Neuropsychological Assessment Scores Research Articles

Longitudinal neuropsychological performance of post-stroke adults with and without rehabilitation

This study compared the neuropsychological performance of two post-stroke groups, one undergoing rehabilitation and the other not receiving any intervention, on the acute and chronic stroke phases, and explored sociodemographic and neurological variables associated with changes in performance over time. Sixty-three adults underwent neuropsychological assessment with the Cognitive Screening Instrument (TRIACOG) less than thirty days after having a stroke and were reassessed three to six months after stroke. Thirty-eight participants did not undertake rehabilitation and twenty-five did physiotherapy and/or speech therapy between the two time points. The frequency of cognitive deficits (between groups) and the range of cognitive assessment scores over time (between and within groups) were analyzed. There was a significant decrease in the frequency of neuropsychological deficits and improvement on neuropsychological assessment scores over time only in the group undergoing rehabilitation. Severity of the neurological condition, years of education and being in rehabilitation explained the longitudinal changes in several cognitive domains measured by TRIACOG. Engaging in rehabilitation within three to six months post-stroke is crucial for enhancing the recovery of neuropsychological deficits. Cognitive screening instruments like TRIACOG can be used by health professionals to identify stroke-related neuropsychological changes and plan interventions.

Free water in gray matter linked to gut microbiota changes with decreased butyrate producers in Alzheimer's disease and mild cognitive impairment

Neuroinflammation contributes to the pathology and progression of Alzheimer's disease (AD), and it can be observed even with mild cognitive impairment (MCI), a prodromal phase of AD. Free water (FW) imaging estimates the extracellular water content and has been used to study neuroinflammation across several neurological diseases including AD. Recently, the role of gut microbiota has been implicated in the pathogenesis of AD. The relationship between FW imaging and gut microbiota was examined in patients with AD and MCI. Fifty-six participants underwent neuropsychological assessments, FW imaging, and gut microbiota analysis targeting the bacterial 16S rRNA gene. They were categorized into the cognitively normal control (NC) (n = 19), MCI (n = 19), and AD (n = 18) groups according to the neuropsychological assessments. The correlations of FW values, neuropsychological assessment scores, and the relative abundance of gut microbiota were analyzed. FW was higher in several white matter tracts and in gray matter regions, predominantly the frontal, temporal, limbic and paralimbic regions in the AD/MCI group than in the NC group. In the AD/MCI group, higher FW values in the temporal (superior temporal and temporal pole), limbic and paralimbic (insula, hippocampus and amygdala) regions were the most associated with worse neuropsychological assessment scores. In the AD/MCI group, FW values in these regions were negatively correlated with the relative abundances of butyrate-producing genera Anaerostipes, Lachnospiraceae UCG-004, and [Ruminococcus] gnavus group, which showed a significant decreasing trend in the order of the NC, MCI, and AD groups. The present study showed that increased FW in the gray matter regions related to cognitive impairment was associated with low abundances of butyrate producers in the AD/MCI group. These findings suggest an association between neuroinflammation and decreased levels of the short-chain fatty acid butyrate that is one of the major gut microbial metabolites having a potentially beneficial role in brain homeostasis.

Robust reference group normative data for neuropsychological tests accounting for primary language use in Asian American older adults.

The present study aimed to develop neuropsychological norms for older Asian Americans with English as a primary or secondary language, using data from the National Alzheimer's Coordinating Center (NACC). A normative sample of Asian American participants was derived from the NACC database using robust criteria: participants were cognitively unimpaired at baseline (i.e., no MCI or dementia) and remained cognitively unimpaired at 1-year follow-up. Clinical and demographic characteristics were compared between Primary and Secondary English speakers using analyses of variance for continuous measures and chi-square tests for categorical variables. Linear regression models compared neuropsychological performance between the groups, adjusting for demographics (age, sex, and education). Regression models were developed for clinical application to compute demographically adjusted z-scores. Secondary English speakers were younger than Primary English speakers (p < .001). There were significant differences between the groups on measures of mental status (Mini-Mental State Examination, p = .002), attention (Trail Making Test A, Digit Span Forward Total Score, p <.001), language (Boston Naming Test, Animal Fluency, Vegetable Fluency, p < .001), and executive function (Trail Making Test B, p = .02). Separate normative data are needed for Primary vs. Secondary English speakers from Asian American backgrounds. We provide normative data on older Asian Americans to enable clinicians to account for English use in the interpretation of neuropsychological assessment scores.

