Processing Executive Functions Research Articles

Effects of Type 2 Diabetes on the Neuropsychological Profile in Mild Cognitive Impairment.

Diabetes is one of the main risk factors for developing mild cognitive impairment (MCI) and Alzheimer's disease. Most studies have demonstrated a worse performance in executive function, verbal fluency, and information processing speed in patients with diabetes. To assess the cognitive functioning of persons with type 2 diabetes and amnesic mild cognitive impairment (aMCI-T2DM) compared to persons with aMCI without diabetes and persons without diabetes or aMCI as controls, to understand the role of diabetes in the neuropsychological profile. Cross-sectional study involving a sample of 83 patients, ranging in age from 61 to 85 years and divided into three groups: aMCI-T2DM (27 patients), aMCI (29 patients), Controls (27 individuals). All the participants undertook an exhaustive neuropsychological assessment (auditory-verbal and visual memory, attention, information processing speed, language, executive function, and depression). Both groups of aMCI patients performed significantly worse than the controls in all the neuropsychological tests. A significant linear tendency (p trend < 0.05) was found between groups, with the aMCI-T2DM group presenting worse results in global cognition assessed by the Mini-Mental State Examination and Montreal Cognitive Assessment; Rey-Osterrieth Complex Figure Test; Auditory Verbal Learning Test; Trail Making Test A and B, Verbal Fluency Test, and Hamilton Depression Rating Scale. aMCI patients with or without diabetes showed worse cognitive function compared to persons without diabetes or aMCI. Additionally, aMCI patients without T2DM presented a different cognitive profile than aMCI patients with T2DM, which tended towards presenting worse cognitive functions such as global cognition, memory, attention, executive function, and language.

Neurodevelopmental outcomes and occupational participation of preterm children at school age: a scoping review

Preterm children may experience major challenges that affect their occupational participation and daily functioning, especially at school age. This scoping review aims to examining and synthesizing the available literature about adverse neurodevelopmental outcomes and occupational participation restrictions of preterm children born &lt; 37 weeks of gestation. The MEDLINE, Science Direct, CINAHL databases were searched from January 2013 to December 2023, for published cohort studies that assessed the neurodevelopmental outcomes and occupational participation of school-aged preterm children, compared to full-term born peers. Out of 6631 identified articles, 13 studies met the inclusion criteria and involved 958 preterm children, aged 6-10 years old. Studies included in the current scoping review reported adverse neurodevelopmental outcomes, such as cognitive impairment, executive function and sensory processing deficits, emotional and behavioral problems, language and visual perception difficulties, as well as occupational participation restrictions, like feeding difficulties, academic challenges and peer relationship problems. Findings suggest that neurodevelopmental deficits and occupational participation restrictions, especially in extremely preterm children, not only exist in early childhood but persist during school age. Future research should focus on exploring potential differences or patterns in neurodevelopmental outcomes and occupational participation between preterm groups with different gestational age ranges.

Strategic white matter hyperintensity locations associated with post-stroke cognitive impairment: a multicenter study in 1568 stroke patients.

Post-stroke cognitive impairment (PSCI) occurs in up to 50% of stroke survivors. Presence of pre-existing vascular brain injury, in particular the extent of white matter hyperintensities (WMH), is associated with worse cognitive outcome after stroke, but the role of WMH location in this association is unclear. We determined if WMH in strategic white matter tracts explain cognitive performance after stroke. Individual patient data from 9 ischemic stroke cohorts with MRI were harmonized through the Meta VCI Map consortium. The association between WMH volumes in strategic tracts and domain-specific cognitive functioning (attention and executive functioning, information processing speed, language and verbal memory) was assessed using linear mixed models and lasso regression. We used a hypothesis-driven design, primarily addressing four white matter tracts known to be strategic in memory clinic patients: the left and right anterior thalamic radiation, forceps major and left inferior fronto-occipital fasciculus. The total study sample consisted of 1568 patients (39.9% female, mean age: 67.3 years). Total WMH volume was strongly related to cognitive performance on all four cognitive domains. WMH volume in the left anterior thalamic radiation was significantly associated with cognitive performance on attention and executive functioning and information processing speed, and WMH volume in the forceps major with information processing speed. The multivariable lasso regression showed that these associations were independent of age, sex, education, and total infarct volume and had larger coefficients than total WMH volume. These results show tract-specific relations between WMH volume and cognitive performance after ischemic stroke, independent of total WMH volume. This implies that the concept of strategic lesions in PSCI extends beyond acute infarcts and also involves pre-existing WMH. The Meta VCI Map consortium is dedicated to data sharing, following our guidelines.

