Neuropsychological Changes Research Articles

Temporosylvian arachnoid cysts in children. Part 2: Postoperative neuropsychological and clinical improvement.

The authors' objective was to study clinical, imaging, and neuropsychological changes in children who underwent surgery for a temporal arachnoid cyst (TAC). Thirty-four children were prospectively assessed similarly at diagnosis and postoperatively (mean 14 months) with clinic visits, images, cognitive tests, and parental questionnaires on mood/behavior and executive functions. The scores were compared pre- and postoperatively for the entire cohort and individually. The scores of 25 children were also compared with a control group of 23 healthy age-matched children. Parents were administered an outcome questionnaire on average 4 years postoperatively. The 34 children selected for surgery had signs of raised intracranial pressure (74%) and/or selective neuropsychological disorders presumably linked to cyst location (learning difficulties in 65%, cognitive difficulties in 56%, and mood/behavior difficulties in 47%). The majority of patients had a convex cyst (85%) and underwent microsurgical fenestration (85%). The TAC volume decreased ≥ 50% for 59% of children. On the Wechsler Intelligence Scale, the entire cohort significantly improved on Full Scale IQ and verbal and perceptual nonverbal indexes. Individually, nearly half of the children (47%) highly increased their scores (≥ 15 points) on at least one IQ index and 26% on at least two indexes. Language, working memory, episodic memory, and executive functions were also significantly improved. Improvements were more pronounced in patients with a preoperative heterogeneous profile with isolated lower scores and a left-sided cyst. Parental questionnaires showed reduction in anxiety, aggressiveness, social problems, and daily life executive disorders. Preschool-aged children improved significantly in language and verbal IQ, as did middle/high school-aged children in many domains. Individual analyses revealed improvement in 76% of cases. Cognitive scores were lower for patients preoperatively than for controls and were no longer significantly different postoperatively in verbal fluency, visual memory, and working memory. Four years later, 97% of parents described an improvement in their child, correlated with cognitive improvements. Among children with a TAC, some have no clinical signs or neuropsychological difficulties, and others may show signs of raised intracranial pressure and/or specific neuropsychological disorders that impact daily life and require significant and long-lasting rehabilitation. In these cases, consideration may be given to surgical decompression. It is interesting to note that 76% of this surgically treated cohort improved regardless of the child's age, particularly in patients with selective disorders and an impact on daily life. However, a larger number of children will need to be investigated before the true benefit of such treatment can be known.

Altered Prefrontal Blood Flow Related With Mild Cognitive Impairment in Parkinson's Disease: A Longitudinal Study.

Cognitive impairment is a common non-motor symptom in Parkinson's disease (PD), with executive dysfunction being an initial manifestation. We aimed to investigate whether and how longitudinal changes in the prefrontal perfusion correlate with mild cognitive impairment (MCI) in patients with PD. We recruited 49 patients with PD with normal cognition and 37 matched healthy control subjects (HCs). Patients with PD completed arterial spin labeling MRI (ASL–MRI) scans and a comprehensive battery of neuropsychological assessments at baseline (V0) and 2-year follow-up (V1). HCs completed similar ASL–MRI scans and neuropsychological assessments at baseline. At V1, 10 patients with PD progressed to MCI (converters) and 39 patients remained cognitively normal (non-converters). We examined differences in the cerebral blood flow (CBF) derived from ASL–MRI and neuropsychological measures (a) between patients with PD and HCs at V0 (effect of the disease), (b) between V1 and V0 in patients with PD (effect of the disease progression), and (c) between converters and non-converters (effect of the MCI progression) using t-tests or ANOVAs with false discovery rate correction. We further analyzed the relationship between longitudinal CBF and neuropsychological changes using multivariate regression models with false discovery rate correction, focusing on executive functions. At V0, no group difference was found in prefrontal CBF between patients with PD and HCs, although patients with PD showed worse performances on executive function. At V1, patients with PD showed significantly reduced CBF in multiple prefrontal regions, including the bilateral lateral orbitofrontal, medial orbitofrontal, middle frontal, inferior frontal, superior frontal, caudal anterior cingulate, and rostral anterior cingulate. More importantly, converters showed a more significant CBF reduction in the left lateral orbitofrontal cortex than non-converters. From V0 to V1, the prolonged completion time of Trail Making Test-B (TMT-B) negatively correlated with longitudinal CBF reduction in the right caudal anterior cingulate cortex. The decreased accuracy of the Stroop Color-Word Test positively correlated with longitudinal CBF reduction in the left medial orbitofrontal cortex. In addition, at V1, the completion time of TMT-B negatively correlated with CBF in the left caudal anterior cingulate cortex. Our findings suggest that longitudinal CBF reduction in the prefrontal cortex might impact cognitive functions (especially executive functions) at the early stages of PD.

