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The pathology of Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) peptide, hyperphosphorylated tau protein, neuronal death, and synaptic loss. By means of long-term two-photon in vivo imaging and confocal imaging, we characterized the spatio-temporal pattern of dendritic spine loss for the first time in 3xTg-AD mice. These mice exhibit an early loss of layer III neurons at 4 months of age, at a time when only soluble Aβ is abundant. Later on, dendritic spines are lost around amyloid plaques once they appear at 13 months of age. At the same age, we observed spine loss also in areas apart from amyloid plaques. This plaque independent spine loss manifests exclusively at dystrophic dendrites that accumulate both soluble Aβ and hyperphosphorylated tau intracellularly. Collectively, our data shows that three spatio-temporally independent events contribute to a net loss of dendritic spines. These events coincided either with the occurrence of intracellular soluble or extracellular fibrillar Aβ alone, or the combination of intracellular soluble Aβ and hyperphosphorylated tau.

Many in vivo studies suggest that inhalational anesthetics can accelerate or prevent the progression of neuropathology and cognitive impairments in Alzheimer Disease (AD), but the synaptic mechanisms mediating these ambiguous effects are unclear. Here, we show that repeated exposures of neonatal and old triple transgenic AD (3xTg) and non-transgenic (NonTg) mice to isoflurane (Iso) distinctly increased neurodegeneration as measured by S100β levels, intracellular Aβ, Tau oligomerization, and apoptotic markers. Spatial cognition measured by reference and working memory testing in the Morris Water Maze (MWM) were altered in young NonTg and 3xTg. Field recordings in the cornu ammonis 1 (CA1) hippocampus showed that neonatal control 3xTg mice exhibited hypo-excitable synaptic transmission, reduced paired-pulse facilitation (PPF), and normal long-term potentiation (LTP) compared to NonTg controls. By contrast, the old control 3xTg mice exhibited hyper-excitable synaptic transmission, enhanced PPF, and unstable LTP compared to NonTg controls. Repeated Iso exposures reduced synaptic transmission and PPF in neonatal NonTg and old 3xTg mice. LTP was normalized in old 3xTg mice, but reduced in neonates. By contrast, LTP was reduced in old but not neonatal NonTg mice. Our results indicate that Iso-mediated neuropathologic and cognitive defects in AD mice are associated with synaptic pathologies in an age-dependent manner. Based on these findings, the extent of this association with age and, possibly, treatment paradigms warrant further study. [ABSTRACT FROM AUTHOR]

Background: Episodic memory impairments have been described as initial clinical findings in the Alzheimer's Disease (AD) spectrum, which could be associated with the presence of early hippocampal dysfunction. However, correlates between performances in neuropsychological tests and hippocampal volumes in AD were inconclusive in the literature. Divergent methods to assess episodic memory have been depicted as a major source of heterogeneity across studies. Methods: We examined correlates among performances in three different delayed-recall tasks (Rey-Auditory Verbal-Learning Test–RAVLT, Logical Memory and Visual Reproduction subtests from the Wechsler Memory Scale) and fully-automated volumetric measurements of the hippocampus (estimated using Neuroquant®) of 83 older subjects (47 controls, 27 Mild Cognitive Impairment individuals and 9 participants with Dementia due to AD). Results: Inter-method correlations of episodic memory performances were at most moderate. Scores in the RAVLT predicted up to 48% of variance in HOC (Hippocampal Occupancy Score) among subjects in the AD spectrum. Discussion: Tests using different stimuli (verbal or visual) and presenting distinct designs (word list, story or figure learning) may assess divergent aspects in episodic memory, with heterogeneous anatomical correlates. Conclusions: Different episodic memory tests might not assess the same construct and should not be used interchangeably. Scores in RAVLT may correlate with the presence of neurodegeneration in AD. [ABSTRACT FROM AUTHOR]

Introduction: Bexarotene, a retinoid X receptor agonist, improves cognition in murine models of Alzheimer’s disease (AD). This study evaluated the effects of bexarotene on pathological and electrophysiological changes in very old triple transgenic AD mice (3xTg-AD mice). Methods: 24-month-old 3xTg-AD mice were treated with bexarotene (100 mg/kg/day for 30 days). The Morris water maze was used to evaluate spatial memory; immunofluorescence and confocal microscopy were used to evaluate pathological changes; and in vivo electrophysiological recordings were used to evaluate basal transmission and plasticity in the commissural CA3-CA1 pathway. Results: In addition to cognitive improvement, bexarotene-treated 3xTg-AD mice were found to have 1) reductions of astrogliosis and reactive microglia both in cortex and hippocampus; 2) increased ApoE expression restricted to CA1; 3) increased number of cells co-labeled with ApoE and NeuN; 4) recovery of NeuN expression, suggesting neuronal protection; and, 5) recovery of basal synaptic transmission and synaptic plasticity. Discussion: These results indicate that bexarotene-induced improvement in cognition is due to multiple changes that contribute to recovery of synaptic plasticity. [ABSTRACT FROM AUTHOR]

This paper explores which demographic characteristics substantially bias self-reported physical and cognitive health status of older Europeans. The analysis utilises micro-data for 19 European countries from the Survey of Health, Ageing and Retirement in Europe to compare performance-tested outcomes of mobility and memory with their self-reported equivalents. Relative importance analysis based on multinomial logistic regressions shows that the bias in self-reported health is mostly due to reporting heterogeneities between countries and age groups, whereas gender contributes little to the discrepancy. Concordance of mobility and cognition measures is highly related; however, differences in reporting behaviour due to education and cultural background have a larger impact on self-assessed memory than on self-assessed mobility. Southern as well as Central and Eastern Europeans are much more likely to misreport their physical and cognitive abilities than Northern and Western Europeans. Overall, our results suggest that comparisons of self-reported health between countries and age groups are prone to significant biases, whereas comparisons between genders are credible for most European countries. These findings are crucial given that self-assessed data are often the only information available to researchers and policymakers when asking health-related questions. [ABSTRACT FROM AUTHOR]

Electroencephalographic (EEG) activity in the gamma (30–80 Hz) range is related to a variety of sensory and cognitive processes which are frequently impaired in schizophrenia. Auditory steady-state response at 40-Hz (40-Hz ASSR) is utilized as an index of gamma activity and is proposed as a biomarker of schizophrenia. Nevertheless, the link between ASSRs and cognitive functions is not clear. This study explores a possible relationship between the performance on cognitive tasks and the 40-Hz ASSRs in a controlled uniform sample of young healthy males, as age and sex may have complex influence on ASSRs. Twenty-eight young healthy male volunteers participated (mean age ± SD 25.8±3.3) in the study. The 40-Hz click trains (500 ms) were presented 150 times with an inter-stimulus interval set at 700–1000 ms. The phase-locking index (PLI) and event-related power perturbation (ERSP) of the ASSR were calculated in the 200–500 ms latency range, which corresponds to the steady part of the response. The Psychology Experiment Building Language (PEBL) task battery was used to assess five cognitive subdomains: the Choice response time task, the Stroop test, the Tower of London test, the Lexical decision task and the Semantic categorisation task. Pearson‘s correlation coefficients were calculated to access the relationships; no multiple-test correction was applied as the tests were explorative in nature. A significant positive correlation was observed for the late-latency gamma and the mean number of steps in the Tower of London task reflecting planning and problem-solving abilities. These findings support the concept that 40-Hz ASSR might highlight top-down mechanisms which are related to cognitive functioning. Therefore, 40-Hz ASSRs can be used to explore the relationship between cognitive functioning and neurophysiological indices of brain activity. [ABSTRACT FROM AUTHOR]

Stress has become a widely experienced state all around the world, and previous literature has found that stress impacts individuals’ cognition, emotion, coping behaviors and psychological well-being in general. Relatively little is known about how stress influences individuals’ perception of stimuli changes, a ubiquitous phenomenon known as scope sensitivity. In the current work, we explore whether individuals with higher levels of chronic stress are sensitive to stimuli changes, such as price and quantity differences. Two empirical studies consistently show that chronically stressed individuals exhibit scope insensitivity, as they rated the expensiveness of two hotel rooms with different prices as being less different and indicated a smaller difference in their willingness-to-buy five CDs versus ten CDs. Possible explanations and theoretical and practical implications in the broader field are discussed. [ABSTRACT FROM AUTHOR]

