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Epub 2021 Jun 12. Significance: Early monolingual versus bilingual experience induces adaptations in the development of linguistic and cognitive processes, and it modulates functional activation patterns during the first months of life. Resting-state functional connectivity (RSFC) is a convenient approach to study the functional organization of the infant brain. RSFC can be measured in infants during natural sleep, and it allows to simultaneously investigate various functional systems. Adaptations have been observed in RSFC due to a lifelong bilingual experience. Investigating whether bilingualism- induced adaptations in RSFC begin to emerge early in development has important implications for our understanding of how the infant brain’s organization can be shaped by early environmental factors. Aims: We attempt to describe RSFC using functional near-infrared spectroscopy (fNIRS) and to examine whether it adapts to early monolingual versus bilingual environments. We also present an fNIRS data preprocessing and analysis pipeline that can be used to reliably characterize RSFC in development and to reduce false positives and flawed results interpretations. Methods: We measured spontaneous hemodynamic brain activity in a large cohort (N ¼ 99) of 4-month-old monolingual and bilingual infants using fNIRS. We implemented group-level approaches based on independent component analysis to examine RSFC, while providing proper control for physiological confounds and multiple comparisons. Results: At the group level, we describe the functional organization of the 4-month-old infant brain in large-scale cortical networks. Unbiased group-level comparisons revealed no differences in RSFC between monolingual and bilingual infants at this age. Conclusions: High-quality fNIRS data provide a means to reliably describe RSFC patterns in the infant brain. The proposed group-level RSFC analyses allow to assess differences in RSFC across experimental conditions. An effect of early bilingual experience in RSFC was not observed, suggesting that adaptations might only emerge during explicit linguistic tasks, or at a later point in development. The authors would like to thank all the parents and infants who generously participate in our studies. The authors also would like to thank Elena Aguirrebengoa for her assistance on recruiting and testing participants and Enrico Amico for discussion regarding the connICA approach. This work was supported by the Basque Government (Nos. PRE_2018_2_0154, PIBA_2019_ 104, and BERC 2018-2021); the Spanish Ministry of Economy and Competitiveness (Nos. RYC-2017-21845, PID2019-105520GB-100, and PSI2014-5452-P); the Natural Sciences and Engineering Research Council of Canada (Nos. 506948 and 506993); and the Engineering and Physical Sciences Research Council (Nos. EP/N025946/1 and EP/509577/1).

SignificanceClinical use of fNIRS derived features has always suffered low sensitivity and specificity due to signal contamination from background systemic physiological fluctuations. This article provides an algorithm to extract cognition related features by eliminating the effect of background signal contamination; hence, improves the classification accuracy.AimThe aim in this study is to investigate the classification accuracy of an fNIRS derived biomarker based on global efficiency. To this end, fNIRS data were collected during a computerized Stroop Task from healthy controls, and patients with migraine, obsessive compulsive disorder, and schizophrenia.ApproachFunctional connectivity (FC) maps were computed from [HbO] time series data for Neutral, Congruent and Incongruent stimuli using the partial correlation approach. Reconstruction of FC matrices with optimal choice of principal components yielded two independent networks: Cognitive Mode Network (CM) and Default Mode Network(DM).ResultsGlobal Efficiency (GE) values computed for each FC matrix after applying principal component analysis yielded strong statistical significance leading to a higher specificity and accuracy. A new index, Neurocognitive Ratio (NCR), was computed by multiplying the Cognitive Quotients (CQ) and ratio of GE of CM to GE of DM. When mean values of NCR over all stimuli were computed, they showed high sensitivity (100%), specificity (95.5%), and accuracy (96.3%) for all subjects groups.Conclusions can reliable be used as a biomarker to improve the classification of healthy to neuropsychiatric patients.

Competing theories of dyslexia posit that reading difficulties arise from impaired visual, auditory, phonological, or statistical learning mechanisms. Importantly, many theories posit that dyslexia reflects a cascade of impairments emanating from a single “core deficit”. Here we report two studies evaluating core deficit and multifactorial models. In Study 1, we use publicly available data from the Healthy Brain Network to test the accuracy of phonological processing measures for predicting dyslexia diagnosis and find that over 30% of cases are misclassified (sensitivity = 66.7%; specificity = 68.2%). In Study 2, we collect a battery of psychophysical measures of visual motion processing and standardized measures of phonological processing in 106 school‐aged children to investigate whether dyslexia is best conceptualized under a core‐deficit model, or as a disorder with heterogenous origins. Specifically, by capitalizing on the drift diffusion model to analyze performance on a visual motion discrimination experiment, we show that deficits in visual motion processing, perceptual decision‐making, and phonological processing manifest largely independently. Based on statistical models of how variance in reading skill is parceled across measures of visual processing, phonological processing, and decision‐making, our results challenge the notion that a unifying deficit characterizes dyslexia. Instead, these findings indicate a model where reading skill is explained by several distinct, additive predictors, or risk factors, of reading (dis)ability., Using predictors from a visual motion processing experiment and linguistic measures, we show that a single‐mechanism model of reading disability cannot account for the range of linguistic and sensory processing outcomes observed in children. We propose an additive risk factor model where different aspects of sensory, cognitive and language function each contribute independently to reading development.

Objective: Although meningioma patients show deficits in objective cognitive functioning (OCF) measured with neuropsychological tests, subjective cognitive functioning (SCF) has received little attention. We investigate SCF from pre- to post-surgery and its associations with OCF, psychological, sociodemographic, and clinical characteristics.Methods: SCF was measured using the Cognitive Failures Questionnaire (CFQ) one day before (T0), and three (T3) and twelve months (T12) after surgery. Patients' scores were compared to normative data and changes over time were assessed. The neuropsychological battery CNS Vital Signs and the Hospital Anxiety and Depression Scale were administered. Correlations of SCF with OCF, psychological, sociodemographic, and clinical characteristics were explored.Results: Patients reported significantly better SCF as compared with controls at T0 (N=54) and T3 (N=242), but not at T12 (N=50). A significant decrease in group level SCF was observed from T0 to T12 (n=24, pConclusions: Meningioma patients experienced better SCF as compared to controls before and three months after surgery, which might be the result of phenomena related to disease and recovery. As the findings suggest that cognitive symptoms might increase later on, future studies should further investigate the course of SCF in meningioma patients. In clinical practice, measurements of SCF should be combined with those of OCF and psychological distress in order to determine whether and which interventions are needed.

