cooling vibration analgesia during vascular access reduced pain in children with cognitive impairment.

Background and objective Delirium is an important predictor of negative clinical outcomes in intensive care unit (ICU), including prolonged mechanical ventilation (MV). However, delirium has not yet proven to be directly linked to weaning difficulties. The objective of this cohort study was to evaluate the association between delirium, as observed on the day of the weaning trial, and subsequent weaning outcomes in medical patients. Methods This is a retrospective analysis with prospectively collected data on weaning from mechanical ventilation (MV) and delirium, as assessed by bedside ICU nurses using the Confusion Assessment Method for the ICU (CAM-ICU) between October 2011 and September 2013. Results During the study period, a total of 393 patients with MV support underwent a spontaneous breathing trial (SBT) according to the standardized protocol. Of these patients, 160 (40.7%) were diagnosed with delirium on the day of the first SBT. Patients without delirium were more successfully extubated than those with delirium (81.5% vs 69.4%, P = 0.005). Delirium was found to be associated with final weaning outcomes, including difficult (OR 1.962, 95% CI 1.201–3.205) and prolonged weaning (OR 2.318, 95% CI 1.272–4.226) when simple weaning was used as a reference category. After adjusting for potential confounding factors, delirium was still significantly associated with difficult weaning (adjusted OR 2.073, 95% CI 1.124–3.822), but not with prolonged weaning (adjusted OR 2.001, 95% CI 0.875–4.575). Conclusion Delirium, as assessed by the CAM-ICU at the time of first weaning trial, was significantly associated with weaning difficulties in medical patients.

A gene association study of factors regulating antiviral response such as interferon (IFN)-λ3, also known as IL-28B, mediator complex (Med) 23, and interferon regulatory factor (IRF) 7 with cognitive deterioration and Alzheimer's disease (AD) was performed. Differences in the TT genotype distribution of IL-28B single nucleotide polymorphism (SNP) between AD patients and controls were found. The GG genotype of Med23 gene appeared to influence the progression of the disease, being more frequent in the APOE ɛ4 negative elderly that developed AD during the five year follow-up. Leukocyte positivity for Epstein Barr virus (EBV) and human herpes virus (HHV)-6 DNA was analyzed. Med23 GG genotype correlated with the positivity to HHV-6 DNA. EBV and HHV-6 plasma IgG levels were also investigated and EBV IgG levels were increased in AD with the IRF7 GG genotype. A differential genetic background in genes regulating anti-virus responses was associated with an increased risk of cognitive decline and AD. EBV and HHV-6 appeared to be risk factors for AD in genetically susceptible elderly.

Background: Recently, a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) has been developed as an international and standardized brief cognitive test, which is easily performed in everyday clinical practice for neuropsychological assessment in multiple sclerosis (MS). However, we need to gather more information about this tool compared to other neuropsychological batteries. The aim of our study is to compare the performance of BICAMS and Brief Repeatable Battery (BRB) in MS subjects. Methods: Tests of the BRB and BICAMS were administered to MS patients recruited from 11 Italian MS centres. Cognitive impairment (CI) was defined as the failure on at least two tests (scores below the fifth percentile) on the BRB and as the failure on at least one test of the BICAMS. The agreement between the performances on the two batteries was assessed through Cohen's K statistic. Finally we calculated the effects sizes for each test of the two batteries using Cohen's d. Results: The two batteries were administered to 192 MS patients (142 women, 50 men; mean age 41.4 ± 10.8 years, mean education 12.3 ± 3.5 years). Mean scores of patients were lower compared to those of healthy subjects in all the cognitive measures examined. Forty-six MS patients were identified as impaired and 48 as unimpaired on both of the batteries, when the Symbol Digit Modalities Test (SDMT) was included in the analysis. Cohen's K statistic was 0.46 which corresponds to a moderate accord. If the SDMT was excluded from the BRB, 37 MS patients were identified as impaired and 57 as unimpaired on both of the batteries. Cohen's K statistic was 0.3 which corresponds to a poor accord. The SDMT, the Paced Auditory Serial Addition Test (PASAT) 3 and 2 yielded higher d values (SDMT 0.83, PASAT 3 0.65, PASAT 2 0.84). Conclusions: This study confirms the feasibility of BICAMS in everyday clinical practice for the identification of CI and highlights the good psychometric properties of the SDMT.

This study was designed to determine whether there is a lateralized pattern of cognitive dysfunction in patients with systemic lupus erythematosus (SLE). Fifty right-handed patients with SLE, but no history of cerebrovascular disease participated in the study. Thirty right-handed healthy subjects matched for age and education served as controls. SLE and healthy control subjects underwent a three-hour neuropsychological evaluation designed to measure attention, memory, visual spatial skills, verbal skills reasoning, psychomotor speed, and motor function. A cognitive disability index was created to identify cognitive impairment. Percentile tables based on the performance of all subjects were constructed for 20 component scores. Any subject with five or more component scores below the 25th percentile was designated impaired. Using this criterion, cognitive impairment was identified in 50% of patients with SLE and 20% of healthy controls. Patients with SLE were impaired on measures of psychomotor speed/fluency, verbal speed/fluency and verbal memory. This pattern of performance on neuropsycholgical testing was consistent with left hemisphere brain dysfunction. The observed deficits were not clearly attributable to vascular lesions and suggest immune-mediated effects on specific brain regions in a subgroup of patients with SLE.

Different aspects of episodic long-term, short-term and implicit long-term memory were investigated in subjects who strictly fulfilled the criteria for the amnestic form of Mild Cognitive Impairment (a-MCI). Results showed normal short-term memory abilities in these subjects, while each of the episodic long-term memory indices explored showed poorer results in a-MCI subjects with respect to normal controls. Although some episodic memory functions were relatively well preserved, others appeared to have deteriorated to a level comparable to that of mild AD patients. The finding of an extensive impairment of all memory functions depending on hippocampal structures in a population with a high risk of developing dementia is strongly supportive of the hypothesis that a pure amnesic syndrome characterizes the preclinical phase of AD. Copyright © Taylor & Francis Ltd.