In recent years, several high-dimensional, accurate, and effective classification methods have been proposed for the automatic discrimination of the subject between Alzheimer’s disease (AD) or its prodromal phase {i.e., mild cognitive impairment (MCI)} and healthy control (HC) persons based on T1-weighted structural magnetic resonance imaging (sMRI). These methods emphasis only on using the individual feature from sMRI images for the classification of AD, MCI, and HC subjects and their achieved classification accuracy is low. However, latest multimodal studies have shown that combining multiple features from different sMRI analysis techniques can improve the classification accuracy for these types of subjects. In this paper, we propose a novel classification technique that precisely distinguishes individuals with AD, aAD (stable MCI, who had not converted to AD within a 36-month time period), and mAD (MCI caused by AD, who had converted to AD within a 36-month time period) from HC individuals. The proposed method combines three different features extracted from structural MR (sMR) images using voxel-based morphometry (VBM), hippocampal volume (HV), and cortical and subcortical segmented region techniques. Three classification experiments were performed (AD vs. HC, aAD vs. mAD, and HC vs. mAD) with 326 subjects (171 elderly controls and 81 AD, 35 aAD, and 39 mAD patients). For the development and validation of the proposed classification method, we acquired the sMR images from the dataset of the National Research Center for Dementia (NRCD). A five-fold cross-validation technique was applied to find the optimal hyperparameters for the classifier, and the classification performance was compared by using three well-known classifiers: K-nearest neighbor, support vector machine, and random forest. Overall, the proposed model with the SVM classifier achieved the best performance on the NRCD dataset. For the individual feature, the VBM technique provided the best results followed by the HV technique. However, the use of combined features improved the classification accuracy and predictive power for the early classification of AD compared to the use of individual features. The most stable and reliable classification results were achieved when combining all extracted features. Additionally, to analyze the efficiency of the proposed model, we used the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset to compare the classification performance of the proposed model with those of several state-of-the-art methods. [ABSTRACT FROM AUTHOR]

Background: Prior studies of healthy populations have found religious practices to be associated with survival. However, no contemporary studies have examined whether religiosity influences survival among patients discharged from the hospital after an acute coronary syndrome (ACS). The present study examined the relationship between religious practices and 2-year all-cause mortality among hospital survivors of an ACS. Methods: Patients hospitalized for an ACS were recruited from 6 medical centers in Massachusetts and Georgia between 2011 and 2013. Study participants self-reported three items assessing religiosity: strength/comfort from religion, petition prayers for health, and awareness of intercessory prayers by others. All cause-mortality within 2-years of hospital discharge was ascertained by review of medical records at participating study hospitals and from death certificates. Cox proportional hazards models were used to estimate the multivariable adjusted risk of 2-year all-cause mortality. Results: Participants (n = 2,068) were on average 61 years old, 34% were women, and 81% were non-Hispanic White. Approximately 85% derived strength/comfort from religion, 61% prayed for their health, and 89% were aware of intercessions. Overall, 6% died within 2 years post-discharge. After adjusting for sociodemographic variables (age, sex, and race/ethnicity), petition prayers were associated with an increased risk of 2-year all-cause mortality (HR: 1.64; 95% CI: 1.01–2.66). With further adjustment for several clinical and psychosocial measures, this association was no longer statistically significant. Strength and comfort from religion and intercessory prayers were not significantly associated with mortality. Conclusions: Most ACS survivors acknowledge deriving strength and comfort from religion, praying for their health, and intercessions made by others for their health. Although the reported religious practices were not associated with post-discharge survival after multivariable adjustment, acknowledging that patients utilize their religious beliefs and practices as strategies to improve their health would ensure a more holistic approach to patient management and promote cultural competence in healthcare. [ABSTRACT FROM AUTHOR]

This study’s main objective was to assess the sensitivity and specificity of the interRAI Community Health Assessment (CHA) for detecting the presence of vision loss (VL), hearing loss (HL) or both (Dual Sensory Loss, DSL) when compared against performance-based measures of vision and hearing. The interRAI CHA and the Montreal Cognitive Assessment (MoCA) were administered to 200 adults (61+ years of age) who had VL, HL or DSL. We calculated the sensitivity and specificity of the interRAI CHA for detecting sensory impairments using as the gold standard performance based measurements of hearing (pure-tone audiogram) and vision (distance acuity) as determined from the rehabilitation centre record. Results were divided according to participants’ cognitive status, as measured by the MoCA and the Cognitive Performance Scale (CPS, embedded within the interRAI CHA). Overall, sensitivity was 100% for VL, 97.1% for HL, and 96.9% for DSL. Specificity was at least 93% in all three groups. In participants who failed the MoCA (i.e., at risk of mild cognitive impairment), the sensitivity was 100% for VL, 96.8% for HL and 96.2% for DSL; in those who were not at risk, the sensitivity was 100% for VL, and 97.4% for HL and DSL. In participants classified by the CPS as borderline intact or mild cognitively impaired, sensitivity was 100% in all groups; in those classified as cognitively intact, sensitivity was 100% for VL, 97.0% for HL, and 96.8% for DSL. These results suggest that the interRAI CHA detects VL, HL, and DSL in high agreement with performance-based measurements of vision and hearing. The interRAI CHA shows high accuracy even in participants with mild cognitive difficulties. Since results were found in a specific population of older rehabilitation clients who all had sensory difficulties, further research is needed to understand its role in screening in other more diverse groups. [ABSTRACT FROM AUTHOR]

Cognitive impairments are a common consequence of traumatic brain injury (TBI). The hippocampus is a subcortical structure that plays a key role in the formation of declarative memories and is highly vulnerable to TBI. The α7 nicotinic acetylcholine receptor (nAChR) is highly expressed in the hippocampus and reduced expression and function of this receptor are linked with cognitive impairments in Alzheimer’s disease and schizophrenia. Positive allosteric modulation of α7 nAChRs with AVL-3288 enhances receptor currents and improves cognitive functioning in naïve animals and healthy human subjects. Therefore, we hypothesized that targeting the α7 nAChR with the positive allosteric modulator AVL-3288 would enhance cognitive functioning in the chronic recovery period of TBI. To test this hypothesis, adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury or sham surgery. At 3 months after recovery, animals were treated with vehicle or AVL-3288 at 30 min prior to cue and contextual fear conditioning and the water maze task. Treatment of TBI animals with AVL-3288 rescued learning and memory deficits in water maze retention and working memory. AVL-3288 treatment also improved cue and contextual fear memory when tested at 24 hr and 1 month after training, when TBI animals were treated acutely just during fear conditioning at 3 months post-TBI. Hippocampal atrophy but not cortical atrophy was reduced with AVL-3288 treatment in the chronic recovery phase of TBI. AVL-3288 application to acute hippocampal slices from animals at 3 months after TBI rescued basal synaptic transmission deficits and long-term potentiation (LTP) in area CA1. Our results demonstrate that AVL-3288 improves hippocampal synaptic plasticity, and learning and memory performance after TBI in the chronic recovery period. Enhancing cholinergic transmission through positive allosteric modulation of the α7 nAChR may be a novel therapeutic to improve cognition after TBI. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment is a common systemic manifestation of chronic obstructive pulmonary disease (COPD). However, its pathophysiological origins are not understood. Since, cognitive function relies on efficient communication between distributed cortical and subcortical regions, we investigated whether people with COPD have disruption in white matter connectivity. Methods: Structural networks were constructed for 30 COPD patients (aged 54–84 years, 57% male, FEV1 52.5% pred.) and 23 controls (aged 51–81 years, 48% Male). Networks comprised 90 grey matter regions (nodes) interconnected by white mater fibre tracts traced using deterministic tractography (edges). Edges were weighted by the number of streamlines adjusted for a) streamline length and b) end-node volume. White matter connectivity was quantified using global and nodal graph metrics which characterised the networks connection density, connection strength, segregation, integration, nodal influence and small-worldness. Between-group differences in white matter connectivity and within-group associations with cognitive function and disease severity were tested. Results: COPD patients’ brain networks had significantly lower global connection strength (p = 0.03) and connection density (p = 0.04). There was a trend towards COPD patients having a reduction in nodal connection density and connection strength across the majority of network nodes but this only reached significance for connection density in the right superior temporal gyrus (p = 0.02) and did not survive correction for end-node volume. There were no other significant global or nodal network differences or within-group associations with disease severity or cognitive function. Conclusion: COPD brain networks show evidence of damage compared to controls with a reduced number and strength of connections. This loss of connectivity was not sufficient to disrupt the overall efficiency of network organisation, suggesting that it has redundant capacity that makes it resilient to damage, which may explain why cognitive dysfunction is not severe. This might also explain why no direct relationships could be found with cognitive measures. Smoking and hypertension are known to have deleterious effects on the brain. These confounding effects could not be excluded. [ABSTRACT FROM AUTHOR]