An event-related potential investigation of the influence of bilingualism on disambiguating homonyms in older adults.

Ambiguity is ubiquitous in language; lexical ambiguity refers to instances where a single word has multiple meanings. The current investigation examined homonyms, words that have the same orthography and pronunciation in English but multiple meanings (e.g., BANK, meaning "financial institution" or "river's edge"). The processing of homonyms requires the engagement of executive control processes, for example, to select the appropriate meaning of the homonym while reducing interference from other meanings. Executive function processes are known to change over the lifespan and may be impacted by experiential factors such as bilingualism. The present study uses event-related brain potentials as an index of lexical access to examine whether bilingualism influences homonym processing in older adults. The results indicate that patterns of lexical access differ as a function of bilingual status in older adults and compared to young adults, suggesting that language experience may moderate language processing in both young and older adults, at least in situations where language processing is demanding on executive function, such as in the processing of homonyms. Importantly, we show that older bilinguals show a somewhat similar pattern of ambiguity processing as their younger counterparts, while age differences were observed in monolinguals when comparing across studies. This suggests that bilingual language experience may have a mitigating impact on age-related changes in ambiguity processing. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Brain and brawn in balance: Central processing speed and muscle torque development speed are independently associated with the ability to recover balance with feet-in-place

BackgroundStepping thresholds, i.e. the maximum perturbation one can withstand without taking a step, predict falls in older people. This ability requires fast central processing of sensory information followed by rapid execution of adequate motor responses, both of which are affected by age. However, there is limited evidence on their combined effect on stepping thresholds. Research questionAre cognitive and motor speeds important for stepping thresholds and do they interact, allowing for compensation? MethodsTwo-hundred forty-two people (mean age: 80 years, standard deviation 4; 110 women) underwent a series of waist-pulls of increasing magnitude to assess stepping thresholds in anterior, posterior and mediolateral directions. Cognitive function was assessed as simple hand reaction time and trail making test performance, and muscle function was assessed as isometric peak and rate of torque development of dominant leg muscles. Principal component analysis reduced these variables to four factors: peak muscle strength, muscle torque development speed (motor speed), executive function and central processing speed (cognitive speed). These factors were used in univariable and multivariable regression models to determine their association with stepping thresholds. ResultsFaster central processing speed (beta:2.69; 95 %CI:1.49–3.88) and faster muscle torque development speed (beta:2.60, 95 %CI:0.63–4.57) were associated with higher stepping thresholds. These associations remained in a multivariable model. No interaction was found between cognitive and motor speed on stepping thresholds (p = 0.602). SignificanceCentral processing speed and muscle torque development speed affect stepping thresholds independently from each other and may both be important age-related motor impairment targets for preventing falls in older people.

Mapping Treatment Advances in the Neurobiology of Binge Eating Disorder: A Concept Paper.

Binge eating disorder (BED) is a complex and heritable mental health disorder, with genetic, neurobiological, neuroendocrinological, environmental and developmental factors all demonstrated to contribute to the aetiology of this illness. Although psychotherapy is the gold standard for treating BED, a significant subgroup of those treated do not recover. Neurobiological research highlights aberrances in neural regions associated with reward processing, emotion processing, self-regulation and executive function processes, which are clear therapeutic targets for future treatment frameworks. Evidence is emerging of the microbiota-gut-brain axis, which may mediate energy balance, high-lighting a possible underlying pathogenesis factor of BED, and provides a potential therapeutic strategy.

