Cognitive Phenotypes of Older Adults with Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment: The Czech Brain Aging Study.

OBJECTIVE: To compare cognitive phenotypes of participants with subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI), estimate progression to MCI/dementia by phenotype and assess classification error with machine learning. METHOD: Dataset consisted of 163 participants with SCD and 282 participants with aMCI from the Czech Brain Aging Study. Cognitive assessment included the Uniform Data Set battery and additional tests to ascertain executive function, language, immediate and delayed memory, visuospatial skills, and processing speed. Latent profile analyses were used to develop cognitive profiles, and Cox proportional hazards models were used to estimate risk of progression. Random forest machine learning algorithms reported cognitive phenotype classification error. RESULTS: Latent profile analysis identified three phenotypes for SCD, with one phenotype performing worse across all domains but not progressing more quickly to MCI/dementia after controlling for age, sex, and education. Three aMCI phenotypes were characterized by mild deficits, memory and language impairment (dysnomic aMCI), and severe multi-domain aMCI (i.e., deficits across all domains). A dose-response relationship between baseline level of impairment and subsequent risk of progression to dementia was evident for aMCI profiles after controlling for age, sex, and education. Machine learning more easily classified participants with aMCI in comparison to SCD (8% vs. 21% misclassified). CONCLUSIONS: Cognitive performance follows distinct patterns, especially within aMCI. The patterns map onto risk of progression to dementia.

Interactions of 17ß-Hydroxysteroid Dehydrogenase Type 10 and Cyclophilin D in Alzheimer's Disease.

The nucleus-encoded 17ß-hydroxysteroid dehydrogenase type 10 (17ß-HSD10) regulates cyclophilin D (cypD) in the mitochondrial matrix. CypD regulates opening of mitochondrial permeability transition pores. Both mechanisms may be affected by amyloid ß peptides accumulated in mitochondria in Alzheimer's disease (AD). In order to clarify changes occurring in brain mitochondria, we evaluated interactions of both mitochondrial proteins in vitro (by surface plasmon resonance biosensor) and detected levels of various complexes of 17ß-HSD10 formed in vivo (by sandwich ELISA) in brain mitochondria isolated from the transgenic animal model of AD (homozygous McGill-R-Thy1-APP rats) and in cerebrospinal fluid samples of AD patients. By surface plasmon resonance biosensor, we observed the interaction of 17ß-HSD10 and cypD in a direct real-time manner and determined, for the first time, the kinetic parameters of the interaction (ka 2.0 × 105 M1s-1, kd 5.8 × 104 s-1, and KD 3.5 × 10-10 M). In McGill-R-Thy1-APP rats compared to controls, levels of 17ß-HSD10-cypD complexes were decreased and those of total amyloid ß increased. Moreover, the levels of 17ß-HSD10-cypD complexes were decreased in cerebrospinal fluid of individuals with AD (in mild cognitive impairment as well as dementia stages) or with Frontotemporal lobar degeneration (FTLD) compared to cognitively normal controls (the sensitivity of the complexes to AD dementia was 92.9%, that to FTLD 73.8%, the specificity to AD dementia equaled 91.7% in a comparison with the controls but only 26.2% with FTLD). Our results demonstrate the weakened ability of 17ß-HSD10 to regulate cypD in the mitochondrial matrix probably via direct effects of amyloid ß. Levels of 17ß-HSD10-cypD complexes in cerebrospinal fluid seem to be the very sensitive indicator of mitochondrial dysfunction observed in neurodegeneration but unfortunately not specific to AD pathology. We do not recommend it as the new biomarker of AD.

Eye movements in idiopathic rapid eye movement sleep behaviour disorder: High antisaccade error rate reflects prefrontal cortex dysfunction.