Discriminant Subspace Low-Rank Representation Algorithm for Electroencephalography-Based Alzheimer's Disease Recognition.

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease that often occurs in the elderly. Electroencephalography (EEG) signals have a strong correlation with neuropsychological test results and brain structural changes. It has become an effective aid in the early diagnosis of AD by exploiting abnormal brain activity. Because the original EEG has the characteristics of weak amplitude, strong background noise and randomness, the research on intelligent AD recognition based on machine learning is still in the exploratory stage. This paper proposes the discriminant subspace low-rank representation (DSLRR) algorithm for EEG-based AD and mild cognitive impairment (MCI) recognition. The subspace learning and low-rank representation are flexibly integrated into a feature representation model. On the one hand, based on the low-rank representation, the graph discriminant embedding is introduced to constrain the representation coefficients, so that the robust representation coefficients can preserve the local manifold structure of the EEG data. On the other hand, the least squares regression, principle component analysis, and global graph embedding are introduced into the subspace learning, to make the model more discriminative. The objective function of DSLRR is solved by the inexact augmented Lagrange multiplier method. The experimental results show that the DSLRR algorithm has good classification performance, which is helpful for in-depth research on AD and MCI recognition.

One-year neuropsychological outcome after temporal lobe epilepsy surgery in large Czech sample: Search for factors contributing to memory decline.

Background: Assessment of cognitive functions is an integral part of the evaluation the efficacy of temporal resections. We studied postoperative neuropsychological changes and factors contributing to worse memory outcomes in patients who experienced a significant decline using reliable change indices.Methods: We prospectively studied 110 patients in whom we indicated anteromesial temporal resection (AMTR) and 46 patients who underwent selective amygdalohippocampectomy (SAHE). We administrated Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale-Revised, and the Verbal Fluency Test before and 1 year after the operation.Results: At a group level, we did not observe any statistically significant changes in global, verbal, and visual MQ in either the AMTR or the SAHE group. At an individual level, we found a mean decrease of verbal MQ after left-sided AMTR by −4.43 points (P = 0.01). We detected no significant differences between the left and right side of surgery in the SAHE group. In patients with significant postoperative memory decline, we found either pre-existing extrahippocampal deficits/postoperative complications or incomplete hippocampal resection or a combination of these factors.Conclusion: In addition to the side of surgery, structural integrity and functional adequacy of resected hippocampus and volume of resected tissue and preoperative extrahippocampal lesions/postoperative complications also contribute to postoperative memory decline after temporal lobe epilepsy surgery.

Depression history modulates effects of subthalamic nucleus topography on neuropsychological outcomes of deep brain stimulation for Parkinson’s disease