Author(s): Tan, Chia Jie; Mah, Jaclyn Jia Jun; Goh, Wei Lin; Poon, Eileen; Harunal Rashid, Mohamad Farid; Chan, Alexandre | Abstract: ObjectiveCancer-related cognitive impairment (CRCI) among adolescent and young adult (AYA) cancer patients with noncentral nervous system (CNS) cancers has not been well studied. In this study, we aimed to describe CRCI-associated trends and characteristics among AYA cancer patients.MethodsIn a longitudinal cohort of AYA cancer patients without CNS disease, CRCI was evaluated over 1 year using the Functional Assessment of Cancer Therapy-Cognitive Function Instrument, a self-reported cognitive outcome measure. CRCI prevalence was quantified using the previously established minimal clinically important difference. CRCI-associated longitudinal trends and factors were evaluated with mixed-effects model analysis.ResultsNinety-one patients (mean age = 28.4 ± 6.7 years) were included. Approximately one-third (34.1%) experienced CRCI at least once during the study follow-up. Female gender (P = .02), Indian ethnicity (P l .01), current smokers (P l .01), anxiety/depressive symptoms (P l .01) and fatigue (P l .01) were found to be associated with poorer cognitive function among AYAs.ConclusionsAlthough AYA cancer patients were relatively young and without CNS disease involvement, a significant proportion of them experienced clinically important decline in cognitive function. With improved understanding of this subject, effective strategies can be formulated to promote awareness of CRCI and mitigate its negative effects among AYA cancer patients.

Dopamine transmission in the prefrontal cortex (PFC) supports working memory (WM), the temporary holding, processing and manipulation of information in one's mind. The gene coding the catechol‐O‐methyltransferase (COMT) enzyme, which degrades dopamine, in particular in the PFC, has a common single nucleotide polymorphism leading to two versions of the COMT enzyme which vary in their enzymatic activity. The methionine (Met) allele has been associated with higher WM performance and lower activation of the PFC in executive function tasks than the valine (Val) allele. In a previous study, COMT genotype was associated with performance on verbal and visuospatial WM tasks in adults, as well as with performance on a novel social WM paradigm that requires participants to maintain and manipulate information about the traits of their friends or family over a delay. Here, data collected in children and adolescents (N = 202) were compared to data from the adult sample (N = 131) to investigate possible age differences in genetic associations. Our results replicate and extend previous work showing that the pattern of superior WM performance observed in Met/Met adults emerges during development. These findings are consistent with a decrease in prefrontal dopamine levels during adolescence. Developmentally moderated genetic effects were observed for both visuospatial and social WM, even when controlling for non‐social WM performance, suggesting that the maintenance and manipulation of social information may also recruit the dopamine neurotransmitter system. These findings show that development should be considered when trying to understand the impact of genetic polymorphisms on cognitive function., Rs4680 is a genetic polymorphism with two allelic variants (Met vs. Val) that affects the enzymatic activity of the catechol‐O‐methyltransferase (COMT) enzyme, which degrades dopamine. Met/Met adults have been found to have better performance and lower prefrontal cortex activity during working memory (WM) tasks. This study shows that the genetic association with visuospatial WM, but not verbal WM performance, emerges during development, and that the same pattern can be observed in a WM task requiring participants to manipulate social information. These results are consistent with a decrease in prefrontal dopamine levels during development and suggest an involvement of dopaminergic neurotransmission in social cognition.

In a non‐randomized controlled study, we investigated the efficacy of a school‐based mindfulness curriculum delivered by schoolteachers to older secondary school students (16–18 years). We measured changes in emotion processing indexed by P3b event‐related potential (ERP) modulations in an affective oddball task using static human faces. ERPs were recorded to happy and sad face oddballs presented in a stimulus stream of frequent faces with neutral expression, before and after 8 weeks of mindfulness training. Whilst the mean amplitude of the P3b, an ERP component typically elicited by infrequent oddballs, decreased between testing sessions in the control group, it remained unchanged in the training group. Significant increases in self‐reported well‐being and fewer doctor visits for mental health support were also reported in the training group as compared to controls. The observed habituation to emotional stimuli in controls thus contrasted with maintained sensitivity in mindfulness‐trained students. These results suggest that in‐school mindfulness training for adolescents has scope for increasing awareness of socially relevant emotional stimuli, irrespective of valence, and thus may decrease vulnerability to depression.

BackgroundSymptoms of anxiety and depression are prevalent in older adults.AimsTo compare clinician-guided and self-guided versions of a transdiagnostic internet-delivered cognitive–behavioural therapy (iCBT) intervention for adults aged 60 years and above.MethodAdults (n=433) with symptoms of anxiety and depression were randomly allocated to: (1) clinician-guided treatment (n=153); (2) initial clinician interview followed by self-guided treatment (n=140); or (3) self-guided treatment without interview (n=140).ResultsLarge reductions (d ≥1.00) in symptoms of depression and anxiety were observed across groups, and sustained at follow-up. No differences were observed in clinical outcomes or satisfaction ratings. Age did not affect outcomes.ConclusionsCarefully developed iCBT interventions may significantly reduce symptoms of anxiety and depression in older adults when delivered in either clinician-guided or self-guided formats.

BackgroundHealth anxiety and medically unexplained symptoms cost the National Health Service (NHS) an estimated £3 billion per year in unnecessary costs with little evidence of patient benefit. Effective treatment is rarely taken up due to issues such as stigma or previous negative experiences with mental health services. An approach to overcome this might be to offer remotely delivered psychological therapy, which can be just as effective as face-to-face therapy and may be more accessible and suitable.AimsTo investigate the clinical outcomes and cost-effectiveness of remotely delivered cognitive–behavioural therapy (CBT) to people with high health anxiety repeatedly accessing unscheduled care (trial registration: NCT02298036).MethodA multicentre randomised controlled trial (RCT) will be undertaken in primary and secondary care providers of unscheduled care across the East Midlands. One hundred and forty-four eligible participants will be equally randomised to receive either remote CBT (6–12 sessions) or treatment as usual (TAU). Two doctoral research studies will investigate the barriers and facilitators to delivering the intervention and the factors contributing to the optimisation of therapeutic outcome.ResultsThis trial will be the first to test the clinical outcomes and cost-effectiveness of remotely delivered CBT for the treatment of high health anxiety.ConclusionsThe findings will enable an understanding as to how this intervention might fit into a wider care pathway to enhance patient experience of care.

