Cognitive Executive Function Research Articles

Intelligence and executive function are associated with age at insult, time post-insult, and disability following chronic pediatric acquired brain injury.

Pediatric acquired brain injury (pABI) profoundly affects cognitive functions, encompassing IQ and executive functions (EFs). Particularly, young age at insult may lead to persistent and debilitating deficits, affecting daily-life functioning negatively. This study delves into the intricate interplay of age at insult, time post-insult, and their associations with IQ and EFs during chronic (>1 year) pABI. Additionally, we investigate cognitive performance across different levels of global function, recognizing the multifaceted nature of developmental factors influencing outcomes. Drawing upon insult data and baseline information analyzing secondary outcomes from a multicenter RCT, including comprehensive medical and neuropsychological assessments of participants aged 10 to 17 years with pABI and parent-reported executive dysfunctions. The study examined associations between age at insult (early, EI; ≤7y vs. late, LI; > 7y) and time post-insult with IQ and EFs (updating, shifting, inhibition, and executive attention). Additionally, utilizing the Pediatric Glasgow Outcome Scale-Extended, we explored cognitive performance across levels of global functioning. Seventy-six participants, median 8 years at insult and 5 years post-insult, predominantly exhibiting moderate disability (n = 38), were included. Notably, participants with LI demonstrated superior IQ, executive attention, and shifting compared to EI, [adjusted mean differences with 95% Confidence Intervals (CIs); 7.9 (1.4, 14.4), 2.48 (0.71, 4.24) and 1.73 (0.03, 3.43), respectively]. Conversely, extended post-insult duration was associated with diminished performances, evident in mean differences with 95% CIs for IQ, updating, shifting, and executive attention compared to 1-2 years post-insult [-11.1 (-20.4, -1.7), -8.4 (-16.7, -0.1), -2.6 (-4.4, -0.7), -2.9 (-4.5, -1.2), -3.8 (-6.4, -1.3), -2.6 (-5.0, -0.3), and -3.2 (-5.7, -0.8)]. Global function exhibited a robust relationship with IQ and EFs. Early insults and prolonged post-insult durations impose lasting tribulations in chronic pABI. While confirmation through larger studies is needed, these findings carry clinical implications, underscoring the importance of vigilance regarding early insults. Moreover, they dispel the notion that children fully recover from pABI; instead, they advocate equitable rehabilitation offerings for pABI, tailored to address cognitive functions, recognizing their pivotal role in achieving independence and participation in society. Incorporating disability screening in long-term follow-up assessments may prove beneficial.

The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis.

This study aimed to evaluate the effects of creatine monohydrate supplementation on cognitive function in adults and explore its potential role in preventing and delaying cognitive impairment-related diseases. Following the PRISMA 2020 guidelines, a systematic review with meta-analysis was conducted. Randomized controlled trials (RCTs) published between 1993 and 2024 were retrieved from PubMed, Scopus, and Web of Science databases. The study protocol was registered with PROSPERO (registration number: CRD42024533557). The impact of creatine supplementation on overall cognitive function, memory, executive function, attention, and information processing speed was assessed using standardized mean differences (SMD) and Hedge's g with 95% confidence intervals (CI). Sixteen RCTs involving 492 participants aged 20.8-76.4 years, including healthy individuals and patients with specific diseases, were selected. Creatine monohydrate was the form used in all included studies. Creatine supplementation showed significant positive effects on memory (SMD = 0.31, 95% CI: 0.18-0.44, Hedges's g = 0.3003, 95% CI: 0.1778-0.4228) and attention time (SMD = -0.31, 95% CI: -0.58 to -0.03, Hedges's g = -0.3004, 95% CI: -0.5719 to -0.0289), as well as significantly improving processing speed time (SMD = -0.51, 95% CI: -1.01 to -0.01, Hedges's g = -0.4916, 95% CI: -0.7852 to -0.1980). However, no significant improvements were found on overall cognitive function or executive function. Subgroup analyses revealed that creatine supplementation was more beneficial in individuals with diseases, those aged 18-60 years, and females. No significant differences were found between short- (<4 weeks) and long-term (≥4 weeks) interventions for improving cognitive function. Low-to-moderate risk of bias was found, and no significant publication bias was detected. The GRADE assessment indicates that the certainty of evidence for memory function is moderate, suggesting a reasonable level of confidence in the positive effects of creatine on memory. However, the evidence for processing speed, overall cognitive function, executive function, and attention is of low certainty, indicating that further research is needed to confirm these potential benefits. Current evidence suggests that creatine monohydrate supplementation may confer beneficial effects on cognitive function in adults, particularly in the domains of memory, attention time, and information processing speed. Larger robust clinical trials are warranted to further validate these findings. Furthermore, future research should investigate the influence of different populations and intervention durations on the effects of creatine monohydrate supplementation, as well as elucidate the precise mechanisms underlying its potential cognitive-enhancing properties.