Patients with psychiatric symptoms, such as depression, anxiety, and visual hallucinations, may be at increased risk for adverse effects following deep brain stimulation of the subthalamic nucleus for Parkinson’s disease, but there have been relatively few studies of associations between locations of chronic stimulation and neuropsychological outcomes. We sought to determine whether psychiatric history modulates associations between stimulation location within the subthalamic nucleus and postoperative affective and cognitive changes. We retrospectively identified 42 patients with Parkinson’s disease who received bilateral subthalamic nucleus deep brain stimulation and who completed both pre- and postoperative neuropsychological testing. Active stimulation contacts were localized in MNI space using Lead-DBS software. Linear discriminant analysis identified vectors maximizing variance in postoperative neuropsychological changes, and Pearson’s correlations were used to assess for linear relationships. Stimulation location was associated with postoperative change for only 3 of the 18 neuropsychological measures. Variation along the superioinferior (z) axis was most influential. Constraining the analysis to patients with a history of depression revealed 10 measures significantly associated with active contact location, primarily related to location along the anterioposterior (y) axis and with worse outcomes associated with more anterior stimulation. Analysis of patients with a history of anxiety revealed 5 measures with location-associated changes without a predominant axis. History of visual hallucinations was not associated with significant findings. Our results suggest that a history of depression may influence the relationship between active contact location and neuropsychological outcomes following subthalamic nucleus deep brain stimulation. These patients may be more sensitive to off-target (nonmotor) stimulation.

Clinical markers of hyperactivity in patients with autism spectrum disorder

Introduction: A comorbid diagnosis of Attention Deficit Hyperactive Disorder (ADHD) and Autism Spectrum Disorder (ASD) is associated with neuropsychological and neurophysiological changes, unlike those found in individuals with ASD but without ADHD. The comorbidity of the two disorders appears to further compromise the prognosis of individuals with ASD. The objective of the present study was to identify clinical characteristics that differentiate patients with ASD and hyperactivity from patients with ASD without hyperactivity. Methods: This is a case-control study, nested within a cross-sectional study, to analyze the clinical characteristics of individuals with ASD with and without hyperactivity. Results: The study sample consisted of 30 cases and 22 controls. The risk of hyperactivity was found to increase 4.5-fold when digestive complaints were present, 3.8-fold when dysarthria was present, 4.9-fold when concentration problems were present and 3.9-fold when there was psychomotor agitation. Conclusion: These findings suggest that the presence of symptoms of hyperactivity in individuals with ASD is associated with differences in their clinical profile, specifically a greater prevalence of complains of digestive abnormalities, dysarthria, psychomotor agitation and concentration problems.

Neuropsychological changes in FMR1 premutation carriers and onset of fragile X-associated tremor/ataxia syndrome

BackgroundCarriers of the FMR1 premutation are at increased risk of developing a late-onset progressive neurodegenerative disease, fragile X-associated tremor/ataxia syndrome (FXTAS), characterized by intention tremor, gait ataxia, and cognitive decline. Cross-sectional studies to date have provided evidence that neuropsychological changes, such as executive function alterations, or subtle motor changes, may precede the onset of formal FXTAS, perhaps characterizing a prodromal state. However, the lack of longitudinal data has prevented the field from forming a clear picture of progression over time within individuals, and we lack consensus regarding early markers of risk and measures that may be used to track response to intervention.MethodsThis was a longitudinal study of 64 male FMR1 premutation carriers (Pm) without FXTAS at study entry and 30 normal controls (Nc), aged 40 to 80 years (Pm M = 60.0 years; Nc M = 57.4 years). Fifty of the Pm and 22 of the Nc were re-assessed after an average of 2.33 years, and 37 Pm and 20 Nc were re-assessed a third time after an average of another 2.15 years. Eighteen of 64 carriers (28%) converted to FXTAS during the study to date. Neuropsychological assessments at each time point, including components of the Cambridge Neuropsychological Test Automated Battery (CANTAB), tapped domains of episodic and working memory, inhibitory control, visual attention, planning, executive control of movement, and manual speed and dexterity. Age-based mixed models were used to examine group differences in change over time on the outcomes in the full sample, and differences were further evaluated in 15 trios (n = 45; 15 Pm “converters,” 15 Pm “nonconverters,” 15 Nc) that were one-one matched on age, education, and socioeconomic status.ResultsCompared to Nc, Pm showed significantly greater rates of change over time in visual working memory, motor dexterity, inhibitory control, and manual movement speed. After multiple comparison correction, significant effects remained for motor dexterity. Worsening inhibitory control and slower manual movements were related to progression in FXTAS stage, but these effects became statistically non-significant after correcting for multiple comparisons. Higher FMR1 mRNA correlated with worsening manual reaction time but did not survive multiple comparisons and no other molecular measures correlated with neuropsychological changes. Finally, trio comparisons revealed greater rate of decline in planning and manual movement speed in Pm converters compared to Pm nonconverters.ConclusionsAccelerated decline in executive function and subtle motor changes, likely mediated by frontocerebellar circuits, may precede, and then track with the emergence of formal FXTAS symptoms. Further research to develop and harmonize clinical assessment of FMR1 carriers across centers is needed to prepare for future prophylactic and treatment trials for this disorder.