Literacy and numeracy are important skills that are typically learned during childhood, a time that coincides with considerable shifts in large‐scale brain organization. However, most studies emphasize focal brain contributions to literacy and numeracy development by employing case‐control designs and voxel‐by‐voxel statistical comparisons. This approach has been valuable, but may underestimate the contribution of overall brain network organization. The current study includes children (N = 133 children; 86 male; mean age = 9.42, SD = 1.715; age range = 5.92–13.75y) with a broad range of abilities, and uses whole‐brain structural connectomics based on diffusion‐weighted MRI data. The results indicate that academic attainment is associated with differences in structural brain organization, something not seen when focusing on the integrity of specific regions. Furthermore, simulated disruption of highly‐connected brain regions known as hubs suggests that the role of these regions for maintaining the architecture of the network may be more important than specific aspects of processing. Our findings indicate that distributed brain systems contribute to the etiology of difficulties with academic learning, which cannot be captured using a more traditional voxel‐wise statistical approach.

OBJECTIVE: Hot flushes and night sweats (HFNS) are experienced by up to 80% of prostate cancer patients undergoing androgen deprivation therapy (ADT). This study evaluates the effects of a guided self-help cognitive behavioural therapy (CBT) intervention on HFNS problem-rating (primary outcome), HFNS frequency, mood and health-related quality of life (secondary outcomes) in patients undergoing ADT.METHODS: Patients reporting treatment-induced HFNS were randomly assigned to CBT (n = 33) or treatment as usual (TAU) (n = 35), stratified for cancer type. The CBT intervention included a booklet, CD plus telephone contact during a 4-week period. Validated self-report questionnaires were completed at baseline, 6 weeks and 32 weeks after randomisation. The primary outcome was HFNS problem rating (perceived burden of HFNS) at 6 weeks after randomisation. Potential moderators and mediators were examined. Data analysis was conducted on a modified intention-to-treat basis.RESULTS: Compared with TAU, CBT significantly reduced HFNS problem rating (adjusted mean difference: -1.33, 95% CI -2.07 to -0.58; p = 0.001) and HFNS frequency (-12.12, 95% CI -22.39 to -1.84; p = 0.02) at 6 weeks. Improvements were maintained at 32 weeks, but group differences did not reach significance. There were significant reductions in negative HFNS Beliefs and Behaviours following CBT, but not in mood or quality of life.CONCLUSIONS: Guided self-help CBT appears to be a safe and effective brief treatment for men who have problematic HFNS following prostate cancer treatments. Further research might test the efficacy of the intervention in a multicentre trial. © 2015 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.

Functional connectivity is the statistical association of neuronal activity time courses across distinct brain regions, supporting specific cognitive processes. This coordination of activity is likely to be highly important for complex aspects of cognition, such as the communication of fluctuating task goals from higher‐order control regions to lower‐order, functionally specific regions. Some of these functional connections are identifiable even when relevant cognitive tasks are not being performed (i.e. at rest). We used magnetoencephalographic recordings projected into source space to demonstrate that resting state networks in childhood have electrophysiological underpinnings that are evident in the spontaneous fluctuations of oscillatory brain activity. Using the temporal structure of these oscillatory patterns we were able to identify a number of functional resting state networks analogous to those reported in the adult literature. In a second analysis we fused this dynamic temporal information with the spatial information from a functional magnetic resonance imaging analysis of functional connectivity, to demonstrate that inter‐subject variability in these electrophysiological measures of functional connectivity is correlated with individual differences in cognitive ability: the strength of connectivity between a fronto‐parietal network and lower‐level processing areas in inferior temporal cortex was associated with spatial working memory capacity, as measured outside the scanner with educationally relevant standardized assessments. This study represents the first exploration of the electrophysiological mechanisms underpinning resting state functional connectivity in source space in childhood, and the extent to which the strength of particular connections is associated with cognitive ability.

BackgroundStudies of the association between pre-deployment cognitive ability and post-deployment post-traumatic stress disorder (PTSD) have shown mixed results.AimsTo study the inflence of pre-deployment cognitive ability on PTSD symptoms 6–8 months post-deployment in a large population while controlling for pre-deployment education and deployment-related variables.MethodStudy linking prospective pre-deployment conscription board data with post-deployment self-reported data in 9695 Danish Army personnel deployed to different war zones in 1997–2013. The association between pre-deployment cognitive ability and post-deployment PTSD was investigated using repeated-measure logistic regression models. Two models with cognitive ability score as the main exposure variable were created (model 1 and model 2). Model 1 was only adjusted for pre-deployment variables, while model 2 was adjusted for both pre-deployment and deployment-related variables.ResultsWhen including only variables recorded pre-deployment (cognitive ability score and educational level) and gender (model 1), all variables predicted post-deployment PTSD. When deployment-related variables were added (model 2), this was no longer the case for cognitive ability score. However, when educational level was removed from the model adjusted for deployment-related variables, the association between cognitive ability and post-deployment PTSD became significant.ConclusionsPre-deployment lower cognitive ability did not predict post-deployment PTSD independently of educational level after adjustment for deployment-related variables.

Infants are curious learners who drive their own cognitive development by imposing structure on their learning environment as they explore. Understanding the mechanisms by which infants structure their own learning is therefore critical to our understanding of development. Here we propose an explicit mechanism for intrinsically motivated information selection that maximizes learning. We first present a neurocomputational model of infant visual category learning, capturing existing empirical data on the role of environmental complexity on learning. Next we “set the model free”, allowing it to select its own stimuli based on a formalization of curiosity and three alternative selection mechanisms. We demonstrate that maximal learning emerges when the model is able to maximize stimulus novelty relative to its internal states, depending on the interaction across learning between the structure of the environment and the plasticity in the learner itself. We discuss the implications of this new curiosity mechanism for both existing computational models of reinforcement learning and for our understanding of this fundamental mechanism in early development.

Children who experience severe early life stress show persistent deficits in many aspects of cognitive and social adaptation. Early stress might be associated with these broad changes in functioning because it impairs general learning mechanisms. To explore this possibility, we examined whether individuals who experienced abusive caregiving in childhood had difficulties with instrumental learning and/or cognitive flexibility as adolescents. Fifty‐three 14–17‐year‐old adolescents (31 exposed to high levels of childhood stress, 22 control) completed an fMRI task that required them to first learn associations in the environment and then update those pairings. Adolescents with histories of early life stress eventually learned to pair stimuli with both positive and negative outcomes, but did so more slowly than their peers. Furthermore, these stress‐exposed adolescents showed markedly impaired cognitive flexibility; they were less able than their peers to update those pairings when the contingencies changed. These learning problems were reflected in abnormal activity in learning‐ and attention‐related brain circuitry. Both altered patterns of learning and neural activation were associated with the severity of lifetime stress that the adolescents had experienced. Taken together, the results of this experiment suggest that basic learning processes are impaired in adolescents exposed to early life stress. These general learning mechanisms may help explain the emergence of social problems observed in these individuals.