Various modalities of resistance exercise promote similar acute cognitive improvements and hemodynamic increases in young, healthy adults

The aim was to examine the effects of modalities of acute resistance exercise (RE) on cognition and hemodynamics including internal carotid artery (ICA) blood flow (BF). Twenty adults completed familiarization and experimental visits. One-repetition maximum (1RM) for bilateral leg extension was quantified, and baseline executive functioning was determined from three run-in visits. Subsequent visits included three randomized, volume-equated, acute exercise bouts of 30%1RM+blood flow restriction (BFR), 30%1RM, and 70%1RM. Both 30%1RM trials completed four sets of exercise (1 × 30, 3 × 15), and the 70%1RM condition completed four sets of 8 repetitions. BFR was induced with 40% of the pressure to occlude the femoral arteries. 11 minutes following each exercise, participants completed the Stroop and Shifting Attention Tests. Baseline and post-exercise values were used to calculate change scores. The resulting mean change scores were evaluated with mixed factorial ANOVAs. A p≤0.05 was considered significant. All measured outcome variables increased in response to exercise. The ANOVAs for cognitive scores indicated no significant (p>0.05) interactions. For cognitive flexibility and executive function index, there were main effects of Sex. Change scores of the females were significantly greater than the males for cognitive flexibility (7.6 ± 5.9 vs. -2.6 ± 8.4 au; p=0.007) and executive function index (7.4 ± 4.6 vs. -2.5 ± 6.5 au; p=0.001). For ICA BF, there was no significant interaction or any main effect. The females exhibited a smaller exercise-induced increase in blood pressure compared to the males (17.7 ± 5.9 vs. 11.0 ± 4.1 mmHg; p=0.010). Each RE modality yielded acute improvements in cognition, but only for females. There were no cognitive improvements related to BFR such that each RE bout yielded similar results.

The dynamic strategy shifting task: Optimisation of an operant task for assessing cognitive flexibility in rats.

Although schizophrenia is associated with a broad range of symptoms including hallucinations, delusions, and reduced motivation, measures of cognitive dysfunction, including cognitive flexibility and executive function, are the strongest predictors of functional outcomes. Antipsychotic medications are useful for reducing psychotic symptoms, but they are ineffective at improving cognitive deficits. Despite extensive investment by industry, the transition from preclinical to clinical trials has not been successful for developing precognitive medications for individuals with schizophrenia. Here, we describe the optimisation of a novel dynamic strategy shifting task (DSST) using standard operant chambers to investigate the optimal stimuli required to limit the extensive training times required in previous tasks. We determined that optimal learning by male and female Sprague Dawley rats for the flexibility task incorporated dynamic strategy shifts between spatial rules, such as following a visual cue or responding at one location, and non-spatial rules, such as responding to a central visual or auditory cue. A minimum of 6 correct consecutive responses were required to make a within-session change in the behavioural strategies. As a proof of concept, we trained and tested 84 Sprague Dawley rats on the DSST, and then assessed their cognitive flexibility using a within-subject design after an acute dose of ketamine (0, 3, 10 mg/kg). Rats made fewer premature and more perseverant responses to initiate a trial following ketamine. The effects of ketamine on trials to criterion was dependent on the rule. Ketamine induced a significant improvement on the reversal of a non-spatial visual discrimination rule. There was no significant effect of ketamine on the spatial visual or response discrimination rules. The DSST is a novel assay for studying distinct forms of cognitive flexibility and offers a rapid and adaptable means of assessing the ability to shift between increasingly challenging rule conditions. The DSST has potential utility in advancing our understanding of cognitive processes and the underlying neurobiological mechanisms related to flexibility in neuropsychiatric and neurological conditions where executive dysfunctions occur.>.