APPLICATION OF NEUROLOGICAL RATING SCALES IN THE ACUTE AND EARLY RECOVERY PERIODS IN SELECTED

A study was made of the validity of some neurological assessment scales in the acute and early rehabilitation periods for certain subtypes of ischemic stroke. 110 patients with ischemic stroke (IS) were examined. In the study of neurological status, the international scale NIHSS was used, the degree of disability after IS was studied using the Rankin scale. tests were carried out in the acute period in the hospital and in the early period of rehabilitation. Both in general and in individual pathogenetic subtypes, there is a tendency (in most cases, statistically significant) to a decrease in the severity of stroke and the severity of neurological and neuropsychological changes, which is assessed in a scoring system using scales and allows you to more accurately track the dynamics of each individual patient or patient groups.

Multidomain and long-term cognitive evaluation in malignant glioma patients.

Aim: We performed longitudinal evaluations of the neurocognitive status in glioma patients to describe possible variations over the course of illness. Materials and methods: Glioma patients underwent a complete battery of standardized neuropsychological tests pre-radiotherapy at 6, 12and 24 months. Results: We enrolled 130 patients, 67.7% of whom had a deficit in at least one cognitive domain. The most affected domains included executive function (n=68, 52.3%), long-term memory (n=46, 35.3%) and short-term memory (n=39, 30%). At follow-up, cognitive status worsened in 31.5%, remained unchanged in 38.4% and improved in 30.1% of patients. Conclusion: This is one of few studies investigating longitudinal neurocognitive status in a wide sample of patients to monitor neuropsychological changes due to tumor progression and treatment administration.

Time Course of Neurobehavioral Disruptions and Regional Brain Metabolism Changes in the Rotenone Mice Model of Parkinson's Disease.

Parkinson’s disease (PD) is characterized by slow progression with a long prodromal stage and the gradual evolution of both neuropsychological symptoms and subtle motor changes, preceding motor dysfunction. Thus, in order for animal models of PD to be valid, they should reproduce these characteristics of the disease. One of such models, in which neuropathology is induced by chronic injections of low doses of mitochondrial toxin rotenone, is well established in rats. However, data on this model adapted to mice remain controversial. We have designed the study to describe the timecourse of motor and non-motor symptoms during chronic subcutaneous administration of rotenone (4 mg/kg daily for 35 days) in C57BL/6 mice. We characterize the underlying neuropathological processes (dopaminergic neuron degeneration, regional brain metabolism, monoamine neurotransmitter and lipid peroxidation changes) at different timepoints: 1 day, 2 weeks and 5 weeks of daily rotenone exposure. Based on the behavioral data, we can describe three stages of pathology: cognitive changes from week 2 of rotenone exposure, subtle motor changes in week 3–4 and motor dysfunction starting roughly from week 4. Neuropathological changes in this model include a general decrease in COX activity in different areas of the brain (acute effect of rotenone) and a more specific decrease in midbrain (chronic effect), followed by significant neurodegeneration in SNpc but not VTA by the 5th week of rotenone exposure. However, we were unable to find changes in the level of monoamine neurotransmitters neither in the striatum nor in the cortex, nor in the level of lipid peroxidation in the brainstem. Thus, the gradual progression of pathology in this model is linked with metabolic changes, rather than with oxidative stress or tonic neurotransmitter release levels. Overall, this study supports the idea that a low-dose rotenone mouse model can also reproduce different stages of PD as well as rats.

"Spazio Huntington": Tracing the Early Motor, Cognitive and Behavioral Profiles of Kids with Proven Pediatric Huntington Disease and Expanded Mutations > 80 CAG Repeats.