SUMMARY The most diffuse questionnaires on health-related quality of life (HRQL) and/or psychological status (PS) consider all subjects older than 74 years, for normative reference values, in a single group without any further separation for age decades. Their authors assume that there are no further age-related differences, since older patients had a severely limited autonomy and lose the capacity of grading the severity of the diseases they are affected. Healthy subjects older than 80, without mental impairment (WMI) present an acceptable HRQL, PS and a perception of health status. No data are available on the oldest patients, carrying chronic diseases, admitted to hospital departments for acute health problems. We collected 46 WMI oldest patients (≥ 80 years), admitted for such troubles. They were investigated by the mini mental state examination (MMSE) and, in random order, the Nottingham health profile (NHP) and the psychological general well-being instrument (PGWBI). Clinical data recordings were carried out by the medical personnel, using standardized forms. The value of any individual domain of each patient was compared to the age - (≥ 75-year) and sex-matched control group derived from two large Italian population studies, using the Z-score. Charlson's comorbidity index, the index of coexistent disease (ICED), and the cumulative illness rating scale (CIRS) were also calculated. Patients older than 80 did show difference in NHP domains in comparison with normative values only for social isolation, but presented significantly worse Z-scores in all domains of PGWBI. A relationship was observed between number of daily medications and Z-scores of physical mobility and energy (NHP). Similarly, vitality (PGWBI) correlated with all comorbidity indices, ICED with positive well-being (PGWBI), pain (NHP) with CIRS subscales. Hospitalized WMI oldest subjects maintain a HRQL quite comparable to normative group of subjects older than 74 years. Furthermore, they showed a preserved correct perception of factors/diseases that possibly affect their psychological status and autonomy.

Part B of the Trail Making Test (TMT-B) is one of the most widely used neuropsychological tests of “executive” function. A commonly held assumption is that the TMT-B can be used to detect frontal executive dysfunction. However, so far, research evidence has been limited and somewhat inconclusive. In this retrospective study, performance on the TMT-B of 55 patients with known focal frontal lesions, 27 patients with focal non-frontal lesions and 70 healthy controls was compared. Completion time and the number of errors made were examined. Patients with frontal and non-frontal lesions performed significantly worse than healthy controls for both completion time and the number of errors. However, there was no significant difference for both completion time and the number of errors when patients with frontal and non-frontal lesions were compared. Performance was also not significantly different between patients with focal lesions within different regions of the frontal lobe (orbital, left lateral, right lateral, medial). Our findings suggest that the TMT-B is a robust test for detection of brain dysfunction. However, its capacity for detecting frontal executive dysfunction appears rather limited. Clinicians should be cautious when drawing conclusions from performance on the TMT-B alone. (JINS, 2015, 21, 169–174)

Background It is well known that atrial fibrillation (AF) and chronic kidney disease (CKD) are associated with a higher risk of stroke, and new evidence links AF to cognitive impairment, independently from an overt stroke (CI). Our aim was to investigate, assuming an underlying role of atrial microembolism, the impact of CI and CKD in elderly hospitalized patients with AF. Methods We retrospectively analyzed the data collected on elderly patients in 66 Italian hospitals, in the frame of the REPOSI project. We analyzed the clinical characteristics of patients with AF and different degrees of CI. Multivariate logistic analysis was used to explore the relationship between variables and mortality. Results Among the 1384 patients enrolled, 321 had AF. Patients with AF were older, had worse CI and disability and higher rates of stroke, hypertension, heart failure, and CKD, and less than 50% were on anticoagulant therapy. Among patients with AF, those with worse CI and those with lower estimated glomerular filtration rate (eGFR) had a higher mortality risk (odds ratio 1.13, p = 0.006). Higher disability levels, older age, higher systolic blood pressure, and higher eGFR were related to lower probability of oral anticoagulant prescription. Lower mortality rates were found in patients on oral anticoagulant therapy. Conclusions Elderly hospitalized patients with AF are more likely affected by CI and CKD, two conditions that expose them to a higher mortality risk. Oral anticoagulant therapy, still underused and not optimally enforced, may afford protection from thromboembolic episodes that probably concur to the high mortality.

Uric acid (UA) is reduced in multiple sclerosis (MS), and possibly relates to MS outcomes, with lower UA levels in subjects experiencing a relapse or presenting higher disability scores. The present retrospective longitudinal study evaluated UA variations in MS, in relation to clinical relapses, disability progression, and cognitive functions. We included 141 subjects with relapsing-remitting MS (RRMS) and performed expanded disability status scale (EDSS), symbol digit modalities test (SDMT) and UA evaluation at baseline visit and after 2-year follow-up. Paired t test showed significantly lower UA levels after 2-year follow-up than at baseline (3.987 ± 1.135 and 4.167 ± 1.207 mg/dL, respectively) (p = 0.001). The difference in UA levels between 2-year follow-up and baseline related to EDSS sustained progression (p0.001; OR = 0.099), and presented a trend for clinical relapses at logistic regression (p = 0.211; OR = 0.711) and for the time to relapse at Cox regression (p = 0.236; HR = 0.792). Analysis of variance showed reduced baseline UA levels in subjects with impaired SDMT at baseline (p = 0.045; adjusted R(2) = 0.473) and after 2-year follow-up (p = 0.034; adjusted R(2) = 0.470). This is the first study showing a progressive reduction of UA levels during the course of RRMS, suggesting a progressive decrease of antioxidant reserves, in relation to relapse risk, disability progression and cognitive function.

