scholarly journals Postseptic Cognitive Impairment and Expression of APOE in Peripheral Blood: The Cognition After SepsiS (CASS) Observational Pilot Study

2020 ◽  
pp. 088506661989760
Author(s):  
Samuel M. Brown ◽  
Sarah J. Beesley ◽  
Chris Stubben ◽  
Emily L. Wilson ◽  
Angela P. Presson ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Executive Function ◽  
Peripheral Blood ◽  
Medical Center ◽  
Executive Dysfunction ◽  
Clinical Problem ◽  
Primary Analysis ◽  
Tertiary Referral Center ◽  
Peripheral Leukocytes

Background: Cognitive impairment after sepsis is an important clinical problem. Determinants of postseptic cognitive impairment are not well understood. We thus undertook a systems biology approach to exploring a possible role for apolipoprotein E (APOE) in postseptic cognitive impairment. Design: Prospective, observational cohort. Setting: Intermountain Medical Center, a tertiary referral center in Utah. Patients/Participants: Patients with sepsis admitted to study intensive care units. Interventions: None. Methods: We obtained peripheral blood for deep sequencing of RNA and followed up survivors at 6 months with a battery of cognitive instruments. We defined cognitive impairment based on the 6-month Hayling test of executive function. In our primary analysis, we employed weighted network analysis. Secondarily, we compared variation in gene expression between patients with normal versus impaired cognition. Measurements and Main Results: We enrolled 40 patients, of whom 34 were follow-up eligible and 31 (91%) completed follow-up; 1 patient’s RNA sample was degraded—the final analytic cohort was 30 patients. Mean Hayling test score was 5.8 (standard deviation 1.1), which represented 20% with impaired executive function. The network module containing APOE was dominated by low-expression genes, with no association on primary analysis ( P = .8). Secondary analyses suggested several potential lines of future investigation, including oxidative stress. Conclusions: In this prospective pilot cohort, executive dysfunction affected 1 in 5 survivors of sepsis. The APOE gene was sparsely transcribed in peripheral leukocytes and not associated with cognitive impairment. Future lines of research are suggested.

The Ten Point Clock Test: A Quick Screen and Grading Method for Cognitive Impairment in Medical and Surgical Patients

1994 ◽  
Vol 24 (3) ◽  
pp. 229-244 ◽  
Author(s):  
Peter J. Manos ◽  
Rae Wu
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Deficits ◽  
Neuropsychological Tests ◽  
Medical Center ◽  
Neuropsychological Test ◽  
Hospitalized Patients ◽  
Surgical Patients ◽  
Tertiary Referral Center ◽  
The Mean ◽  
State Examination

Objective: The objective of this study was to evaluate the clinical utility of the ten point clock test in screening for and grading cognitive deficits in medical and surgical patients. Method: The setting was the hospital and clinics of Virginia Mason Medical Center, a tertiary referral center. Consecutive samples of hospitalized patients, and clinic outpatients—with and without a dementia—were administered the ten point clock test as well as a number of other neuropsychological tests and measures of cognitive impairment. Results: Clock scores correlated with neuropsychological test scores and with the mini-mental state examination. They were stable from rater to rater, and from day to day in stable patients. The mean clock score of elderly outpatient controls was 8.5, significantly different from the mean of 5.5 scored by patients with a dementia. A cut off score of seven identified 76 percent of outpatients with dementia and 78 percent of elderly controls. Clock scores correlated well with nurses' ratings of their inpatients' cognitive deficits (Spearman's rs = −0.61). The test was easy to administer, even to hospitalized patients. Conclusions: The ten point clock test is reliable, valid, and useful as a quick screen and grading method for cognitive deficits in medical and surgical patients.

scholarly journals Working Memory and Executive Function Decline across Normal Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Anna-Mariya Kirova ◽  
Rebecca B. Bays ◽  
Sarita Lagalwar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Working Memory ◽  
Cognitive Impairment ◽  
Executive Function ◽  
Mild Cognitive Impairment ◽  
Executive Dysfunction ◽  
Normal Aging ◽  
Future Research ◽  
Neurological Differences

Alzheimer’s disease (AD) is a progressive neurodegenerative disease marked by deficits in episodic memory, working memory (WM), and executive function. Examples of executive dysfunction in AD include poor selective and divided attention, failed inhibition of interfering stimuli, and poor manipulation skills. Although episodic deficits during disease progression have been widely studied and are the benchmark of a probable AD diagnosis, more recent research has investigated WM and executive function decline during mild cognitive impairment (MCI), also referred to as the preclinical stage of AD. MCI is a critical period during which cognitive restructuring and neuroplasticity such as compensation still occur; therefore, cognitive therapies could have a beneficial effect on decreasing the likelihood of AD progression during MCI. Monitoring performance on working memory and executive function tasks to track cognitive function may signal progression from normal cognition to MCI to AD. The present review tracks WM decline through normal aging, MCI, and AD to highlight the behavioral and neurological differences that distinguish these three stages in an effort to guide future research on MCI diagnosis, cognitive therapy, and AD prevention.

