Neuropsychiatric Assessment Research Articles

Neuropsychological assessment of Romanian burning mouth syndrome patients: stress, depression, sleep disturbance, and verbal fluency impairments.

Burning Mouth Syndrome (BMS) is a chronic condition characterized by a burning sensation in the oral mucosa, lasting more than 2 hours daily for more than 3 months, without clinical and/or laboratory evidence. BMS is often comorbid with mood, and psychiatric disorders, and a complex pathophysiology and interaction between impairments in nociceptive processing and psychologic function is occurring. In this work, we aimed to define the neuropsychological profile specific for BMS patients for a better management of this complex disease. We conducted a case-control study comparing 120 BMS patients and 110 non-BMS individuals (CTRL). Sociodemographic data and lifestyle habits, were collected, along with data regarding quality of life (SF-36 scale), stress (PSS), depression and anxiety (MADRS and HADS scales), sleep quality (PSQI scale), and cognitive functions (MoCA, SVF and PVF tests). The statistical analysis revealed a lower general quality of life (p < 0.001), worse sleep quality (p < 0.001) in BMS patients than CTRL. The BMS patients also displayed a higher prevalence of mild depressive symptoms than CTRL applying the MADRS (p < 0.001) and HADS-Depression scales (p = 0.001), whereas no differences in anxiety symptoms were found between the two groups (p = 0.174). Moreover, reduced scores semantic and phonemic verbal fluency tests (p < 0.05) were found, but no change in cognition was observed through MoCA (p = 0.551). Our results highlight that synergy between dentistry and neuropsychiatric assessment is essential for a successful management of BMS.

Clinical features and magnesium levels: Novel insights in 15q11.2 BP1-BP2 copy number variants.

Investigating copy number variations (CNVs) such as microdeletions or microduplications can significantly contribute to discover the aetiology of neurodevelopmental disorders. 15q11.2 genomic region, including NIPA1 and NIPA2 genes, contains a recurrent but rare CNV, flanked by the break points BP1 and BP2. Both BP1-BP2 microdeletion and microduplication have been associated with intellectual disability (ID), neuropsychiatric/behavioural disturbances and mild clinical features, even if with incomplete penetrance and variable expressivity. The pathogenic role of this CNV is quite unclear though. Unknown variants in other DNA regions and parent-of-origin effect (POE) are some of the mechanisms that have been proposed as an explanation of the wide phenotypic variability. As NIPA1 and NIPA2 encode for proteins that mediate magnesium (Mg2+ ) metabolism, it has been suggested that urinary Mg2+ levels could potentially represent informative and affordable biomarkers for a rapid screening of 15q11.2 duplications or deletions. Furthermore, magnesium supplementation has been proposed as possible therapeutic strategy. Thirty one children with ID and/or other neurodevelopmental disorders carrying either a duplication or a deletion in 15q11.2 BP1-BP2 region have been recruited. When available, blood samples from parents have been analysed to identify the CNV origin. All participants underwent family and medical data collection, physical examination and neuropsychiatric assessment. Electroencephalogram (EEG) and brain magnetic resonance imaging (MRI) scan were performed in 15 children. In addition, 11 families agreed to participate to the assessment of blood and urinary Mg2+ levels. We observed a highly variable phenotypic spectrum of developmental issues encompassing ID in most subjects as well as a variety of behavioural disorders such as autism and attention-deficit disorder/attention-deficit hyperactivity disorder. Dysmorphic traits and malformations were detected only in a minority of the participants, and no clear association with growth anomalies was found. Abnormal brain MRI and/or EEG were reported respectively in 64% and 92% of the subjects. Inheritance assessment highlighted an excess of duplication of maternal origin, while cardiac alterations were detected only in children with 15q11.2 CNV inherited from the father. We found great variability in Mg2+ urinary values, without correlation with 15q11.2 copy numbers. However, the variance of urinary Mg2+ levels largely increases in individuals with 15q11.2 deletion/duplication. This study provides further evidence that 15q11.2 BP1-BP2 CNV is associated with a broad spectrum of neurodevelopmental disorders and POE might be an explanation for clinical variability. However, some issues may question the real impact of 15q11.2 CNV on the phenotype in the carriers: DNA sequencing could be useful to exclude other pathogenic gene mutations. Our results do not support the possibility that urinary Mg2+ levels can be used as biomarkers to screen children with neurodevelopmental disorders for 15q11.2 duplication/deletion. However, there are evidences of correlations between 15q11.2 BP1-BP2 CNV and Mg2+ metabolism and future studies may pave the way to new therapeutic options.