Objective: Differently than Schizophrenia, the investigation of cognitive impairment in bipolar disorder and major depressive disorder (MDD) attracted the interest of research only recently. Therefore, it is worth understanding clinicians perception about cognitive dysfunction in MDD and raising awareness about this issue. Methods: Between December 2014 and January 2015, 128 Italian psychiatrists participated in an on-line survey aiming at understanding psychiatrists perception about cognitive symptoms in MDD. The questionnaire comprised three sections: the first investigating psychiatrists socio-demographic profile, the second assessing cognitive symptoms relevance without mentioning that they represented the study focus and the third explicitly investigating cognitive symptoms. Results: Cognitive symptoms were considered as a relevant dimension of MDD and appeared among the most frequently cited residual symptoms influencing patients work and relapse risk. About 70% of psychiatrists declared that cognitive symptoms significantly influence antidepressant choice. However, in the second questionnaire section cognitive symptoms appeared less frequently considered for antidepressant choice. Conclusions: Results revealed a clear understanding of cognitive symptoms relevance in MDD. Nevertheless, the discrepancy between psychiatrists perception and their therapeutical choices underlines the presence of an unmet-need that should be addressed increasing the awareness about the positive effects on cognitive symptoms of existing drugs, which could allow a more symptom-oriented therapeutical intervention.Key pointsMajor depressive disorder (MDD) is a common mental disorder often associated with deficits in cognitive function.Psychiatrists considered cognitive symptoms among the most relevant residual symptoms in MDD patients that compromise patients working and influence the relapse risk.The importance given to residual cognitive symptoms seemed not to be reflected by psychiatrists therapeutical choice.There is a gap between what psychiatrists know and what psychiatrists apply to their clinical practice reflecting the feeling of a therapeutical unmet need.

Cognitive impairment is a common cause of morbidity in the elderly. The relationship between dietary habits and cognitive impairment in a female population living in the metropolitan area of Naples, in the Mediterranean part of Italy, has been evaluated in the Naples EPIC prospective cohort study. The study cohort, enrolled between 1993 and 1997, is composed of 5062 women aged 30-69 years. At time of enrolment anthropometric measures were performed and information about socio-demographic details, clinical data, lifestyle and dietary habits were collected. During 2008 and 2009, women 65 years of age or older received a telephone interview to evaluate cognitive status (TICS); the derived score was used as proxy of cognitive impairment. Analyses were carried out on 1514 participants. Linear regression model showed negative association between TICS score and, respectively, age at baseline (β = -.31, 95% CI -.34, -.24), body mass index (BMI) (β = -.08, 95% CI -.16, -.01), and glycemic load (GL) (β = -.02, 95% CI -.03, -.01), whereas education level (β = 0.62, 95% CI .56, .69) showed positive association. A logistic regression model, used to evaluate determinants of the low cognitive score (TICS score ≤ 15, 1st tertile), confirmed association for previous variables [age (OR 1.1, 95% CI 1.08, 1.15); BMI (OR 1.03, 95% CI 1.001, 1.07); GL (OR 1.005, 95% CI 1.001, 1.011); education level (OR .82, 95% CI .79, .84)] with, in addition, type II diabetes (OR 1.85, 95% CI 1.014, 3.4). This study indicates that GL may play a role in determining risk of cognitive impairment, besides age, BMI, education and diabetes.

Objectives: To determine the usefulness of physical phenotype of frailty, cognitive impairment, and serum albumin for risk stratification of elderly medical impatients. Design: Prospective, observational cohort study. Setting: A general internal medicine unit of a university hospital in Italy. Participants: Inpatients with an average age of 80.8 ± 7.5 yr (N=470). Measurements: Frailty was defined using the Study of Osteoporotic Fractures Index, a parsimonious version of the physical phenotype (two of the following markers: weight loss, inability to rise five times from a chair, and exhaustion). Two frailty markers from non-physical dimensions were also evaluated: cognitive impairment (Mini-Cog score < 3) and low serum albumin on ward admission (< 3,5 gr/dl). Logistic regression adjusted for preadmission and admission-related confounders was used to investigate whether the physical phenotype of frailty and the two non-physical markers were associated with ward length of stay and unfavorable discharge (death plus any other ward discharge disposition different from direct return home). Areas Under the receiver operating characteristic Curve (AUCs) and Likelihood Ratios (LRs) were used for evaluation of discriminatory ability and clinical usefulness of significant predictors. Results: The physical phenotype of frailty was associated with both study outcomes (p

Several studies indicate that school-age children with specific language impairment (SLI) have difficulties with tasks that rely on executive functions. Whether executive function deficits in children with SLI emerge during preschool age remains unclear. Our aim was to fill this gap by investigating executive function performances in two age groups of preschoolers with and without SLI. Children with SLI (N = 60; young: 53.6 ± 5.3 months; old: 65.4 ± 3.8 months) and age-matched control children (N = 58) were tested for problem-representation ability, using the Flexible Item Selection Task (FIST), rule-use skills, using a Stroop-like Day–Night test (D/N), and planning skills, using the Tower of London test (TOL). Older children performed better than younger children did across tasks. Children with SLI had poorer performance, compared to typically developing children, on measures of problem representation, planning skills, and use of rules. Our results clearly indicate that executive function impairment is evident during the preschool period. Although old children with SLI performed better than young children with SLI, their performances were still poor, compared to those of control peers. These findings suggest that children with SLI have altered executive functioning at 53.6 months.