Introduction: The earliest changes in the brain due to Alzheimer’s disease are associated with the neural networks related to memory function. We investigated changes in functional and structural connectivity among regions that support memory function in prodromal Alzheimer’s disease, i.e., during the mild cognitive impairment (MCI) stage. Methods: Twenty-three older healthy controls and 25 adults with MCI underwent multimodal MRI scanning. Limbic white matter tracts–the fornix, parahippocampal cingulum, retrosplenial cingulum, subgenual cingulum and uncinate fasciculus–were reconstructed in ExploreDTI using constrained spherical deconvolution-based tractography. Using a network-of-interest approach, resting-state functional connectivity time-series correlations among sub-parcellations of the default mode and limbic networks, the hippocampus and the thalamus were calculated in Conn. Analysis: Controlling for age, education, and gender between group linear regressions of five diffusion-weighted measures and of resting state connectivity measures were performed per hemisphere. FDR-corrections were performed within each class of measures. Correlations of within-network Fisher Z-transformed correlation coefficients and the mean diffusivity per tract were performed. Whole-brain graph theory measures of cluster coefficient and average path length were inspecting using the resting state data. Results & conclusion: MCI-related changes in white matter structure were found in the fornix, left parahippocampal cingulum, left retrosplenial cingulum and left subgenual cingulum. Functional connectivity decreases were observed in the MCI group within the DMN-a sub-network, between the hippocampus and sub-areas -a and -c of the DMN, between DMN-c and DMN-a, and, in the right hemisphere only between DMN-c and both the thalamus and limbic-a. No relationships between white matter tract ‘integrity’ (mean diffusivity) and within sub-network functional connectivity were found. Graph theory revealed that changes in the MCI group was mostly restricted to diminished between-neighbour connections of the hippocampi and of nodes within DMN-a and DMN-b. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to explore the experiences, needs, and preferences regarding follow-up perceived by people with stroke and healthcare professionals. Methods: This is a qualitative exploratory study using focus groups. Patients and healthcare professionals, participating in a clinical visit in primary care or specialised care, were purposively sampled. Data were analysed using a framework of analysis developed by Krueger. Results: Focus groups were conducted with two patient groups (n = 10, range 45–78 years) and two multidisciplinary healthcare professional groups (n = 8, range 35–55 years). The overarching theme elucidates stroke as a long-term condition requiring complex follow-up. Three organisational themes and six subthemes were identified. People with stroke discovered feelings and changes after returning home. In daily life, problems and feelings of abandonment became evident. Participants expressed experiences of unequal access to health care services. Barriers for accessing appropriate treatment and support included difficulties in communicating one’s needs and lack of coherent follow-up. Follow-up activities were well functioning in certain clinics but did not provide continuity over the long term. Participants made suggestions for a comprehensive, planned, and tailored follow-up to meet patient needs. Conclusion: Comprehensive long-term follow-up that is accessible to all patients is essential for equal support. Our findings raised awareness about problems discovered after returning home and the obstacles individuals face in communicating their needs. Structured follow-up, which is individually tailored, can empower patients. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies evaluating the association between clinically diagnosed Alzheimer’s disease (AD) and age-related macular degeneration (AMD) have generated conflicting results. This study is the first to assess whether AMD prevalence is higher in AD patients than non-AD controls by using histopathology to definitively diagnose AD. Methods: This was a retrospective case-control study utilizing diagnostic information extracted from autopsy reports of patients age 75 and above, including 115 with a neuropathological diagnosis of AD and 57 age-matched normal controls. Results: The rate of AMD was not significantly higher in AD cases (53.0%) than in controls (59.6%) (z = 0.820, p = 0.794). AMD severity as determined by Sarks score was similar between AD patients and controls (χ2 = 2.96, p = 0.706). There was also no significant association between Braak stage of AD severity and AMD (χ2 = 4.55, p = 0.602). Discussion: No significant effect of AD diagnosis or pathologic severity on AMD comorbidity was found, suggesting that any shared mechanisms between AMD and AD may be nondeterministic. [ABSTRACT FROM AUTHOR]

Background: Accurate prognostic evaluation is a key factor in the clinical management of patients affected by severe acute brain injury (ABI) and helps planning focused therapies, better caregiver’s support and allocation of resources. Aim of the study was to assess factors independently associated with both the short and long-term outcomes after rehabilitation in patients affected by ABI in the setting of a single Rehabilitation Unit specifically allocated to these patients. Methods and findings: In all patients (567) with age ≥ 18 years discharged from the Unit in the period 2006/2015 demographic, etiologic, comorbidity indicators, and descriptors of the disability burden (at hospital admission and discharge) were evaluated as potential prognostic factors of both short-term (4 classes of disability status at discharge) and long-term (mortality) outcomes. A comprehensive analytical method was adopted to combine several tasks. Select the factors with a significant independent association with the outcome, assess the relative weights and the “stability” (by bootstrap resampling) of them and estimate the role of the prognostic models in the clinical framework considering “cost” and “benefits”. The generalized ordered logistic model for ordinal dependent variables was used for the short-term outcome while the Cox proportional hazard model was used for the long-term outcome. The final short-term model identified 7 factors that independently account for 37% of the outcome variability as shown by pseudo R2 (pR2) = 0.37. The disability status descriptors show the strongest association since they account for more than 60% of the pR2, followed by age (14.8%), the presence of percutaneous endoscopic gastrostomy or nasogastric intubation (14.4%), a longer stay in the acute ward (5.9%) and concomitant coronary disease (1.3%). The final multivariable Cox model identified 4 factors that independently account for 52% of the outcome variability (R2 = 0.52). The disability extent and the disability recovered lead the long-term mortality since they account for the 53% of the global R2. The relevant effect of age (42%) is appreciable only after 2 years given the significant interaction with time. A longer stay in the acute ward explains the remaining fraction (5%). Considering ‘cost and benefits’, the decision curve analysis shows that the clinical benefit achieved by using both prognostic models is greater than the other possible action strategies, namely ‘treat all’ and ‘treat none. Several less obvious characteristics of the prognostic models are appreciated by integrating the results of multiple analytical methods. Conclusion: The comprehensive analytical tool aimed to integrate statistical significance, weight, “stability” and clinical “net” benefit, gives back a prognostic framework explaining a relevant portion of both outcomes’ variability in which the strong association of the disability status with both outcomes is comparable to and followed by a time modulated role of age. Our data do not support a differentiated association of traumatic vs non-traumatic etiology. The results encourage the use of integrated approach to analyze cohort data. [ABSTRACT FROM AUTHOR]

While internal migration is widely occurring in countries across the world and older people are more likely to be left behind by family members who out-migrated to other locations, little attention has been paid to the cognitive health of those people who have been left behind (PLB). Understanding how these demographic patterns relate to older persons’ cognitive health may inform efforts to reduce the disease burden due to cognitive decline. Data came from the China Health and Nutrition Survey in 1997, 2000 and 2004. Participants aged 55 to 93 who participated in a cognitive function screening test (score range: 0–31) in two or more waves and provided information on family members’ migration (n = 1,267) were included in the analysis. A mixed linear model was used to investigate the association between being left behind by any members who had not resided in the household for at least 6 months at baseline and cognitive function. Approximately 10% of the participants had been left behind by family members who migrated out of their communities. A significant interaction was observed in relation to cognitive function between being left behind and the number of years from the first test. Specifically, there was a less steep decline in cognitive function of PLB compared to people not left behind. This longitudinal study showed that PLB tended to have a higher cognitive function compared to those not left behind due to their relatively stable transition in cognitive function during the study period. [ABSTRACT FROM AUTHOR]

The anti-saccade task is a commonly used method of assessing individual differences in cognitive control. It has been shown that a number of clinical disorders are characterised by increased anti-saccade cost. However, it remains unknown whether this reflects impaired goal identification or impaired goal execution, because, to date, no procedure has been developed to independently assess these two components of anti-saccade cost. The aim of the present study was to develop such an assessment task, which we term the Goal Identification Vs. Execution (GIVE) task. Fifty-one undergraduate students completed a conventional anti-saccade task, and our novel GIVE task. Our findings revealed that individual differences in anti-saccade goal identification costs and goal execution costs were uncorrelated, when assessed using the GIVE task, but both predicted unique variance in the conventional anti-saccade cost measure. These results confirm that the GIVE task is capable of independently assessing variation in the goal identification and goal execution components of the anti-saccade effect. We discuss how this newly introduced assessment procedure now can be employed to illuminate the specific basis of the increased anti-saccade cost that characterises various forms of clinical dysfunction. [ABSTRACT FROM AUTHOR]

Objective: Previous research associated the left inferior frontal cortex with implicit structure learning. The present study tested patients with lesions encompassing the left inferior frontal gyrus (LIFG; including Brodmann areas 44 and 45) to further investigate this cognitive function, notably by using non-verbal material, implicit investigation methods, and by enhancing potential remaining function via dynamic attending. Patients and healthy matched controls were exposed to an artificial pitch grammar in an implicit learning paradigm to circumvent the potential influence of impaired language processing. Methods: Patients and healthy controls listened to pitch sequences generated within a finite-state grammar (exposure phase) and then performed a categorization task on new pitch sequences (test phase). Participants were not informed about the underlying grammar in either the exposure phase or the test phase. Furthermore, the pitch structures were presented in a highly regular temporal context as the beneficial impact of temporal regularity (e.g. meter) in learning and perception has been previously reported. Based on the Dynamic Attending Theory (DAT), we hypothesized that a temporally regular context helps developing temporal expectations that, in turn, facilitate event perception, and thus benefit artificial grammar learning. Results: Electroencephalography results suggest preserved artificial grammar learning of pitch structures in patients and healthy controls. For both groups, analyses of event-related potentials revealed a larger early negativity (100–200 msec post-stimulus onset) in response to ungrammatical than grammatical pitch sequence events. Conclusions: These findings suggest that (i) the LIFG does not play an exclusive role in the implicit learning of artificial pitch grammars, and (ii) the use of non-verbal material and an implicit task reveals cognitive capacities that remain intact despite lesions to the LIFG. These results provide grounds for training and rehabilitation, that is, learning of non-verbal grammars that may impact the relearning of verbal grammars. [ABSTRACT FROM AUTHOR]