Abnormalities of eye movements have been reported in patients with Parkinson's disease (PD). However, it is unclear if they occur in the prodromal stage of synucleinopathy represented by idiopathic rapid eye movement sleep behaviour disorder (iRBD). We thus aimed to study eye movements in subjects with iRBD and in de novo PD, to assess if their abnormalities may serve as a clinical biomarker of neurodegeneration. Fifty subjects with polysomnography-confirmed iRBD (46 male, age 40-79 years), 18 newly diagnosed, untreated PD patients (13 male, age 43-75 years) and 25 healthy controls (20 male, age 42-79 years) were prospectively enrolled. Horizontal and vertical ocular prosaccades and antisaccades were investigated with video-oculography. All patients completed the MDS-UPDRS and the Montreal Cognitive Assessment. In addition, a neuropsychological battery was performed on iRBD subjects. When compared with healthy controls, both de novo PD patients and iRBD subjects showed increased error rates in the horizontal antisaccade task (p < 0.01, p < 0.05 respectively). In the iRBD group, the error rates in horizontal and vertical antisaccades correlated with performances in the Prague Stroop Test and the Grooved Pegboard Test, as well as with motor scores of the MDS-UPDRS. De novo PD patients showed a lower gain (p < 0.01) compared with controls. In conclusion, the increased error rate in the antisaccade task of iRBD and PD patients reflects a dysfunction of the dorsolateral prefrontal cortex and is related to the impairment of executive functions and attention.

Fragmentary myoclonus in idiopathic rapid eye movement sleep behaviour disorder.

Fragmentary myoclonus is a result of muscle activity consisting of brief potentials in surface electromyography during polysomnography. Excessive fragmentary myoclonus is defined by increased intensity of the potentials. A few studies report excessive fragmentary myoclonus occurrence in neurodegenerative diseases. Because idiopathic rapid eye movement sleep behaviour disorder is considered as an early stage of neurodegeneration with involvement of the brainstem, we charted the prevalence and quantified the intensity of excessive fragmentary myoclonus in idiopathic rapid eye movement sleep behaviour disorder. Twenty-nine patients (one woman, 28 men, mean age 68 years, SD 6.2) and 29 controls (two women, 27 men, mean age 65.6 years, SD 8.6) underwent polysomnography. Fragmentary myoclonus potentials were identified and counted according to internationally used criteria. Fragmentary myoclonus intensity was quantified by the fragmentary myoclonus index. Excessive fragmentary myoclonus was diagnosed in 75.9% (22 subjects) in idiopathic rapid eye movement sleep behaviour disorder, while in 34.5% (10 subjects) among the controls (p = 0.003). Quantitative analysis showed a wide-range fragmentary myoclonus index in idiopathic rapid eye movement sleep behaviour disorder (4.0-632.4; median 60.7) and in the controls (0.8-938.1; median 34.3). The overall difference in fragmentary myoclonus index was not significant between the groups; however, patients with idiopathic rapid eye movement sleep behaviour disorder showed trends for higher fragmentary myoclonus index scores in wakefulness (p = 0.027), N1 (p = 0.032), N3 (p = 0.046) and R (p = 0.007). Fragmentary myoclonus index does not correlate with age, idiopathic rapid eye movement sleep behaviour disorder duration or R stage atonia deficiency. The prevalence of excessive fragmentary myoclonus is higher in idiopathic rapid eye movement sleep behaviour disorder compared with the controls, so fragmentary myoclonus should be taken into account in future research of rapid eye movement sleep behaviour disorder and motor control in sleep.

Amygdala and emotionality in Parkinson's disease: An integrative review of the neuropsychological evidence.

Parkinson's disease (PD) is often accompanied by significant changes in emotionality, such as apathy, anhedonia, anxiety and depression. The present review summarizes the empirical evidence, including amygdala changes and psychological changes in emotionality in people suffering from PD. Seventeen empirical full-text articles including research on both amygdala and emotionality in PD were reviewed. The changes in amygdala volumes as well as changes in binding potentials, functional connectivity, regional homogeneity and regional cerebral blood flow were found to have various impacts on emotionality in people with PD. The integration of the results showed that some effects of amygdala changes on emotionality were lateralized. Some of the reviewed studies indicated that the volume loss in the left amygdala was found to be related to increased anxiety, whereas bilateral volume loss in amygdala was linked to increased depressivity. The reviewed results also support a hypothesis of bradylimbic affective disturbance in patients with PD. The disturbed activation of amygdala accompanying the evaluation of negative facial expressions implies that the evaluation of the content of affective stimuli in terms of their affective meanings is disturbed in PD patients. Impaired evaluation of affective attributes given by amygdala-based translational deficits is likely to be related to problems in translating the results of cognitive appraisal into somatomotor, arousal and other changes. This mechanism is suggested to be responsible for apathy as well as for other changes in emotionality accompanying PD.