Cognitive and neuropsychiatric endophenotypes in amyotrophic lateral sclerosis.

First- and second-degree relatives of people with amyotrophic lateral sclerosis report higher rates of neuropsychiatric disorders, indicating that risk genes may be pleiotropic, causing multiple phenotypes within kindreds. Such phenotypes may constitute a disease endophenotype that associates with disease liability. We have directly investigated cognitive functioning and neuropsychiatric traits among relatives of people with amyotrophic lateral sclerosis to identify potential endophenotypes of the disease. In a family-based, cross-sectional study design, first- and second-degree relatives of people with amyotrophic lateral sclerosis (n = 149) were compared to controls (n = 60) using an in-depth neuropsychological and neuropsychiatric assessment. Subgroup analyses examined the effect of family history and C9orf72 repeat expansion status (n = 16 positive carriers). Relatives of people with amyotrophic lateral sclerosis had lower scores on executive functioning, language and memory tasks compared to controls, with large effect sizes observed on object naming (d = 0.91, P = 0.00001) and phonemic verbal fluency (d = 0.81, P = 0.0003). Relatives also had higher autism quotient attention to detail traits (d = -0.52, P = 0.005), lower conscientiousness (d = 0.57, P = 0.003) and lower openness to experience personality traits (d = 0.54, P = 0.01) than controls. These effects were typically larger in relatives of people with familial, rather than sporadic, amyotrophic lateral sclerosis and were present in both gene carrier and non-carrier relatives of probands with a C9orf72 repeat expansion. Poorer phonemic fluency and object naming, along with autism and personality traits, are more frequent in relatives of people with amyotrophic lateral sclerosis. Among kindreds carrying the C9orf72 repeat expansion, these traits were identified in relatives regardless of their carrier status, suggesting the presence of a disease-associated endophenotype that is not exclusively mediated by the C9orf72 expansion.

Emotion dysregulation, impulsivity and anger rumination in borderline personality disorder: the role of amygdala and insula

Borderline Personality Disorder (BPD) is a severe mental disorder, characterized by deficits in emotion regulation, interpersonal dysfunctions, dissociation and impulsivity. Brain abnormalities have been generally explored; however, the specific contribution of different limbic structures to BPD symptomatology is not described. The aim of this study is to cover this gap, exploring functional and structural alterations of amygdala and insula and to highlight their contribution to neuropsychiatric symptoms. Twenty-eight BPD patients (23.7 ± 3.42years; 6M/22F) and twenty-eight matched healthy controls underwent a brain MR protocol (1.5T, including a 3D T1-weighted sequence and resting-state fMRI) and a complete neuropsychiatric assessment. Volumetry, cortical thickness and functional connectivity of amygdala and insula were evaluated, along with correlations with the neuropsychiatric scales. BPD patients showed a lower cortical thickness of the left insula (p = 0.027) that negatively correlated with the Anger Rumination Scale (p = 0.019; r = -0.450). A focused analysis on female patients showed a significant reduction of right amygdala volumes in BPD (p = 0.037), that correlate with Difficulties in Emotion Regulation Scale (p = 0.031; r = - 0.415), Beck Depression Inventory (p = 0.009; r = - 0.50) and Ruminative Response Scale (p = 0.045; r = - 0.389). Reduced functional connectivity was found in BPD between amygdala and frontal pole, precuneus and temporal pole. This functional connectivity alterations correlated with Anger Rumination Scale (p = .009; r = -0.491) and Barratt Impulsiveness Scale (p = 0.020; r = -0.447). Amygdala and insula are altered in BPD patients, and these two limbic structures are implicated in specific neuropsychiatric symptoms, such as difficulty in emotion regulation, depression, anger and depressive rumination.

Signatures of HIV and Major Depressive Disorder in the Plasma Microbiome.

Inter-individual differences in the gut microbiome are linked to alterations in inflammation and blood-brain barrier permeability, which may increase the risk of depression in people with HIV (PWH). The microbiome profile of blood, which is considered by many to be typically sterile, remains largely unexplored. We aimed to characterize the blood plasma microbiome composition and assess its association with major depressive disorder (MDD) in PWH and people without HIV (PWoH). In this cross-sectional, observational cohort, we used shallow-shotgun metagenomic sequencing to characterize the plasma microbiome of 151 participants (84 PWH and 67 PWoH), all of whom underwent a comprehensive neuropsychiatric assessment. The microbial composition did not differ between PWH and PWoH or between participants with MDD and those without it. Using the songbird model, we computed the log ratio of the highest and lowest 30% of the ranked classes associated with HIV and MDD. We found that HIV infection and lifetime MDD were enriched in a set of differentially abundant inflammatory classes, such as Flavobacteria and Nitrospira. Our results suggest that the circulating plasma microbiome may increase the risk of MDD related to dysbiosis-induced inflammation in PWH. If confirmed, these findings may indicate new biological mechanisms that could be targeted to improve treatment of MDD in PWH.