Non-alcoholic steatohepatitis (NASH) is one of the most prevalent diseases worldwide. While it has been suggested to cause nervous impairment, its neurophysiological basis remains unknown. Therefore, the aim of this study is to unravel the effects of NASH, through the interrelationship of liver, gut microbiota, and nervous system, on the brain and human behavior. To this end, 40 Sprague-Dawley rats were divided into a control group that received normal chow and a NASH group that received a high-fat, high-cholesterol diet. Our results show that 14 weeks of the high-fat, high-cholesterol diet induced clinical conditions such as NASH, including steatosis and increased levels of ammonia. Rats in the NASH group also demonstrated evidence of gut dysbiosis and decreased levels of short-chain fatty acids in the gut. This may explain the deficits in cognitive ability observed in the NASH group, including their depressive-like behavior and short-term memory impairment characterized in part by deficits in social recognition and prefrontal cortex-dependent spatial working memory. We also reported the impact of this NASH-like condition on metabolic and functional processes. Brain tissue demonstrated lower levels of metabolic brain activity in the prefrontal cortex, thalamus, hippocampus, amygdala, and mammillary bodies, accompanied by a decrease in dopamine levels in the prefrontal cortex and cerebellum and a decrease in noradrenalin in the striatum. In this article, we emphasize the important role of ammonia and gut-derived bacterial toxins in liver-gut-brain neurodegeneration and discuss the metabolic and functional brain regional deficits and behavioral impairments in NASH. [ABSTRACT FROM AUTHOR]

The path signature is a means of feature generation that can encode nonlinear interactions in data in addition to the usual linear terms. It provides interpretable features and its output is a fixed length vector irrespective of the number of input points or their sample times. In this paper we use the path signature to provide features for identifying people whose diagnosis subsequently converts to Alzheimer’s disease. In two separate classification tasks we distinguish converters from 1) healthy individuals, and 2) individuals with mild cognitive impairment. The data used are time-ordered measurements of the whole brain, ventricles and hippocampus from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We find two nonlinear interactions which are predictive in both cases. The first interaction is change of hippocampal volume with time, and the second is a change of hippocampal volume relative to the volume of the whole brain. While hippocampal and brain volume changes are well known in Alzheimer’s disease, we demonstrate the power of the path signature in their identification and analysis without manual feature selection. Sequential data is becoming increasingly available as monitoring technology is applied, and the path signature method is shown to be a useful tool in the processing of this data. [ABSTRACT FROM AUTHOR]

Introduction: Analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs), weak and strong opioids are commonly used among elderly persons. The aim of this study was to describe the demographic and clinical characteristics of elderly analgesic users and to measure the frequency of analgesic use, including the frequency of potentially inappropriate analgesic use. Methods: The Arianna database was used to carry out this study. This database contains prescription data with associated indication of use for 1,076,486 inhabitants registered with their general practitioners (GPs) in the Caserta Local Health Unit (Caserta district, Campania region in Italy). A cohort of persons aged ≥65 years old with >1 year of database history having at least one analgesic drug (NSAIDs, strong or weak opioids) between 2010 and 2014 were identified. The date of the first analgesic prescription in the study period was considered the index date (ID). Results: From a source population of 1,076,486 persons, 116,486 elderly persons were identified. Of these, 94,820 elderly persons received at least one analgesic drug: 36.6% were incident NSAID users (N = 36,629), while 13.2% were incident weak opioid users (N = 12,485) and 8.1% were incident strong opioid users (N = 7,658). In terms of inappropriate analgesic use, 9.2% (N = 10,763) of all elderly users were prescribed ketorolac/indomethacin inappropriately, since these drugs should not be prescribed to elderly persons. Furthermore, at least half all elderly persons with chronic kidney disease or congestive heart failure were prescribed NSAIDs, while these drugs should be avoided. Conclusion: Analgesics are commonly used inappropriately among elderly persons, suggesting that prescribing practice in the catchment area may yet be improved. [ABSTRACT FROM AUTHOR]

Background: Veteran patients with traumatic brain injury (TBI) and their family members regularly receive care from nurses. Understanding nurses’ training and beliefs can provide direction for intervention work aimed at ensuring the best possible care is delivered to this population. Aims: We examined Veterans Health Administration (VHA) nurses’ training and beliefs related to care of patients with moderate-to-severe TBI. Design and methods: We conducted an exploratory, cross-sectional survey with 211 VHA nurses and analyzed data using descriptive statistics. Results: The average years of nursing experience was 18 years, and 90% reported ever caring for a patient with TBI. Most nurses (70%) reported only seeing patients with TBI ≤1–2 times per year in their current role; 20% reported seeing these patients 1–2 times per month. Even with infrequent care, almost 50% reported previously receiving TBI-related training. Beliefs items with the highest accuracy indicated nurses agreed that they need specialized training to care for patients with TBI and that TBI recovery may continue for several years (96.39% accuracy respectively). The beliefs item with the lowest accuracy indicated focus on whether nurses agreed that TBI severity was important in developing care plans (27.84% accuracy). Nurses reported the need for clarity of the nursing role in caring for patients with TBI (77.32% agreement). Conclusion: VHA nurses do have accurate beliefs about caring for Veteran patients with moderate-to-severe TBI; however, there is the need for further role clarification regarding nursing care of patients with TBI. Impact: These findings have implications for development of education and training interventions for nurses who care for Veteran patients with TBI. [ABSTRACT FROM AUTHOR]

A recently published review of 45 studies concluded that approximately half of individuals who sustain a single mild traumatic brain injury (MTBI) experience long-term cognitive impairment (McInnes et al. Mild Traumatic Brain Injury (mTBI) and chronic cognitive impairment: A scoping review. PLoS ONE 2017;12:e0174847). Stratified by age, they reported that 50% of children and 58% of adults showed some form of cognitive impairment. We contend that the McInnes et al. review used a definition of “cognitive impairment” that was idiosyncratic, not applicable to individual patients or subjects, inconsistent with how cognitive impairment is defined in clinical practice and research, and resulted in a large number of false positive cases of cognitive impairment. For example, if a study reported a statistically significant difference on a single cognitive test, the authors concluded that every subject with a MTBI in that study was cognitively impaired–an approach that cannot be justified statistically or psychometrically. The authors concluded that impairment was present in various cognitive domains, such as attention, memory, and executive functioning, but they did not analyze or report the results from any of these specific cognitive domains. Moreover, their analyses and conclusions regarding many published studies contradicted the interpretations provided by the original authors of those studies. We re-reviewed all 45 studies and extracted the main conclusions from each. We conclude that a single MTBI is not associated with a high incidence of chronic cognitive impairment. [ABSTRACT FROM AUTHOR]

A relatively unexplored aspect in bipolar disorder (BD) is the ability to accurately judge other´s nonverbal behavior. To explore this aspect of social cognition in this population is particularly meaningful, as it may have an influence in their social and interpersonal functioning. The aim of this research was to study interpersonal accuracy (IPA) in remitted BDs, that is, the specific skills that fall under the general term Theory of Mind (ToM). Study participants included 119 remitted individuals with BD (70 BD I and 49 BD II), and they were compared with a group of 39 persons diagnosed with unipolar depression (UD) and 119 control participants. The MiniPONS was used to test the whole spectrum of nonverbal cues as facial expressions, body language and voice. Results indicated a superiority of the control group with statistically significant differences both in the performance in the MiniPONS (number of right answers) and in each of the areas evaluated by this test. BD groups, in recognition of the meaning of gestures in face, body and voice intonation, performed significantly worse than controls. ANCOVA analysis controlling the effect of age shows that control group performed significantly better compared to clinical groups, and there were no differences between UD and BD groups. The results indicate a deficit in IPA and suggest that better comprehension of deficiencies in interpersonal accuracy in BD may help to develop new training programs to improve in these patients the understanding of others, which might have a positive impact in their psychosocial functionality, and thus lead to the objective of functional rehabilitation. [ABSTRACT FROM AUTHOR]