Clock drawing test in screening for Alzheimer's dementia and mild cognitive impairment in clinical practice.

OBJECTIVES: The clock drawing test (CDT) is a commonly used brief cognitive measure. We evaluated diagnostic accuracy of subjective ratings of CDT by physicians (with/without specialty in cognitive neurology) and neuropsychologists in discriminating amnestic mild cognitive impairment (aMCI), Alzheimer's dementia (AD) and cognitively healthy older adults. We further compared the diagnostic accuracy of subjective categorical ratings with complex scoring of CDT. METHODS: Three cognitive neurologists, three neuropsychologists and six neurology residents without experience in cognitive neurology blinded to the diagnosis rated 187 CDTs (50 mild AD, 49 aMCI and 88 cognitively healthy older adults) using a "yes" (abnormal) versus "suspected" versus "no" (normal) classification. The rating suspected was combined with yes or no to obtain two sets of sensitivity estimates. We also used a 17-point CDT rating system. RESULTS: When using the categorical rating, neuropsychologists had highest sensitivity (89%) in differentiating patients with mild AD (yes/suspected versus no), followed by neurologic residents (80%) and cognitive neurologists (79%). When differentiating patients with aMCI (yes/suspected versus no), the sensitivity was 84% for neuropsychologists, 64% for cognitive neurologists and 62% for residents. The sensitivity using the complex scoring system was 92% in patients with mild AD and 69% in patients with aMCI. CONCLUSIONS: A categorical rating of CDT shows high sensitivity for mild AD even in non-experienced raters. Neuropsychologists outperformed physicians in differentiating patients with aMCI from cognitively healthy older adults (specificity), which was counterbalanced by the lower specificity of their ratings. The diagnostic accuracy was not substantially improved by using complex scoring system. Copyright © 2016 John Wiley & Sons, Ltd.

Clinical validity of the Mattis Dementia Rating Scale in differentiating mild cognitive impairment in Parkinson's disease and normative data.

BACKGROUND/AIMS: The aim of the present study was to provide normative data and determine the validity of the Czech version of the Mattis Dementia Rating Scale 2 (czDRS-2) in screening for mild cognitive impairment in Parkinson's disease (PD-MCI) based on the Movement Disorder Society (MDS) Level II criteria. METHODS: For validation purposes, 41 healthy controls (HC), 46 patients with PD-NI (Parkinson's disease, no impairment) and 41 patients with PD-MCI (all groups assessed by the MDS Level II criteria for PD-MCI) were matched according to age and education. RESULTS: With screening and diagnostic cutoff scores determined at ≤139 points, the czDRS-2 showed a sensitivity of 78% and a specificity of 88% in the detection of PD-MCI versus HC and a sensitivity of 78% and a specificity of 76% in the detection of PD-MCI versus PD-NI. The AUC (95% confidence interval) for the czDRS-2 was 84% (75-93) and 82% (73-91), respectively. We report percentile values for 286 subjects from the Czech population stratified by education level. CONCLUSION: Our results show that the czDRS-2 is a valid instrument at Level I for screening PD-MCI and support its construct validity and diagnostic equivalence in a cross-cultural setting.

Efficacy of non-computerized cognitive rehabilitation in Parkinson's disease: A one year follow up study.