Sensitivity of Clock Drawing Test Alone to Screen for Cognitive Impairment in Patients with Parkinson's Disease.

Cognitive impairment is a prevalent non-motor symptom of Parkinson's disease (PD), significantly impacting patient quality of life. The Clock Drawing Test (CDT) evaluates cognitive abilities, including planning, organization, and executive functions such as attention, memory, and visuospatial skills. This study aimed to determine the sensitivity of the CDT in diagnosing cognitive impairment in PD. We reviewed the records of 44 PD patients (16 female, 28 male) diagnosed with dementia (30 patients) or mild cognitive impairment (14 patients) between 2018 and 2022. These patients were compared to 106 visitors to the neurological outpatient clinic, serving as a control group. A separate researcher assessed the patients' CDT scores, maintaining confidentiality of all other patient data except age and education level. Among the 44 PD patients, two with mild cognitive impairment were rated as normal, while all PD dementia cases were identified solely through the CDT. In the healthy control group, 72 out of 106 individuals reported no cognitive complaints, whereas 34 individuals (32.1%) reported cognitive complaints as assessed by a blind investigator. The CDT demonstrated a positive predictive value of 55.3% and a negative predictive value of 97.3%. Sensitivity was calculated at 95.5%, and specificity was 67.9%. The findings suggest that the CDT is sensitive in detecting cognitive impairment in PD patients with cognitive deficits. While the CDT serves as an effective rapid screening tool, high scores indicate the absence of cognitive impairment, but low scores alone are insufficient for a definitive diagnosis of dementia. Comprehensive neurological evaluation and detailed cognitive assessment remain essential for confirming dementia diagnoses.

Effectiveness of Mindfulness-Based Stress Reduction on Executive Functions in Patients with Hypertension: A Randomized Clinical Trial

Background: Hypertension one of the main risk factors of cardiovascular diseases and premature death worldwide. Researches indicate different cognitive activities and executive functions in cardiovascular and hypertension patients compared to non-afflicted people. Objectives: Therefore, the purpose of this study was to investigate the effectiveness of mindfulness-based stress reduction (MBSR) on executive functions in patients with hypertension. Materials &amp; Methods: The present study was a randomized clinical trial based on the pre-test, post-test, follow-up design. The statistical population consisted of all the people with hypertension who referred to Heshmat Heart Hospital in Rasht city, Iran, in 2021. Thirty-four qualified volunteers were included in the study by purposive sampling method and randomly assigned to two groups of MBSR and control. Wisconsin Card Sorting Test (computer version) were the instrument employed in this research; and MBSR sessions were held for 2 months (8 sessions, one 120-minute session each week). The research data were analyzed using repeated measures ANOVA and Bonferroni post-hoc test. Results: In the pre-test design, there wasn't a difference in the completed categories and perseverative errors, between the MBSR group (2±0.485 and 30.06±6.60) and the control group (2.06±0.659 and 29.88±9.4. In the post-test design, a significant difference in the completed categories and perseverative errors was found between the MBSR group (3.29±0.848 and 20.94±5.71) and the control group (2.18±0.636 and 29.94±8.70); which implies the MBSR group outperformed the control group in Improving executive functions of patients with hypertension. Finally, at the follow-up, all changes were still stable. Conclusions: MBSR was effective on executive functions of patients with hypertension. Therefore, it is suggested that the mentioned intervention be used in medical centres to improve the cognitive activities of patients with hypertension, so that its positive results include the condition of these patients.

Цифровые устройства в жизни современных дошкольников

Today, preschoolers actively use digital devices. Therefore, we investigated how digital devices potentially affect significant predictors of preschoolers’ social-emotional and cognitive development, executive functions, and speech. The results obtained revealed that 5-6-year-old children who used digital devices for less than 1.5 hours per day demonstrated an improvement in cognitive flexibility level within a year, while 2.5 hours of screen time caused a decrease in cognitive flexibility. Passive screen time negatively affects children’s phonemic hearing. Opposite to that, active screen time does not affect it. The study revealed that 5-6-year-old children who usually played digital games and watched video content together with their siblings demonstrated more noticeable positive dynamics in inhibitory control than those who did it alone. Moreover, if it was the parents who determined what digital content would be available to their children, the latter demonstrated an increment in inhibitory control compared to the children who made the choice themselves. Junior school children who used digital devices in a cultural way at preschool age had higher level of executive functions development than the children who used the devices only in a natural way. Thus, digital devices are multidimensional tools and, depending on how they are used, the impact on a child’s development may be different.