Digital technologies have opened new opportunities for psychological testing, allowing new computerized testing tools to be developed and/or paper and pencil testing tools to be translated to new computerized devices. The question that rises is whether these implementations may introduce some technology-specific effects to be considered in neuropsychological evaluations. Two core aspects have been investigated in this work: the efficacy of tests and the clinical ecology of their administration (the ability to measure real-world test performance), specifically (1) the testing efficacy of a computerized test when response to stimuli is measured using a touch-screen compared to a conventional mouse-control response device; (2) the testing efficacy of a computerized test with respect to different input modalities (visual versus verbal); and (3) the ecology of two computerized assessment modalities (touch-screen and mouse-control), including preference measurements of participants. Our results suggest that (1) touch-screen devices are suitable for administering experimental tasks requiring precise timings for detection, (2) intrinsic nature of neuropsychological tests should always be respected in terms of stimuli presentation when translated to new digitalized environment, and (3) touch-screen devices result in ecological instruments being proposed for the computerized administration of neuropsychological tests with a high level of preference from elderly people.

A reduced risk of Alzheimer’s disease (AD) associated with the apolipoprotein E (APOE) Ε4 allele is reported in populations of African origin. In order to clarify possible reasons for this, we examined the association between APOE genotype and early cognitive impairment in a community-based African Caribbean UK population aged 55–75 years. APOE genotype was available for 202 participants, 57 (28%) of whom were classified as having relative cognitive impairment on a battery of neuropsychological tests. Cognitive impairment was negatively associated with Ε2 and positively but more weakly associated with Ε4. Effects of both alleles increased markedly after age 70. The effect of Ε4 was increased in combination with hypertension, diabetes or lower educational attainment, but these factors did not influence Ε2 effects. Cholesterol and triglyceride levels partially explained effects of Ε2, but did not account for those of Ε4. A reduced association between Ε4 and later AD in populations of African origin is unlikely to be explained by reduced cognitive effects or by differential mortality. However, it may be accounted for by vascular comorbidity. The different patterns of association between Ε2 and Ε4 alleles suggest different pathways of effect.