Children with reading difficulties and children with a history of repeated ear infections (Otitis Media, OM) are both thought to have phonological impairments, but for quite different reasons. This paper examines the profile of phonological and morphological awareness in poor readers and children with OM. Thirty‐three poor readers were compared to individually matched chronological age and reading age controls. Their phonological awareness and morphological awareness skills were consistently at the level of reading age matched controls. Unexpectedly, a significant minority (25%) of the poor readers had some degree of undiagnosed mild or very mild hearing loss. Twenty‐nine children with a history of OM and their matched controls completed the same battery of tasks. They showed relatively small delays in their literacy and showed no impairment in morphological awareness but had phonological awareness scores below the level of reading age matched controls. Further analysis suggested that this weakness in phonological awareness was carried by a specific weakness in segmenting and blending phonemes, with relatively good performance on phoneme manipulation tasks. Results suggest that children with OM show a circumscribed deficit in phoneme segmentation and blending, while poor readers show a broader metalinguistic impairment which is more closely associated with reading difficulties.

BACKGROUND: Cognitive improvement has been reported in patients receiving centrally acting angiotensin-converting enzyme inhibitors (C-ACEIs). AIMS: To compare cognitive decline and survival after diagnosis of Alzheimer's disease between people receiving C-ACEIs, non-centrally acting angiotensin-converting enzyme inhibitors (NC-ACEIs), and neither. METHOD: Routine Mini-Mental State Examination (MMSE) scores were extracted in 5260 patients receiving acetylcholinesterase inhibitors and analysed against C-/NC-ACEI exposure at the time of Alzheimer's disease diagnosis. RESULTS: In the 9 months after Alzheimer's disease diagnosis, MMSE scores significantly increased by 0.72 and 0.19 points per year in patients on C-ACEIs and neither respectively, but deteriorated by 0.61 points per year in those on NC-ACEIs. There were no significant group differences in score trajectories from 9 to 36 months and no differences in survival. CONCLUSIONS: In people with Alzheimer's disease receiving acetylcholinesterase inhibitors, those also taking C-ACEIs had stronger initial improvement in cognitive function, but there was no evidence of longer-lasting influence on dementia progression. DECLARATION OF INTEREST: R.S. has received research funding from Pfizer, Lundbeck, Roche, Janssen and GlaxoSmithKline. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Sleep spindles are related to sleep-dependent memory consolidation and general cognitive abilities. However, they undergo drastic maturational changes during adolescence. Here we used a longitudinal approach (across 7 years) to explore whether developmental changes in sleep spindle density can explain individual differences in sleep-dependent memory consolidation and general cognitive abilities. Ambulatory polysomnography was recorded during four nights in 34 healthy subjects (24 female) with two nights (baseline and experimental) at initial recording (age range 8-11 years) and two nights at follow-up recording (age range 14-18 years). For declarative learning, participants encoded word pairs with a subsequent recall before and after sleep. General cognitive abilities were measured by the Wechsler Intelligence Scale. Higher slow (11-13 Hz) than fast (13-15 Hz) spindle density at frontal, central, and parietal sites during initial recordings, followed by a shift to higher fast than slow spindle density at central and parietal sites during follow-up recordings, suggest that mature spindle topography develops throughout adolescence. Fast spindle density increases from baseline to experimental night were positively related to sleep-dependent memory consolidation. In addition, we found that the development of fast spindles predicted the improvement in memory consolidation across the two longitudinal measurements, a finding that underlines a crucial role for mature fast spindles for sleep-dependent memory consolidation. Furthermore, slow spindle changes across adolescence were related to general cognitive abilities, a relationship that could indicate the maturation of frontal networks relevant for efficient cognitive processing., SCOPUS: ar.j, info:eu-repo/semantics/published

Low executive function (EF) during early childhood is a major risk factor for developmental delay, academic failure, and social withdrawal. Susceptible genes may affect the molecular and biological mechanisms underpinning EF. More specifically, genes associated with the regulation of prefrontal dopamine may modulate the response of prefrontal neurons during executive control. Several studies with adults and older children have shown that variants of the catechol‐O‐methyltransferase (COMT) gene are associated with behavioral performance and prefrontal activations in EF tasks. However, the effect of the COMT genotype on prefrontal activations during EF tasks on young children is still unknown. The present study examined whether a common functional polymorphism (Val158Met) in the COMT gene was associated with prefrontal activations and cognitive shifting in 3‐ to 6‐year‐old children. The study revealed that, compared with children with at least one Met allele (Met/Met and Met/Val), children who were Val homozygous (i) were more able to flexibly switch rules in cognitive shifting tasks and (ii) exhibited increased activations in lateral prefrontal regions during these tasks. This is the first evidence that demonstrates the relationship between a gene polymorphism and prefrontal activations in young children. It also indicates that COMT Val homozygosity may be advantageous for cognitive shifting and prefrontal functions, at least during early childhood, and children who possess this variant may have a lower risk of developing future cognitive and social development issues.

© 2017 The Authors. Developmental Science Published by John Wiley & Sons Ltd. Analogical reasoning, or the ability to find correspondences between entities based on shared relationships, supports knowledge acquisition. As such, the development of this ability during childhood is thought to promote learning. Here, we sought to better understand the mechanisms by which analogical reasoning about semantic relations improves over childhood and adolescence (e.g. chalk is to chalkboard as pen is to…?). We hypothesized that age-related differences would manifest as differences in the brain regions associated with one or more of the following cognitive functions: (1) controlled semantic retrieval, or the ability to retrieve task-relevant semantic associations; (2) response control, or the ability to override the tendency to respond to a salient distractor; and/or (3) relational integration, or the ability to consider jointly two mental relations. In order to test these hypotheses, we analyzed patterns of fMRI activation during performance of a pictorial propositional analogy task across 95 typically developing children between the ages of 6 and 18 years old. Despite large age-related differences in task performance, particularly over ages 6–10 but through to around age 14, participants across the whole age range recruited a common network of frontal, parietal and temporal regions. However, activation in a brain region that has been implicated in controlled semantic retrieval – left anterior prefrontal cortex (BA 47/45) – was positively correlated with age, and also with performance after controlling for age. This finding indicates that improved performance over middle childhood and early adolescence on this analogical reasoning task is driven largely by improvements in the ability to selectively retrieve task-relevant semantic relationships.