Metabotropic glutamate receptor 5 (mGluR5) is associated with neurodegeneration and amyloid deposition in Alzheimer’s disease: A [18F]PSS232 PET/MRI study

BackgroundMetabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the initial pathophysiological mechanism of Alzheimer’s disease (AD). The study aims to investigate the association between mGluR5 availability and AD’s biomarkers and cognitive function.MethodsWe examined 35 individuals with mGluR5 tracer [18F]PSS232 to assess mGluR5 availability, and with [18F]Florbetapir PET to assess global amyloid deposition, and [18F]FDG PET to assess glucose metabolism. The plasma neurofilament light (NfL) and p-tau181 levels in a subset of individuals were measured (n = 27). The difference in mGluR5 availability between the AD and normal control (NC) groups was explored. The associations of mGluR5 availability with amyloid deposition, glucose metabolism, gray matter volume (GMV), neuropsychological assessment scores, and plasma biomarkers were analyzed.ResultsThe mGluR5 availability was significantly reduced in AD patients’ hippocampus and parahippocampal gyrus compared to NCs. Global amyloid deposition was positively associated with mGluR5 availability in the AD group and reversely associated in the NC group. The mGluR5 availability was positively correlated with regional glucose metabolism in the overall and stratified analyses. The availability of mGluR5 in the hippocampus and parahippocampal gyrus demonstrated a strong relationship with the GMV of the medial temporal lobe, plasma p-tau181 or NfL levels, and global cognitive performance.Conclusions[18F]PSS232 PET can quantify the changes of mGluR5 availability in the progression of AD. mGluR5 availability correlated not only with neuropathological biomarkers of AD but also with neurodegenerative biomarkers and cognitive performance. mGluR5 may be a novel neurodegenerative biomarker, and whether mGluR5 could be a potential therapeutic target for AD needs to be further studied.

Neuroinflammation and cognitive decline: a TSPO‐PET imaging study.

AbstractBackgroundNeuroinflammation is a key driving factor of the pathophysiology of neurodegenerative diseases, including Alzheimer’s disease (AD). Microglia, a major immune cell of the central nervous system, may exert protective effects in the early stages of AD, while may damage the brain milieu in later stages of the disease continuum. The microglial response is mirrored by an increase in the detection of translocator protein (TSPO), a mitochondrial membrane protein that can be targeted with positron emission tomography (PET) imaging. Here, we aim to assess the impact of neuroinflammation on cognition across the AD continuum.Method48 participants (23 patients with AD, 14 patients with mild cognitive impairment (MCI), and 11 cognitively normal controls (CN)) underwent TSPO‐PET (flutriciclamide, [18F]GE180) imaging, magnetic resonance imaging (MRI), and neuropsychological testing. All participants were either high‐ or mixed‐affinity binders for TSPO‐PET tracers, as revealed by TSPO genotyping. The spectral analysis generated a flutriciclamide impulse response function at 90 minutes (IRF90) image, which reflects its volume of distribution. Region of interest and voxel‐wise analyses were conducted to explore the relationship between IRF90 and neuropsychological assessment performance on a group‐level.ResultTSPO‐PET binding was significantly higher in patients with AD compared to CNs across the whole brain, while patients with MCI demonstrated greater TSPO‐PET binding in the hippocampus and medial temporal lobe, compared to CNs. Significant negative associations were observed between neuropsychological assessment scores and IRF90, particularly in the temporal lobe (table 1). At a voxel level, negative correlations were seen between mini‐mental state examination score and IRF90 in temporoparietal regions (figure 1).ConclusionMicroglial response, a marker of neuroinflammation, is elevated in patients with AD and MCI, as measured using TSPO‐PET (flutriciclamide, [18F]GE180) imaging. Heightened neuroinflammation, measured by TSPO‐PET, may exert damaging effects on the brain, as highlighted here by the negative association between TSPO‐PET binding and neuropsychometric assessment performance. This study emphasises the requirement to improve our understanding of the role of neuroinflammation in AD in order to identify pharmacological targets in the future.