scholarly journals Chemotherapy Pharmacodynamics and Neuroimaging and Neurocognitive Outcomes in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia

2016 ◽  
Vol 34 (22) ◽  
pp. 2644-2653 ◽  
Author(s):  
Kevin R. Krull ◽  
Yin Ting Cheung ◽  
Wei Liu ◽  
Slim Fellah ◽  
Wilburn E. Reddick ◽  
...  
Keyword(s):  
Executive Function ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Executive Dysfunction ◽  
Brain Regions ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Long Term Follow Up ◽  
Long Term Survivors

Purpose To examine associations among methotrexate pharmacodynamics, neuroimaging, and neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on a contemporary chemotherapy-only protocol. Patients and Methods This longitudinal study linked pharmacokinetic assays collected during therapy to neurocognitive and brain imaging outcomes during long-term follow-up. A total of 218 (72.2%) of 302 eligible long-term survivors were recruited for outcome studies when they were more than 5 years post-diagnosis and older than 8 years of age. At long-term follow-up, survivors were an average of 13.8 years old and 7.7 years from diagnosis, and 51% were male. Neurocognitive testing, functional magnetic resonance imaging (MRI) during an executive function task, and structural MRI with diffusion tensor imaging were conducted. Generalized linear models were developed to identify predictors, and models were adjusted for age at diagnosis, sex, and parent education. Results Intelligence was within normal limits (mean, 98; standard deviation, 14) compared with population expectations (mean, 100; standard deviation, 15), though measures of executive function, processing speed, and memory were less than population means (all P < .02 after correction for false discovery rates). Higher plasma concentration of methotrexate was associated with a poorer executive function score (P < .02). Higher plasma methotrexate was also associated with higher functional MRI activity, with thicker cortices in dorsolateral prefrontal brain regions, and with white matter microstructure in the frontostriatal tact. Neurocognitive impairment was associated with these imaging findings as well. Associations did not change after adjustment for age or dose of leucovorin rescue. Conclusion Survivors of childhood acute lymphoblastic leukemia treated on contemporary chemotherapy-only protocols demonstrate executive dysfunction. A higher plasma concentration of methotrexate was associated with executive dysfunction as well as with a thicker cortex and higher activity in frontal brain regions, regions often associated with executive function.

scholarly journals Dysexecutive syndrome and cerebrovascular disease in non-amnestic mild cognitive impairment: a systematic review of the literature

2012 ◽  
Vol 6 (3) ◽  
pp. 145-151 ◽  
Author(s):  
Felipe Kenji Sudo ◽  
Carlos Eduardo Oliveira Alves ◽  
Gilberto Sousa Alves ◽  
Letice Ericeira-Valente ◽  
Chan Tiel ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Executive Function ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Executive Dysfunction ◽  
Subcortical White Matter ◽  
Review Of The Literature ◽  
Extrapyramidal Signs ◽  
Made In

ABSTRACT Objective: Non-amnestic dysexecutive Vascular Mild Cognitive Impairment (VaMCI) may represent preclinical Vascular Dementia (VaD). The aim of this study was to summarize the clinical, neuropsychological and neuroimaging aspects of VaMCI; and to assess its patterns of progression to dementia. Methods: Searches were made in the ISI Web of Knowledge, PubMed and Lilacs databases, using the terms "mild cognitive impairment" and "executive function". Altogether, 944 articles were retrieved. Results: VaMCI cases had poorer performances on fronto-executive tasks, a higher prevalence of stroke, presence of periventricular and profound white matter hyperintensities on MRI images, as well as more extrapyramidal signs and behavioral symptoms. Executive dysfunction might be associated with disconnection of fronto-parietal-subcortical circuits. Progression to dementia was associated with baseline deficits in executive function, in simple sustained attention and language, and large periventricular WMH. Discussion: VaMCI develops with impairment in non-memory domains and subcortical white matter changes on MRI images, which are consistent with clinical and neuroimaging findings in VaD.

scholarly journals Symptomatic Treatment of Vascular Cognitive Impairment (STREAM-VCI): Protocol for a Cross-Over Trial (Preprint)