Children with Developmental Coordination Disorder (DCD) fail to acquire adequate motor skill, yet surprisingly little is known about the oculomotor system in DCD. Successful completion of motor tasks is supported by accurate visual feedback. The purpose of this study was to determine whether any oculomotor differences can distinguish between children with and without a motor impairment. Using eye tracking technology, visual fixation, smooth pursuit, and pro‐ and anti‐saccade performance were assessed in 77 children that formed three groups: children with DCD (aged 7–10), chronologically age (CA) matched peers, and a motor‐match (MM) group (aged 4–7). Pursuit gain and response preparation in the pro‐ and anti‐saccade tasks were comparable across groups. Compared to age controls, children with DCD had deficits in maintaining engagement in the fixation and pursuit tasks, and made more anti‐saccade errors. The two typically developing groups performed similarly, except on the fast speed smooth pursuit and antisaccade tasks, where the CA group outperformed the younger MM group. The findings suggest that children with DCD have problems with saccadic inhibition and maintaining attention on a visual target. Developmental patterns were evident in the typically developing groups, suggesting that the pursuit system and cognitive control develop with age. This study adds to the literature by being the first to systematically identify specific oculomotor differences between children with and without a motor impairment. Further examination of oculomotor control may help to identify underlying processes contributing to DCD. A video abstract of this article can be viewed at: https://youtu.be/NinXa2KlB4M. [Correction added on 27 January 2017, after first online publication: The video abstract link was added.]

Background Attention-deficit hyperactivity disorder (ADHD) shows clear, albeit heterogeneous, cognitive dysfunctions. However, personality traits are not well understood in adults with ADHD, and it is unclear whether they are predisposing factors or phenotypical facets of the condition. Aims To assess whether personality traits of impulsivity, sensation seeking and sensitivity to punishment and reward are predisposing factors for ADHD or aspects of the clinical phenotype. Method Twenty adults with ADHD, 20 unaffected first-degree relatives and 20 controls completed rating scales assessing traits of impulsivity, sensation seeking and sensitivity to punishment/reward. Results Compared with relatives and controls, individuals with ADHD showed increased impulsive personality traits, were more susceptible to boredom and presented hypersensitivity to reward but normal sensitivity to punishment. Conclusions High impulsivity traits, heightened sensitivity to reward and boredom are associated with the phenotype of ADHD, rather than being predisposing factors, as these traits were not shared between ADHD probands and their relatives. Declaration of interest E.T.B. is employed part-time by GSK and part-time by the University of Cambridge; he holds stock in GSK. B.J.S. consults for Cambridge Cognition, Servier and Lundbeck; she holds a grant from Janssen/J&J. U.M. has received honoraria for consultancy and speaking at conferences and travel expenses from Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Pharmacia-Upjohn and UCB Pharma. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

In MRI, the coherence lifetime T2 is sensitive to the magnetic environment imposed by tissue microstructure and biochemistry in vivo. Here we explore the possibility that the use of T2 relaxometry may provide information complementary to that provided by diffusion tensor imaging (DTI) in ageing of healthy controls (HC), Alzheimer’s disease (AD) and mild cognitive impairment (MCI). T2 and diffusion MRI metrics were quantified in HC and patients with MCI and mild AD using multi-echo MRI and DTI. We used tract-based spatial statistics (TBSS) to evaluate quantitative MRI parameters in white matter (WM). A prolonged T2 in WM was associated with AD, and able to distinguish AD from MCI, and AD from HC. Shorter WM T2 was associated with better cognition and younger age in general. In no case was a reduction in T2 associated with poorer cognition. We also applied principal component analysis, showing that WM volume changes independently of T2, MRI diffusion indices and cognitive performance indices. Our data add to the evidence that age-related and AD-related decline in cognition is in part attributable to WM tissue state, and much less to WM quantity. These observations suggest that WM is involved in AD pathology, and that T2 relaxometry is a potential imaging modality for detecting and characterising WM in cognitive decline and dementia.

BackgroundThere is a growing interest in using cognitive–behavioural therapy (CBT) with people who have Asperger syndrome and comorbid mental health problems.AimsTo examine whether modified group CBT for clinically significant anxiety in an Asperger syndrome population is feasible and likely to be efficacious.MethodUsing a randomised assessor-blind trial, 52 individuals with Asperger syndrome were randomised into a treatment arm or a waiting-list control arm. After 24 weeks, those in the waiting-list control arm received treatment, while those initially randomised to treatment were followed up for 24 weeks.ResultsThe conversion rate for this trial was high (1.6:1), while attrition was 13%. After 24 weeks, there was no significant difference between those randomised to the treatment arm compared with those randomised to the waiting-list control arm on the primary outcome measure, the Hamilton Rating Scale for Anxiety.ConclusionsTrials of psychological therapies with this population are feasible. Larger definitive trials are now needed.

Purpose With the global expansion of technology, our reading platform has shifted from traditional text to hypertext, yet little consideration has been given to how this shift might help or hinder students' reading comprehension. The purpose of this study was to compare reading comprehension of computer-based and paper-based texts in adolescents with and without language-learning disabilities (LLD). Method Fourteen adolescents with LLD and 25 adolescents with typical language development (TLD) read literary texts in computer-based and paper-based formats and then answered reading comprehension questions. Results The LLD group scored significantly lower than the TLD group on the reading comprehension measure, but there were no significant between-group differences for reading or answering time. In addition, there were no significant within-group differences for the computer-based or paper-based conditions. Predictors for reading comprehension varied by group and condition. Conclusion Neither group appeared to be affected by the additional cognitive load imposed by hypertext in the computer-based condition; however, the load between conditions may not have been sufficient to differentially impact reading comprehension. Based on the regression analyses, it appears that working memory, oral language, and decoding differed in their contribution to reading comprehension for each group and condition.

The psychometric properties of two paper-and-pencil versions of the Children’s Attributional Style Interview (i.e., CASI-I and CASI-II) were evaluated in a sample of 166 third and fourth graders and a sample of 245 sixth and seventh graders. The results demonstrated strong internal consistency reliability, convergent validity, and a factor structure that was consistent with theory in both samples. Furthermore, analyses demonstrated adequate evidence of the reliability and validity of several dimensional subscale scores and the composite measures of attributional style for both positive and negative events. These results suggest the utility of the CASI in research testing specific attributional predictions of cognitive theories of depression with the dimensional subscale scores. They further add to the literature by demonstrating item-level factor analytic support for a children’s attributional style measure and the feasibility of administration sizes larger than previously tested, which add to the utility of the CASI in large-scale research designs.