Decreased beta-band activity in left supramarginal gyrus reflects cognitive decline: Evidence from a large clinical dataset in patients with dementia.

Cognitive impairment is a major concern in clinical medicine. It is usually evaluated with neuropsychological assessments, which have inherent limitations. To compensate for them, magnetoencephalography has already come into clinical use to evaluate the level of cognitive impairment. It evaluates global changes in the frequency of resting-state brain activity, which are associated with cognitive status. However, it remains unclear what neural mechanism causes the frequency changes. To understand this, it is important to identify cortical regions that mainly contribute to these changes. We retrospectively analysed the clinical records from 310 individuals with cognitive impairment who visited the outpatient department at our hospital. The analysis included resting-state magnetoencephalography, neuropsychological assessment, and clinical diagnosis data. Regional oscillatory intensities were estimated from the magnetoencephalography data, which were statistically analysed, along with neuropsychological assessment scores, and the severity of cognitive impairment associated with clinical diagnosis. The regional oscillatory intensity covering a wide range of regions and frequencies was significantly associated with neuropsychological assessment scores and differed between healthy individuals and patients with cognitive impairment. However, these associations and differences in all conditions were overlapped by a single change in beta frequency in the left supramarginal gyrus. High frequency oscillatory intensity in the left supramarginal gyrus is associated with cognitive impairment levels among patients who were concerned about dementia. It provides new insights into cognitive status measurements using magnetoencephalography, which is expected to develop as an objective index to be used alongside traditional neuropsychological assessments.

Plasma Phosphorylated Tau181 and Amyloid-β42 in Dementia with Lewy Bodies Compared with Alzheimer's Disease and Cognitively Healthy People.

Increasing evidence illustrates the value of plasma biomarkers of Alzheimer's disease (AD) to screen for and identify dementia with Lewy bodies (DLB). However, confirmatory studies are needed to demonstrate the feasibility of these markers. To determine the feasibility of plasma tau phosphorylated at threonine 181 (p-tau181) and amyloid-β42 (Aβ42) as potential biomarkers to differentiate AD and DLB. We evaluated plasma samples from patients with DLB (n = 47) and AD (n = 55) and healthy controls (HCs, n = 30), using ELISAs to measure p-tau181 and Aβ42. Additionally, we examined neuropsychological assessment scores for participants. The plasma biomarkers were investigated for correlation with neuropsychological assessments and discriminant ability to identify DLB. Plasma p-tau181 was significantly lower in DLB than in AD and HCs. Plasma Aβ42 was significantly higher in DLB than in AD but lower in DLB than in HCs. We found good correlations between plasma Aβ42 and neuropsychological scores in the whole cohort, while p-tau181 was associated with cognitive status in DLB. In the distinction between DLB and HCs, plasma p-tau181 and Aβ42 showed similar accuracy, while Aβ42 showed better accuracy than p-tau181 in discriminating DLB and AD. In a single-center clinical cohort, we confirmed the high diagnostic value of plasma p-tau181 and Aβ42 for distinguishing patients with DLB from HCs. Plasma Aβ42 improved the differential diagnosis of DLB from AD.

Enhancing precision of the Telephone Interview for Cognitive Status–Modified (TICS-M) using the Rasch model.