“My mind goes dead … I cannot speak”: an expression of DPD

ABSTRACT Introduction Here we present a case of Depersonalisation–Derealisation Disorder which involves an unusual environmental trigger and profile of symptoms in a patient with an underlying left frontal encephalomalacia. Methods The clinical information has been collected from multiple neurological, psychiatric, neuropsychological examinations and from the patient’s medical records. Results The neuropsychiatric assessment showed depersonalisation, derealisation, de-somatisation and de-affectualisation, along with a good response to SSRI + Lamotrigine; all typical features of DPD. The neuropsychological assessment showed language problems, and other mild cognitive difficulties that may provide a neuropsychological foundation contributing to the DPD episodes. Discussion and conclusion Given Mr R’s underlying neuropsychological deficit, hearing voices without speech-associated gestures might place excessive demands on his ability to process the information, exacerbating his feelings of threat. This sets up the pattern of suppressed insula activation, and possibly the suppression of the auditory cortex leading to the presented unusual DPD symptoms.

Students and young trade workers neuropsychiatric maladjustment assessment under COVID-19 epidemic restrictions

Introduction. Since March 2020, the introduction of a self-isolation regime and significant restrictions on personal contacts at work and school in connection with the COVID-19 pandemic has led to an expansion of the introduction of information technologies and a sharp restriction of direct interpersonal communication. The introduction of these restrictions has had a stressful effect on the body of both workers and students of various age groups, including young people. For a successful analysis of the impact of COVID-19 restrictions on the psychophysiological state of these categories of young workers and students, it seems appropriate to assess the state of maladaptation, self-assessment of nervous and somatic well-being.&#x0D; The study aims to assess the impact on the adaptive psychophysiological parameters of young trade workers and students of the changed working and study conditions against the background of the COVID–19 epidemic situation (self-isolation).&#x0D; Materials and methods. The object of the study was two groups of people who have a wide range of communication with colleagues and people around them, but differ in the content of their activities: students and trade workers. Scientists have conducted the study in two stages: before the pandemic (2013) and during the pandemic (December 2020) due to drastic changes in the algorithm of existence and work/study. We have examined 119 students aged 20–24 years (RGSU). There were 61 people at the first stage of the study (2013), there were 58 people at the second stage (2020, December). The second group (trade workers): 66 people aged 20–29 years. At the first stage of the study (2013), 34 people were included, at the second stage — 32 people. Experts have carried out the assessment of the psychophysiological parameters of the examined according to the questionnaire of neuropsychiatric maladjustment (ONPD). The condition for inclusion in the groups in 2020–2021 is the absence of a history of transferred COVID-19.&#x0D; Results. During the tense epidemic situation (2019-2021), against the background of the spread of COVID-19 and forced self-isolation of all population groups, the lifestyle has radically changed. Face-to-face communication has been minimized, but communication using information technology in all spheres of life (daily life, study, work) has increased dramatically. The researchers found that among the surveyed population groups (students and sales workers), the spread of signs of mental discomfort increased.&#x0D; Limitations. The study was limited to a sample of age groups: 20–24 years for students, 20–29 years for trade workers (in both periods).&#x0D; Conclusion. The calculation of the odds ratio (OR) allowed us to establish with a high degree of confidence that signs of mental discomfort, including asthenic and depressive signals, were significantly more often recorded during the period of self-isolation in both study groups: for students who are on distance learning (December 2020 compared to 2013): the coefficient of OR=5.4, (χ2=14.7; p&lt;0.001); for sales workers: coefficient OR=15.0; (χ2=9.5; p&lt;0.001).

Neuropsychiatric profile in average intelligent individuals with coexisting epilepsy and psychogenic non-epileptic seizures.