Objective: To investigate the ability of patients with myotonic dystrophy type 1 to recognise basic facial emotions. We also explored the relationship between facial emotion recognition, neuropsychological data, personality, and CTG repeat expansion data in the DM-1 group. Methods: In total, 50 patients with DM-1 (28 women and 22 men) participated, with 41 healthy controls. Recognition of facial emotional expressions was assessed using photographs of basic emotions. A set of tests measured cognition and personality dimensions, and CTG repeat size was quantified in blood lymphocytes. Results: Patients with DM-1 showed impaired recognition of facial emotions compared with controls. A significant negative correlation was found between total score of emotion recognition in a forced choice task and CTG repeat size. Furthermore, specific cognitive functions (vocabulary, visuospatial construction ability, and speed) and personality dimensions (reward dependence and cooperativeness) correlated with scores on the forced choice emotion recognition task. Conclusion: These findings revealed a CTG repeat dependent facial emotion recognition deficit in the DM-1 group, which was associated with specific neuropsychological functions. Furthermore, a correlation was found between facial emotional recognition ability and personality dimensions associated with sociability. This adds a new clinically relevant dimension in the cognitive deficits associated with DM-1.

Background: Cognitive impairment plays a role in Parkinson’s disease (PD) and has important consequences for patient management. However, many aspects of cognitive impairment in PD remain unclear because of the use of different and often invalid measurement instruments. In this study, a reliable and valid instrument, the SCales for Outcomes in PArkinson’s disease-COGnition (SCOPA-COG), was used. Aim: To evaluate cognitive functioning in a large cohort of patients with Parkinson’s disease and to assess the relations with demographic, disease related and clinical variables. Methods: A cohort of 400 patients with PD was evaluated for cognition, motor and non-motor domains, as well as for demographic and disease related characteristics. Results were compared with 150 controls matched for overall age, sex and education distribution. Results: Patients with PD scored significantly lower on all cognitive subdomains compared with controls, with the largest differences for executive functioning and memory. After correction for age and years of education, 22% of patients had impaired cognition, as measured by the total SCOPA-COG score, compared with controls. Across all patients, more severe cognitive impairment was associated with significantly more impairment in motor, autonomic, depressive and psychotic domains. Patients with the postural instability gait difficulty (PIGD) dominant phenotype showed more cognitive impairment compared with patients with the tremor dominant phenotype. Contrary to tremor scores, PIGD scores significantly worsened with increasing disease severity. Conclusions: Cognition is an important domain of the clinical spectrum of PD and poorer cognitive performance is associated with greater impairment in motor and non-motor domains in PD. The difference in cognitive scores between PIGD dominant patients and tremor dominant patients likely reflects more advanced disease.

Contains fulltext : 51936.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To evaluate cognitive outcome in adult survivors of bacterial meningitis. METHODS: Data from three prospective multicentre studies were pooled and reanalysed, involving 155 adults surviving bacterial meningitis (79 after pneumococcal and 76 after meningococcal meningitis) and 72 healthy controls. RESULTS: Cognitive impairment was found in 32% of patients and this proportion was similar for survivors of pneumococcal and meningococcal meningitis. Survivors of pneumococcal meningitis performed worse on memory tasks (p

Background: Neurofibromatosis type 1 (NF1) is a single gene disorder associated with a high frequency of cognitive deficits and a complex cognitive phenotype. These cognitive deficits have been associated with focal areas of high signal intensity on T2 weighted MRI images but the relationship remains controversial. Method: A cohort of 76 children with NF1 and 45 unaffected sibling controls (aged 8–16 years) underwent extensive neuropsychological assessment, with the NF1 children having MRI examinations. Results: The presence or number of T2 hyperintensities (T2H) was not associated with cognitive dysfunction. However, the location of discrete (well circumscribed) T2H in the thalamus was associated with severe and generalised cognitive impairment. More diffuse lesions in the thalamus were also associated with reductions in IQ but the effects were less marked compared with the discrete lesions. Comparing children with NF1 to their unaffected siblings revealed more subtle effects of the lesions on cognitive ability. Conclusions: T2H cannot be used in general as a radiological marker for cognitive deficits in children with NF1; however, lesions in the thalamus are strongly associated with cognitive impairment. It is possible that lesions in the thalamus in conjunction with more general thalamic hypometabolism may compound the level of thalamic dysfunction, resulting in cognitive deficits well beyond those produced by T2H in other regions.

Background: Psychiatric symptoms are a common feature of Huntington’s disease (HD) and often precede the onset of motor and cognitive impairments. However, it remains unclear whether psychiatric changes in the preclinical period result from structural change, are a reaction to being at risk or simply a coincidental occurrence. Few studies have investigated the temporal course of psychiatric disorder across the preclinical period. Objectives: To compare lifetime and current prevalence of psychiatric disorder in presymptomatic gene carriers and non-carriers and to examine the relationship of psychiatric prevalence in gene carriers to temporal proximity of clinical onset. Methods: Lifetime and current psychiatric histories of 204 at risk individuals (89 gene carriers and 115 non-carriers) were obtained using a structured clinical interview, the Composite International Diagnostic Interview. Psychiatric disorders were classified using both standardised diagnostic criteria and a more subtle symptom based approach. Follow-up of gene carriers (n = 51) enabled analysis of the role of temporal proximity to clinical onset. Results: Gene carriers and non-carriers did not differ in terms of the lifetime frequency of clinical psychiatric disorders or subclinical symptoms. However, gene carriers reported a significantly higher rate of current depressive symptoms. Moreover, the rate of depression increased as a function of proximity to clinical onset. Conclusions: Affective disorder is an important feature of the prodromal stages of HD. The findings indicate that depression cannot be accounted for by natural concerns of being at risk. There is evidence of a window of several years in which preclinical symptoms are apparent.

Objective: To investigate in a longitudinal cohort of people with Alzheimer’s disease whether taking antipsychotics is associated with more rapid cognitive deterioration. Method: From a sample of 224 people with Alzheimer’s disease recruited as epidemiologically representative, those taking antipsychotic drugs for more than 6 months were compared with those who were not, in terms of change in three measures of cognition. The effects of potential mediators and confounders (demographic factors, neuropsychiatric symptoms, cognitive severity and cholinesterase inhibitors) were also examined. Results: No significant difference was observed in cognitive decline between those taking antipsychotics (atypical or any) and others on any measure of cognition. The only predictor of more cognitive decline was greater baseline cognitive severity (B = 3.3, 95% confidence interval 0.6 to 6.1, t = 2.4, p Conclusions: In this, the first cohort study investigating the effects of atypical antipsychotics on cognitive outcome in Alzheimer’s disease, those taking antipsychotics were no more likely to decline cognitively over 6 months. Although clinicians should remain cautious when prescribing antipsychotic drugs to people with Alzheimer’s disease, any increase in cognitive deterioration is not of the magnitude previously reported. There is a need for cohort studies that follow up patients from first prescription in clinical practice for a period of months rather than weeks to determine “real-life” risks and benefits.