Background: While drink driving continues to be significantly more common among male drivers, there is evidence from many countries that shows a growing trend of women engaging in this risky behaviour. The aims of the current study were threefold: (i) determine to what extent a sample of women drivers reported engaging in drink driving behaviour by expanding the construct into a range of definitions, (ii) determine if there were significant differences in self-reported engagement in drink driving behaviours in accordance with hazardous drinking behaviour, and (iii) identify which situational or personal factors would increase women drivers’ likelihood to engage in drink driving through presenting a range of scenarios. Method: Data were collected using an on-line, purpose-designed survey and promoted to reach women aged 17 years and older, living in Queensland, Australia. In addition to questions relating to demographic characteristics, participants completed items relating to engagement in seven drink driving related behaviours in the previous 12-month period, hazardous drinking as measured by the Alcohol Use Disorders Identification Test, and likelihood of driving when unsure if over the legal limit for licence type across a range of scenarios manipulating different situational factors. A total of 644 valid responses were received in the two-week period the study was advertised. Results: The results demonstrate women’s self-reported engagement in drink driving behaviour ranged from 12.6% (driving when they believed they were over the legal limit) to over 50.0% (driving when unsure if over the legal limit the morning after drinking alcohol) and was significantly more likely among those who reported hazardous levels of alcohol use. Circumstances in which women reported they would drive when unsure if over the legal BAC limit were when they were a few blocks from home, if they subjectively felt they were not too intoxicated, or if they needed their car to get somewhere the next morning. Conclusion: Examining drink driving behaviour by way of responses to nuanced definitions provided valuable insight into self-reported engagement in the behaviour and highlights the usefulness of multi-measure dependent variables in order to illuminate a more accurate acknowledgement into both the type (and extent) of drink driving behaviours. [ABSTRACT FROM AUTHOR]

Executive functions are affected differently in healthy aging, Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD), and evaluating them is important for differential diagnosis. The INECO Frontal Screening (IFS) is a brief neuropsychological screening tool, developed to assess executive dysfunction in neurodegenerative disorders. Goals: We aimed to examine whether and how MCI patients can be differentiated from cognitively healthy controls (HC) and mild to moderate AD patients based on IFS performance. We also explored how IFS scores are associated with age, years of education, and depressive/anxious symptoms (as assessed by the Hospital Anxiety and Depression Scale). Method: IFS total scores were compared between 26 HC, 32 MCI and 21 mild to moderate AD patients. The three groups were matched for age and education. The Area Under the Curve (AUC) was analyzed and optimal cut-offs were determined. Results: Healthy participants had higher IFS scores than both clinical groups, and MCI patients had higher scores than AD patients. IFS showed high diagnostic accuracy for the detection of MCI (AUC = .89, p < .001) and AD (AUC = .99, p < .001), and for the differentiation between the clinical groups (AUC = .76, p < .001). We provide optimal cut-offs for the identification of MCI and AD and for their differentiation. We also found that, in general, higher education predicted higher IFS scores (no associations with age and depressive/anxious symptoms were observed). Altogether, these findings indicate that evaluating executive functions with the IFS can be valuable for the identification of MCI, a high-risk group for dementia, and for differentiating this condition from healthy aging and AD. [ABSTRACT FROM AUTHOR]

Background: Falls among older adults is a common precipitating factor for unintentional injuries and represent a major health problem associated with increased morbidity, mortality, and health care cost in low-and-middle-income countries. The burden of fall in this population is well established in high-income countries and scant attention is given to this precipitating factor in low-and-middle-income countries, including Ethiopia. Therefore, this study aimed to estimate the prevalence and factors associated with fall among community-dwelling older adults in Ethiopia. Methods: A community-based cross-sectional study was conducted among community-dwelling older adults of Gondar. Multi-stage random sampling technique was used across administrative areas. Six hundred and five households were selected proportionally using systematic random sampling technique. Physical measurement and face to face interview method were employed using a structured questionnaire for data collection. Data were analyzed descriptively and through uni- and multivariate logistic regression model. Results: One hundred and seventy (n = 170, 28.4%; 95% CI 24.7–32.1) community-dwelling older adults reported having experienced fall in the past 12 months. Sex (OR = 1.91, 95% CI: 1.24–2.95), low educational status (OR = 2.37, 95% CI: 1.19–4.74), uncomfortable home environment (OR = 2.02, 95% CI: 1.34, 3.04), having diagnosed medical condition (OR = 4.659, 95% CI: 1.20–18.02), and use of medication (OR = 5.57, 95% CI: 1.19–26.21) were significantly associated risk factors of self-reported fall in the past 12 months. Most outdoor falls are associated with females and participants aged below 66 years. Conclusion: In conclusion, more than 1/4th of the community-dwelling older adults experienced at least one episode of fall and about 60% of them reported recurrent falls. Identifying risk group and risk factors that could be modified so as to prevent falls in older adults deserves attention. Outdoor falls are usually attributable to modifiable environmental aspects and improvements in outdoor environment needed. [ABSTRACT FROM AUTHOR]

Neuropsychiatric systemic lupus erythematosus (NPSLE) is associated with learning and memory deficit. Murine model of lupus induced by pristane in BALB/c mice is an experimental model that resembles some clinical and immunological SLE pathogenesis. Nevertheless, there is no experimental evidence that relates this model to cognitive dysfunction associated with NR2A/2B relative expression. To evaluate cognitive impairment related to memory deficits in a murine model of lupus induced by pristane in BALB/c mice related to mRNA relative expression levels of NR2A/2B hippocampal subunits in short and long-term memory task at 7 and 12 weeks after LPS exposition in a behavioral test with the use of Barnes maze. A total of 54 female BALB/c mice 8–12 weeks old were included into 3 groups: 7 and 12 weeks using pristane alone (0.5 mL of pristane) by a single intraperitoneal (i.p.) injection. A control group (single i.p. injection of 0.5 mL NaCl 0.9%) and pristane plus LPS exposure using single i.p. pristane injection and LPS of E. coli O55:B5, in a dose of 3mg/kg diluted in NaCl 0.9% 16 weeks post-pristane administration. To determine cognitive dysfunction, mice were tested in a Barnes maze. Serum anti-Sm antibodies and relative expression of hippocampal NR2A/2B subunits (GAPDH as housekeeping gene) with SYBR green quantitative reverse transcription polymerase chain reaction and 2-ΔΔCT method were determined in the groups. Downregulation of hippocampal NR2A subunit was more evident than NR2B in pristane and pristane+LPS at 7 and 12 weeks of treatment and it is related to learning and memory disturbance assayed by Barnes maze. This is the first report using the murine model of lupus induced by pristane that analyzes the NMDA subunit receptors, finding a downregulation of NR2A subunit related to learning and memory disturbance being more evident when they were exposed to LPS. [ABSTRACT FROM AUTHOR]

Introduction: Amyotrophic lateral sclerosis (ALS) is a rare, progressive neurodegenerative disease. There is heterogeneity of clinical phenotypes while a clinical characterization of ALS in Cyprus is still lacking. The aim of this 30-year retrospective study of ALS in Cyprus is to determine the demographic characteristics of patients, the clinical features of the disease, the uptake of supportive therapies and factors influencing survival. Methods: All ALS patients seen at the Cyprus Institute of Neurology and Genetics from January 1985 until July 2015 were included. Medical records of eligible patients were used for data extraction and compilation of an ALS database. Clinical features were compared between gender categories using univariate tests, while survival was assessed using Kaplan-Meier curves. Cox proportional hazards models were used to identify prognostic factors for survival. Results: One hundred and seventy-nine ALS patients were included in the study, of whom 7 had a positive family history. Most clinical characteristics of ALS did not differ from what is observed in other European countries. However, some clinical characteristics were unique to our population, such as an increased acceptability and utilisation of supportive treatments such as gastrostomy. Conclusions: Overall, clinical characteristics of patients with ALS in the Republic of Cyprus do not differ from other European counties. Our study demonstrates a high acceptance and utilisation of supportive interventions enhancing survival, in the context of a multidisciplinary approach offered in the single tertiary centre that services the whole Cypriot ALS population. The findings of this paper are of value to the health professionals treating ALS in Cyprus. [ABSTRACT FROM AUTHOR]

The integral role of sleep in cognition, such as night-time sleep and napping duration, has yielded mixed findings, especially in healthy elderly adults. This study aimed to identify the heterogeneous classes of the cognitive trajectories and investigated the associations between sleep parameters and the trajectories of cognition in different elderly subpopulations. The study was based on a large, national representative sample aged 60 years or older. Two cognitive measures were assessed, including executive function and episodic memory. Sleep parameters were evaluated, including post-lunch napping, night-time sleep duration, and sleep disturbances. Latent growth mixture model (LGMM) was used to describe the trajectories of cognition and investigate the effects of sleep factors on cognition. Three heterogeneous trajectories were identified for executive cognition and four for episodic memory. Inverted U-shape associations of cognition with night-time sleep and napping duration were found. In LGMM, night-time sleep duration was negatively associated with the baseline episodic memory in elderly adults. Post-lunch napping was positively associated with the baseline executive function (β = 0.078, P<0.05) and episodic memory (β = 0.084, P<0.05) in men, whereas it was only associated with impaired episodic memory (β = -0.152, P<0.05) in women. Frequent sleep disturbances were only associated with the impaired executive function at baseline (β = -0.088, 95%CI -0.162, -0.013) among older men. Overall, sleep parameters played different roles in heterogeneous trajectories of cognition by sex difference. Sleep factors may not be related to the rate of cognition decline, but these factors, independent of time-variant depressive symptoms, were associated with the initial status of cognition at baseline. [ABSTRACT FROM AUTHOR]