In this study, we explored the effect of non-computerized cognitive rehabilitation in patients with Parkinson's disease in comparison with an intervention with elements of music therapy after the completion of a three-month program and one year after the end of the intervention. After the initial neuropsychological examination, the respondents were divided into two intervention groups. The experimental group (n = 26) underwent a twelve-week program of cognitive rehabilitation at a frequency of 60 minutes once a week. The control group (n = 27) underwent an intervention program with elements of music therapy at the same frequency. Respondents who underwent the cognitive rehabilitation program improved in the delayed recall from visual memory in the follow-up examination after the end of the cognitive intervention. One year after the end, the effect of cognitive rehabilitation persisted in delayed recall from visual memory and in executive mental flexibility. Cognitive rehabilitation is an effective approach to compensate for cognitive deficits in P D, but other approaches to cognitive stimulation may be equally effective.

Evaluation of Differential Diagnostics Potential of Uniform Data Set 2 Neuropsychology Battery Using Alzheimer's Disease Biomarkers.

OBJECTIVE: This study aims to evaluate the efficacy of the Uniform Data Set (UDS) 2 battery in distinguishing between individuals with mild cognitive impairment (MCI) attributable to Alzheimer's disease (MCI-AD) and those with MCI due to other causes (MCI-nonAD), based on contemporary AT(N) biomarker criteria. Despite the implementation of the novel UDS 3 battery, the UDS 2 battery is still used in several non-English-speaking countries. METHODS: We employed a cross-sectional design. A total of 113 Czech participants with MCI underwent a comprehensive diagnostic assessment, including cerebrospinal fluid biomarker evaluation, resulting in two groups: 45 individuals with prodromal AD (A+T+) and 68 participants with non-Alzheimer's pathological changes or normal AD biomarkers (A-). Multivariable logistic regression analyses were employed with neuropsychological test scores and demographic variables as predictors and AD status as an outcome. Model 1 included UDS 2 scores that differed between AD and non-AD groups (Logical Memory delayed recall), Model 2 employed also Letter Fluency and Rey's Auditory Verbal Learning Test (RAVLT). The two models were compared using area under the receiver operating characteristic curves. We also created separate logistic regression models for each of the UDS 2 scores. RESULTS: Worse performance in delayed recall of Logical Memory significantly predicted the presence of positive AD biomarkers. In addition, the inclusion of Letter Fluency RAVLT into the model significantly enhanced its discriminative capacity. CONCLUSION: Our findings demonstrate that using Letter Fluency and RAVLT alongside the UDS 2 battery can enhance its potential for differential diagnostics.

Reducing misclassification of mild cognitive impairment based on base rate information from the Uniform data set.

The current study aimed to define and validate the criteria for characterizing possible and probable cognitive deficits based on the psychometric approach using the Uniform data set Czech version (UDS-CZ 2.0) to reduce the rate of misdiagnosis. We computed the prevalence of low scores on the 14 subtests of UDS-CZ 2.0 in a normative sample of healthy older adults and validated criteria for possible and probable cognitive impairment on the sample of amnestic Mild Cognitive Impairment (MCI) patients. The misclassification rate of the validation sample using psychometrically derived criteria remained low: for classification as possible impairment, we found 66-76% correct classification in the clinical sample and only 2-8% false positives in the healthy control validation sample, similar results were obtained for probable cognitive impairment. Our findings offer a psychometric approach and a computational tool to minimize the misdiagnosis of mild cognitive impairment compared to traditional criteria for MCI.

Combining Neuropsychological Assessment with Neuroimaging to Distinguish Early-Stage Alzheimer's Disease from Frontotemporal Lobar Degeneration in Non-Western Tonal Native Language-Speaking Individuals Living in Taiwan: A Case Series.

Neuropsychological tests (NPTs), which are routinely used in clinical practice for assessment of dementia, are also considered to be essential for differential diagnosis of Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), especially the behavioral variants of frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA) at their initial clinical presentations. However, the heterogeneous features of these diseases, which have many overlapping signs, make differentiation between AD and FTLD highly challenging. Moreover, NPTs were primarily developed in Western countries and for native speakers of non-tonal languages. Hence, there is an ongoing dispute over the validity and reliability of these tests in culturally different and typologically diverse language populations. The purpose of this case series was to examine which of the NPTs adjusted for Taiwanese society may be used to distinguish these two diseases. Since AD and FTLD have different effects on individuals' brain, we combined NPTs with neuroimaging. We found that participants diagnosed with FTLD had lower scores in NPTs assessing language or social cognition than AD participants. PPA participants also had lower measures in the Free and Cued Selective Reminding Test than those diagnosed with bvFTD, while bvFTD participants showed poorer performances in the behavioral measures than PPA participants. In addition, the initial diagnosis was supported by the standard one-year clinical follow-up.