The Telephone Interview for Cognitive Status-modified (TICS-M) is a well-established and widely used screening instrument for dementia and assessment of global cognitive function in older people. This study aimed to evaluate the psychometric properties of the TICS-M and to enhance the accuracy of the instrument using Rasch methodology. Partial Credit Rasch model was applied to the TICS-M scores. The sample selected for Rasch analysis consisted of 432 participants aged 70-90 years (M = 78.85, SD = 4.73) including 195 males (237 females), and 132 (30.56%) of whom were diagnosed with dementia after the baseline assessment. Initial analysis indicated good reliability of the TICS-M assessment scores, but there were three misfitting items and local dependency issues. Combining locally dependent and misfitting items into super-items achieved the best Rasch model fit for the TICS-M. This modification improved reliability of the assessment scores and resulted in no misfitting items, no local dependency, strict unidimensionality, and invariance across individual factors such as participants age, sex, diagnosis, and in-person neuropsychological assessment scores. Satisfying Rasch model expectations allowed for creation of a transformation table to convert raw TICS-M scores into interval-level data, which improves precision of the instrument. In summary, the TICS-M assessment scores demonstrated excellent reliability as reflected by Person Separation Index (PSI = 0.86) and met expectations of the unidimensional Rasch model after minor adjustments. The ordinal-to-interval transformation table can be used to increase accuracy of the TICS-M without altering its current format. These findings contribute to more accurate assessments of cognitive decline in older people and screening for conditions such as dementia. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Brain Imaging Databases.

The availability of neuroimaging-based databases is helping immensely to understand the brain function in healthy and diseased conditions. This viewpoint highlights the objectives, commonalities, and differences within these existing databases and pointers for researchers to choose a particular database. We introduce a multimodal multidisease database, SWADESH, and its comparison with the existing databases. A futuristic database blueprint is proposed for housing multidisease, multimodal, and longitudinal brain imaging data systematically organized in a matrix form along with neuropsychological assessment scores for the identification of causal disease processes. The information-rich databases will ultimately assist with the systematic identification of prime features linked to causal disease processes, leading to the design of appropriate clinical trials for successful therapeutic interventions.

Neurocognitive and radiological follow-up of children under 5 years of age treated for medulloblastoma according to the HIT-SKK protocol.

The HIT-SKK protocol is used for low/standard-risk medulloblastomas in young children with the aim to eliminate cranial irradiation and its neuropsychological (NP) sequelae. This therapy includes IV and intraventricular (ITV) methotrexate (MTX) potentially responsible for leukoencephalopathy (LE) and neurocognitive disorders. This study describes the risk factors and course of LE, and investigates its correlation with neurocognitive impact. A retrospective, multicenter study was conducted in 35 children under 5 years old, with a median follow-up of 72 months (range 14 to 130). The main analysis was performed in 30 patients who received cumulative doses of MTX as per-protocol (group 1). Five patients who received higher cumulative doses of MTX were analyzed separately. All follow-up MRIs and NP assessments were centrally reviewed by experts. Twenty patients in group 1 developed LE, grade 2 and 3 abnormalities did not correlate with higher cumulative doses of ITV-MTX (p = 0.698). Considering the most recent NP evaluation, the Full-Scale IQ (FSIQ) and Wechsler indices were in the average to lower average range. The FSIQ was deficient in 6/17 evaluable patients. Cumulative dose of ITV-MTX was almost associated with decreased processing speed competence (p = 0.055) which was the most frequently impaired neurocognitive domain. Neuropsychological assessment scores were not statistically lower in patients with persistent grade 2 LE at the end of follow-up. This study described that the use of cumulative dose of MTX (IV and ITV) according to the HIT-SKK protocol resulted in LE that tented to decrease over time, without significant correlation with a decline in neuro-intellectual skills.

What are the most important prognosticators of Alzheimer's disease progression? – Answers from machine learning