2017 ◽  
Author(s):  
Jolien Fleur Leijenaar ◽  
Geert Jan Groeneveld ◽  
Wiesje Maria van der Flier ◽  
Philip Scheltens ◽  
Erica Surya Klaassen ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Functional Connectivity ◽  
Positive Response ◽  
Medical Center ◽  
Competent Authority ◽  
Executive Dysfunction ◽  
Symptomatic Treatment ◽  
Vascular Cognitive Impairment ◽  
Vascular Damage ◽  
Double Blind

BACKGROUND People with vascular cognitive impairment (VCI) constitute a clinically heterogeneous group, but previous symptomatic drug trials in VCI did not take this clinical heterogeneity into account. Executive dysfunction and memory impairment are the cognitive domains that are most frequently impaired in VCI, and these impairments are likely to reflect vascular damage to specific neurotransmitter systems, which opens the possibility for targeted symptomatic treatment directed at specific neurotransmitters. OBJECTIVE Here we describe the design of the “Symptomatic Treatment of Vascular Cognitive Impairment” (STREAM-VCI) trial. In this proof-of-concept study, we investigate whether people with VCI with executive dysfunction due to vascular damage to the monoaminergic neurotransmitter system differentially respond to a monoaminergic challenge, whereas people with VCI with memory dysfunction associated with vascular damage to the cholinergic system will in turn respond to a cholinergic challenge. METHODS The STREAM-VCI is a single center, double blind, three-way cross-over trial among 30 people with VCI, in which subjects received a single dose of galantamine, methylphenidate, or placebo on separate occasions. The most important inclusion criteria were a diagnosis of VCI with a Mini-Mental State Examination score of ≥16 and a Clinical Dementia Rating of 0.5-1.0. For each person, the challenges consisted of a single 16 mg dose of galantamine, 10 mg of methylphenidate, and placebo, in random order on three separate visits. Change in performance in executive functioning and memory was assessed directly after the challenge using standardized neuropsychological tests. We will correlate a positive response to the cholinergic and monoaminergic treatment with differences in structural and functional connectivity at baseline using structural magnetic resonance imaging (MRI), diffusion tension MRI, and resting-state functional MRI. RESULTS The protocol of this study is approved by the Medical Ethics Committee of VU University Medical Center and the competent authority. The first participant was enrolled in April 2014. In September 2017, enrolment for the study was completed. We expect to publish the results in 2018. CONCLUSIONS STREAM-VCI is the first study to investigate the association of a response to a cholinergic and monoaminergic treatment with structural and functional connectivity of the monoaminergic and/or cholinergic systems on MRI. We aim to predict on an individual basis which individuals show a positive response to a cholinergic and/or monoaminergic challenge in people with VCI. This may be instrumental in moving in the direction of individually-tailored pharmacological interventions based on MRI measures in people with VCI. CLINICALTRIAL ClinicalTrials.gov NCT02098824; https://clinicaltrials.gov/ct2/show/NCT02098824 (Archived by WebCite at http://www.webcitation.org/6xhO7Ya1q)

scholarly journals Eye Movement Technique to Improve Executive Function in Patients With Stroke: A Randomized Controlled Trial

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen He ◽  
Yazheng Ji ◽  
Xiating Wei ◽  
Fan Wang ◽  
Feng Xu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Executive Function ◽  
Reaction Time ◽  
Eye Movement ◽  
Controlled Trial ◽  
Executive Dysfunction ◽  
Wisconsin Card Sorting Test ◽  
Single Center ◽  
Randomized Controlled

Objective: To investigate the efficacy of eye movement technique for the treatment of executive dysfunction of patients with stroke.Methods: This was a prospective, single-blinded, randomized, controlled, single-center clinical trial conducted from June 2018 to December 2019 in patients with stroke. The patients were randomized 1:1 to the routine (conventional management) and eye-move group (routine management plus eye movement technique: 5-min goal management training, 5-min computer-aided working memory, and 10 min of inhibitory control training and set conversion training). The intervention lasted 6 weeks, followed by a 4-week follow-up. The primary endpoint was the Behavioral Assessment of the Dysexecutive Syndrome (BADS) score. The secondary endpoints mainly included the Montreal Cognitive Assessment (MoCA), Wisconsin Card Sorting Test (WCST), and modified Barthel Index (MBI) scores.Results: Sixty-four patients were enrolled (32/group). After the 6-week intervention, the BADS and WCST scores of the eye-move group were significantly improved than those of the routine group (all P &lt; 0.05), but the effects were attenuated in certain subscores after follow-up (all P &gt; 0.05). The MoCA and MBI scores of the eye-move group were significantly higher, and the reaction time was significantly lower than those of the routine group at 4 weeks after the intervention (all P &lt; 0.05). After follow-up, the MBI scores of the eye-move group were still higher than that of the routine group (P &lt; 0.001), but there were no differences for MoCA scores and reaction time (both P &gt; 0.05).Conclusion: The eye movement technique could improve the executive function of patients with stroke. These results have to be confirmed.This was a prospective, single-blinded, randomized, controlled, single-center clinical trial (ChiCTR2000036393).Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR2000036393].