none 330 Women live longer and outnumber men. On the other hand, older women develop more chronic diseases and conditions such as arthritis, osteoporosis and depression, leading to a greater number of years of living with disabilities. The aim of this study was to describe whether or not there are gender differences in the demographic profile, disease distribution and outcome in a population of hospitalized elderly people.Retrospective observational study including all patients recruited for the REPOSI study in the year 2010. Analyses are referred to the whole group and gender categorization was applied.A total of 1380 hospitalized elderly subjects, 50.5\% women and 49.5\% men, were considered. Women were older than men, more often widow and living alone or in nursing homes. Disease distribution showed that malignancy, diabetes, coronary artery disease, chronic kidney disease and chronic obstructive pulmonary disease were more frequent in men, but hypertension, osteoarthritis, anemia and depression were more frequent in women. Severity and comorbidity indexes according to the Cumulative Illness Rating Scale (CIRS-s and CIRS-c) were higher in men, while cognitive impairment evaluated by the Short Blessed Test (SBT), mood disorders by the Geriatric Depression Scale (GDS) and disability in daily life measured by Barthel Index (BI) were worse in women. In-hospital and 3-month mortality rates were higher in men.Our study showed a gender dimorphism in the demographic and morbidity profiles of hospitalized elderly people, emphasizing once more the need for a personalized process of healthcare. none S. Corrao;P. Santalucia;C. Argano;C. D. Djade;E. Barone;M. Tettamanti;L. Pasina;C. Franchi;T. K. Eldin;A. Marengoni;F. Salerno;M. Marcucci;P. M. Mannucci;A. Nobili; and R. E. P. collaborators; Mannucci M; Nobili A; Tettamanti M; Pasina L; Franchi C; Salerno F; Corrao S; Marengoni A; Marcucci M; Sparacio E; Alborghetti S; Di Costanzo R; Tettamanti M; Djignefa Djade C; Prisco D; Silvestri E; Cenci C; Barnini T; Delitala G; Carta S; Atzori S; Guarnieri G; Zanetti M; Spalluti A; Serra MG; Bleve MA; Vanoli M; Grignani G; Casella G; Gasbarrone L; Maniscalco G; Gunelli M; Tirotta D; Brucato A; Ghidoni S; Bernardi M; Bassi SL; Santi L; Agnelli G; Iorio A; Marcucci M; Marchesini E; Mannarino E; Lupattelli G; Rondelli P; Paciullo F; Fabris F; Carlon M; Turatto F; Baroni MC; Zardo M; Manfredini R; Molino C; Pala M; Fabbian F; Nuti R; Valenti R; Ruvio M; Cappelli S; Paolisso G; Rizzo MR; Laieta MT; Salvatore T; Sasso FC; Utili R; Durante Mangoni E; Pinto D; Olivieri O; Stanzial AM; Fellin R; Volpato S; Fotini S; Barbagallo M; Dominguez L; Plances L; D'Angelo D; Rini G; Mansueto P; Pepe I; Licata G; Calvo L; Valenti M; Borghi C; Strocchi E; Rinaldi ER; Zoli M; Fabbri E; Magalotti D; Auteri A; Pasqui AL; Puccetti L; Laghi Pasini F; Capecchi PL; Bicchi M; Sabbà C; Vella FS; Marseglia A; Luglio CV; Palasciano G; Modeo ME; Aquilino A; Raffaele P; Pugliese S; Capobianco C; Postiglione A; Barbella MR; De Stefano F; Fenoglio L; Brignone C; Bracco C; Giraudo A; Musca G; Cuccurullo O; Cricco L; Fiorentini A; Cappellini MD; Fabio G; Seghezzi S; De Amicis MM; Fargion S; Bonara P; Bulgheroni M; Lombardi R; Magrini F; Massari F; Tonella T; Peyvandi F; Tedeschi A; Rossio R; Moreo G; Ferrari B; Roncari L; Monzani V; Savojardo V; Folli C; Magnini M; Mari D; Rossi PD; Damanti S; Prolo S; Lilleri MS; Cricco L; Fiorentini A; Micale G; Podda M; Selmi C; Meda F; Salerno F; Accordino S; Conca A; Monti V; Corazza GR; Miceli E; Lenti MV; Padula D; Balduini CL; Bertolino G; Provini S; Quaglia F; Murialdo G; Bovio M; Dallegri F; Ottonello L; Quercioli A; Barreca A; Secchi MB; Ghelfi D; Chin WS; Carassale L; Caporotundo S; Anastasio L; Carbone M; Traisci G; De Feudis L; Davì G; Guagnano MT; Sestili S; Bergami E; Rizzioli E; Cagnoni C; Bertone L; Manucra A; Buratti A; Tognin T; Liberato NL; Bernasconi G; Nardo B; Bianchi GB; Benetti G; Quagliolo M; Centenaro GR; Purrello F; Di Pino A; Piro S; Mancuso G; Calipari D; Bartone M; Gullo F; Cortellaro M; Magenta M; Perego F; Meroni MR; Cicardi M; Magenta AG; Sacco A; Bonelli A; Dentamaro G; Rozzini R; Falanga L; Giordano A; Perin PC; Lorenzati B; Gruden G; Bruno G; Montrucchio G; Greco E; Tizzani P; Fera G; Di Luca ML; Renna D; Perciccante A; Coralli A; Tassara R; Melis D; Rebella L; Menardo G; Bottone S; Sferrazzo E; Ferri C; Striuli R; Scipioni R; Salmi R; Gaudenzi P; Gamberini S; Ricci F; Morabito C; Fava R; Semplicini A; Gottardo L; Delitala G; Carta S; Atzori S; Vendemiale G; Serviddio G; Forlano R; Bolondi L; Rasciti L; Serio I; Masala C; Mammarella A; Raparelli V; Rossi Fanelli F; Delfino M; Amoroso A; Violi F; Basili S; Perri L; Serra P; Fontana V; Falcone M; Landolfi R; Grieco A; Gallo A; Zuccalà G; Franceschi F; De Marco G; Chiara C; Marta S; Bellusci M; Setti D; Pedrazzoli F; Romanelli G; Pirali C; Amolini C; Rosei EA; Rizzoni D; Castoldi L; Picardi A; Gentilucci UV; Mazzarelli C; Gallo P; Guasti L; Castiglioni L; Maresca A; Squizzato A; Contini S; Molaro M; Annoni G; Corsi M; Zazzetta S; Bertolotti M; Mussi C; Scotto R; Ferri MA; Veltri F; Arturi F; Succurro E; Sesti G; Gualtieri U; Perticone F; Sciacqua A; Quero M; Bagnato C; Loria P; Becchi MA; Martucci G; Fantuzzi A; Maurantonio M; Corinaldesi R; De Giorgio R; Serra M; Grasso V; Ruggeri E; Carozza LM; Pignatti F) S. Corrao;P. Santalucia;C. Argano;C. D. Djade;E. Barone;M. Tettamanti;L. Pasina;C. Franchi;T. K. Eldin;A. Marengoni;F. Salerno;M. Marcucci;P. M. Mannucci;A. Nobili; and R. E. P. collaborators; Mannucci M; Nobili A; Tettamanti M; Pasina L; Franchi C; Salerno F; Corrao S; Marengoni A; Marcucci M; Sparacio E; Alborghetti S; Di Costanzo R; Tettamanti M; Djignefa Djade C; Prisco D; Silvestri E; Cenci C; Barnini T; Delitala G; Carta S; Atzori S; Guarnieri G; Zanetti M; Spalluti A; Serra MG; Bleve MA; Vanoli M; Grignani G; Casella G; Gasbarrone L; Maniscalco G; Gunelli M; Tirotta D; Brucato A; Ghidoni S; Bernardi M; Bassi SL; Santi L; Agnelli G; Iorio A; Marcucci M; Marchesini E; Mannarino E; Lupattelli G; Rondelli P; Paciullo F; Fabris F; Carlon M; Turatto F; Baroni MC; Zardo M; Manfredini R; Molino C; Pala M; Fabbian F; Nuti R; Valenti R; Ruvio M; Cappelli S; Paolisso G; Rizzo MR; Laieta MT; Salvatore T; Sasso FC; Utili R; Durante Mangoni E; Pinto D; Olivieri O; Stanzial AM; Fellin R; Volpato S; Fotini S; Barbagallo M; Dominguez L; Plances L; D'Angelo D; Rini G; Mansueto P; Pepe I; Licata G; Calvo L; Valenti M; Borghi C; Strocchi E; Rinaldi ER; Zoli M; Fabbri E; Magalotti D; Auteri A; Pasqui AL; Puccetti L; Laghi Pasini F; Capecchi PL; Bicchi M; Sabbà C; Vella FS; Marseglia A; Luglio CV; Palasciano G; Modeo ME; Aquilino A; Raffaele P; Pugliese S; Capobianco C; Postiglione A; Barbella MR; De Stefano F; Fenoglio L; Brignone C; Bracco C; Giraudo A; Musca G; Cuccurullo O; Cricco L; Fiorentini A; Cappellini MD; Fabio G; Seghezzi S; De Amicis MM; Fargion S; Bonara P; Bulgheroni M; Lombardi R; Magrini F; Massari F; Tonella T; Peyvandi F; Tedeschi A; Rossio R; Moreo G; Ferrari B; Roncari L; Monzani V; Savojardo V; Folli C; Magnini M; Mari D; Rossi PD; Damanti S; Prolo S; Lilleri MS; Cricco L; Fiorentini A; Micale G; Podda M; Selmi C; Meda F; Salerno F; Accordino S; Conca A; Monti V; Corazza GR; Miceli E; Lenti MV; Padula D; Balduini CL; Bertolino G; Provini S; Quaglia F; Murialdo G; Bovio M; Dallegri F; Ottonello L; Quercioli A; Barreca A; Secchi MB; Ghelfi D; Chin WS; Carassale L; Caporotundo S; Anastasio L; Carbone M; Traisci G; De Feudis L; Davì G; Guagnano MT; Sestili S; Bergami E; Rizzioli E; Cagnoni C; Bertone L; Manucra A; Buratti A; Tognin T; Liberato NL; Bernasconi G; Nardo B; Bianchi GB; Benetti G; Quagliolo M; Centenaro GR; Purrello F; Di Pino A; Piro S; Mancuso G; Calipari D; Bartone M; Gullo F; Cortellaro M; Magenta M; Perego F; Meroni MR; Cicardi M; Magenta AG; Sacco A; Bonelli A; Dentamaro G; Rozzini R; Falanga L; Giordano A; Perin PC; Lorenzati B; Gruden G; Bruno G; Montrucchio G; Greco E; Tizzani P; Fera G; Di Luca ML; Renna D; Perciccante A; Coralli A; Tassara R; Melis D; Rebella L; Menardo G; Bottone S; Sferrazzo E; Ferri C; Striuli R; Scipioni R; Salmi R; Gaudenzi P; Gamberini S; Ricci F; Morabito C; Fava R; Semplicini A; Gottardo L; Delitala G; Carta S; Atzori S; Vendemiale G; Serviddio G; Forlano R; Bolondi L; Rasciti L; Serio I; Masala C; Mammarella A; Raparelli V; Rossi Fanelli F; Delfino M; Amoroso A; Violi F; Basili S; Perri L; Serra P; Fontana V; Falcone M; Landolfi R; Grieco A; Gallo A; Zuccalà G; Franceschi F; De Marco G; Chiara C; Marta S; Bellusci M; Setti D; Pedrazzoli F; Romanelli G; Pirali C; Amolini C; Rosei EA; Rizzoni D; Castoldi L; Picardi A; Gentilucci UV; Mazzarelli C; Gallo P; Guasti L; Castiglioni L; Maresca A; Squizzato A; Contini S; Molaro M; Annoni G; Corsi M; Zazzetta S; Bertolotti M; Mussi C; Scotto R; Ferri MA; Veltri F; Arturi F; Succurro E; Sesti G; Gualtieri U; Perticone F; Sciacqua A; Quero M; Bagnato C; Loria P; Becchi MA; Martucci G; Fantuzzi A; Maurantonio M; Corinaldesi R; De Giorgio R; Serra M; Grasso V; Ruggeri E; Carozza LM; Pignatti F)