AbstractBackgroundNumerous variables that influence the risk of decline in Alzheimer’s disease (AD) have been identified. Previous studies have only examined a relatively small number of these variables. To our knowledge, no study has compared all variables in a large dataset to determine which are the most important.We hypothesised that the most important variables are neuropsychological assessment (NPA) scores and neuroimaging findings; moreover, the prognostic value of all variables will vary with disease stage: normal control (NC), mild cognitive impairment (MCI) or dementia. Secondly, we hypothesised that non‐NPA variables, such as imaging, cerebrospinal fluid (CSF) and genetics, will add prognostic value to that provided by NPA variables alone.MethodWe analysed all relevant variables in the Alzheimer’s Disease Neuroimaging Initiative database – the largest open‐access dataset of subjects with or at risk of AD. With machine learning, we identified those variables which are the strongest predictors of the annual rate of change in up to the first 10 years of Alzheimer’s Disease Assessment Scale – Cognitive Subscale, 13‐item version (ADAS‐Cog13) and Clinical Dementia Rating, Sum of Boxes (CDR‐SB) scores. We repeated this analysis for each disease stage subgroup. Secondly, we compared models that only used NPA‐related variables (NPA‐only) with those that used up to 2 non‐NPA modalities (NPA‐plus) and contrasted the findings between the same subgroups.ResultAcross all subjects, the strongest predictors of the rate of change of both ADAS‐Cog13 and CDR‐SB scores are CSF total tau and amyloid levels, fluorodeoxyglucose (FDG) positron emission tomography (PET) findings, and certain NPA measures. At the NC and MCI stages, CSF and imaging variables are strong predictors, but only NPA variables remained useful at the dementia stage. Secondly, NPA‐plus models consistently outperformed NPA‐only models. The non‐NPA modalities which added the most predictive power varied based on a subject’s disease stage in a manner similar to the previous findings.ConclusionWe identified a multi‐modal set of variables that have the strongest impact on predicting decline during different stages of AD. Our findings are clinically relevant as they recommend the investigations that are of most prognostic yield for clinicians to undertake at each stage of AD progression.

Experiences of Discrimination on Cognitive Function and Aging among the Oldest Old: LifeAfter90 (LA90) Study

AbstractBackgroundDiscrimination is a primary cause of health inequities, and racial/ethnic disparities in dementia are well documented. However, it is unclear whether longevity into old age indicates overcoming discriminatory experiences. Using data from the LifeAfter90 (LA90) Study, we examined the impact of major lifetime discrimination on cognitive function and decline in those 90+.MethodLA90 enrolled Asian, Black, Latino, white, and multi‐racial Kaiser Permanente Northern California members who were followed for incident dementia and aged 90+. Discrimination was measured using the Major Experiences of Discrimination Scale. Latent class analysis identified three groups based on responses to the 10‐item scale, gender, and race/ethnicity. Executive function, verbal episodic memory, and semantic memory were assessed every six months with the Spanish and English Neuropsychological Assessment Scales and scores were z‐standardized to baseline. Linear mixed models with random intercepts and slopes associated latent classes of discrimination with cognitive change over 3 waves (mean = 1.2 years). Models adjusted for age, education, cognitive status (normal/mild cognitive impairment‐ accounting for recall bias), practice effects, follow‐up time, and class*time interactions.ResultOur analytic sample of 445 participants had a mean age of 92.7(SD = 2.3) (Table 1). Class‐1 included mostly white men who reported workplace discrimination and had an average of 2 major discrimination experiences. Class‐2 included white women and non‐white participants who reported little/no discrimination averaging 0 experiences. Class‐3 included all non‐white participants who reported a mean of 4 discrimination experiences. At baseline, using Class‐2 as reference, participants in Class‐1 had significantly better executive function (β(95% CI): 0.28(0.03, 0.52) while Class‐3 did not differ (Table 2). Baseline semantic memory was significantly better for Class‐1 (β(95% CI): 0.33(0.07, 0.58)) and significantly worse for Class‐3 (β(95% CI): ‐0.24(‐0.48, ‐0.00)) compared to Class‐2. We found no class differences in baseline verbal episodic memory. Cognition declined over time across all three cognitive domains (β range: ‐0.31 to ‐0.46), but rate of change did not differ significantly by latent class (Table 3).ConclusionAmong the oldest old, inequalities in cognition persist after accounting for experiences of lifetime discrimination. Despite participants’ incredible longevity, experiences of discrimination have an indelible association with cognitive health.