Sleep plays an active role in memory consolidation. Because children with Down syndrome (DS) and Williams syndrome (WS) experience significant problems with sleep and also with learning, we predicted that sleep‐dependent memory consolidation would be impaired in these children when compared to typically developing (TD) children. This is the first study to provide a cross‐syndrome comparison of sleep‐dependent learning in school‐aged children. Children with DS (n = 20) and WS (n = 22) and TD children (n = 33) were trained on the novel Animal Names task where they were taught pseudo‐words as the personal names of ten farm and domestic animals, e.g. Basco the cat, with the aid of animal picture flashcards. They were retested following counterbalanced retention intervals of wake and sleep. Overall, TD children remembered significantly more words than both the DS and WS groups. In addition, their performance improved following night‐time sleep, whereas performance over the wake retention interval remained stable, indicating an active role of sleep for memory consolidation. Task performance of children with DS did not significantly change following wake or sleep periods. However, children with DS who were initially trained in the morning continued to improve on the task at the following retests, so that performance on the final test was greater for children who had initially trained in the morning than those who trained in the evening. Children with WS improved on the task between training and the first retest, regardless of whether sleep or wake occurred during the retention interval. This suggests time‐dependent rather than sleep‐dependent learning in children with WS, or tiredness at the end of the first session and better performance once refreshed at the start of the second session, irrespective of the time of day. Contrary to expectations, sleep‐dependent learning was not related to baseline level of performance. The findings have significant implications for educational strategies, and suggest that children with DS should be taught more important or difficult information in the morning when they are better able to learn, whilst children with WS should be allowed a time delay between learning phases to allow for time‐dependent memory consolidation, and frequent breaks from learning so that they are refreshed and able to perform at their best.

BackgroundInternet cognitive–behavioural therapy (iCBT) for panic disorder of up to 10 lessons is well established. The utility of briefer programmes is unknown.AimsTo determine the efficacy and effectiveness of a five-lesson iCBT programme for panic disorder.MethodStudy 1 (efficacy): Randomised controlled trial comparing active iCBT (n=27) and waiting list control participants (n=36) on measures of panic severity and comorbid symptoms. Study 2 (effectiveness): 330 primary care patients completed the iCBT programme under the supervision of primary care practitioners.ResultsiCBT was significantly more effective than waiting list control in reducing panic (g=0.97, 95% CI 0.34 to 1.61), distress (g=0.92, 95% CI 0.28 to 1.55), disability (g=0.81, 95% CI 0.19 to 1.44) and depression (g=0.79, 95% CI 0.17 to 1.41), and gains were maintained at 3 months post-treatment (iCBT group). iCBT remained effective in primary care, but lower completion rates were found (56.1% in study 2 v. 63% in study 1). Adherence appeared to be related to therapist contact.ConclusionsThe five-lesson Panic Program has utility for treating panic disorder, which translates to primary care. Adherence may be enhanced with therapist contact.

Background Cognitive complaints are common amongst breast cancer survivors, and no standard treatment exists. The present study evaluates whether web-based cognitive training can alleviate subjectively reported and objectively assessed cognitive complaints in a sample of breast cancer survivors. The primary and secondary outcomes were an objective measure of working memory and a measure of perceived cognitive functioning. Additional outcomes were neuropsychological tests of memory, executive function, working memory and questionnaire-based assessment of anxiety, depression and somatization. Methods A total of 157 female breast cancer survivors were recruited from an existing cohort and through announcements in open access cancer-related Internet fora and randomly allocated to either web-based cognitive training (eCogT) with telephone support (n = 94) or a waitlist control (WLC) condition (n = 63). eCogT encompassed 30 training sessions over 6 weeks. Neuropsychological assessments were undertaken over the telephone, and questionnaire data was collected online. Data was collected at baseline, post-intervention and at 5-month follow-up. Results Mixed linear models revealed no statistically significant change in primary or secondary outcome at follow-up in either group. Statistically significant improvements (p 0.040–0.043) were found in the eCogT group for verbal learning and on a working memory test. Conclusions Web-based cognitive training did not result in improvements of the primary or secondary outcome. Improved performance was observed on verbal learning and working memory. These effects were observed at 5-month follow-up, indicating long-term effects of training. The intervention may be applied in a clinical setting at low cost and without risk of adverse effects. © 2016 The Authors. Psycho-Oncology Published by John Wiley & Sons Ltd.

Aim: To assess the long-term cognitive and behavioural outcome after bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients affected by Parkinson’s disease, with a 5-year follow-up after surgery. Methods: 11 patients with Parkinson’s disease treated by bilateral DBS of STN underwent cognitive and behavioural assessments before implantation, and 1 and 5 years after surgery. Postoperative cognitive assessments were carried out with stimulators turned on. Results: A year after surgery, there was a marginally significant decline on a letter verbal fluency task (p = 0.045) and a significant improvement on Mini-Mental State Examination (p = 0.009). 5 years after surgery, a significant decline was observed on a letter verbal fluency task (p = 0.007) and an abstract reasoning task (p = 0.009), namely Raven’s Progressive Matrices 1947. No significant postoperative change was observed on other cognitive variables. No patient developed dementia 5 years after surgery. A few days after the implantation, two patients developed transient manic symptoms with hypersexuality and one patient developed persistent apathy. Conclusion: The decline of verbal fluency observed 5 years after implantation for DBS in STN did not have a clinically meaningful effect on daily living activities in our patients with Parkinson’s disease. As no patient developed global cognitive deterioration in our sample, these findings suggest that DBS of STN is associated with a low cognitive and behavioural morbidity over a 5-year follow-up, when selection criteria for neurosurgery are strict.

Objective: To study the ability of patients with semantic dementia to understand actions, in order to examine the contribution of semantic memory to action comprehension. Methods: The ability to comprehend symbolic and instrumental actions was assessed in 6 patients with semantic dementia and 10 healthy controls. The patients were also given the imitation test of meaningful and meaningless actions. Results: In all patients with semantic dementia, comprehension of both symbolic and instrumental actions was defective. The comprehension of symbolic actions was more impaired than that of instrumental actions. Their ability to imitate other’s actions was well preserved. Conclusion: This study showed that comprehension of action was impaired in semantic dementia, suggesting that semantic memory has an important role in comprehension of human action.