Memory Binding Test and Its Associations With Hippocampal Volume Across the Cognitive Continuum Preceding Dementia.

Innovative memory paradigms have been introduced to capture subtle memory changes in early Alzheimer's disease (AD). We aimed to examine the associations between different indexes of the challenging Memory Binding Test (MBT) and hippocampal volume (HV) in a sample of individuals with subjective cognitive decline (SCD; n = 50), amnestic mild cognitive impairment (aMCI) due to AD (n = 31), and cognitively normal (CN) older adults (n = 29) recruited from the Czech Brain Aging Study, in contrast to traditional verbal memory tests. Both MBT free and cued recall scores in immediate and delayed recall conditions were associated with lower HV in both SCD and aMCI due to AD, whereas in traditional verbal memory tests only delayed recall scores were associated with lower HV. In SCD, the associations with lower HV in the immediate recall covered specific cued recall indexes only. In conclusion, the MBT is a promising test for detecting subtle hippocampal-associated memory decline during the predementia continuum.

Decreased emotional creativity and its relationship with cognitive functions in Parkinson's disease: A preliminary study.

Patients with Parkinson's disease (PD) suffer from a wide range of non-motor symptoms, including cognitive deficits and impairment of emotional processing. The present study aimed to explore in PD patients compared to healthy adults the relationship between cognitive performance and emotional creativity (EC), defined as a set of cognitive abilities and personality traits related to originality and appropriateness of emotional experience. PD patients (n = 22) and healthy controls (n = 40) underwent a complex neuropsychological assessment and were administrated with the self-reported Emotional Creativity Inventory (ECI) questionnaire. To explore the relationship between cognitive tests and the ECI, a regression analysis was conducted. PD patients and healthy controls differed significantly in the EC component Preparedness as well as in the neuropsychological test battery scores. PD patients showed lower scores in cognitive tests and a lower score in Preparedness compared to healthy adults. The output of the regression analysis showed that the extent to which the neuropsychological tests relate to the ECI components is low.

Corrigendum: Mild Behavioral Impairment Is Associated With Atrophy of Entorhinal Cortex and Hippocampus in a Memory Clinic Cohort.

[This corrects the article DOI: 10.3389/fnagi.2021.643271.].

Progression from Subjective Cognitive Decline to Mild Cognitive Impairment or Dementia: The Role of Baseline Cognitive Performance.

BACKGROUND: Older adults with subjective cognitive decline (SCD) are at an increased risk of progression to mild cognitive impairment (MCI) or dementia. However, few have examined the specific cognitive tests that are associated with progression. OBJECTIVE: This study examined performance on 18 neuropsychological tests among participants with SCD who later progressed to MCI or dementia. METHODS: We included 131 participants from the Czech Brain Aging Study that had SCD at baseline. They completed a comprehensive neuropsychological battery including cognitive tests from the Uniform Data Set 2.0 enriched by the verbal memory test Rey Auditory Verbal Learning Test (RAVLT) and Rey-Osterrieth Complex Figure Test (ROCFT). RESULTS: Fifty-five participants progressed: 53% to non-amnestic MCI (naMCI), 44% to amnestic MCI (aMCI), and 4% to dementia. Scoring one SD below the mean at baseline on the RAVLT 1 and RAVLT 1-5 was associated with 133% (RAVLT 1; HR: 2.33 [1.50, 3.62]) and 122% (RAVLT 1-5; HR: 2.22 [1.55, 3.16]) greater risk of progression to MCI or dementia over 3.84 years on average. Worse performance on the RAVLT 5, RAVLT 1-5, RAVLT 30, and ROCFT-Recall was associated with progression to aMCI whereas worse performance on the RAVLT 1, TMT B, and Boston Naming Test was associated with progression to naMCI. CONCLUSION: At baseline, lower verbal memory performance was most strongly associated with progression to aMCI whereas lower executive or language performance was most strongly associated with progression to naMCI.