Association of adverse childhood experiences and late‐life cognition in Black Americans from the Study of Healthy Aging in African Americans (STAR)

AbstractBackgroundThough Black Americans are more likely to experience adverse childhood experiences (ACEs) not much is known how these experiences are associated with late‐life cognitive outcomes in Black Americans. We examined the association between ACEs and late life cognition in the Study of Healthy Aging in African Americans (STAR).MethodsLaunched in 2018, STAR is a cohort study of cognitive aging and brain health in 764 Black Americans ages ≥50 years. ACEs were self‐reported via a nine‐item questionnaire. Executive function, semantic memory, and verbal episodic memory were measured using the Spanish and English Neuropsychological Assessment Scales (SENAS) and scores were z‐standardized. Linear regression models were used to associate ACEs exposure with cognitive domains adjusting for age, gender, participant education, and parental education (proxy for childhood socioeconomic status).ResultsThe majority of participants were female (69%) and the mean age was 69 years (SD=8.7) Table 1. Most of the respondents (73%) reported having one or more ACEs with parental separation (39%), serious family illness (36%), and witnessing domestic violence (31%) being most common. Other ACEs included parent remarried (26%), substance abuse by a family member (25%), parental job loss (15%), parental incarceration (8%), maternal death (6.5%), and paternal death (10.4%). Most ACEs were not significantly associated with domain specific cognitive scores, except experiencing the death of a father, which was associated with lower semantic memory (β=‐0.36; 95% CI: ‐0.56, ‐0.15; Table 2). Gender‐stratified models showed that the association between death of a father and lower semantic memory was significant for female (β=‐0.45; 95% CI: ‐0.69, ‐0.21) but not males (β=‐0.17; 95% CI: ‐0.54, 0.20). There was no evidence that the relationship between other ACEs and domain‐specific cognitive scores varied by gender.ConclusionsACEs were common among Black Americans in this cohort, but only death of a father in early life was associated with lower late life semantic memory, especially among women. Mechanisms of this association are unclear. Future studies with longitudinal data are needed to understand whether ACEs are related to cognitive decline over time in this population.

Brain magnetic resonance imaging and cognitive alterations after ablation in patients with atrial fibrillation

Catheter ablation is an important non-pharmacological intervention for atrial fibrillation (AF), but its effect on the incidence of asymptomatic cerebral emboli and long-term effects on cognitive function remain unknown. We prospectively enrolled 101 patients who underwent AF ablation. Brain magnetic resonance imaging (MRI) (72 patients) and neuropsychological assessments (66 patients) were performed 1–3 days (baseline) and 6 months after ablation. Immediately after ablation, diffusion-weighted MRI and 3-dimensional double inversion recovery (3D-DIR) detected embolic microinfarctions in 63 patients (87.5%) and 62 patients (86.1%), respectively. After 6 months, DIR lesions disappeared in 41 patients. Microbleeds (MBs) increased by 17%, and 65% of the de novo MBs were exactly at the same location as the microinfarctions. Average Mini-Mental State Examination scores improved from 27.9 ± 2.4 to 28.5 ± 1.7 (p = 0.037), and detailed neuropsychological assessment scores showed improvement in memory, constructional, and frontal lobe functions. Ejection fraction, left atrial volume index and brain natriuretic peptide level improved from baseline to 3–6 months after ablation. Despite incidental microemboli, cognitive function was preserved 6 months after ablation.

Factors associated with employment stability following traumatic brain injury, in a sample who have received comprehensive vocational rehabilitation

Purpose To quantify employment stability of individuals with traumatic brain injury (TBI) who received comprehensive vocational rehabilitation (VR) using different measures to identify difficulties experienced and factors associated with employment stability. Materials and methods 72 individuals with predominantly moderate-severe TBI were interviewed. Neuropsychological assessment scores were collected. Three employment stability measures were used: number of post-injury employers, duration with employer and average weekly hours. Descriptive and predictive analyses were performed. Results 90.2% remained employed at time of interview (Mean = 4.83 years post-injury). However, participants worked significantly fewer hours, 63.9% had changed roles or employers at least once and only 51% achieved their pre-injury level of responsibility. 61% reported a high level of employer support. Self-reported difficulties included physical sequelae, memory problems and fatigue. Post-injury testing found impaired memory (34.4%) and processing speed (49.2%). After accounting for time since injury, demographic and employment variables (older age, male gender, higher pre-injury skill-level, higher level of employer support), higher level of injury-related difficulties and lower level of cognitive function significantly predicted employment stability. Conclusion Injury-related difficulties impact employment long-term, necessitating ongoing work modifications. Individualised VR is important, not only to facilitate return to work but to support long-term employment stability after TBI. Implications for rehabilitation Being male was associated with working more hours, and having faster processing speed, lower levels of fatigue and ongoing physical sequelae were associated with a longer duration with the same employer. Initial return to work is often the first step on a long journey as injury-related difficulties can continue to impact work in the-long term and require lasting modifications to duties and working hours. VR should include ongoing follow-up to facilitate work modifications and support both the employer and the employee in adjusting to these. VR should be individualised to support the impact of the unique cognitive and physical limitations experienced by each individual with TBI, based on the needs and employment demands of each workplace.