The “Spazio Huntington—A Place for Children” program was launched in 2019. The aim was to contact at risk kids within Huntington disease (HD) families, to provide counseling to their parents and to start a prospective follow-up of kids suspicious to manifest pediatric HD (PHD). We met 25 at risk kids in two years, four of whom with PHD and highly expanded (HE) mutations beyond 80 CAG repeats. We rated motor, neuropsychological and behavioral changes in all PHD kids by the Unified HD Rating Scale (UHDRS)-total motor score (TMS) and additional measures of (1) cognitive level (Leiter International Performance Scale), (2) adaptive functioning (Adaptive Behavior Assessment Systems), (3) receptive language (Peabody Picture Vocabulary Test) and (4) behavioral abnormalities (Child Behavior Check List and Children’s Yale–Brown Obsessive Compulsive Scale). All PHD kids showed a severe progression of neurological and psychiatric manifestations including motor, cognitive and behavioral changes. The magnetic resonance imaging contributed to confirm the suspicious clinical observation by highlighting very initial striatum abnormalities in PHD. Spazio Huntington is a program to prospectively study PHD, the most atypical face of HD, and may represent the basis to recruit PHD patients in future clinical trials.

Interaction of Gut Microbiota and Brain Function in Patients With Chronic Insomnia: A Regional Homogeneity Study.

Recent studies have shown that the human gut microbiota (GM) plays a critical role in brain function and behavior via the complex microbiome–gut–brain axis. However, knowledge about the underlying relationship between the GM and changes in brain function in patients with chronic insomnia (CI) is still very limited. In this prospective study, 31 CI patients and 30 healthy controls were recruited. Resting-state functional magnetic resonance imaging scans were performed and brain functional alterations in CI patients were evaluated using the regional homogeneity (ReHo) method. We collected fecal samples of CI patients and used 16S rDNA amplicon sequencing to assess the relative abundance (RA) and alpha diversity of the GM. We also performed extensive sleep, mood, and cognitive assessments. Then, we tested for potential associations between the GM profile, ReHo alterations, and neuropsychological changes in CI patients. Our results showed associations between the RA of Lactobacilli, ReHo values in the left fusiform gyrus, and depression scores in CI patients. We also found some bacterial genera related to ReHo values of the right triangular inferior frontal gyrus. In addition, the RA of genus Coprobacter was correlated with ReHo values of the left angular gyrus and with specific cognitive performance. These findings revealed complex relationships between GM, brain function, and behavior in patients with CI.

Eight-week multi-domain cognitive training does not impact large-scale resting-state brain networks in Parkinson’s disease

There is meta-analytic evidence for the efficacy of cognitive training (CT) in Parkinson’s disease (PD). We performed a randomized controlled trial where we found small positive effects of CT on executive function and processing speed in individuals with PD (ntotal = 140). In this study, we assessed the effects of CT on brain network connectivity and topology in a subsample of the full study population (nmri = 86). Participants were randomized into an online multi-domain CT and an active control condition and performed 24 sessions of either intervention in eight weeks. Resting-state functional MRI scans were acquired in addition to extensive clinical and neuropsychological assessments pre- and post-intervention. In line with our preregistered analysis plan (osf.io/3st82), we computed connectivity between ‘cognitive’ resting-state networks and computed topological outcomes at the whole-brain and sub-network level. We assessed group differences after the intervention with mixed-model analyses adjusting for baseline performance and analyzed the association between network and cognitive performance changes with repeated measures correlation analyses. The final analysis sample consisted of 71 participants (n CT = 37). After intervention there were no group differences on between-network connectivity and network topological outcomes. No associations between neural network and neuropsychological performance change were found. CT increased segregated network topology in a small sub-sample of cognitively intact participants. Post-hoc nodal analyses showed post-intervention enhanced connectivity of both the dorsal anterior cingulate cortex and dorsolateral prefrontal cortex in the CT group. The results suggest no large-scale brain network effects of eight-week computerized CT, but rather localized connectivity changes of key regions in cognitive function, that potentially reflect the specific effects of the intervention.