Cognitive Constructs and Personality Profiles in Youth with Deliberate Self-Harm Behaviours: A Scoping Review

This scoping review explored the relationship between cognitive constructs and personality profiles in deliberate selfharm among youth, with the objective of proposing preventive and intervention strategies based on the findings. The review analysed the correlation between cognitive constructs and Deliberate Self-Harm behaviors in youth with diverse personality profiles. It investigated the role of cognitive distortions, emotional regulation, reasoning, and executive functioning in youth engaged in deliberate self-harm. A comprehensive search using the Scopus database yielded 72 relevant articles for analysis. The prevalence rates of deliberate self-harm among youth range from 7.5% to 46.5%, emphasizing the need for targeted interventions. Promising approaches include cognitive restructuring, mindfulnessbased therapies, and interventions focusing on challenging cognitive distortions to promote adaptive thinking patterns. Training interventions addressing executive functioning skills can effectively target impulsive and risky behaviors. Personality traits such as neuroticism, sensation seeking, borderline personality disorder, and perfectionism require interventions focused on emotional resilience, coping strategies, risk assessment, self-control, and impulse management

Effects of demographic and lifestyle factors on cognitive speed, attention and executive function measured by the Trail Making Tests A and B in healthy adults

Effects of demographic and lifestyle factors on cognitive speed, attention and executive function measured by the Trail Making Tests A and B in healthy adults

Citiholin u neurologiji i psihijatriji

Citicoline is a supplement-nootropic with potential applications in treating various neurological, psychiatric, and other conditions. There is experimental and clinical evidence of the benefits of citicoline in individuals after stroke, traumatic brain injury, and cognitive decline of various etiologies. Preclinical studies suggest that citicoline has neuroprotective and neurorestorative effects, which can be explained by its antioxidant, anti-inflammatory, and metabolic actions. Citicoline is necessary for the synthesis and stabilization of biological membranes, improves mitochondrial function, and is crucial in the synthesis of acetylcholine and other neurotransmitters in the central nervous system. No specific drugs are available for treating cognitive sequelae of stroke and traumatic brain injury. In experimental and clinical studies, citicoline has shown a safe profile with positive clinical effects on overall cognitive abilities, attention, executive function, and mood. There are also positive results of its use in patients with neurodegenerative diseases, although on a small number of participants. In psychiatry, the beneficial effects of citicoline on depression, negative symptoms of schizophrenia, and substance use disorders are described. This review provides an overview of the mechanisms of action of citicoline and summarizes the published research on its use in neurology and psychiatry.

Impact of Optimism on Cognitive Performance of People Living in Rural Area: Findings From a 20-Year Study in US Adults.

Objectives: Mid- or early-late-life cognitive function is an indicator for developing late-life dementia. However, it is still unclear whether rural/urban living contexts provide cognitive benefits across adulthood. Further, higher optimism serves as a general protective factor for many health outcomes. The present study examines associations between rurality/urbanicity, optimism, and change in mid/late-life cognitive functions over time. Methods: Data were from waves 1 to 3 (1995-2015) of the Midlife in the United States (MIDUS) study (N = 2,507). Structural equation models examine whether long-term rural living across both waves (1-2) or intermittent rural living at one wave is associated with better cognitive function over 20 years, compared to no rural living, while controlling for prior cognitive function and covariates (baseline socio-demographics, health, and functional status). Additionally, we assessed if optimism mediates the above associations. Results: After controlling for covariates, long-term rural living (waves 1-2) was indirectly (through less optimism) associated with significantly lower levels of cognitive executive function and episodic memory in wave 3. Conclusions: While long-term rural living and cognitive outcomes have no direct association for MIDUS middle-aged and older adults, mediating roles of optimism in these associations were evident. Future investigations could examine mechanisms that underlie these risk/protective factors on late-life cognition.