Frequencies and Neuropsychological Characteristics of Errors in the Clock Drawing Test.

Few studies have investigated associations between types of clock drawing test (CDT) errors and cognitive impairment. To explore associations of qualitative errors in the CDT with comprehensive neurocognitive assessment scores and clinical diagnosis. Outpatients at a memory clinic were enrolled. Frequencies of errors determined by Cahn's method were explored according to cognitive status (cognitively normal [CN] (n = 279), mild cognitive impairment [MCI] (n = 321), and Alzheimer's disease [AD]) (n = 575). Neuropsychological assessment scores were compared between participants with and without errors. Stimulus-bound response (SB) was relatively rare (6.8%) in the CN group but was markedly more common in the MCI (23.4%) and AD (33.2%) groups. Conceptual deficit (CD) was found in more than 20%of CN individuals, as well as about 50%of AD patients. Planning deficit (PD) frequencies were relatively similar among the groups. SB in both of CN and MCI individuals, and CD in both of CN and MCI individuals were associated with lower scores in several neuropsychological assessments. Meanwhile, PD was not associated with lower assessment scores in any of CN, MCI, or AD individuals. The frequencies of SB and CD increased from CN, MCI, to AD but showed somewhat different patterns. Both SB and CD were associated with lower cognition in all three cognitive stages.

Intrathecal enzyme replacement for cognitive decline in mucopolysaccharidosis type I, a randomized, open-label, controlled pilot study

Central nervous system manifestations of mucopolysaccharidosis type I (MPS I) such as cognitive impairment, hydrocephalus, and spinal cord compression are inadequately treated by intravenously-administered enzyme replacement therapy with laronidase (recombinant human alpha-L-iduronidase). While hematopoietic stem cell transplantation treats neurological symptoms, this therapy is not generally offered to attenuated MPS I patients. This study is a randomized, open-label, controlled pilot study of intrathecal laronidase in eight attenuated MPS I patients with cognitive impairment. Subjects ranged between 12 years and 50 years old with a median age of 18 years. All subjects had received intravenous laronidase prior to the study over a range of 4 to 10 years, with a mean of 7.75 years. Weekly intravenous laronidase was continued throughout the duration of the study. The randomization period was one year, during which control subjects attended all study visits and assessments, but did not receive any intrathecal laronidase. After the first year, all eight subjects received treatment for one additional year. There was no significant difference in neuropsychological assessment scores between control or treatment groups, either over the one-year randomized period or at 18 or 24 months. However, there was no significant decline in scores in the control group either. Adverse events included pain (injection site, back, groin), headache, neck spasm, and transient blurry vision. There were seven serious adverse events, one judged as possibly related (headache requiring hospitalization). There was no significant effect of intrathecal laronidase on cognitive impairment in older, attenuated MPS I patients over a two-year treatment period. A five-year open-label extension study is underway.

Uncoupled relationship in the brain between regional homogeneity and attention function in first-episode, drug-naïve schizophrenia

The relationship between the cognitive impairment and the structural and functional abnormalities in the brains of patients with schizophrenia (SZ) is not yet clear. This study aims to investigate the relationship, thereby exploring the neuromechanism underlying SZ. We collected multimodal MRI data from 68 first-episode, drug-naïve patients with SZ, and 64 well-matched healthy controls, and used regional homogeneity (ReHo) and gray matter volume (GMV) to assess the functional and structural integrity of the brains, respectively. We then evaluated in the entire brain the correlations between ReHo/GMV and the participants’ neuropsychological assessment scores for each group using a partial correlation analysis controlling for age and sex. We found significant uncoupling between attention performance and mean ReHo in the left middle frontal gyrus, right superior/inferior parietal lobe (IPL), right angular gyrus (AG) and right middle/inferior temporal lobe (ITG) in SZ compared with healthy controls. Moreover, we found that the SZ group showed decreased GMV in the right IPL and AG, and a significant coupling between ReHo and GMV in the right ITG. Our findings suggest that the attention dysfunction found in SZ may be associated with the structural and functional abnormalities as well as the structure-function interrelation in several SZ-related brain regions.