Background: Attentional dysfunction is believed to be a prominent and distinguishing neuropsychological feature of dementia with Lewy bodies (DLB); yet, the specific nature of the attentional deficit and factors that can potentially influence attentional processing in DLB have not been fully defined. Aims: To clarify the nature of the attentional deficit in early-stage DLB relative to patients with early-stage dementia of the Alzheimer’s type (DAT) and elderly controls, and examine the effect of task complexity and type of cognitive load on attentional processing in DLB. Methods: Attentional impairment and fluctuating attention were investigated in three groups of subjects—patients with clinical features of early probable DLB (n = 20), a group with early probable DAT (n = 19) and healthy elderly controls (n = 20)—using an experimental computerised reaction time paradigm. Results: Patients with DLB showed greater attentional impairment and fluctuations in attention relative to patients with DAT and elderly controls. The attentional deficit was generalised in nature but increased in magnitude as greater demands were placed on attentional selectivity. Attentional deficits in DLB were most pronounced under task conditions that required more active recruitment of executive control and visuospatial cognitive processes. Conclusions: Attentional deficits in DLB are widespread and encompass all aspects of attentional function. Deficits in higher cortical function influence the degree of attentional impairment and fluctuating attention, suggesting that attentional processing in DLB is mediated by interacting cortical and subcortical mechanisms. These findings serve to clarify the nature of the attentional deficit in DLB and have potentially important ramifications for our understanding of the neurocognitive underpinnings of fluctuations.

Background: The memory deficits in patients with temporal lobe epilepsy (TLE) are associated with epileptogenic lesions of the temporal lobes, especially hippocampal sclerosis. Memory deficits have been extensively studied in TLE, but the presence of pre-existing temporal lobe abnormality has confounded studies on the relationship between memory dysfunction and seizure activity. Idiopathic generalised epilepsy (IGE) is characterised by primary generalised seizures and is found to occur in the absence of any macroscopic brain abnormalities. IGE is therefore ideal for investigations on the effects of seizure activity on memory and cognition. Aim and methods: Magnetic resonance spectroscopy (MRS) and neuropsychological testing were used to investigate the relationship between epileptic seizures, memory performance and neuronal dysfunction in the temporal lobes of a group of patients with IGE. 30 patients and 15 healthy controls participated in the study. Results: Patients with IGE were found to perform worse than controls on tests of speed of information processing, general cognitive performance and a range of memory tests, including face recognition, word recognition, verbal recall and complex figure recall. The performance of the patient group on the visual recognition and verbal recall sections of the Doors and People Test was found to correlate with MRS ratios of N-acetyl aspartate:choline and N-acetyl aspartate:creatine in the temporal lobes. Conclusion: This result supports the hypothesis that memory deficits in epilepsy may be due to neuronal dysfunction secondary to epileptic activity itself in the absence of any macroscopic lesions in the temporal lobes.

Objective: To investigate the influence of deep white matter hyperintensities (DWMH) and periventricular white matter hyperintensities (PVWMH) on progression of cognitive decline in non-demented elderly people. Methods: All data come from the nested MRI sub-study of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). We performed a 3 year follow up study on 554 subjects of the PROSPER study using both repeated magnetic resonance imaging and cognitive testing. Cognitive decline and its dependency on WMH severity was assessed using linear regression models adjusted for sex, age, education, treatment group, and test version when applicable. Results: We found that the volume of PVWMH at baseline was longitudinally associated with reduced mental processing speed (p = 0.0075). In addition, we found that the progression in PVWMH volume paralleled the decline in mental processing speed (p = 0.024). In contrast, neither presence nor progression of DWMH was associated with change in performance on any of the cognitive tests. Conclusion: PVWMH should not be considered benign but probably underlie impairment in cognitive processing speed.

Apathy and depression are the most frequent behavioural and psychiatric disorders in Alzheimer's disease, and may both have a negative impact on the progression of the illness.To examine the clinical correlates of apathy in Alzheimer's disease (AD), and to determine whether apathy is a significant predictor of more rapid cognitive, functional and emotional decline.Using a structured psychiatric evaluation, we examined a consecutive series of 354 subjects meeting clinical criteria for AD. Apathy was assessed by the Apathy Scale, and diagnosed using standardised criteria. Additional measurements included scales for depression, functional impairment, and global cognitive functions. A follow up evaluation was carried out in 247 patients (70% of the total sample) between 1 and 4 years after the baseline evaluation.Apathy was significantly associated with older age (p = 0.009), and a higher frequency of minor and major depression (p0.0001). Apathy at baseline was a significant predictor of depression at follow up (p = 0.01), and was associated with a faster cognitive (p = 0.0007) and functional decline (p = 0.006).Apathy in AD is a behavioural marker of a more aggressive dementia, characterised by a faster progression of cognitive, functional, and emotional impairment.

Background: There may be difficulties in the use of self report measurements in patients with cognitive impairment or serious mood disturbances which interfere with reliable self assessment, as may be the case in multiple sclerosis (MS). In such cases proxies may provide valuable information. However, before using any questionnaires in a proxy sample, the questionnaire should be evaluated for proxy use. Objective: To evaluate the psychometric properties of the 29 item Multiple Sclerosis Impact Scale (MSIS- 29) when used by proxies of MS patients. Methods: A sample of 62 partners of MS patients completed the MSIS-29. The data were evaluated for the psychometric criteria of the MSIS-29, including data quality, scaling assumptions, acceptability, reliability, validity, and responsiveness. Results: Psychometric evaluation was satisfactory; data quality was high, and scaling assumptions and acceptability were good. Reliability was high (a.0.80). Findings were consistent with results of a psychometric evaluation in a patient sample. Conclusions: The MSIS-29 can be used reliably in proxies of patients with MS. As a next step the relation between data obtained from patients and proxies needs to be studied, focusing on factors that may affect agreement and discrepancies. I n recent years, there has been increasing use of self report measurements for assessing quality of life, disease impact, or disability. The underlying assumption when using self report measurements is that the patient fully understands the questions and can give a reliable judgment on their situation. Problems may arise when the cognitive or communication abilities are insufficient. Moreover, emotional factors may interfere with self assessment, which will affect reliability. Therefore self report measurements may be less suitable in cases of cognitive dysfunction or severe mood disturbance. When applying self report measurements, the presence of such factors could lead to unreliable information or loss of information. It has been suggested that in these situations the use of proxies (for example, partners, relatives, or close friends) to assess the situation of the patient should be considered. 1 These considerations are relevant for multiple sclerosis (MS) because self report measures are often used in MS, and both cognitive decline and severe mood disturbances may be present during the course of the disease. 23 These disorders could lead to invalid self reporting of quality of life, 4-8 although there are also papers suggesting that in cognitively impaired and depressed patients self reports may be valid. 9-12 Nevertheless, proxy measurements could be important in MS and useful under certain circumstances. We are not aware of any studies that have assessed systematically the value and limitations of proxy measurements in MS. Of all available self report measurements that can be used in MS, the Multiple Sclerosis Impact Scale (MSIS-29) is disease specific and has been rigorously evaluated for its psychometric proper- ties. 13