Enhanced Soccer Training Simulation Using Progressive Wasserstein GAN and Termite Life Cycle Optimization in Virtual Reality

Virtual Reality (VR) offers the possibility of creating engaging and intensive training programs to enhance sports performance. Football, a widely popular sport worldwide, attracts millions of spectators. However, the physical demands and risks inherent in the game necessitate the creation of a training environment immune to external influences, minimizing sports-related injuries while enhancing player immersion. Existing training methods are affected by external factors like, weather, injuries, and space limitations, hindering effectiveness and skill development. To overcome these issues, in this research, enhanced soccer training simulation using Progressive Wasserstein GAN and Termite Life Cycle Optimization in Virtual Reality (PWGAN-TLCOA-ST-VRT) are proposed. This study begins by analyzing the fundamental features of computer-generated soccer training techniques and introduces the implementation of VRT in football training via PWGAN technology. The goal is to develop virtual systems resilient to external factors and provide theoretical support for the expansion of virtual football sports software. By overcoming constraints like, weather, player injuries, space limitations, and financial constraints, the proposed approach aims to enhance training effectiveness, teaching techniques, and football skill development. Software tools like Poser 8.0, 3Ds MAX and EON Studio are introduced for system development. Evaluation of the proposed PWGAN-TLCOA-ST-VRT method is examined using performance metrics including, precision, accuracy, F1-score, recall, specificity, error rate, computation time, and Receiver Operating Characteristic (ROC) analysis. The proposed PWGAN-TLCOA-ST-VRT technique achieves significant improvements compared to existing approaches like, Analysis of the application of virtual reality technology in football training (AI-ST-VRT), Cortex VR: Immersive analysis and training of cognitive executive functions of soccer players using VR and machine learning, Predict the value of football players using FIFA video game data and machine learning techniques (MLR-ST-VRT)

Effects of Virtual Reality Physical and Cognitive Training Intervention On Cognitive Abilities of Elders with Mild Cognitive Impairment.

Virtual reality (VR) technology has become increasingly used for assessment and intervention in the neuroscience field. We aimed to investigate the effects of a VR Training System, named VRADA (VR Exercise App for Dementia and Alzheimer's Patients), on the cognitive functioning of older people with mild cognitive impairment (MCI). In this intervention study, 122 older adults with MCI were randomly assigned to five groups (the VRADA group (n = 28), a bike group (n = 11), a physical exercise group (n = 24), a mixed group (physical and cognitive exercise) (n = 31), and a non-contact control group (n = 28). The VRADA group underwent 32 physical and cognitive training sessions, performed 2 or 3 times weekly for 12 weeks in the VR environment. All participants had detailed neuropsychological assessments before and after intervention. A series of linear regression models revealed that the VRADA group showed improvement or no deterioration in cognitive decline in global cognitive function (MMSE), verbal memory (Rey Auditory Verbal Learning Test and WAIS forward test), and executive functions, mental flexibility (Trail Making Test B). This interventionstudy indicates that the VRADA system improves the cognitive function of elders with MCI.

Mind in Crisis: Examining the Cognitive Consequences of the COVID-19 Pandemic

The coronavirus disease-2019 (COVID-19) pandemic devastated the world, leaving in its wake not only physical devastation but also significant psychological trauma. Fear and uncertainty became pervasive, leading to widespread anxiety, depression, and post-traumatic stress disorder. While the pandemic’s impact on mental health received significant attention, its effects on cognitive function were overlooked until recently. Studies suggest that the pandemic led to declines in cognitive performance, affecting memory, attention, and executive functioning. The present article explores the cognitive impact of the pandemic, examining the mechanisms through which it affected cognitive function and analyzing its long-term consequences. While the pandemic’s immediate impact has waned, its long-term cognitive effects may linger, emphasizing the need to address this overlooked aspect of the pandemic’s impact. By understanding the pandemic’s cognitive impact and taking steps to mitigate it, individuals and society can better recover and move forward from this unprecedented global crisis.