Global neuropsychological impairments with intellectual disability (ID) seem to play a major role in the occurrence of psychogenic non-epileptic seizures (PNES) in epilepsy. Conversely, the pathophysiology underlying PNES combined with epilepsy without ID remains elusive. We investigated the neuropsychiatric profile in 26 average intelligent subjects (15 women, mean age: 40.04 ± 13.53 years) with temporal lobe epilepsy (TLE) plus PNES (TLE + PNES), compared with 28 with TLE and 22 with PNES alone, matched for age and sex. All subjects underwent neuropsychiatric assessment, including Beck Depression Inventory-2 (BDI-2), State-Trait Anxiety Inventory (STAI), Dissociative Experiences Scale (DES), Toronto Alexithymia Scale (TAS-20), Traumatic Experience Checklist (TEC), and cognitive evaluation. TLE + PNES and PNES groups shared a similar psychiatric profile with higher levels of depression (BDI-2, P < 0.001), anxiety (STAI-S, P < 0.001; STAI-T, P < 0.001), dissociation (DES, P < 0.001), and alexithymia (TAS, P=0.005) scales than the TLE group. Nonetheless, like individuals with TLE, patients with TLE + PNES had a lower rate of a potentially traumatizing event than PNES. The very low rate of potentially traumatizing event in subjects with TLE + PNES leads us to hypothesize that epilepsy itself may be the psychophysiological distress that contributed to PNES. A psychopathological assessment in subjects with epilepsy is crucial to identify those more likely to develop PNES.

A feasibility study of a new instrument for detection of autism signs in preschool settings. Psychometric properties of the joint attention observation schedule preschool (JA-OBS preschool)

BackgroundIdentifying signs of autism is essential for enabling timely diagnosis and intervention. Children from multiethnic and socioeconomic disadvantaged settings are typically diagnosed with autism later than their general peers. This feasibility study explored the psychometric properties of a new instrument, Joint Attention Observation Schedule Preschool (JA-OBS Preschool), in children with suspected autism.MethodsData were collected from a prospective longitudinal study of 46 children aged 2–4 years who lived in a multiethnic, low resource area. The children had been referred from the Child Health Centre to a multiprofessional team for a neuropsychiatric assessment. In the diagnostic process, the instrument JA-OBS Preschool for observation of a child's capability of engaging in joint attention was included. Descriptive statistics and Cronbach's alfa were used to analyze the psychometric properties, including internal consistency reliability and inter-rater consistency.ResultsAll 46 children with suspected autism screened positive on the JA-OBS Preschool. The internal consistency reliability of the instrument was calculated at 0.8 (Cronbach's alfa). Percent agreement between two examiners in JA-OBS Preschool ranged from 77% to 100%.ConclusionJA-OBS Preschool was found to be a promising instrument for identifying signs of autism in children in this setting. However, further research is needed to determine the psychometric properties of the JA-OBS Preschool in a general child population as well as in a younger age group.

Construction of a computerized adaptive test (CAT-CCNB) for efficient neurocognitive and clinical psychopathology assessment

BackgroundTraditional paper-and-pencil neurocognitive evaluations and semi-structured mental health interviews can take hours to administer and score. Computerized assessment has decreased that burden substantially, and contemporary psychometric tools such as item response theory and computerized adaptive testing (CAT) allow even further abbreviation. New methodThe goal of this paper was to describe the application of CAT and related methods to the Penn Computerized Neurocognitive Battery (CNB) and a well-validated clinical assessment in order to increase efficiency in assessment and relevant domain coverage. To calibrate item banks for CAT, N = 5053 participants (63% female; mean age 45 years, range 18–80) were collected from across the United States via crowdsourcing, providing item parameters that were then linked to larger item banks and used in individual test construction. Tests not amenable to CAT were abbreviated using complementary short-form methods. ResultsThe final “CAT-CCNB” battery comprised 21 cognitive tests (compared to 14 in the original) and five adaptive clinical scales (compared to 16 in the original). Comparison with existing methodsThis new battery, derived with contemporary psychometric approaches, provides further improvements over existing assessments that use collections of fixed-length tests developed for stand-alone administration. The CAT-CCNB provides an improved version of the CNB that shows promise as a maximally efficient tool for neuropsychiatric assessment. ConclusionsWe anticipate CAT-CCNB will help satisfy the clear need for broad yet efficient measurement of cognitive and clinical domains, facilitating implementation of large-scale, “big science” approaches to data collection, and potential widespread clinical implementation.