Motivation and emotional distraction interact and affect executive functions

Previous research on cool-hot executive function (EF) interactions has examined the effects of motivation and emotional distraction on cool EF separately, focusing on one EF component at a time. Although both incentives and emotional distractors have been shown to modulate attention, how they interact and affect cool EF processes is still unclear. Here, we used an experimental paradigm that manipulated updating, inhibition, and shifting demands to determine the interactions of motivation and emotional distraction in the context of cool EF. Forty-five young adults (16 males, 29 females) completed the go/no-go (inhibition), two-back (updating), and task-switching (shifting) tasks. Monetary incentives were implemented to manipulate motivation, and task-irrelevant threatening or neutral faces were presented before the target stimulus to manipulate emotional distraction. We found that incentives significantly improved no-go accuracy, two-back accuracy, and reaction time (RT) switch cost. While emotional distractors had no significant effects on overall task performance, they abolished the incentive effects on no-go accuracy and RT switch cost. Altogether, these findings suggest that motivation and emotional distraction interact in the context of cool EF. Specifically, transient emotional distraction disrupts the upregulation of control activated by incentives. The present investigation has advanced knowledge about the relationship between cool and hot EF and highlights the importance of considering motivation–emotion interactions for a fuller understanding of control.

Writing performance in primary grade: exploring the links between cognitive and motivational variables

Current theoretical models of writing suggest that cognitive and motivational processes interact with each other during written production. However, despite the growing interest in motivational variables in writing, there are still few efforts to study them together with cognitive variables. Therefore, this study aimed to test the possibility that the cognitive processes of transcription and executive functions may be related to writing performance, through their link with the writing-motivational variables of self-efficacy and attitudes. For that, 157 Portuguese third and fourth graders planned and completed one opinion essay, performed transcription tasks, and completed motivation-related questionnaires. Furthermore, schoolteachers completed an executive function questionnaire about each student and provided their school grades. Results showed that motivation, specifically self-efficacy, did not predict Grade 3 and 4 writing performance. However, attitudes were predictors of written planning and text length. More specifically, attitudes and handwriting fluency contributed to text length just as attitudes and spelling accuracy contributed to written planning. There was no evidence of indirect effects from cognitive variables on writing performance via motivation variables. These findings provide original information on the links between cognition and motivation in writing, which may be useful to guide the teaching of writing. In line with effective instructional approaches to writing, current findings further support the importance of jointly targeting the cognitive and affective dimensions of writing.

Neurocognitive and psycho-emotional profile of children with disabilities

Objective Neurocognitive deficits in attention, short-term memory, and sequential information processing are present in children with a variety of disabilities, whereas language and visuospatial abilities vary. Method We compared the performance of 59 children (mean age, 15 years) with learning disabilities (n = 18), Down syndrome (n = 21), and intellectual disabilities (n = 20). A series of neuropsychological tests were used to evaluate the neurocognitive processes of memory, attention, visuospatial perception, and executive function. To better understand what emotions they experience, we assessed emotions like anxiety, depression, and positive and negative mood. Results The performance of children with Down syndrome was statistically significantly different from that of other groups, indicating lower performance (p = 0.001). In comparison to other groups, children with Down syndrome performed significantly worse across all cognitive domains. Additionally, there were no statistically significant differences between groups and low emotional functioning scores across the board for all children. People with DS frequently have distinctive neurocognitive and neurobehavioral profiles that appear during particular developmental phases and have many distinct strengths and weaknesses that should be respected as they mature over the course of their lives. The current findings have substantial consequences for interventions that are focused on achieving the best results.

Information needs of stroke survivors and their family members regarding post-stroke cognition: a scoping review protocol.

The aim of this review is to map current evidence describing the information needs of stroke survivors and family members regarding cognition. Managing cognitive changes is the most frequently reported unmet need among stroke survivors; hence, there is an urgent need to improve support for post-stroke cognitive impairment. While there is evidence that psychoeducation may help stroke survivors and their family members develop awareness about cognitive impairment and self-management strategies, it is unclear what information stroke survivors and their family members want to receive and how their needs change over time. This review will consider peer-reviewed articles describing information needs relating to the following cognitive domains: memory, language, attention, executive function, praxis, and number processing. Stroke survivors and/or their family members must comprise at least 50% of the study population and must be aged at least 18 years. Quantitative, qualitative, and mixed methods studies will be included. The review will be conducted in line with the JBI methodology for scoping reviews. A full literature search will be conducted in MEDLINE (PubMed), PsycINFO (Ovid), Embase, CINAHL (EBSCOhost), and Scopus using a search strategy developed in consultation with an expert university librarian. Articles will be screened by title, abstract, and full text; then, data will be extracted by 2 independent reviewers. The reference lists of included articles will be hand-searched for additional material. Data analysis and reporting will involve qualitative (textual narrative synthesis) and quantitative (descriptive statistics) methods.