scholarly journals The Number Symbol Coding Task: A brief measure of executive function to detect dementia and cognitive impairment

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242233 ◽  
Author(s):  
James E. Galvin ◽  
Magdalena I. Tolea ◽  
Claudia Moore ◽  
Stephanie Chrisphonte
Keyword(s):  
Cognitive Impairment ◽  
Executive Function ◽  
Problem Solving ◽  
Comprehensive Evaluation ◽  
Clinical Care ◽  
Executive Dysfunction ◽  
Structured Interview ◽  
Assessment Tools ◽  
Quality Data ◽  
Clinical Dementia Rating

Introduction Alzheimer’s disease and related dementias (ADRD) affect over 5.7 million Americans and over 35 million people worldwide. Detection of mild cognitive impairment (MCI) and early ADRD is a challenge to clinicians and researchers. Brief assessment tools frequently emphasize memory impairment, however executive dysfunction may be one of the earliest signs of impairment. To address the need for a brief, easy-to-score, open-access test of executive function for use in clinical practice and research, we created the Number Symbol Coding Task (NSCT). Methods This study analyzed 320 consecutive patient-caregiver dyads who underwent a comprehensive evaluation including the Clinical Dementia Rating (CDR), patient and caregiver versions of the Quick Dementia Rating System (QDRS), caregiver ratings of behavior and function, and neuropsychological testing, with a subset undergoing volumetric magnetic resonance imaging (MRI). Estimates of cognitive reserve were calculated using education, combined indices of education and occupation, and verbal IQ. Psychometric properties of the NSCT including data quality, data distribution, floor and ceiling effects, construct and known-groups validity, discriminability, and clinical profiles were determined. Results The patients had a mean age of 75.3±9.2 years (range 38-98y) with a mean education of 15.7±2.8 years (range 6-26y) of education. The patients had a mean CDR-SB of 4.8±4.7 (range 0–18) and a mean MoCA score of 18.6±7.1 (range 1–30). The mean NSCT score was 30.1±13.8 and followed a normal distribution. All healthy controls and MCI cases were able to complete the NSCT. The NSCT showed moderate-to-strong correlations with clinical and neuropsychological measures with the strongest association (all p’s < .001) for measures with executive components (e.g., Judgement and Problem Solving box of the CDR, Decision Making and Problem Solving domain of the QDRS, Trailmaking B, and Cognigram Attention and Executive Composite Scores). Women slightly outperformed men, and individuals with lower educational attainment and lower education-occupation indices had lower NSCT scores. Decreasing NSCT scores corresponded to older age, worse cognitive scores, higher CDR sum of boxes scores, worse caregiver ratings of function and behavior, worse patient and informant QDRS ratings, and smaller hippocampal volumes and hippocampal occupancy scores. The NSCT provided excellent discrimination (AUC: .866; 95% CI: .82-.91) with a cut-off score of 36 providing the best combination of sensitivity (0.880) and specificity (0.759). Combining the NSCT with patient QDRS and caregiver QDRS ratings improved discrimination (AUC: .908; 95% CI: .87-.94). Discussion The NSCT is a brief, 90-second executive task that incorporates attention, planning and set-switching that can be completed by individuals into the moderate-to-severe stages of dementia. The NSCT may be a useful tool for dementia screening, case-ascertainment in epidemiological or community-based ADRD studies, and in busy primary care settings where time is limited. Combining the NSCT with a brief structured interview tool such as the QDRS may provide excellent power to detect cognitive impairment. The NSCT performed well in comparison to standardized scales of a comprehensive cognitive neurology evaluation across a wide array of sociodemographic variables in a brief fashion that could facilitate its use in clinical care and research.