Previous research has demonstrated that people with Parkinson’s disease (PD) have difficulties with the perceptual discrimination of rhythms, relative to healthy controls. It is not however clear if this applies only to simpler rhythms (a so called “beat-based” deficit), or if it is a more generalized deficit that also applies to more complex rhythms. Further insight into how people with PD process and perceive rhythm can refine our understanding of the well known problems of temporal processing in the disease. In this study, we wanted to move beyond simple/complex-dichotomy in previous studies, and further investigate the effect of tempo on the perception of musical rhythms. To this end, we constructed ten musical rhythms with a varied degree of complexity across three different tempi. Nineteen people with PD and 19 healthy controls part-took in an internet based listening survey and rated 10 different musical rhythms for complexity and likeability. In what we believe is the first study to do so, we asked for the participants subjective ratings of individual rhythms and not their capacity to directly compare or discriminate between them. We found an overall between-group difference in complexity judgments that was modulated by tempo, but not level of complexity. People with PD rated all rhythms as more complex across tempi, with significant group differences in complexity ratings at 120 and 150bpm, but not at 90bpm. Our analysis found a uniform elevated baseline for complexity judgments in the PD-group, and a strong association between the two groups’ rank-ordering the rhythms for complexity. This indicates a preserved ability to discriminate between relative levels of complexity. Finally, the two groups did not significantly differ in their subjective scoring of likeability, demonstrating a dissimilarity between judgment of complexity and judgment of likeability between the two groups. This indicates different cognitive operations for the two types of judgment, and we speculate that Parkinson’s disease affects judgment of complexity but not judgment of likeability. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to investigate whether noise in delivery rooms is associated with impaired performance of obstetric teams managing major (≥1000 mL) postpartum hemorrhage. Material and methods: We included video recordings of 96 obstetric teams managing real-life major postpartum hemorrhage. Exposure was noise defined as the occurrence of sound level pressures (SPL) above 90 dB. The outcome was high clinical performance assessed through expert ratings using the TeamOBS-PPH tool. Results: The 23 teams unexposed to noise had a significantly higher chance of high clinical performance than the 73 teams exposed to noise: 91.3% (95% CI; 72.0–98.9) versus 58.9% (95% CI; 46.8–70.3) (p < 0.001). The results remained significant when adjusting for the following possible confounders: team size, non-technical performance, bleeding velocity, hospital type, etiology of bleeding, event duration and time of day. Typical sources of noise above 90 dB SPL were mother or baby crying, dropping of instruments, and slamming of cupboard doors. Conclusion: Noise in delivery rooms may be an independent source of impaired clinical performance. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment affects up to 80 percent of the stroke population, however, both the available evidence about post-stroke cognition and the measures used to evaluate it longitudinally have not been well described. The aims of this systematic scoping review were: to identify and characterize studies evaluating cognition longitudinally after stroke; to summarize the cognitive instruments used and the domains they target; and to organize cognitive domains assessed using the International Classification of Functioning, Disability and Health (ICF). Methods: We used a systematic scoping approach to search for peer-reviewed articles involving adults with stroke that evaluated cognition longitudinally. Screening of titles, abstracts, and full reports was completed independently by two reviewers, across six electronic databases (PubMed, PsycInfo, Medline, Cinahl Plus, Embase, and Web of Science). Cognitive domains were mapped to an ICF function independently by the same two reviewers, using a previously tested, standardized approach. Results: A total of 5,540 records were found; 257 were included, representing a total pooled sample of 120,860 stroke survivors. Of these studies, 200 (78%) provided specific cognitive outcomes from the longitudinal evaluations, 57 (22%) reported model predictions, and 77 (30%) included interventions. Cognition was evaluated with 356 unique instruments, targeting 95 distinct cognitive domains, and 17 mental functions from the ICF. The Mini-Mental State Examination was the most frequently used instrument (117 reports, 46%). Other tools used longitudinally were the Trail Making Test (17% of reports), tests of verbal fluency (14%), the Functional Independence Measure (14%), the Montreal Cognitive Assessment (13%), the Digit Span (11%), and the Stroop test (10%). Global cognition was evaluated in 170 reports (66%), followed by higher-level cognitive functioning (29%), memory (28%), language (21%), attention (21%), and perceptual skills (14%). Studies using functional (or performance-based) cognitive assessments over time were scarce (< 1%). Conclusion: Our findings indicate that whilst there is a substantial number of studies available that report longitudinal evaluations of cognition after stroke, there is large variability in the measures used and the cognitive domains they target. Nonetheless, the available data for evaluation of cognition over time after stroke can be organized and described systematically. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) may lead to cognitive decline over-time. Objectives: Characterize cognitive performance in MS patients with long disease duration treated with disease modifying drugs (DMD) in relation to disability and determine the prevalence of cognitive resilience. Methods: Cognitive and functional outcomes were assessed in 1010 DMD-treated MS patients at least 10 years from onset. Cognitive performance was categorized as high, moderate or low, and neurological disability was classified according to the Expanded Disability Status Scale (EDSS) as mild, moderate or severe. Relationship between cognitive performance and disability was examined. Results: After a mean disease duration of 19.6 (SD = 7.7) years, low cognitive performance was observed in 23.7% (N = 239), moderate performance in 42.7% (N = 431), and 33.7% (N = 340) had high cognitive performance, meeting the definition of cognitively resilient patients. Within the group of patients with low cognitive performance, severe disability was observed in 50.6% (121/239), while in the group of patients with high cognitive performance, mild disability was observed in 64.4% (219/340). Differences between the group of patients with high cognitive performance and severe disability (4.5%) and the group of patients with low cognitive performance and mild disability (5.0%) were not accounted for by DMD treatment duration. Conclusions: The majority of DMD treated MS patients did not have cognitive decline that could impair their quality of life after disease of extended duration. [ABSTRACT FROM AUTHOR]

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a hepatic enzyme that regulates circulating low-density lipoprotein (LDL) cholesterol levels by binding to LDL receptors (LDLR) and promoting their degradation. Although PCSK9 inhibitors were shown to reduce the risk of cardiovascular disease, a warning was issued concerning their possible impact on cognitive functions. In Alzheimer’s disease (AD), it is believed that cognitive impairment is associated with cholesterol metabolism alterations, which could involve PCSK9. The main objective of this study is to determine if PCSK9 plays a significant role in the pre-symptomatic phase of the disease when the pathophysiological markers of AD unfolds and, later, when cognitive symptoms emerge. Methods and findings: To test if PCSK9 is associated with AD pathology, we measured its expression levels in 65 autopsy confirmed AD brains and 45 age and gender matched controls. Messenger ribonucleic acid (mRNA) were quantified using real-time polymerase chain reaction (RT-PCR) and protein levels were quantified using enzyme-linked immunosorbent assay (ELISA). PCSK9 was elevated in frontal cortices of AD subjects compared to controls, both at the mRNA and protein levels. LDLR protein levels were unchanged in AD frontal cortices, despite and upregulation at the mRNA level. To verify if PCSK9 dysregulation was observable before the onset of AD, we measured its expression in the cerebrospinal fluid (CSF) of 104 “at-risk” subjects and contrasted it with known apolipoproteins levels and specific AD biomarkers using ELISAs. Positive correlations were found between CSF PCSK9 and apolipoprotein E (APOE), apolipoprotein J (APOJ or CLU), apolipoprotein B (APOB), phospho Tau (pTau) and total Tau. To investigate if PCSK9 levels were driven by genetic variants, we conducted an expression quantitative trait loci (eQTL) study using bioinformatic tools and found two polymorphisms in strong association. Further investigation of these variants in two independent cohorts showed a female specific association with AD risk and with CSF Tau levels in cognitively impaired individuals. Conclusions: PCSK9 levels differ between control and AD brains and its protein levels correlate with those of other lipoproteins and AD biomarkers even before the onset of the disease. PCSK9 regulation seems to be under tight genetic control in females only, with specific variants that could predispose to increased AD risk. [ABSTRACT FROM AUTHOR]