The BrainDrugs-epilepsy study: A prospective open-label cohort precision medicine study in epilepsy

IntroductionThe BrainDrugs-Epilepsy Study is part of the established Lundbeck Foundation funded BrainDrugs research alliance (braindrugs.nru.dk). The study aims to identify biomarkers of treatment outcome as well as cognitive and psychiatric comorbidity in patients with a first epileptic seizure and epilepsy. Our goal is to provide a patient-level prediction of treatment response. MethodsIn a prospective cohort study design, we will consecutively include a total of 200 patients who have experienced their first epileptic seizure and 150 newly diagnosed patients with epilepsy (≥ 16 years old). We will systematically collect data at baseline and one, three, and five years after inclusion. Neuropsychiatric and neuropsychological assessments will be combined with electroencephalography (EEG) and neuroimaging tools such as Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) brain scans using the synaptic vesicle glycoprotein 2A-binding radioligand [11C]-UCB-J. After completing the baseline investigations, patients diagnosed with epilepsy start anti-seizure medication (ASM) treatment with either lamotrigine or levetiracetam. Patients will be monitored every three months. For daily monitoring, we will use a mobile app. Our clinical endpoints are 1) ASM treatment response, 2) development of a second seizure/epilepsy diagnosis, 3) psychiatric symptoms, 4) cognitive disturbances, and 5) quality of life. DiscussionWe hypothesize that seizures, cognitive impairment, and psychiatric symptoms share common neurobiological mechanisms that can be identified using MRI, PET, and EEG. We will assess how these biomarkers change over time and in response to treatment, providing novel insights into disease trajectories in the first years of epilepsy. Clinical trial registrationNCT05450822. Retrospectively registered July 5, 2022 (https://clinicaltrials.gov/ct2/results?term=NCT05450822&Search=Search).

Contribution of the μ-opioid receptor system to affective disorders in temporal lobe epilepsy: A bidirectional relationship?

Affective disorders are frequent comorbidities of temporal lobe epilepsy (TLE). The endogenous opioid system has been implicated in both epilepsy and affective disorders, and may play a significant role in their bidirectional relationship. In this cross-sectional study, we investigated the association between μ-opioid receptor binding and affective disorders in patients with TLE. Nine patients with TLE and depression/anxiety underwent 11 C-carfentanil positron emission tomography (CFN PET) and neuropsychiatric assessment, including the Hospital Anxiety and Depression Scale and the Positive and Negative Affect Schedule. The normalized CFN PET scans were compared with those of 26 age-matched healthy controls. Correlation analyses with affective symptoms were performed by region of interest-based analysis focusing on the limbic circuit and orbitofrontal cortex. We observed widely reduced CFN binding potential (BP) in bilateral frontal lobes and striata in patients with TLE compared to healthy controls. In the TLE group, more severe anxiety and negative affect were associated with decreased CFN BP in the posterior cingulate gyrus. In patients with TLE, interictally reduced binding in the opioid system was associated with higher levels of anxiety and negative affect. We speculate that seizure-related agonist-driven desensitization and downregulation of opioid receptors could be a potential underlying pathomechanism.

Aged Patients With Severe Small Vessel Disease Exhibit Poor Bimanual Coordination During the Anti-Phase Horizontal Line Drawing Task.

The present study explores whether SVD affects bimanual coordination, which is easier to detect than by conventional, MRI-based methods. We tested nine severe SVD patients, eight non-severe (i.e., moderate or mild) SVD patients, eleven healthy age-matched controls, and eight young adults. They were grouped according to Fazekas scale and by age. Participants performed horizontal line drawings with both hands simultaneously on two pen tablets. The movements consisted of rhythmic patterns where participants used both hands to draw horizontal lines in anti-phase on two pen tablets. Each participant underwent a series of neuropsychiatric assessments. Results showed that SVD patients exhibited in each hand smaller horizontal movement amplitudes with variability larger compared to the healthy age-matched controls. Only movement amplitudes appeared to decrease significantly with severity of SVD. Interestingly, we found no relevant differences between the age-matched, elderly controls and the young controls. Therefore, this effect appeared indicative of SVD. The variability of the lines orthogonal to the horizontal lines of the left, non-dominant hand differed only between the severe SVD group and the other groups. Furthermore, partial correlations demonstrated that the mean horizontal movement amplitude of the left hand was positively associated with the clock drawing test score, and the inter-manual asynchrony of the horizontal movements was positively associated with the Trail Making Test-B time. These results indicated that SVD patients show poor bimanual coordination, as reflected by spatial features such as movement amplitudes and variabilities, and abnormal bimanual coordination was associated with executive dysfunction.

Cognitive adverse effects of epilepsy and its predictors attending outpatient department of South Gondar zone hospitals, Amhara Region, Ethiopia 2020 /2021.