Profiles of Cognitive Functioning at 6 Months After Traumatic Brain Injury Among Patients in Level I Trauma Centers

Cognitive dysfunction is common after traumatic brain injury (TBI), with a well-established dose-response relationship between TBI severity and likelihood or magnitude of persistent cognitive impairment. However, patterns of cognitive dysfunction in the long-term (eg, 6-month) recovery period are less well known. To characterize the prevalence of cognitive dysfunction within and across cognitive domains (processing speed, memory, and executive functioning) 6 months after injury in patients with TBI seen at level I trauma centers. This prospective longitudinal cohort study used data from Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) and included patients aged 17 years or older presenting at 18 US level I trauma center emergency departments or inpatient units within 24 hours of head injury, control individuals with orthopedic injury recruited from the same centers, and uninjured friend and family controls. Participants were enrolled between March 2, 2014, and July 27, 2018. Data were analyzed from March 5, 2020, through October 3, 2023. Traumatic brain injury (Glasgow Coma Scale score of 3-15) or orthopedic injury. Performance on standard neuropsychological tests, including premorbid cognitive ability (National Institutes of Health Toolbox Picture Vocabulary Test), verbal memory (Rey Auditory Verbal Learning Test), processing speed (Wechsler Adult Intelligence Scale [4th edition] Processing Speed Index), and executive functioning (Trail Making Test). The sample included 1057 persons with TBI (mean [SD] age, 39.3 [16.4] years; 705 [67%] male) and 327 controls without TBI (mean [SD] age, 38.4 [15.1] years; 222 [68%] male). Most persons with TBI demonstrated performance within 1.5 SDs or better of the control group (49.3% [95% CI, 39.5%-59.2%] to 67.5% [95% CI, 63.7%-71.2%] showed no evidence of impairment). Similarly, 64.4% (95% CI, 54.5%-73.4%) to 78.8% (95% CI, 75.4%-81.9%) of participants demonstrated no evidence of cognitive decline (defined as performance within 1.5 SDs of estimated premorbid ability). For individuals with evidence of either cognitive impairment or decline, diverse profiles of impairment across memory, speed, and executive functioning domains were observed (ie, the prevalence was >0 in each of the 7 combinations of impairment across these 3 cognitive domains for most TBI subgroups). In this cohort study of patients seen at level I trauma centers 6 months after TBI, many patients with TBI demonstrated no cognitive impairment. Impairment was more prevalent in persons with more severe TBI and manifested in variable ways across individuals. The findings may guide future research and treatment recommendations.

Effect of Baduanjin exercise on executive function in older adults with cognitive frailty: A randomized controlled trial

Objective To investigate the effectiveness of Baduanjin exercise on executive function in community-dwelling older adults with cognitive frailty. Design Randomized controlled trial. Setting Community residential centers. Subjects 120 eligible older adults. Interventions Baduanjin training group received supervised Baduanjin training, 60 min sessions three times per week for 24 weeks. The control group did not receive any exercise intervention. Main measures Primary outcome was executive function, assessed using Clock Drawing Test. Secondary outcomes included the subcomponents of executive function (working memory, inhibitory control and cognitive flexibility), attention and cognitive frailty (global cognitive function, physical frailty) assessed using Verbal Fluency Test, Trail Making Test-A/B, Stroop Test, Montreal Cognitive Assessment and Edmonton Frailty Scale, respectively, at baseline and 24 weeks after intervention. Results After the 24-week intervention, the scores of Clock Drawing Test and Verbal Fluency Test, the Trail Making Test-B time and the Card correct numbers of Stroop Test in Baduanjin training group showed significant improvement compared with control group (all P < 0.05) with small to moderate effect sizes and the significant interaction effect of group by time in the Clock Drawing Test and Trail Making Test-B test (P = 0.003 and P = 0.043); cognitive frailty variables, including Montreal Cognitive Assessment and Edmonton Frail Scale scores, also showed significant improvement (P = 0.002 and P = 0.004) with a moderate effect sizes and a significant interaction effect (P < 0.001, P = 0.013). No adverse events were reported. Conclusion Regular Baduanjin training may be an effective and safe intervention to improve cognitive frailty and executive function in community-dwelling older adults with cognitive frailty. Trial registration Chinese Clinical Trial Registry, ChiCTR2100050857. Data of registration: 8/5/2020, https://www.chictr.org.cn/showproj.html?proj = 133037.