The link between the early surgery-induced inflammatory response and postoperative cognitive dysfunction in older patients.

Postoperative cognitive dysfunction (POCD) is a common complication in older patients with cancer and is associated with decreased quality of life and increased disability and mortality rates. Systemic inflammation resulting in neuroinflammation is considered important in the pathogenesis of POCD. The aim of this study was to explore the association between the early surgery-induced inflammatory response and POCD within 3 months after surgery in older cancer patients. Patients ≥65 years in need of surgery for a solid tumor were included in a prospective cohort study. Plasma levels of C-reactive protein (CRP), interleukin-1 beta (IL-1β), IL-6, IL-10, and Neutrophil gelatinase-associated lipocalin (NGAL) were measured perioperatively. Cognitive performance was assessed preoperatively and 3 months after surgery. POCD was defined as a decline in cognitive test scores of ≥25% on ≥2 of five tests within the different cognitive domains of memory, executive functioning, and information processing speed. Logistic regression analysis was performed. POCD was observed in 44 (17.7%) of 248 included patients. Age >75, preoperative Mini-Mental State Examination (MMSE) score ≤26 and major surgery were independent significant predictors for POCD. In multivariate logistic regression analysis, no significant associations were shown between the early surgery-induced inflammatory response and either POCD or decline within the different cognitive domains. This study shows that one out of six older patients with cancer developed POCD within 3 months after surgery. The early surgery-induced inflammatory response was neither associated with POCD, nor with decline in the separate cognitive domains. Further research is necessary for better understanding of the complex etiology of POCD.

Executive function and decision-making in Colombian patients with paranoid schizophrenia

Background Schizophrenia (SCZD) is a mental disorder characterized by cognitive dysfunction, impaired decision-making abilities, abnormalities in brain functioning, and specific genetic markers. Ethnic and racial factors influence the development and presentation of schizophrenia, with different groups experiencing different levels of risk and exhibiting different patterns of mental disorders. Objective We sought to investigate the executive function and decision-making profile of Schizophrenia participants from Barranquilla, Colombia, which have a high genetic mixture and significant ethnic and racial diversity. Methods The sample consists of 40 individuals, 20 diagnosed with paranoid schizophrenia and 20 controls. We use the BANFE neuropsychological battery and the Iowa Gambling task to measure executive function and decision-making processes. Results The study found differences in cognitive performance, measured by the Neuropsychological Battery of Executive Functions and Frontal Lobes, in the medial orbit, anterior prefrontal, dorsolateral, and total executive function measures. In decision-making, as measured by the Iowa Gambling Test, there were also differences between the two groups, with those with schizophrenia performing worse and showing a preference for disadvantageous options. The study also found that there were no significant differences in socio-demographic characteristics between the two groups but that there were differences in terms of socio-economic status and educational level. Conclusion This study found that individuals with paranoid schizophrenia had significant differences in their prefrontal cortex compared to those without the condition, specifically in the dorsolateral and orbital-prefrontal cortex. These differences may be linked to difficulties adjusting to their environment and processing reinforcement, leading to impaired learning and arousal disturbances.

Neuropsychological correlates of early grief in bereaved older adults.

Prolonged grief disorder (PGD) is associated with impairments in cognitive functioning, but the neuropsychological correlates of early grief in older adults are poorly understood. This preliminary study cross-sectionally examined neuropsychological functioning in bereaved adults with high and low grief symptoms and a non-bereaved comparison sample and further explored the relationship between multidomain cognitive measures and grief severity. A total of ninety-three nondemented older adults (high grief: n = 44; low grief: n = 49) within 12 months post-bereavement and non-bereaved comparison participants (n = 43) completed neuropsychological battery including global and multiple domain-specific cognitive functioning. Linear regression models were used to analyze differences in multidomain cognitive measures between the groups and specifically examine the associations between cognitive performance and grief severity in the bereaved, after covariate adjustment, including depressive symptoms. Bereaved older adults with higher grief symptoms performed worse than those with lower symptoms and non-bereaved participants on executive functioning and attention and processing speed measures. In the bereaved, poorer executive functioning, attention and processing speed correlated with higher grief severity. Attention/processing speed-grief severity correlation was seen in those with time since loss ≤ 6 months, but not > 6 months. Intense early grief is characterised by poorer executive functioning, attention, and processing speed, resembling findings in PGD. The putative role of poorer cognitive functioning during early grief on the transition to integrated grief or the development of PGD remains to be elucidated.