Epilepsy is the most common neurologic disorder which is further complicated by neurobehavioral co-morbidities, cognitive impairment, psychiatric disorders, and social problems. However, assessments of cognitive status of epileptic patients are far too low during clinical visits. This calls for early neuropsychological assessment soon after the diagnosis of epilepsy for a better treatment plan and outcome for epileptic patients. This study aimed to assess the cognitive adverse effects of epilepsy and its predictors attending outpatient departments of South Gondar Zone hospitals Amhara region Ethiopia 2020/2021. A multi-center institutional-based cross-sectional study was conducted. A total of 509 respondents were included with a response rate of 93.9%. Previously adapted pretested structured questionnaire was used containing, socio-demographic, clinical, and seizure related factors. Mini-Mental State Examination (MMSE) was used to measure cognitive impairment. A systematic random sampling technique was applied. Data were entered into Epi data version 4.4.2 then exported to SPSS version 24 for analysis. Descriptive statistics, bivariable and multivariable binary logistic regressions with odds ratios and 95% confidence interval were employed. The level of significance of association was determined at a p-value < 0.05. Prevalence of cognitive impairment in this study was 69.2% (95%CI; 65.4, 73.1). Rural residents (AOR = 4.16,95%CI, 1.99,8.67), respondents who couldn't read and write (AOR = 2.62, 95%CI; 1.24, 5.5,) longer duration of seizure disorder (AOR = 4.59,95%CI; 2.01,10.52), taking combined Phenobarbital and Phenytoin (AOR = 4.69,95%CI; 1.88,11.69), having history of head injury (AOR = 3.29,95%CI;1.30,8.32), having depression (AOR = 4.76,95%CI;2.83,7.98), and anxiety (AOR = 3.11,95%CI; 1.58,6.12) were significantly associated with cognitive impairment. Prevalence of cognitive impairment in this study was high. Regular neuropsychiatric assessment of patients with epilepsy should be encouraged especially for those participants with longer durations of illness, who are rural residents, who take combined Phenobarbital and Phenytoin, participants who had a history of head injury, depression, and anxiety.

Mild behavioral impairment is associated with sleep apnea, insomnia and brain white matter hyperintensity burden

AbstractBackgroundMild behavioral impairment (MBI) is a neurobehavioral syndrome associated with increased risk for Alzheimer’s disease (AD) and other neurodegenerative disorders. White matter hyperintensities (WMH) are brain lesions associated with cerebrovascular insult and contribute to cognitive decline across the cognitive spectrum (normal cognition, mild cognitive impairment (MCI) and dementia). Sleep disturbance is common among older adults with cognitive impairment and like MBI, is a modifiable AD risk factor that can affect brain structure including WMH. We sought to examine the prevalence of MBI and its relationship with sleep and WMH in a community cohort of older adults.MethodParticipants enrolled in the Wake Forest AD Research Center (ADRC) Clinical Core cohort (N = 633, mean age = 70.4 years) provided history of sleep apnea and insomnia, underwent neuropsychological assessment and neuropsychiatric symptom assessment, as reported by an informant on the Neuropsychiatric Inventory Questionnaire (NPI‐Q). MBI scores were derived from the NPI‐Q severity and included 10 symptoms reflecting affective dysregulation, impulse control, decreased motivation, social inappropriateness and abnormal perception or thought content, and excluded NPI‐Q questions on sleep and appetite. T1 and T2 FLAIR MRI were obtained; T1 and FLAIR were segmented to quantify WMH volume, which was scaled by head size and log transformed. Global cognitive status was assessed using the clinical dementia rating (CDR) global score.ResultIn our sample, 24% of participants had MBI. Normal cognition (CDR = 0) participants had significantly lower rates of MBI compared to both MCI (CDR = 0.5) and dementia (CDR ≥ 1, Figure 1, p&lt;.001). MBI scores were also significantly higher in participants with than without sleep apnea (Fig. 2, p = 0.003) and insomnia (Figure 3, p = 0.043). Further, WMH volume was higher in participants with MBI (Figure 4, p&lt;.001).ConclusionMBI increased in prevalence with cognitive impairment. Sleep disturbances and greater WMH burden in our MBI participants may increase their risk of cognitive decline for normal cognition and MCI groups and relate to poor behavioral and health outcomes in participants with dementia. Future studies will assess interactions of sleep, MBI and WMH across cognitive groups and their association with risk of conversion to MCI or AD.

Cognitive impairment one year after hospitalization due to COVID‐19 infection in Brazil: preliminary results.