Cerebral Microbleeds are Associated with Impairments in Executive Function and Processing Speed

2021 ◽  
pp. 1-8
Author(s):  
Xuanting Li ◽  
Junliang Yuan ◽  
Wei Qin ◽  
Lei Yang ◽  
Shuna Yang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Executive Function ◽  
Cognitive Function ◽  
Processing Speed ◽  
Population Aging ◽  
Brain Magnetic Resonance Imaging ◽  
Executive Dysfunction ◽  
Linear Regression Models ◽  
Cross Sectional ◽  
Global Cognitive Function

Background: Cerebral microbleed (CMB) is an increasingly important risk factor for cognitive impairment due to population aging. Controversies, however, remain regarding the exact association between CMB and cognitive dysfunction. Objective: We aimed to determine the relationship between CMB burden and cognitive impairment, and also explore the characteristics of cognitive decline in CMB patients for middle-aged and elderly people. Methods: The present cross-sectional study included 174 participants (87 CMB patients and 87 controls) who underwent brain magnetic resonance imaging and a battery of neuropsychological test. Global cognitive function was measured using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Compound z-scores were calculated for three cognitive subdomains: memory, executive function and processing speed. Results: CMB patients had lower scores of MMSE (p <  0.001) and MoCA (p <  0.001). Patients at each category of CMB count had worse performance in global cognitive function and all three cognitive subdomains (p <  0.001). In multiple linear regression models, CMB patients had significantly greater declines in executive function (p <  0.001), processing speed (p <  0.001), and MoCA (p = 0.003) with increasing number of CMB. We found no relationship between CMB location and cognition (p <  0.05). Conclusion: CMB is associated with impairment in global cognition as well as for all tested subdomains. Strongest effect sizes were seen for tests which rely on executive functioning, where performance deficits increased in proportion to degree of CMB burden. Prospective studies are needed to evaluate whether the association between CMB and executive dysfunction is causal.

scholarly journals Rehabilitation of executive function in chronic paediatric brain injury: a randomized controlled trial

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Anne E. Brandt ◽  
Torun G. Finnanger ◽  
Ruth E. Hypher ◽  
Torstein B. Rø ◽  
Eva Skovlund ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Executive Function ◽  
Brain Injury ◽  
Daily Life ◽  
Controlled Trial ◽  
Executive Dysfunction ◽  
Post Intervention ◽  
Randomized Controlled ◽  
Significant Difference

Abstract Background Impaired executive functions (EFs, i.e., purposeful, goal-directed behaviour) cause significant disability after paediatric acquired brain injury (pABI) warranting efficient interventions. Goal Management Training (GMT) is a metacognitive protocol proven effective for executive dysfunction in adults. This pre-registered, blinded, parallel-randomized controlled trial evaluated efficacy of a paediatric adaptation (pGMT) compared to a psychoeducative control (paediatric Brain Health Workshop, pBHW) to improve EF. Methods Children aged 10 to 17 years with pABI (e.g., traumatic brain injury, brain tumour), ≥ 1 year post-onset or ended treatment, with parent-reported EF complaints were eligible. Participants were randomized (computer-algorithm) to either group-based pGMT (n = 38) or pBHW (n = 38). The active control was tailored to keep non-specific factors constant. Thus, both treatments comprised of 7 sessions at hospitals over 3 consecutive weeks, followed by 4 weeks of telephone counselling of participants, parents, and teachers. Parent-reported daily life EF, assessed by the questionnaire Behavior Rating Inventory of Executive Function (BRIEF; Behavioral Regulation Index (BRI) and Metacognition Index (MI)), were co-primary outcomes 6 months post-intervention. Secondary outcomes included neuropsychological tests and a complex naturalistic task (Children’s Cooking Task). Results Seventy-three participants (96%) completed allocated interventions and 71 (93%) attended the 6-month follow-up. The results demonstrated no significant difference in effectiveness for the two interventions on parent-reported EF: For BRIEFBRI, mean (SD) raw score for pGMT was 42.7 (8.8) and 38.3 (9.3) for pBHW. Estimated difference was − 2.3 (95% CI − 5.1 to 0.6). For BRIEFMI, the corresponding results were 80.9 (20.4) for GMT and 75.5 (19.3) for pBHW. Estimated difference was − 1.4 (95% CI −8.5 to 5.8). In performance-based tests, pGMT was associated with improved inhibition and executive attention, while pBHW was associated with fewer errors in the naturalistic task. Conclusions In pABI, metacognitive training (pGMT) did not demonstrate additional effectiveness on parent-reported daily life EF at 6-month follow-up, when compared to a psychoeducative control. Both interventions were well-tolerated and demonstrated distinct improvements at different EF assessment levels. To conclude on pGMT efficacy, larger studies are needed, including further investigation of appropriate assessment levels and possible differences in effect related to treatment duration, developmental factors, and injury characteristics. Trial registration ClinicalTrials.gov, NCT0321534211, 11 July 2017

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