Contribution of Memory Tests to Early Identification of Conversion from Amnestic Mild Cognitive Impairment to Dementia.

BACKGROUND: Memory tests using controlled encoding and cued recall paradigm (CECR) have been shown to identify prodromal Alzheimer's disease (AD), but information about the effectiveness of CECR compared to other memory tests in predicting clinical progression is missing. OBJECTIVE: The aim was to examine the predictive ability of a memory test based on the CECR paradigm in comparison to other memory/non-memory tests for conversion to dementia in patients with amnestic mild cognitive impairment (aMCI). METHODS: 270 aMCI patients from the clinical-based Czech Brain Aging Study underwent a comprehensive neuropsychological assessment including the Enhanced Cued Recall test (ECR), a memory test with CECR, two verbal memory tests without controlled encoding: the Auditory Verbal Learning Test (AVLT) and Logical memory test (LM), a visuospatial memory test: the Rey-Osterrieth Complex Figure test, and cognitive testing based on the Uniform Data Set battery. The patients were followed prospectively. Conversion to dementia as a function of cognitive performance was examined using Cox proportional hazard models. RESULTS: 144 (53%) patients converted to dementia. Most converters (89%) developed dementia due to AD or mixed (AD and vascular) dementia. Comparing the four memory tests, the delayed recall scores on AVLT and LM best predicted conversion to dementia. Adjusted hazard ratios (HR) of immediate recall scores on ECR, AVLT, and LM were similar to the HR of categorical verbal fluency. CONCLUSION: Using the CECR memory paradigm in assessment of aMCI patients has no superiority over verbal and non-verbal memory tests without cued recall in predicting conversion to dementia.

Attention impairment in motor functional neurological disorders: a neuropsychological study.

OBJECTIVE: Our objective was to assess cognitive functioning across multiple cognitive domains using a standardised neuropsychological battery in patients with motor functional neurological disorders (mFND). METHODS: Thirty patients with clinically established mFND and 30 age-, sex- and education-matched control subjects underwent a thorough neuropsychological assessment evaluating (1) attention including processing speed, (2) executive functions including working memory, (3) short-term memory, (4) speech and language and (5) visuospatial functions. Performance validity tests (PVT) and self-report measures of depression, anxiety and cognitive complaints were included in the assessment. Only patients with valid test performance were included in the analysis. RESULTS: Three patients scored below the cut-off scores in PVT. Patients performed significantly worse than controls in the following areas: (1) the attention domain which included a slow processing speed (p = 0.005, Cohen's d = 0.89), (2) executive functions (p = 0.01, Cohen's d = 0.88) and (3) speech and language domains (p = 0.025, Cohen's d = 0.77). Patients with mFND showed greater intra-individual variability in cognitive performance (p = 0.005, Cohen's d = 0.94). Cognitive impairments were independent of depressive symptoms, which were higher in mFND patients. CONCLUSION: This study revealed both subjective and objective cognitive impairment in patients with mFND. The neuropsychological profile in mFND was characterised primarily by attentional impairment including a slow processing speed and a high intra-individual variability in cognitive performance. Cognitive impairment was associated with a valid test performance, highlighting that the deficits observed were not likely to be explained by a lack of effort in the patient group. Attention is considered to play a key role in mFND pathophysiology, and the results suggest that such impairments are objectively measurable.

Core Competencies in Clinical Neuropsychology as a Training Model in Europe.