Altered Lateral Prefrontal Cortex Functioning During Emotional Interference Resistance Is Associated With Affect Lability in Adults With Persisting Symptoms of Attention-Deficit/Hyperactivity Disorder From Childhood

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention and/or impulsivity/hyperactivity. ADHD, especially when persisting into adulthood, often includes emotional dysregulation, such as affect lability; however, the neural correlates of emotionality in adults with heterogeneous ADHD symptom persistence remain unclear. MethodsThe present study sought to determine shared and distinct functional neuroanatomical profiles of neural circuitry during emotional interference resistance using the emotional face n-back task in adult participants with persisting (n = 47), desisting (n = 93), or no (n = 42) childhood ADHD symptoms while undergoing functional magnetic resonance imaging. ResultsParticipants without any lifetime ADHD diagnosis performed significantly better (faster and more accurately) than participants with ADHD diagnoses on trials with high cognitive loads (2-back) that included task-irrelevant emotional distractors, tapping into executive functioning and emotion regulatory processes. In participants with persisting ADHD symptoms, more severe emotional symptoms were related to worse task performance. Heightened dorsolateral and ventrolateral prefrontal cortex activation was associated with more accurate and faster performance on 2-back emotional faces trials, respectively. Reduced activation was associated with greater affect lability in adults with persisting ADHD, and dorsolateral prefrontal cortex activation mediated the relationship between affect lability and task accuracy. ConclusionsThese findings suggest that alterations in dorsolateral prefrontal cortex function associated with greater interference in cognitive processes from emotion could represent a marker of risk for problems with emotional dysregulation in individuals with persisting ADHD and thus represent a potential therapeutic target for those with greater emotional symptoms of ADHD.

Abstract 126: Connectome Gradient Dysfunction Contributes to White Matter Hyperintensity-Related Cognitive Decline

Introduction: Although White matter hyperintensity (WMH) is closely associated with cognitive decline, the precise neurobiological mechanisms underlying this relationship are not fully elucidated. Connectome studies have identified a primary-to-transmodal gradient in functional brain networks that support the spectrum from sensation to cognition. However, whether this gradient structure is altered as WMH progresses and how this alteration is associated with WMH-related cognitive decline remain unknown. Methods: A total of 758 individuals with WMH were enrolled from two medical centers and one community. All these participants completed cognitive assessment and resting-state functional MRI (rs-fMRI). The functional connectome gradient was reconstructed based on rs-fMRI by using a gradient decomposition framework. Interrelations amongst regional WMH, functional gradient measures, and specific cognitive domains were explored. Results: The larger WMH volume, the narrower range ( r = -0.099, p = 0.006) and smaller variance ( r = -0.121, p &lt; 0.001) of the primary-to-transmodal gradient, as well as the poorer executive function ( r = -0.135, p = 0.001) and information processing speed ( r = -0.224, p = 0.001). A narrower range ( r = 0.131, p = 0.001) and smaller variance ( r = 0.136, p = 0.001) of the primary-to-transmodal gradient corresponded to poorer executive function. In particular, the relationship between frontal/occipital WMH and executive function was partly mediated by gradient range/variance of the primary-to-transmodal gradient (the 95% confidence interval did not contain the value 0). WMH-related gradient alterations were associated with gene expression levels involved in the G protein-coupled receptor (GPCR) signaling pathway (FDR q -value &lt; 10 -4 ) and chemical synaptic transmission (FDR q -value &lt; 10 -6 ). Discussion: We found that the primary-to-transmodal gradient dysfunction contributes to WMH-related cognitive decline. The detrimental effect of frontal/occipital WMH on executive function was mediated by decreased differentiation of the connectivity pattern between the primary and transmodal areas. The neurobiological mechanisms may be related to the GPCR signaling pathway and chemical synaptic transmission.

Impact of brain parcellation on prediction performance in models of cognition and demographics.