Investigating Neuropsychological Change and its Neural Correlates in Chronic Stroke Aphasia

Investigating Neuropsychological Change and its Neural Correlates in Chronic Stroke Aphasia

Hal, do I have memory problems? A pilot study investigating a voice recognition cognitive screening tool for detection of neuropsychological changes

AbstractBackgroundThe prevalence of mild, age‐advanced changes in cognition, defined as mild cognitive impairment, is spiking as the baby boomer population ages. Early and accurate detection of age‐advanced changes in thinking abilities leads to proper care, efficient use of resources, and promotion of research. Indeed, government based health care systems and insurance programs incentivize routine neurocognitive assessment. Brief, paper and pencil cognitive screeners such as the MMSE and MOCA are widely utilized in clinical settings. Such screeners lack sensitivity to subtle cognitive change and specificity related to the cause of decline. Moreover, administration and interpretation of these screeners is time consuming in a busy, clinical setting. Prior research has determined that electronic‐based testing is effective in detecting cognitive change (Zygouris & Tsolaki, 2014). This pilot study aimed to investigate a convenient, platform agnostic, voice‐recognition screening tool for detection of mild, age‐advanced neurocognitive problems.MethodParticipants (n=16) were recruited from a large community‐based neurology practice, who underwent a comprehensive neuropsychological (NP) evaluation as part of their standard of care. Participants were administered an auditory list learning/recall test and a verbal fluency test (F/A/S and animals) via a voice recognition cognitive screening tool. Pearson correlations were conducted to examine the concurrent validity between the standard NP measures and those obtained using the current screening tool.ResultPreliminary data suggests a positive correlation between standard NP measures and those obtained using voice recording and speech recognition technologies; language: F/A/S (r = .716, p < .005), animals (r .810, p < .005); memory: delayed recall (r = .515, p < .05).ConclusionThis pilot study demonstrated concurrent validity between standard NP measures of memory and verbal fluency and those obtained using a novel, voice recording and speech recognition screening tool. These initial data provide support for the efficacy of a computerized based screening tool for older adults. Such a screening too has the potential to maximize utilization across multiple settings (e.g., medical office, hospital, in‐home) and improve early detection of cognitive decline.

The influence of known pathogenic gene mutation and ApoEε4 on neuropsychological evaluation and imaging markers in preclinical stage of familial Alzheimer’s disease

AbstractBackgroundIn the preclinical stage of familial Alzheimer's disease (FAD), there have been changes in multi‐dimensional indicators, such as pathology, neuropsychology and imaging. This study explored the effects of known pathogenic gene mutation and ApoE on neuropsychology and imaging markers before the appearance of FAD symptoms.Method102 cases of asymptomatic mutation non‐carriers (26 cases of ApoEε4) and 38 cases of asymptomatic mutation carriers (17 APP, 21 PS1) in FAD families were assessed by a series of neuropsychological scales, including mini mental state scale (MMSE), auditory verbal learning test (AVLT), etc. MRI images were collected. The volume of representative brain regions was obtained, including subregions of striatum, hippocampus, rostral middle frontal gyrus (rMFG), and posterior cingulate cortex (PCC). Diffusion indices and functional connectivity (FC) of neural pathways (striatum subregions to rMFG, hippocampus to PCC) were also obtained. The neuropsychological scores and imaging indexes were compared between groups, and the imaging indexes with group differences were further correlated with neuropsychological scores.ResultCompared with asymptomatic mutation non‐carriers, APP group showed a trend increase in delayed recall score in AVLT (P = 0.08), significantly increased cued recall score, and increased radial diffusivity (RD) of bilateral caudate‐rMFG pathway (fig 1, P's < 0.05). In asymptomatic mutation non‐carriers, compared with APOEε4 non‐carriers, APOEε4 carriers showed increased right hippocampal volume, decreased fractional anisotropy (FA) of bilateral hippocampus‐PCC pathway, and increased FC of left caudate‐rMFG pathway (fig 2, P's < 0.05). The RD of right caudate‐rMFG pathway in PS1 group was positively correlated with MMSE total score (r = 0.749). The FC of left caudate‐rMFG pathway was negatively correlated with MMSE total score (fig 3, r = ‐ 0.623, P’s < 0.05).ConclusionThere are neuropsychological and imaging changes in the early stage of FAD, which are affected by the known pathogenic gene mutation and ApoEε4. APP mutation affected memory domain in cognitive function and the structural connectivity of fronto‐striatal pathway. ApoEε4 mainly affected the structural connectivity of hippocampus‐PCC pathway. The hippocampal volume and the functional connectivity of fronto‐striatal pathway increased compensatively. The overall cognitive function is differently related to the structural and functional connectivity of fronto‐striatal pathway in APP, PS1 and ApoEε4.