Although dyslexia affects 5–8% of the workforce this developmental disorder has not been sufficiently researched in adult populations. Yet a diagnosis confers legal protections as employers must provide disability ‘accommodations’ to assist work functioning and performance. The implementation of such accommodations, including coaching, lacks theoretical framing and evaluations of impact in practice. Recognizing a need for conceptual work, we undertook a narrative, systematic scoping review from a realist pragmatic epistemology, taking an iterative approach to define and address the review question: ‘to what extent, and under what conditions, can face-to-face learning interventions improve Working Memory (WM) and Self-Efficacy (SE) and can these lead to functional improvements related to work performance?’ Informed by expert and stakeholder consultation and user data, our review extracted and synthesized 25 studies from eleven countries to identify potentially applicable learning intervention theories, their effects upon WM and SE but also functional outcomes such as comprehension. We suggest that intervention protocols informed by Social Cognitive Learning Theory can improve SE, as would be expected, and more surprisingly also WM. The development of metacognition, stress management and fidelity to Goal Setting Theory were identified as valuable intervention features. We propose that coaching activities may provide a more contextualized environment for transfer of learning from WM to functional skills such as comprehension, when compared to computerized training interventions. We call for theoretically underpinned, primary studies to evaluate interventions with adult dyslexic populations to further our understanding of disability accommodations. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) remains a clinical diagnosis but biomarkers from cerebrospinal fluid (CSF) and more lately amyloid imaging with positron emission tomography (PET), are important to support a diagnosis of AD. Objective: To compare amyloid-β (Aβ) PET imaging with biomarkers in CSF and evaluate the prediction of Aβ PET on diagnosis in a memory clinic setting. Methods: We included 64 patients who had lumbar puncture and Aβ PET with 18F-Flutemetamol performed within 190 days. PET was binary classified (Flut+ or Flut-) and logistic regression analyses for correlation to each CSF biomarker; Aβ 42 (Aβ42), total tau (T-tau) and phosphorylated tau (P-tau), were performed. Cut-off values were assessed by receiver operating characteristic (ROC) curves. Logistic regression was performed for prediction of clinical AD diagnosis. We assessed the interrater agreement of PET classification as well as for diagnoses, which were made both with and without knowledge of PET results. Results: Thirty-two of the 34 patients (94%) in the Flut+ group and nine of the 30 patients (30%) in the Flut- group had a clinical AD diagnosis. There were significant differences in all CSF biomarkers in the Flut+ and Flut- groups. Aβ42 showed the highest correlation with 18F-Flutemetamol PET with a cut-off value of 706.5 pg/mL, corresponding to sensitivity of 88% and specificity of 87%. 18F-Flutemetamol PET was the best predictor of a clinical AD diagnosis. We found a very high interrater agreement for both PET classification and diagnosis. Conclusions: The present study showed an excellent correlation of Aβ42 in CSF and 18F-Flutemetamol PET and the presented cut-off value for Aβ42 yields high sensitivity and specificity for 18F-Flutemetamol PET. 18F-Flutemetamol PET was the best predictor of clinical AD diagnosis. [ABSTRACT FROM AUTHOR]

Smoking cigarettes and low socioeconomic status (SES) are both related to impaired cognition. However, it is unknown whether people of lower SES, who comprise most tobacco smokers worldwide, are more susceptible to cognitive impairment associated with smoking. In this non-randomized, cross-sectional study we investigated the effects of cigarette smoking, SES and their interaction on dissociable executive or "cool" and "hot" measures of behavioural self-regulation. Participants (n = 80) were selected among young physically and mentally healthy smokers and non-smokers who had graduated high school and were from different SES backgrounds. Cool self-regulation was measured by executive function tasks that tap inhibition, updating, shifting, dual tasking, planning, access to long-term memory (semantic fluency), and working memory capacity. Hot measures assessed self-reported impulsivity, delay discounting and risk taking. Exposure to tobacco (cotinine, exhaled carbon monoxide, tobacco dependence, cigarette consumption) was assessed to determine to what extent it mediated the cognitive effects of smoking. Nicotine abstinence and its acute effects were controlled, as were sex, age, schooling, and psychiatric symptoms despite the fact that smokers and non-smokers were selected as being as similar as possible in these demographic characteristics. Lower SES (less years of parental schooling) was associated with worse performance on tasks that measured all cool domains except dual tasking and fluency, while smoking status was related to impaired delayed discounting and impulsivity (hot domains), effects that were not mediated by tobacco exposure. Smoking and SES, however, did not interact. In short, impaired performance in measures of most cool skills was associated with SES irrespective of smoking status; in contrast, regardless of SES, smokers showed specific impairment in hot self-regulation domains (more difficulty resisting immediate temptations and weighing future consequences of actions). Possible explanations for the lack of mediation of tobacco exposure on hot skills of smokers are discussed. [ABSTRACT FROM AUTHOR]

Although monosodium glutamate (MSG)-induced neurotoxicity has been recognized for decades, the potential similarities of the MSG model to Alzheimer’s disease (AD)-type neuropathology have only recently been investigated. MSG-treated mice were examined behaviourally and histologically in relation to some features of AD. Four-week old mice received 5 subcutaneous MSG (2 g/kg) injections on alternate days, or saline. At age 10–12 weeks, they were given a battery of behavioural tests for species-typical behaviours and working memory. The mice were killed at 12 weeks and the brains excised. Accumulation of hyperphosphorylated tau protein was assessed in cortical and hippocampal neurons by immunohistochemistry, and in cerebral cortical homogenates. A 78% increase in cortical concentrations of phosphorylated tau protein was observed in the MSG mice. Intracellular hyperphosphorylated tau immunostaining was observed diffusely in the cortex and hippocampus, together with cortical atrophic neurons, extensive vacuolation and dysmorphic neuropil suggestive of spongiform neurodegeneration. Nest-building was significantly impaired, and spontaneous T-maze alternation was reduced, suggesting defective short-term working memory. Subcutaneous MSG treatment also induced a 56% reduction in exploratory head dips in a holeboard (P = 0.009), and a non-significant tendency for decreased burrowing behaviour (P = 0.085). These effects occurred in the absence of MSG-induced obesity or gross locomotor deficits. The findings point to subcutaneous MSG administration in early life as a cause of tau pathology and compromised species-typical behaviour in rodents. Determining whether MSG can be useful in modelling AD requires further studies of longer duration and full behavioural characterization. [ABSTRACT FROM AUTHOR]

Background: Alzheimer’s Disease (AD) can cause degeneration in the retina and optic nerve either directly, as a result of amyloid beta deposits, or secondarily, as a result of the degradation of the visual cortex. These effects raise the possibility that tracking ophthalmologic changes in the retina can be used to assess neurodegeneration in AD. This study aimed to detect retinal changes and associated functional changes in three groups of patients consisting of AD patients with mild disease, AD patients with moderate disease and healthy controls by using non-invasive psychophysical ophthalmological tests and optical coherence tomography (OCT). Methods: We included 39 patients with mild AD, 21 patients with moderate AD and 40 age-matched healthy controls. Both patients and controls were ophthalmologically healthy. Visual acuity, contrast sensitivity, colour perception, visual integration, and choroidal thicknesses were measured. In addition, OCT and OCT angiography (OCTA) were applied. Findings: Visual acuity, contrast sensitivity, colour perception, and visual integration were significantly lower in AD patients than in healthy controls. Compared to healthy controls, macular thinning in the central region was significant in the mild AD patients, while macular thickening in the central region was found in the moderate AD group. The analysis of macular layers revealed significant thinning of the retinal nerve fibre layer, the ganglion cell layer and the outer plexiform layer in AD patients relative to controls. Conversely, significant thickening was observed in the outer nuclear layer of the patients. However, mild AD was associated with significant thinning of the subfovea and the nasal and inferior sectors of the choroid. Significant superonasal and inferotemporal peripapillary thinning was observed in patients with moderate disease. Conclusions: The first changes in the mild AD patients appear in the psychophysical tests and in the central macula with a decrease in the central retinal thickness. When there was a disease progression to moderate AD, psychophysical tests remained stable with respect to the decrease in mild AD, but significant thinning in the peripapillary retina and thickening in the central retina appeared. The presence of AD is best indicated based on contrast sensitivity. [ABSTRACT FROM AUTHOR]

Difficulty performing activities of daily living (“functional impairment”) is common in homeless adults aged 50 and older. However, little is known about the trajectory of these impairments, nor the extent to which these trajectories are similar to those of older adults in the general population. We identified trajectories of functional impairment in homeless adults aged 50 and older, and risk factors for differing trajectories. We conducted a prospective cohort study of 350 homeless adults, aged 50 and older, recruited via population-based sampling in Oakland, California and interviewed at 6-month intervals for up to 3 years. We assessed functional trajectories based on self-reported difficulty performing 5 activities of daily living. We used multivariable multinomial logistic regression to identify baseline risk factors for each trajectory. At baseline, participants’ mean age was 58 years (SD, 5.3), 24.1% were women, 80.9% were African American, and 38.6% had difficulty performing 1 or more activities of daily living. We identified 4 distinct functional trajectories: minimal impairment in 136 participants (41.1%); persistent impairment in 81 (25.4%); partial improvement in 74 (23.5%); and decline in 28 (10.0%). Risk factors for persistent impairment included falls in the 6 months before baseline, depressive symptoms, and low physical performance. Although functional impairment improved in some homeless adults, it persisted or worsened in many others. These findings suggest that, similar to older adults in the general population, functional impairment among older homeless persons is not a transient phenomenon, but instead a chronic issue requiring long-term solutions. [ABSTRACT FROM AUTHOR]