Brain connectivity analysis begins with the selection of a parcellation scheme that will define brain regions as nodes of a network whose connections will be studied. Brain connectivity has already been used in predictive modelling of cognition, but it remains unclear if the resolution of the parcellation used can systematically impact the predictive model performance. In this work, structural, functional and combined connectivity were each defined with five different parcellation schemes. The resolution and modality of the parcellation schemes were varied. Each connectivity defined with each parcellation was used to predict individual differences in age, education, sex, executive function, self-regulation, language, encoding and sequence processing. It was found that low-resolution functional parcellation consistently performed above chance at producing generalisable models of both demographics and cognition. However, no single parcellation scheme showed a superior predictive performance across all cognitive domains and demographics. In addition, although parcellation schemes impacted the graph theory measures of each connectivity type (structural, functional and combined), these differences did not account for the out-of-sample predictive performance of the models. Taken together, these findings demonstrate that while high-resolution parcellations may be beneficial for modelling specific individual differences, partial voluming of signals produced by the higher resolution of the parcellation likely disrupts model generalisability.

Transdiagnostic neurocognitive dysfunction in children and adolescents with mental illness

Robust evidence from adult samples indicates that neurocognitive dysfunction is a hallmark of many mental illnesses, contributing to the loss of daily function and quality of life that these illnesses cause. However, it is still unclear whether neurocognitive deficits associated with mental illnesses begin to manifest well before adulthood or impact treatment response. Here we address this gap by evaluating neurocognitive function in four groups of children and adolescents with different mental illnesses compared to their matched healthy peers. Our team evaluated the neurocognitive performance of youth diagnosed with attention deficit and hyperactivity disorder (N = 343), anorexia (N = 40), first onset psychosis (N = 25) and functional neurological disorder (N = 56) versus age-matched healthy controls (N = 483), cross-sectionally. Performance was assessed using an objective assessment battery designed for use across diagnoses and settings and validated for its correlations with underlying brain structure and function. The following cognitive domains were assessed: sustained attention, cognitive flexibility, decision speed, executive function, information processing speed, psychomotor response speed, response inhibition, verbal memory and working memory. Distinct profiles of neurocognitive dysfunction were detected for each diagnosis relative to the healthy reference group. Youth with first onset psychosis displayed the most severe and generalized impairments across domains of sustained attention, verbal memory, response inhibition, cognitive flexibility, information processing speed and working memory. Children and adolescents with attention deficit and hyperactivity disorder showed impairments in multiple domains of at least moderate severity with the most pronounced impairments in executive function, sustained attention and working memory. Children and adolescents with anorexia displayed more specific moderate impairments limited to cognitive flexibility, response inhibition, sustained attention, decision speed and verbal memory. Impairments in functional neurological disorder were also relatively specific and moderate, limited to executive function, working memory, cognitive flexibility, decision speed and information processing speed. These findings suggest that neurocognitive impairment in mental illness is transdiagnostic and can be detected as early as childhood or adolescence with standardized computerized testing.

The Cerebellar Cognitive Affective/Schmahmann Syndrome Scale in Spinocerebellar Ataxias.

The Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) manifests as impaired executive control, linguistic processing, visual spatial function, and affect regulation. The CCAS has been described in the spinocerebellar ataxias (SCAs), but its prevalence is unknown. We analyzed results of the CCAS/Schmahmann Scale (CCAS-S), developed to detect and quantify CCAS, in two natural history studies of 309 individuals Symptomatic for SCA1, SCA2, SCA3, SCA6, SCA7, or SCA8, 26 individuals Pre-symptomatic for SCA1 or SCA3, and 37 Controls. We compared total raw scores, domain scores, and total fail scores between Symptomatic, Pre-symptomatic, and Control cohorts, and between SCA types. We calculated scale sensitivity and selectivity based on CCAS category designation among Symptomatic individuals and Controls, and correlated CCAS-S performance against age and education, and in Symptomatic patients, against genetic repeat length, onset age, disease duration, motor ataxia, depression, and fatigue. Definite CCAS was identified in 46% of the Symptomatic group. False positive rate among Controls was 5.4%. Symptomatic individuals had poorer global CCAS-S performance than Controls, accounting for age and education. The domains of semantic fluency, phonemic fluency, and category switching that tap executive function and linguistic processing consistently separated Symptomatic individuals from Controls. CCAS-S scores correlated most closely with motor ataxia. Controls were similar to Pre-symptomatic individuals whose nearness to symptom onset was unknown. The use of the CCAS-S identifies a high CCAS prevalence in a large cohort of SCA patients, underscoring the utility of the scale and the notion that the CCAS is the third cornerstone of clinical ataxiology.