Recent evidence reveals that inter- and intra-individual variability significantly affects cognitive performance in a number of neuropsychological pathologies. We applied a flexible family of statistical models to elucidate the contribution of inter- and intra-individual variables on cognitive functioning in healthy volunteers and patients at risk for hepatic encephalopathy (HE). Sixty-five volunteers (32 patients with cirrhosis and 33 healthy volunteers) were assessed by means of the Inhibitory Control Task (ICT). A Generalized Additive Model for Location, Scale and Shape (GAMLSS) was fitted for jointly modeling the mean and the intra-variability of Reaction Times (RTs) as a function of socio-demographic and task related covariates. Furthermore, a Generalized Linear Mixed Model (GLMM) was fitted for modeling accuracy. When controlling for the covariates, patients without minimal hepatic encephalopathy (MHE) did not differ from patients with MHE in the low-demanding condition, both in terms of RTs and accuracy. Moreover, they showed a significant decline in accuracy compared to the control group. Compared to patients with MHE, patients without MHE showed faster RTs and higher accuracy only in the high-demanding condition. The results revealed that the application of GAMLSS and GLMM models are able to capture subtle cognitive alterations, previously not detected, in patients’ subclinical pathologies.

Many studies have addressed the relation between orthostatic hypotension (OH) and cognitive impairment (CI) in the elderly, in mild cognitive impairment, vascular and neurodegenerative dementias and movement disorders, such as Parkinson’s disease. However, results concerning both the increased coexistence of the two conditions and their causal relationship remain controversial. According to the literature three hypotheses can be formulated on the relation between OH and CI. In neurodegenerative disease, OH and CI may result from a common pathological process which affects areas involved in both cognition and cardiovascular autonomic control. Alternatively, OH may lead to cerebral hypoperfusion which is supposed to play a role in the development of CI. Finally, recent data suggest that CI should probably be considered more a transient symptom of OH than a chronic effect. This study reviews the literature reports on the relationship between OH and CI, and emphasises the need for longitudinal studies designed to investigate this topic.

We hypothesized that valerian root might prevent cognitive dysfunction in coronary artery bypass graft (CABG) surgery patients through stimulating serotonin receptors and anti-inflammatory activity.The aim of this study was to evaluate the effect of Valeriana officinalis root extract on prevention of early postoperative cognitive dysfunction after on-pump CABG surgery.In a randomized, double-blind, placebo-controlled trial, 61 patients, aged between 30 and 70 years, scheduled for elective CABG surgery using cardiopulmonary bypass (CPB), were recruited into the study. Patients were randomly divided into two groups who received either one valerian capsule containing 530 mg of valerian root extract (1,060 mg/daily) or placebo capsule each 12 h for 8 weeks, respectively. For all patients, cognitive brain function was evaluated before the surgery and at 10-day and 2-month follow-up by Mini Mental State Examination (MMSE) test.Mean MMSE score decreased from 27.03 ± 2.02 in the preoperative period to 26.52 ± 1.82 at the 10th day and then increased to 27.45 ± 1.36 at the 60th day in the valerian group. Conversely, its variation was reduced significantly after 60 days in the placebo group, 27.37 ± 1.87 at the baseline to 24 ± 1.91 at the 10th day, and consequently slightly increased to 24.83 ± 1.66 at the 60th day. Valerian prophylaxis reduced odds of cognitive dysfunction compared to placebo group (OR = 0.108, 95 % CI 0.022-0.545).We concluded that, based on this study, the cognitive state of patients in the valerian group was better than that in the placebo group after CABG; therefore, it seems that the use of V. officinalis root extract may prevent early postoperative cognitive dysfunction after on-pump CABG surgery.