AbstractBackgroundPersistence of symptoms or development of new symptoms after SARS‐CoV‐2 infection is an increasingly recognized problem and the long‐term post‐COVID‐19 outcome and the effects on cognitive function remain poorly understood. This study aims to investigate the long‐term cognitive effects and impacts of COVID‐19 with a special focus on a population with low education and low socioeconomic status.MethodCross‐sectional cognitive assessment of participants with severe forms of Covid‐19 one year after hospital admission. Until now, 187 of 322 patients underwent TICS‐M for brief telephone cognitive screening one year after hospitalization for COVID‐19 in 3 public hospitals in Belo Horizonte, Brazil. This sample was divided into two groups according to scores on the TICS‐M screening test: with or without cognitive impairment. 26 participants were selected by convenience for neuropsychiatric assessment, namely 13 with abnormal TICS‐M scores (cases) and the other 13 controls. They were submitted to the following tests and scales: Addenbrooke’s Cognitive Examination‐Revised (ACE‐R), Symbol Digit Modalities Test (SDMT), Free and Cued Selective Reminding Test (FCSRT‐IR), Hospital Anxiety and Depression Scale (HADS) and Impact of Events Scale‐Revised (IES‐R).ResultThere were no significant differences between groups for age, sex, educational level, need for intensive care unit or use of anticholinergics or sedatives. Although the comparison of SDMT between the groups showed no statistical difference (p = 0.999), all participants showed lower performance compared to normative data. Cases presented lower scores than controls in ACE‐R total (p = 0.034) and in the subdomains Attention and Orientation (p = 0.002), as well as in delayed total recall of the FCSRT‐IR (p = 0.039). Moreover, participants with lower HAD‐D scores had worst performance in Attention and Orientation subdomains of the ACE‐R (p = 0.003).ConclusionOur study shows impairment in global cognition, attention, orientation and episodic memory in individuals previously hospitalized for COVID‐19 infection who presented low scores on TICS‐M. Performance in processing speed tests was impaired among both groups in relation to normative data. Cognitive and mood analyses after COVID‐19 infection can provide information for improving healthcare of these individuals.

An Epigenome‐wide association study of psychosis in Alzheimer's disease dorsolateral prefrontal cortex

AbstractBackgroundPsychosis is a debilitating syndrome occurring in 40‐60% of people with Alzheimer’s disease (AD) and corresponds with a more severe disease course. Evidence suggests that psychosis in AD (AD+P) is associated with a distinct profile of neurobiological changes, but little is known about the molecular processes driving etiology. In this study we performed an epigenome‐wide association study (EWAS) to investigate DNA methylation associated with AD+P in the dorsolateral prefrontal cortex of 192 post‐mortem brain samples.MethodBrain samples with corresponding in life neuropsychiatric assessments were obtained from the University of Pittsburgh Alzheimer’s disease Research Center (PITT‐ADRC). AD pathology was assessed and classified using CERAD neuritic plaque density score, Braak neurofibrillary tangle stages and NIA‐RI criteria. The presence or absence of delusions and hallucinations was scored on the CERAD Behavioral Rating Scale. DNA was extracted, bisulfite treated and then profiled on the Illumina Methylation EPIC Array.ResultAfter data processing and quality control we used linear regression models to compare 152 AD+P samples to 40 AD samples without psychosis (AD‐P). A regional analysis of spatially correlated p‐values highlighted four differentially methylated regions (DMRs) associated with psychosis, which are being replicated in other data sets and validated for cell specificity using fluorescence activated nuclei sorting (FANS).ConclusionThe development of effective therapies for AD+P is an urgent priority. To address this we have collated a well powered study cohort to interrogate the epigenetic basis of AD+P, finding significant methylomic variation. This variation provides an insight into potential mechanisms and biomarkers which will help to identify drug targets and enable better treatment with existing medications.