Long-range connections damage in white matter hyperintensities affects information processing speed.

White matter hyperintensities, one of the major markers of cerebral small vessel disease, disrupt the integrity of neuronal networks and ultimately contribute to cognitive dysfunction. However, a deeper understanding of how white matter hyperintensities related to the connectivity patterns of brain hubs at the neural network level could provide valuable insights into the relationship between white matter hyperintensities and cognitive dysfunction. A total of 36 patients with moderate to severe white matter hyperintensities (Fazekas score ≥ 3) and 34 healthy controls underwent comprehensive neuropsychological assessments and resting-state functional MRI scans. The voxel-based graph-theory approach-functional connectivity strength was employed to systematically investigate the topological organization of the whole-brain networks. The white matter hyperintensities patients performed significantly worse than the healthy controls in episodic memory, executive function and information processing speed. Additionally, we found that white matter hyperintensities selectively affected highly connected hub regions, predominantly involving the medial and lateral prefrontal, precuneus, inferior parietal lobule, insula and thalamus. Intriguingly, this impairment was connectivity distance-dependent, with the most prominent disruptions observed in long-range connections (e.g. 100-150 mm). Finally, these disruptions of hub connectivity (e.g. the long-range functional connectivity strength in the left dorsolateral prefrontal cortex) positively correlated with the cognitive performance in white matter hyperintensities patients. Our findings emphasize that the disrupted hub connectivity patterns in white matter hyperintensities are dependent on connection distance, especially longer-distance connections, which in turn predispose white matter hyperintensities patients to worse cognitive function.

Amyloid and Tau Predominance Subtyping Identifies CI Patients With Different Clinical Phenotypes

AbstractBackgroundThe ATN classification system assumes a sequential model of disease progression. However, there are groups of individuals in the same ATN category that exhibit a predominance of abnormality (higher burden) of one of the biomarkers, creating heterogeneous ATN groups regarding pathological predominance. Thus, we tested the hypothesis that individuals clustered by ATN biomarker abnormality predominance may offer an alternative to groups defined using biomarkers cut‐offs.MethodWe assessed 103 cognitively impaired individuals(CDR&gt; = 0.5) from the TRIAD cohort with available measures of plasma phosphorylated tau‐181, brain MRI, amyloid PET, and tau PET. We used the K‐means algorithm to stratify participants into three clusters. We compared the clusters on composite measures of memory, executive functioning, language, and visuospatial processing. To examine the utility of the discovered clusters, we compared them to traditional ATN categories in the prediction of neuropsychological measures. We did so by creating three categories: patients positive on all three ATN biomarkers, patients positive on two of the three biomarkers, and patients positive on either one or none. Additionally, we created an inflammation, amyloid and tau deposition probabilistic map anchored on young controls(n = 51, mean age = 23.74).ResultsWe uncovered 3 clusters: an amyloid predominant (AP) cluster, a tau/phosphor‐tau predominant cluster (TP), and a cluster showing no predominance with low levels on all biomarkers (CN)(figure 1). Notably, levels of neurodegeneration and inflammation were similar between the AP and TP clusters. The AP cluster significantly differed from the CN cluster in memory only. Participants in the TP cluster had significantly lower scores in memory, executive functioning, language, and visuospatial processing than the other two clusters. In comparison, using threshold‐based ATN groups showed milder differences in memory and executive functioning, and no differences in language and visuospatial processing(figure 2). Furthermore, cluster membership moderated the relationship between various biomarkers, to the point of reversing the direction of correlation(figure 3).ConclusionOur results highlight the biological heterogeneity present within the Alzheimer’s disease continuum and that the pathological predominance of amyloid and tau is associated with different disease phenotypes. Approaching dementia patients with an eye on the predominance of pathology rather than cutoffs for abnormality may provide a better understanding of AD pathological subtypes.