The multitude of training models and curricula for the specialty of clinical neuropsychology around the world has led to organized activities to develop a framework of core competencies to ensure sufficient expertise among entry-level professionals in the field. The Standing Committee on Clinical Neuropsychology of the European Federation of Psychologists' Associations is currently working toward developing a specialty certification in clinical neuropsychology to establish a cross-national standard against which to measure levels of equivalency and uniformity in competence and service provision among professionals in the field. Through structured interviews with experts from 28 European countries, we explored potential areas of core competency. Specifically, questions pertained to the perceived importance of a series of foundational, functional, and other competencies, as well as current training standards and practices, and optimal standards. Our findings revealed considerable agreement (about three quarters and above) on academic and clinical training, despite varied actual training requirements currently, with fewer respondents relegating importance to training in teaching, supervision, and research (a little over half), and even fewer to skills related to management, administration, and advocacy (fewer than half). European expert clinical neuropsychologists were in agreement with previous studies (including those conducted in the United States, Australia, and other countries) regarding the importance of sound theoretical and clinical training but management, administrative, and advocacy skills were not central to their perspective of a competent specialist in clinical neuropsychology. Establishing a specialty certificate in clinical neuropsychology based on core competencies may enable mobility of clinical neuropsychologists across Europe, and, perhaps, provide an impetus for countries with limited criteria to reconsider their training requirements and harmonize their standards with others.

Characterization of memory profile in idiopathic REM sleep behavior disorder.

OBJECTIVE: The present study aims to examine whether declarative memory dysfunction relates to impaired core memory mechanisms or attentional and executive dysfunction in idiopathic REM Sleep Behavior Disorder (iRBD). METHOD: In this observational, cross-sectional study, were enrolled 82 individuals with the diagnosis of iRBD according to the International Classification of Sleep Disorders and 49-matched healthy controls fulfilling inclusion criteria. All participants underwent two memory tasks, namely the Rey Auditory Verbal Learning Test (RAVLT) and Memory Binding Test (MBT), which include conditions of varying degrees of dependence on executive functioning, as well as different indicators of core memory processes (e.g., learning, retention, relational binding). RESULTS: We used Bayesian multivariate generalized linear model analysis to evaluate the effect of iRBD on memory performance controlled for effects of age and sex. Individuals with iRBD displayed worse memory performance in the delayed free recall task (b = -0.37, 95% PPI [-0.69, -0.05]), but not on delayed recognition of the same material. Their performance in cued recall tasks both in immediate and delayed conditions was in comparison to controls relatively spared. Moreover, the deficit in delayed free recall was mediated by attention/processing speed. CONCLUSIONS: In iRBD, we replicated findings of reduced free recall based on inefficient retrieval (retrieval deficit), which was small in terms of effect size. Importantly, the memory profile across measures does not support the presence of core memory dysfunction, such as poor learning, retention or associative binding.

Spatial navigation in early multiple sclerosis: a neglected cognitive marker of the disease?

BACKGROUND: Cognitive deficits are common in early multiple sclerosis (MS), however, spatial navigation changes and their associations with brain pathology remain poorly understood. OBJECTIVE: To characterize the profile of spatial navigation changes in two main navigational strategies, egocentric (self-centred) and allocentric (world-centred), and their associations with demyelinating and neurodegenerative changes in early MS. METHODS: Participants with early MS after the first clinical event (n = 51) and age-, gender- and education-matched controls (n = 42) underwent spatial navigation testing in a real-space human analogue of the Morris water maze task, comprehensive neuropsychological assessment, and MRI brain scan with voxel-based morphometry and volumetric analyses. RESULTS: The early MS group had lower performance in the egocentric (p = 0.010), allocentric (p = 0.004) and allocentric-delayed (p = 0.038) navigation tasks controlling for age, gender and education. Based on the applied criteria, lower spatial navigation performance was present in 26-29 and 33-41% of the participants with early MS in the egocentric and the allocentric task, respectively. Larger lesion load volume in cortical, subcortical and cerebellar regions (ß ≥ 0.29; p ≤ 0.032) unlike brain atrophy was associated with less accurate allocentric navigation performance. CONCLUSION: Lower spatial navigation performance is present in up to 41% of the participants with early MS. Demyelinating lesions in early MS may disrupt neural network forming the basis of allocentric navigation.