Attention upturned: Bias toward and away from the affected side of the body and near space in a case of complex regional pain syndrome

People with Complex Regional Pain Syndrome (CRPS) following limb injury can show neuropsychological symptoms in the absence of observable brain pathologies. These can include sensory changes, distorted body representation, and inattention to their affected limb and its surrounding space, resembling post-stroke hemispatial neglect. The precise nature and mechanisms of these neuropsychological symptoms are unclear, however insights could be gained by testing for dissociations and associations that have been observed in stroke patients. Drawing from clinical and experimental methods for investigating spatial attention bias and related symptoms in stroke patients, we conducted a detailed investigation of neuropsychological symptoms in a woman with CRPS of her left arm who initially presented to us with pronounced inattention to her affected side. The patient showed visual and tactile neglect and extinction on her affected side on confrontation tests, but no attention deficits on “bedside” tests of neglect. On sensitive computer-based measures, attention biases were found in the patient's body and near space (in Temporal Order Judgements), but not far or imagined space (on the Greyscales task and Mental Number Line Bisection). Unique to the current literature, the patient showed a reversal in her Temporal Order Judgement bias across time, from inattention (first and second session) to hyperattention (third session) to her affected side. In contrast, pain and self-reported body representation distortion were similar across the three sessions. The patient had reduced central and peripheral visual acuity, however these deficits were near symmetrical and therefore could not explain her performance on the visual attention tasks. Given that spatial attention bias has been linked to imbalance in relative activation of the two cerebral hemispheres, we administered a Global-Local processing task to test for hemispheric asymmetry. This revealed no difference in global compared to local interference refuting any hemispheric imbalance. Instead, the patient showed impaired performance (compared to controls) on incongruent trials regardless of trial type, consistent with executive impairment. We conclude that spatial attention bias in CRPS can generalize across different sensory modalities and extend beyond the affected limb to the external space around it, independent of any low-level sensory disturbances. This bias is not necessarily directed away from the affected side or stable over time. People with CRPS can also demonstrate more generalized neuropsychological changes in sensory and executive functions. Our observations refute several existing theories about the mechanisms of attention bias in CRPS, and their relationship to pain, and have potential implications for treatment.

Cognitive and social cognition deficits in Huntington's disease differ between the prodromal and the manifest stages of the condition: A scoping review of recent evidence.

Huntington's disease (HD) is a dramatic neurodegenerative disorder encompassing severe motor symptoms coupled to significant cognitive and social cognition deficits. However, it is not clear whether and how patients' neuropsychological profile changes between the prodromal and the manifest stages of the condition. The aim of the present in-depth review is to consider cognitive and social cognition impairment in HD patients by differentiating deficits arising before diagnosis from those evident from the manifest phase onwards. Electronic databases were searched between January 1st , 2010 and December 31st , 2020 by using multiple combinations of keywords related to the investigation of neuropsychological profile in HD for preliminary search, and by defining strict selection criteria for studies to be included. Forty-two studies were included. Evidence suggests that the neuropsychological profile in HD reflects a complex pathological spectrum of deficits. It includes impairment in the realms of executive functions, memory, attention, information processing, and social cognition. Interestingly, patients' profiles differ significantly between the manifest and the prodromal stages of their condition, not only in quantitative terms but also from a qualitative point of view. Researchers and clinicians should thus include in clinical routine timely and specific neuropsychological assessments in order to monitor patients' cognitive status as time goes by, with the ultimate goal to implement effective clinical management strategies. The neuropsychological profile in HD encompasses a complex pathological spectrum of deficits. Patients' profiles differ significantly between the manifest and the prodromal stages of their condition. Clinicians should include in everyday practice a timely and specific neuropsychological assessment. Detecting patients' cognitive status during the early stages of the condition already can contribute significantly to implement effective clinical management strategies.