Subacute and chronic infections with the intracellular protozoan parasite Toxoplasma gondii are associated with an increased risk of psychiatric diseases like schizophrenia. However, little is known about the mechanisms involved in T. gondii-induced neuronal disorders. Recently, we reported that Toll-like receptor 2 (TLR2) was required to initiate the innate immune response in cultured mouse brain cells. However, how TLR2 contributes to latent infection with T. gondii remains unclear. Therefore, we examined the role of TLR2 in brain pathology and behavior using wild-type (TLR2+/+) and TLR2-deficient (TLR2-/-) mice. The behavioral analyses showed that TLR2 deficiency increased the anxiety state of the uninfected and infected animals alike, and TLR2 deficiency showed no relationship with the infection. In the contextual and cued fear-conditioning tests, T. gondii infection decreased the mouse freezing reaction while TLR2 deficiency increased it, but there was no interaction between the two factors. Our histopathological analysis showed that the TLR2+/+ and TLR2-/- mice had similar brain lesions at 30 days post infection (dpi) with T. gondii. Higher numbers of parasites were detected in the brains of the TLR2-/- mice than in those from the TLR2+/+ mice at 30 dpi, but not at 7 and 14 dpi. No significant differences were observed in the proinflammatory gene expression levels in the TLR2+/+ and TLR2-/- mice. Therefore, it appears that TLR2 signaling in the brain might contribute to the control of parasite growth, but not to brain pathology or the impaired fear memory response induced by infection with T. gondii. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease and related disorders (ADRD) may manifest cognitive and non-cognitive phenotypes including motor impairment, suggesting a shared underlying biology. We tested the hypothesis that five cortical proteins identified from a gene network that drives AD and cognitive phenotypes are also related to motor function in the same individuals. We examined 1208 brains of older adults with motor and cognitive assessments prior to death. Cortical proteins were quantified with SRM proteomics and we collected indices of AD and other related pathologies. A higher level of IGFBP5 was associated with poorer motor function proximate to death but AK4, HSPB2, ITPK1 and PLXNB1 were unrelated to motor function. The association of IGFBP5 with motor function was unrelated to the presence of indices of brain pathologies. In contrast, the addition of a term for cognition attenuated the association of IGFBP5 with motor function by about 90% and they were no longer related. These data lend support for the idea that unidentified cortical proteins like IGFBP5, which may not manifest a known pathologic footprint, may contribute to motor and cognitive function in older adults. [ABSTRACT FROM AUTHOR]

Introduction: Cognitive deficits are frequently found after subarachnoid hemorrhage (SAH), but their influence on return to work is largely unknown. To improve identification of those patients at-risk for long-term return to work problems, we aimed to examine the value of cognitive deficits in the prediction of long-term return to work after subarachnoid hemorrhage. Methods: SAH patients (N = 71) who were employed before SAH and were able to undergo neuropsychological assessment, were included. Demographic characteristics and acute SAH-related variables (SAH-type and external cerebrospinal fluid drainage) were taken into account. Neuropsychological tests for memory, speed, attention, executive function, and emotion recognition and a questionnaire for executive functions were used. Return to work was assessed using the Role Resumption List. Results: Results showed that patients with incomplete return to work had significantly lower scores on neuropsychological measures for complex attention and executive functions (p < 0.05) compared to patients with complete return to work. Return to work could not be significantly predicted using only demographic characteristics and acute SAH-related variables, but adding measures of complex attention and executive functions resulted in a prognostic model that could reliably distinguish between complete and incomplete return to work. Statistically significant predictors in the final model were cerebrospinal fluid drainage and scores on a questionnaire for executive functions: patients with cerebrospinal fluid drainage and higher scores on the a questionnaire for executive functions were less likely to return to work. Discussion: Together, these findings show that neuropsychological measures, especially for complex attention and executive functions, have added value to acute SAH-related and demographic variables in the prediction of long-term return to work after SAH. [ABSTRACT FROM AUTHOR]

Aim: The aim of this systematic review was to summarize and critically appraise the quality of published literature on measurement properties of questionnaires assessing Cognitive Reserve (CR) in adults (>18 years). Methods: We systematically searched for published studies on MEDLINE, PsycINFO, and Web of Science through August 2018. We evaluated the methodological quality of the included studies and the results on measurement properties based on a consensus-based standard checklist. Results: The search strategy identified 991 publications, of which 37 were selected evaluating the measurement properties of six different questionnaires. Construct validity of the Cognitive Reserve Index questionnaire was most extensively evaluated, while evaluation of the remaining measurement properties of this questionnaire was scarce. Measurement properties of the Cognitive Reserve Questionnaire and the Cognitive Reserve Scale were assessed more completely. While the Lifetime of Experience Questionnaire seems to be the most thorough instrument, a finale recommendation for one specific questionnaire cannot be drawn, since about half of the measurement properties for each questionnaire were poorly or not assessed at all. Conclusions: There is a need of high quality methodological studies assessing measurement properties of CR questionnaires, especially regarding content validity, structural validity, and responsiveness. Trial registration: PROSPERO Registration number . [ABSTRACT FROM AUTHOR]

Spirometry remains essential for the diagnosis of airway obstruction. Nevertheless, its performance in elderly hospitalized patients with multimorbidity can be difficult. The aim of this study is to assess the utility of the COPD-6 portable device in this population. We included all patients hospitalized for exacerbation of chronic diseases in a medical ward specialized in the care of multimorbidity patients, between September 2017 and May 2018. A questionnaire including sociodemographic, cognitive and functional impairment, among other variables, was completed the last day of admission. Subsequently, patients attempted to perform three valid respiratory manoeuvres with the COPD-6 device and then conventional spirometry. A total of 184 patients were included (mean age of 79.61 years, 55% men). Forty-seven (25.54%) patients were able to perform complete spirometric manoeuvres and 99 (53.8%) could perform a valid FEV1/FEV6 determination. The inability to perform a valid spirometry was related with the patient’s age, functional physical disability, cognitive impairment or the presence of delirium or dysphagia during admission. Only 9% of patients with a Mini Mental Cognitive Examination (MMEC) lower than 24 points could perform a valid spirometry. Of the patients with an MMEC < 24 points and unable to perform spirometry, 34% were able to complete the FEV1/FEV6 manoeuvres. No differences were found in the Charlson index, multimorbidity scale, number of domiciliary drugs, or length of stay between those patients able and those not able to perform respiratory manoeuvres. The agreement between the values for FEV1 measured with COPD-6 and those observed in the spirometry was good (r: 0.71; p<0.0001). Inability to perform a valid spirometry during hospitalization in elderly patients with multimorbidity is frequent and related with functional and cognitive impairment. FEV1/FEV6 determination using the COPD-6 portable device allows an important percentage of the patients with limitations to complete spirometric measurement. [ABSTRACT FROM AUTHOR]

Several metrics of analysis of magnetic resonance imaging (MRI) have been used to assess Alzheimer’s disease (AD)-related neurodegeneration. We compared four structural brain MRI analysis metrics, cortical thickness, volume, surface area, and local gyrification index (LGI), in different stages of AD-related cognitive decline. Participants with normal cognition, mild cognitive impairment, and AD were included (34 participants per group). All undertook the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) battery of neuropsychological tests and brain MRI scanning. We analyzed associations between morphometric measures and CERAD total/ Mini Mental State Examination (MMSE) scores for the regions of interest (ROIs), identifying three types of curves: U-shaped, inverted U-shaped, and linear. Cortical thickness and volume analyses showed linear types in most of the significant ROIs. Significant ROIs for the cortical thickness analysis were located in the temporal and limbic lobes, whereas those for volume and surface area were distributed over more diffuse areas of the brain. LGI analysis showed few significant ROIs. CERAD total scores were more sensitive to early changes of cortical structures than MMSE scores. Cortical thickness analysis may be preferable in assessing brain structural MRI changes during AD-related cognitive decline, whereas LGI analysis may have limited capability to reflect the cognitive decrease. Our findings may provide a reference for future studies and help to establish optimal analytical approaches to brain structural MRI in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background: Social engagement protects against dementia onset. Less is known about patterns of social engagement around the time of dementia diagnosis. We investigated face-to-face and telephone contact at three times (pre-diagnosis, at report of diagnosis, 2 years post-diagnosis) in individuals who developed dementia and a comparison group. Methods: Social engagement was assessed at waves 2–7 of the English Longitudinal Study of Ageing in 4171 individuals aged 50 and older. Dementia was ascertained by either self-reported physician diagnosis or through an informant evaluation of a participant’s functional and cognitive performance compared with a few years earlier. Generalized estimating equations were used to examine differences by group, time, and group-by-time interactions. Results: The dementia group reported less face-to-face (p < 0.001) and telephone contact (p < 0.001) than the dementia-free group pre-diagnosis. The dementia group experienced greater reductions in social engagement leading up to dementia diagnosis and in the 2 years following diagnosis (p’s < 0.001). Conclusion: Given that social engagement reduces dementia risk and supports the lived experience of people with dementia, it is important to find ways of promoting social interaction in older adults. [ABSTRACT FROM AUTHOR]