Correlation between abnormal GSK3β, β Amyloid, total Tau, p-Tau 181 levels and neuropsychological assessment total scores in CKD patients with cognitive dysfunction: Impact of rHuEPO therapy

BackgroundCognitive dysfunction potentially affecting up to 60% of CKD patients. GSK-3β plays a key role in the pathogenesis of AD and Cognitive dysfunction, contributing to Aβ production and Aβ-mediated neuronal death by phosphorylating tau inducing hyperphosphorylation in paired helical filaments. However, studies have shown that plasma p-Tau181 is more specific for AD and cognitive dysfunction. Anemia is a vital risk factor for cognitive dysfunction in CKD patients. EPO is usually to treat anemia in CKD and also improved in cognitive function. The aim of the study is to correlate between the impacts of rHuEPO therapy on platelet GSK3β expression, plasma Aβ, total Tau, p-Tau 181 levels and neuropsychological assessments total scores in CKD patients with Cognitive dysfunction. MethodsThe subjects, 30 CKD without cognitive dysfunction and 30 CKD with cognitive dysfunction patients. To correlate abnormal proteins with neuropsychological tests scoring in CKD with cognitive dysfunction subjects after the six months rHuEPO therapy. ResultsThe p < 0.05 is considered as statistically significant. Pearson and Spearman correlation coefficient was used to determine the potential relationship between abnormal proteins with neuropsychological tests scoring in respective experimental groups. ConclusionsThe use of abnormal protein levels, preferably in association with neuropsychological assessment total scores, appears to be a potential tool that can improve the CKD with cognitive dysfunction diagnosis. In post rHuEPO treatment, the altered protein abnormalities and neuropsychological assessment scores were retrieved significantly compared to pre treatment determined the clinical usefulness of rHuEpo as supplemental therapeutic agent in cognitive dysfunction in CKD.

Uric Acid Has Different Effects on Spontaneous Brain Activities of Males and Females: A Cross-Sectional Resting-State Functional MR Imaging Study.

ObjectiveTo explore the relationship among serum uric acid (SUA) levels in different states of disease, human cognition, and spontaneous brain activities by resting-state functional MRI (rs-fMRI).MethodsWe prospectively recruited 100 subjects (age 58 ± 11 years, 55 females) who underwent fasting blood sampling, cognitive tests and rs-fMRI scans. The subjects were divided into two groups by sex and each sex group was further stratified into three subgroups according to SUA level in different states of disease. The amplitude of low-frequency fluctuation (ALFF) method was applied to assess spontaneous brain activity among groups. Pearson’s correlation analysis was used to investigate the relationships between the mean ALFF values (mALFF) and cognitive tests.ResultsA total of 97 patients completed the study protocol successfully. Significant differences in age, education level, number connection test (NCT), and word fluency were observed among the three subgroups in males (all P < 0.05). Results of group-by-sex interaction were distributed in bilateral pallidum and putamen [voxel P-value < 0.001, cluster P-value < 0.05, Gaussian random field (GRF)-corrected]. The tendency of the SUA effect on mALFF was different in males and females, particularly in corresponding High SUA subgroups (that is pre-hyperuricemia, both P < 0.001). Among the male subjects, mALFF values of the bilateral pallidum and putamen negatively correlated with attention/executive function.ConclusionOur results suggest that elevated SUA levels have different effects on spontaneous brain activities and cognitive function in males and females. Males with pre-hyperuricemia and hyperuricemia are more susceptible to changes in spontaneous brain activities and lower neuropsychological assessment scores, particularly in word fluency tests and NCT, compared to females.