NT‐proBNP and changes in cognition and brain structure: the Rotterdam Study

AbstractBackgroundTo investigate the association between NT‐proBNP and changes in cognition and brain structure.MethodIn the Rotterdam Study, baseline NT‐proBNP was assessed at baseline from 1997 to 2008. Between 1997‐2016, participants without dementia or stroke at baseline (n = 9,566) had repeated cognitive tests (every 3‐6 years) for global cognitive function, executive cognitive function, fine manual dexterity, and memory. Magnetic resonance imaging of the brain was performed repeatedly at re‐examination visits between 2005 and 2015 for 2,607 participants to obtain brain volumes, focal brain lesions, and white matter microstructural integrity as measures of brain structure.ResultAmong 9,566 participants (mean age 65.1±9.8 years), 5,444 (56.9%) were women, and repeated measures of cognition were performed during a median follow‐up time of 5.5 years (range = 1.1‐17.9). For participants with brain imaging data at baseline (mean age 56.8±6.3 years, 55.5% women), repeated scans were completed over a median follow‐up time of 5.6 years (range = 2.8‐8.1). Higher levels of NT‐proBNP were associated with a faster decline of scores in the global cognitive function, the Word‐Fluency test, and the Purdue Pegboard test, but were not related to a steeper deterioration in brain volumes, white matter microstructure, or focal brain lesions.ConclusionHigher baseline NT‐proBNP levels were associated with a faster decline in cognition, but not in structural brain changes. Further studies should focus on the causality of the association between NT‐proBNP and cognition.

Association between G‐Protein Coupled Receptor 55 (GPR55) Single Nucleotide Polymorphisms and Alzheimer’s Disease

AbstractBackgroundG‐protein‐coupled receptor 55 (GPR55) is a lysophosphatidylinositol and novel cannabinoid receptor. GPR55 signalling and single nucleotide polymorphisms (SNPs) have been implicated as a potential therapeutic target for neurodegenerative diseases such as Alzheimer’s Disease (AD); however, foundational knowledge on the role of GPR55 in AD progression remains lacking. We hypothesised GPR55 SNP minor allele carriers would have greater brain atrophy, cognitive decline, and AD‐related biomarker changes.MethodThis retrospective, longitudinal, observational study used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We selected participants with clinically normal cognition, mild cognitive impairment (MCI) or mild AD from ADNI2 and ADNIGO phases as a discovery sample. Exploratory screening of GPR55 SNPs identified rs2969126G/C associated with brain volume. Cerebrospinal fluid amyloid beta‐42 (CSF‐Aβ42), total and phosphorylated‐tau (t/p‐tau) were considered. Mini‐Mental State Exam and the Logical Memory Delayed Recall Test were also selected to evaluate overall cognitive status, executive function, and memory. ANCOVA models evaluated baseline differences between SNP carriers and major allele homozygotes (dominant model), controlling for sex, age, baseline cognitive status and APOE e4 across AD biomarkers, brain volumetrics and cognitive measures. Longitudinal associations were assessed as interactions between SNP and visit (baseline, 12 and 24 months) in mixed models.ResultIn ADNI2/GO (n = 755), minor allele carriers represented 15% of the sample. Significantly greater decline in CSF‐Aβ42 levels was observed in Aβ42‐positive clinically normal minor allele carriers (F(1,45.2) = 6.35, p = 0.015). Carriers with MCI had significantly higher t‐tau (F(1,126) = 4.303, p = 0.04) and p‐tau concentrations (F(1,129) = 6.98, p = 0.009) longitudinally. Significantly smaller hippocampal volumes over time were seen in minor allele carriers in the whole group (F(1,444) = 5.74, p = 0.017), with a trend in the AD/MCI subgroup (F(1,325) = 3.364, p = 0.06). Clinically normal minor allele carriers had significantly poorer baseline logical memory scores (F(1,285) = 6.92, p = 0.009). These results did not replicate in the ADNI3 cohort.ConclusionCarriers of the GPR55 SNP rs2969126G/C minor allele had greater Aβ42 and tau biomarker abnormalities, smaller brain volumes and poorer memory scores over time in different stages of AD. This preliminary study prompts replication studies in different stages of AD progression to implicate GPR55 as a potential therapeutic target for AD.