Cognitive impairment (CI) is a frequent feature associated with both early and advanced stages of Parkinson's disease (PD). An evaluation of cognitive functions is relevant to identify those parkinsonians at risk of developing dementia. In the present study, the Italian version of Parkinson's Disease-Cognitive Rating Scale (PD-CRS) assessing fronto-subcortical and cortical cognitive functions in PD was validated in 387 parkinsonians and was used to test the empirical validity of the item 1.1 (cognitive impairment) of the Italian version of MDS-UPDRS as screening tool for CI in PD. PD-CRS was free from floor and ceiling effect. The mean PD-CRS score was 76.1 (mean cortical score, 24.5 ± 4.6; mean subcortical score, 51.5 ± 17.5). The internal consistency was satisfactory (α = 0.89); corrected item-total correlation was 0.570 (naming) to 0.696 (working memory). The correlation between PD-CRS and part I-IV of MDS-UPDRS was weak. The low agreement between classification of PD sample into patients with mild cognitive impairment (PD-MCI), dementia (PD-D) and normal cognition (PD-NC) according to scores of item 1.1 and classification according to cutoff scores of PD-CRS for PD-MCI, PD-D and PD-NC indicated a poor empirical validity of item 1.1 of MDS-UPDRS as cognitive screening tool for CI in PD (Κ = 0.114; weighted Κ = 0.17; SE of Κ = 0.038; 95 % confidence interval from 0.040 to 0.1895). The Italian version of PD-CRS is an easy, consistent and valid tool for assessment of the cognitive cortical and subcortical impairments in PD. © 2013 Springer-Verlag.

Background The effect of valve surgical procedures on cognition was investigated in patients undergoing conventional or robotically assisted techniques. The confounding factors of surgical procedure, mood state, preexisting cognitive impairment, and repeated experience with cognitive tests were controlled for. Methods Patients undergoing conventional valve procedures (n = 15), robotically assisted valve procedures (n = 15), and thoracic surgical procedures (n = 15), along with a nonsurgical control group (n = 15) were tested preoperatively, 1 week after operation, and 8 weeks after operation by use of a battery of cognitive tests and a mood state assessment. Surgical group data were normalized against data from the nonsurgical control group before statistical analysis. Results Patients undergoing conventional valve procedures performed worse than those undergoing robotically assisted valve procedures on every subtest before operation, and this disadvantage persisted after operation. Age and premorbid intelligence quotient were significantly associated with performance on several cognitive subtests. Anxiety, depression, and stress were not associated with impaired cognitive performance in the surgical groups after operation. A week after operation, patients undergoing conventional valve procedures performed worse on the cognitive tests that had a motor component, which may reflect discomfort caused by the sternotomy. Patients undergoing robotically assisted valve procedures were significantly less impaired on information processing tasks 1 week after operation when compared with those undergoing conventional valve procedures. The majority of patients who were impaired 1 week after operation recovered to preoperation levels within 8 weeks. Conclusions The robotically assisted valve surgical procedure results in more rapid recovery of performance on cognitive tests. However, regardless of the type of surgical intervention, the prospect of a recovery of cognitive performance to preoperative levels is high.

Background Anhedonia has been mainly reported as a symptom of depression and cognitive impairment in Parkinson's disease (PD) patients. Here, we investigated whether hedonic tone depends on depression and clarified its relationship with the cognitive performance of PD patients with different mood disorders. Methods In 254 patients, we assessed hedonic tone using the Snaith-Hamilton Pleasure Scale, depression severity using the Beck Depression Inventory, and cognitive performances using the Mental Deterioration Battery. A structural psychiatric interview was used to diagnose major depressive disorder (MDD) and minor depressive disorder (MIND), according to the DSM-IV-TR criteria. Results PD patients with diagnosis of MDD were more anhedonic than those with MIND and those without depressive disorders. Reduced hedonic tone correlated with depression severity in patients with MDD and no depressive disorders. In multivariate models that consider depression severity and cognitive performances together, anhedonia was related to increased depression severity and episodic memory (auditory-verbal learning) impairment, in patients with MDD and with increased depression severity and attention impairment in patients with no depressive disorders. In patients with MIND, anhedonia did not correlate with depression severity or any cognitive performance score. Discussion Our findings suggest that anhedonia is related to depression severity and specific cognitive performances in patients with MDD and with no depressive disorder. By contrast, the reduced hedonic tone in patients with MIND is independent from depression severity and cognition. Thus, anhedonia in PD is a heterogeneous and multidimensional phenomenon and require investigation at different levels. © 2013 Wiley Periodicals, Inc.

Negative symptoms that do not improve following antipsychotic treatment represent a challenge for development of effective treatments. Few studies have been carried out so far, especially in first-episode schizophrenia patients, to clarify prevalence, correlates and impact of persistent negative symptoms (PNS) on short- and long-term outcome of the disease.All patients from EUFEST study for whom both baseline and 12-month assessments were available were included (N=345). PNS were defined as the presence of at least one negative symptom of moderate or higher severity, not confounded by depression or parkinsonism, at baseline and after 1 year of treatment. Patients with PNS were compared to those with at least one negative symptom of moderate or higher severity at the baseline, not persisting after 1 year, on demographic, clinical, neurocognitive, global functioning and quality of life measures.PNS not confounded by depression or parkinsonism were present in 6.7% of the sample. The symptom that more often persisted was blunted affect. Patients with PNS differed from those without PNS for a longer duration of untreated psychosis (DUP) and a more frequent discontinuation of study treatment; they also had a poorer psychopathological outcome and a worse global functioning after 1 year of treatment.The presence of PNS was associated to poorer improvement of all psychopathological dimensions and worse global functioning after 1 year of treatment. The longer DUP in subjects with PNS suggests that programs aimed at shortening DUP might reduce the prevalence of PNS and improve prognosis of schizophrenia. © 2012 Elsevier B.V. and ECNP.