Declining Gait Speed is associated with Deteriorating Executive Performance in people with Mild Cognitive Impairment

AbstractBackgroundThe Motoric Cognitive Risk Syndrome has highlighted the link between cognitive and motor performance, and the associated incremental higher risk of developing dementia. There is considerable debate regarding what aspects of cognition (working memory, executive function, attention) are most associated with gait changes. This study investigates the relationship between mobility scores and cognitive profiles in individuals with Mild Cognitive Impairment (MCI) specifically with regard to executive performance and amnestic/non‐amnestic profiles.MethodParticipants diagnosed with MCI, (Clinical Dementia Rating scale global score of ≤0.5, sum of boxes score ≤4.0), attending a regional specialist memory service had a three‐meter Timed Up and Go (TUG) gait assessment and multi‐domain neuropsychiatric assessment undertaken. Amnestic neuropsychiatric profile was defined as Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) delayed memory subset score &lt;1SD i.e. ≤16th centile below norm for age/ education. Executive function performance was assessed using the Executive Interview (EXIT‐25) where higher scores reflect poorer executive performance.ResultData was reviewed for 161 patients with MCI; 53% (86/161) women. 80% (129/161) had an amnestic neuropsychiatric profile, mean age 73.8 ±7.2 (51‐94). 20% (32/161) had non‐amnestic MCI, mean age 74 ±7.07 (60‐87). There was no significant difference in TUG results between amnestic and non‐amnestic MCI patients (11.2 ±3.3 vs 10.7 ±3.1 p = NS). There was a significant increase in TUG values with worsening executive function performance [EXIT‐25 score 0–9 (88/161) mean TUG = 10.5 ±3.3 seconds vs EXIT‐25 score 10–14 (43/161) mean TUG = 11.9 ±2.8 seconds vs EXIT‐25 score 15–25 (30/161) mean TUG = 12.1 ±3.9 seconds; p = 0.021] which persisted after controlling for age, gender and other relevant cofactors.ConclusionReflective of the importance of frontal lobe integration to the respective tasks, subtle differences in gait performance are associated with executive function performance regardless of predominant amnestic or non‐amnestic MCI profile.

Neuropsychiatric, neuropsychological, and neuroimaging features in isolated REM sleep behavior disorder: The importance of MCI

BackgroundMild cognitive impairment (MCI) is frequently diagnosed in patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD), although the extent of MCI-associated neuropathology has not yet been quantified. The present study compared the differences in neuropsychiatric, neuropsychological, and neuroimaging markers of neurodegeneration in MCI-iRBD and iRBD patients with normal cognition. MethodsSixty-one patients with iRBD were included in the study: 30 patients were included in the MCI subgroup (RBD-MCI) and 31 in the normal cognition subgroup (RBD-NC). Both groups underwent neuropsychiatric and neuropsychological assessments to evaluate psychopathological symptoms and neuropsychological functions. Brain [18F]FDG PET and 123I-FP-CIT-SPECT were performed to evaluate brain glucose metabolism and nigrostriatal dopaminergic function in convenient subgroups of patients, respectively. ResultsNeuropsychological measures generally confirmed overall cognitive decline in patients with iRBD-MCI. Immediate long-term verbal memory and visuospatial functions, as well as attentional-executive impairment were evident in the MCI group compared to the NC group. Neuroimaging results indicated reduced brain glucose uptake in the bilateral posterior cingulate cortex and more evident nigrostriatal deafferentation in the RBD-MCI group. There were no differences in psychopathological symptoms between the two groups. ConclusionsThis study confirmed that iRBD patients with MCI had a more impaired cognitive status that those with NC. Moreover, the MCI subgroup presented reduced cerebral glucose consumption in brain areas critical for cognition, and a more severe deafferentation of the nigro-striatal regions, highlighting the importance of identifying iRBD patients with MCI for urgent neuroprotective trials.

Dysphagia-related mucositis in children undergoing chemotherapy: The COMEDY pattern.

Children undergoing chemotherapy can experience dysphagia due to non-erosive reflux disease (NERD). Oral mucositis (OM) associated with NERD-dysphagia in children with cancer has recently been defined with the acronym COMEDY (Clenching, Oral Mucositis, closed Eyes, DYsphagia). This study aims to identify the prevalence of the COMEDY pattern among chemotherapy-induced OM. Forty-two medical records of children undergoing chemotherapy for haemato-oncologic diseases and presenting OM were reviewed. The following data were collected: age, type of haemato-oncologic disease, presence of dysphagia, type of oral mucosal lesions (i.e. traditional oral mucositis or COMEDY pattern), site of oral lesions, ear-nose-throat (ENT) assessment for the indirect signs of NERD and paediatric neuro-psychiatric (PNP) assessment. Among 42 children with chemotherapy-related OM, 6 patients (14.2%) showed the COMEDY pattern. Besides the characteristic clinical aspect of the oral mucosa, initially classified as grade II OM, these children suffered from NERD-related dysphagia and PNP issues. A COMEDY pattern can occur in a number of cases of chemotherapy-induced OM; recognizing this pattern may improve the effectiveness of treatment.