Optimizing Subjective Cognitive Concern Assessment to Predict Cognitive Decline in Motoric Cognitive Risk Syndrome: Results from the Einstein Aging Study

AbstractBackgroundMotoric Cognitive Risk Syndrome (MCR) is a predementia condition that combines slow gait speed and subjective cognitive concerns (SCC), and predicts incident dementia in diverse global populations. MCR status is simple and inexpensive to ascertain, facilitating assessment in low resource settings. Though the slow gait component of MCR diagnosis is well operationalized, there is no standardized approach to SCC assessment. We hypothesized that in older adults with slow gait, the SCC questions that best predicted cognitive decline would most successfully operationalize SCC.MethodEinstein Aging Study participants (n = 324; Mage = 70.4; Meducation= 15; 67%women; 46.3%White) completed the Cognitive Change Index Supplement (CCI‐40) as part of a comprehensive neuropsychological assessment (which included the Clinical Dementia Rating Scale [CDR]) at baseline and over up‐to‐5 annual follow‐ups (Mwave= 1.48). The CCI‐40 queries SCC across cognitive domains, including memory (21 items), language (4), executive functioning (5), attention/concentration (4), visuospatial functioning (2), calculation (1), mental clarity (2), and orientation (1). Slow gait was diagnosed based on established MCR criteria (1 SD below age/sex adjusted means). We used linear mixed effects models (LME) for continuous, and generalized LME for binary longitudinal cognitive outcomes, to examine how various definitions of SCC at baseline predict cognitive changes in older adults with slow gait, adjusting for covariates including age, sex, education, race/ethnicity, and depression. We report the interaction terms between SCC and time. The final sample included 43 participants (13%) who met slow gait criteria at baseline.ResultAmong participants with slow gait, the CCI‐40 total score was associated with decline on neuropsychological measures of attention/processing speed (β = ‐0.09, p = 0.05), verbal fluency (β = 0.03, p = 0.01), and a global dementia rating scale (β = 0.04, p = 0.02). Item‐by‐item analysis revealed a subset of items that were significantly associated with decline in key neuropsychological domains, including executive functioning, language, and memory.ConclusionOur findings suggest that attention to SCC assessment in older adults with slow gait may provide key insight into individuals at greatest risk for cognitive decline. SCC in MCR may be best operationalized through comprehensive assessment across broad cognitive domains. Future work will develop a brief SCC screen optimized to predict cognitive decline in this population.

Identifying the optimal age to intervene in Alzheimer’s disease prevention trials: Validation of Emax modelling in sporadic Alzheimer’s disease

AbstractBackgroundMany clinical trials of disease‐modifying therapies which seek to delay or prevent Alzheimer’s disease (AD) currently exist. However, a limitation of these trials is the absence of considering the earliest age groups at which decline in cognition can be detected to guide optimal participant recruitment.Previous work has shown that in people with Down syndrome, Emax modelling can be used to identify the trajectory of cognitive decline in the preclinical and prodromal stages of AD. We aimed to validate Emaxmodelling to identify the earliest age of change in cognition in people who developed sporadic AD and compare these individuals to healthy controls without AD.MethodOur sample consisted of participants aged 65 years old from the Enquête Sante ́ Psychologique – Risques, Incidence et Traitement (ESPRIT) study. Participants were categorised into two groups based on whether they were ever diagnosed with possible and probable AD while enrolled in the study (n = 101) or did not receive a diagnosis of any subtype of dementia (n = 1392, our healthy control group). We included measures of general cognitive functioning (Mini Mental State Examination; MMSE), verbal fluency, visual memory (Benton Visual Retention Test) and executive functioning (Trail Making Test).ResultIn people with AD, the earliest decline in general cognitive functioning could be detected in the 67‐71 age band while verbal fluency appears to decline from the 41‐45 age band and visual memory in the 82‐86 age band according to our model. In healthy controls, general cognitive functioning shows early change in the 87‐91 age band while verbal fluency starts to decline in the 43‐47 age band and executive functioning in the 85‐89 age band. Models for Trail Making Models for people with AD and visual memory for controls were not well fitted to the data.ConclusionWe have shown that sensitivity to change depend on the primary outcome so authors designing trials need to ensure the research question, population and primary outcome are consistent. This has implications particularly for trials targeting the stages of disease before dementia diagnosis.