Our aim in this study was to assess the relationship between the state of cerebral vessels and the risk of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). We included 117 MCI patients. They underwent an ultrasonographic assessment of common carotid arteries intima-media thickness (IMT) and carotid plaque index. Cerebrovascular reactivity to hypercapnia in the middle cerebral arteries was calculated with the Breath-Holding Index (BHI). After a 12-month follow-up period, neuropsychological examinations demonstrated a progression to dementia in 21 patients. Pathological values of BHI and IMT significantly increased the risk of conversion (BHI: odds ratio, 5.80; 95% confidence interval, 1.83-18.37, p < 0.05; IMT: odds ratio, 3.08; 95% confidence interval, 1.02-9.33; p < 0.05, multinomial logistic regression analysis). Comparison between patients with all normal values and those with the simultaneous alteration of the 2 vascular indexes showed an increase in the risk of conversion from 9% to 33% (ordinal regression analysis). Our findings show that alterations of cerebral vessel functional and anatomic status increase the risk of conversion from MCI to dementia. © 2012 IBRO.

Objectives: To evaluate cognitive performance in subjects with bilateral asymptomatic carotid stenosis (B-ACS) compared to subjects with unilateral ACS and to subjects with no carotid stenosis (CS) and to explore the relationship between cognitive performance and cerebral hemodynamics status in B-ACS. Methods: The neuropsychological investigation included phonemic (ph) and categorical (ca) Verbal Fluency (VF) tests for exploring the left brain functions and Colored Progressive Matrices (CPM) and Complex Figure Copy Test (CFCT) for the right brain. Cerebral hemodynamics status was assessed using the transcranial Doppler-based breath-holding index test. Results: A total of 333 subjects were included: 127 B-ACS, 73/77 left/right unilateral ACS, 56 no CS, mean age 70 ± 3.78 years, 65% male. Subjects with B-ACS and subjects with unilateral ACS showed significantly lower scores in all cognitive tests compared to subjects with no CS (p < 0.05). Subjects with B-ACS with left impaired hemodynamics status showed a significantly reduced ph-VF score, from 13.4 (95% confidence interval [CI] 11.2-15.8) to 7.5 (95% CI 5.4-9.7), and a reduced ca-VF score, from 19.7 (95% CI 18.1-24.1) to 10.8 (95% CI 9.5-15.1), compared to subjects with no CS. Similarly, impaired cerebral hemodynamics in the right side was associated with a significantly reduced CPM score, from an estimated mean of 34.2 (95% CI 29.8-35.4) to 24.6 (95% CI 20.2-25.8), and CFCT score from 37.0 (95% CI 32.0-37.4) to 27.1 (95% CI 23.3-28.7). All comparisons were p < 0.05. Conclusion: Subjects with B-ACS and subjects with unilateral ACS are more likely to have cognitive dysfunction compared to subjects with no CS. There appears to be a link between cognitive dysfunction and hemodynamics impairment due to carotid stenosis. Copyright © 2012 by AAN Enterprises, Inc.

Background: Many studies have demonstrated the relationship between multiple sclerosis (MS) and cognition disorder. The objective of this study was to investigate the coping style of patients with mild frontal cognitive disorder. Methods: 135 patients with MS were divided into two groups as a function of their cognitive states (‘mild frontal cognitive impairments’ or ‘without frontal cognitive impairments’). All were seen for a semi-structured interview in order to collect socio-demographic and clinical information, after which there was an assessment of their cognitive and mental states and fatigue (FAB, MADRS). Then, all patients completed three self-report questionnaires concerning their coping strategies (WCC, CHIP) as well as their fatigue state. Results: No significant differences were observed between the two groups as to coping strategies and mood. However, patients with mild cognitive impairments tended to use more emotion-focused coping strategies, especially self-blame (F(133) = 2.2; p = 0.14) and diversion (F(133) = 1.35; p = 0.24) than patients without cognitive impairments. Patients with mild cognitive impairments were more fatigued than other patients. Discussion: Our study showed that patients with mild cognitive impairments did not differ significantly of other MS patients with regard to coping strategies.

Objective: Patient outcome after traumatic brain injury (TBI) is highly variable. The underlying pathophysiology of this is poorly understood, but inflammation is potentially an important factor. Microglia orchestrate many aspects of this response. Their activation can be studied in vivo using the positron emission tomography (PET) ligand [11C](R)PK11195 (PK). In this study, we investigate whether an inflammatory response to TBI persists, and whether this response relates to structural brain abnormalities and cognitive function. Methods: Ten patients, studied at least 11 months after moderate to severe TBI, underwent PK PET and structural magnetic resonance imaging (including diffusion tensor imaging). PK binding potentials were calculated in and around the site of focal brain damage, and in selected distant and subcortical brain regions. Standardized neuropsychological tests were administered. Results: PK binding was significantly raised in the thalami, putamen, occipital cortices, and posterior limb of the internal capsules after TBI. There was no increase in PK binding at the original site of focal brain injury. High PK binding in the thalamus was associated with more severe cognitive impairment, although binding was not correlated with either the time since the injury or the extent of structural brain damage. Interpretation: We demonstrate that increased microglial activation can be present up to 17 years after TBI. This suggests that TBI triggers a chronic inflammatory response particularly in subcortical regions. This highlights the importance of considering the response to TBI as evolving over time and suggests interventions may be beneficial for longer intervals after trauma than previously assumed. © 2011 American Neurological Association.