Presumed small vessel disease, imaging and cognition markers in the Alzheimer's Disease Neuroimaging Initiative.

MRI-derived features of presumed cerebral small vessel disease are frequently found in Alzheimer’s disease. Influences of such markers on disease-progression measures are poorly understood. We measured markers of presumed small vessel disease (white matter hyperintensity volumes; cerebral microbleeds) on baseline images of newly enrolled individuals in the Alzheimer’s Disease Neuroimaging Initiative cohort (GO and 2) and used linear mixed models to relate these to subsequent atrophy and neuropsychological score change. We also assessed heterogeneity in white matter hyperintensity positioning within biomarker abnormality sequences, driven by the data, using the Subtype and Stage Inference algorithm. This study recruited both sexes and included: controls: [n = 159, mean(SD) age = 74(6) years]; early and late mild cognitive impairment [ns = 265 and 139, respectively, mean(SD) ages =71(7) and 72(8) years, respectively]; Alzheimer’s disease [n = 103, mean(SD) age = 75(8)] and significant memory concern [n = 72, mean(SD) age = 72(6) years]. Baseline demographic and vascular risk-factor data, and longitudinal cognitive scores (Mini-Mental State Examination; logical memory; and Trails A and B) were collected. Whole-brain and hippocampal volume change metrics were calculated. White matter hyperintensity volumes were associated with greater whole-brain and hippocampal volume changes independently of cerebral microbleeds (a doubling of baseline white matter hyperintensity was associated with an increase in atrophy rate of 0.3 ml/year for brain and 0.013 ml/year for hippocampus). Cerebral microbleeds were found in 15% of individuals and the presence of a microbleed, as opposed to none, was associated with increases in atrophy rate of 1.4 ml/year for whole brain and 0.021 ml/year for hippocampus. White matter hyperintensities were predictive of greater decline in all neuropsychological scores, while cerebral microbleeds were predictive of decline in logical memory (immediate recall) and Mini-Mental State Examination scores. We identified distinct groups with specific sequences of biomarker abnormality using continuous baseline measures and brain volume change. Four clusters were found; Group 1 showed early Alzheimer’s pathology; Group 2 showed early neurodegeneration; Group 3 had early mixed Alzheimer’s and cerebrovascular pathology; Group 4 had early neuropsychological score abnormalities. White matter hyperintensity volumes becoming abnormal was a late event for Groups 1 and 4 and an early event for 2 and 3. In summary, white matter hyperintensities and microbleeds were independently associated with progressive neurodegeneration (brain atrophy rates) and cognitive decline (change in neuropsychological scores). Mechanisms involving white matter hyperintensities and progression and microbleeds and progression may be partially separate. Distinct sequences of biomarker progression were found. White matter hyperintensity development was an early event in two sequences.

Benchmarks of meaningful improvement on neurocognitive tests in multiple sclerosis

Background: Previous studies have established benchmarks of clinically meaningful decline on neuropsychological tests. However, little is known about meaningful testing benchmarks based on gains in function. Objective: Investigate neuropsychological changes in multiple sclerosis (MS) patients with work gains and calculate benchmarks of meaningful improvement on neuropsychological tests. Methods: A total of 323 people with MS were monitored longitudinally with neuropsychological testing and the Buffalo Vocational Monitoring Survey. Results/Conclusions: Those with work gains showed significant improvement (~3 points) on the Symbol Digit Modalities Test (SDMT) over time, p = 0.01. Benchmarks for clinically meaningful improvement on the SDMT are similar to those previously established for clinically meaningful decline.