Impaired Executive Cognitive Functioning Research Articles

Pre-existing mental health disorders and fear of COVID-19 pandemic: Data from a phone survey in community-dwelling older adults recruited in the NutBrain study.

COVID-19 has caused a parallel epidemic of fear, anxiety, depression, stress, and frustration, particularly among the most fragile and vulnerable individuals, such as older people and those with previous mental health disorders. The present study aims to investigate the association between pre-existing mental health disorders, particularly depressive symptoms and Mild Cognitive Impairment (MCI), and the fear of COVID-19 and to explore which cognitive domains were involved in coping with fear in older people. In April 2020, we conducted a phone-interview questionnaire on community-dwelling older adults living in Lombardy Region (Italy) who participated in the NutBrain study. At baseline, socio-demographic characteristics along with lifestyles, and medical history were recorded. Participants underwent a neuropsychological battery exploring the global cognitive function and specific cognitive domains, to detect cases of MCI. The Center for Epidemiologic Studies Depression scale (CES-D) was used for screening depressive symptoms. During the phone survey, respondents were assessed using a structured questionnaire querying about fear of the COVID-19 pandemic. We performed multivariate logistic regression models to study the association between MCI and depressive symptomatology and fear. We also explored which cognitive domains were associated with fear. Odds Ratios (OR) with Confidence Intervals (95%CI) were estimated adjusting for potential confounders. Out of the 351 respondents (mean age 73.5 ± 6.1 years, 59.8% women, 49.1% high education), at baseline, 22.9% had MCI and 18.8% had depressive symptoms. In the multivariate analyses gender, age, and body mass index were significantly associated with the fear score. Considering different domains of fear, MCI was associated with fear of being infected themselves (OR 2.55, 95%CI 1.39-4.70) while depressive symptoms were associated with fear of contagion for family members (OR 2.38, 95%CI 1.25-4.52). Impaired executive cognitive function was positively associated with the highest tertile of the fear score (OR 3.28, 95%CI 1.37-7.74) and with fear of contagion for themselves (OR 3.39, 95%CI 1.61-7.17). Older adults experienced different fear reactions, particularly when suffering from neurocognitive disorders and depressive symptoms; executive dysfunction was associated with increased fear. These results highlighted the need to pay attention to the psychological effects of the outbreak of COVID-19 to target intervention, especially among vulnerable subgroups of individuals. [ClinicalTrials.gov], identifier [NCT04461951].

Mice heterozygous for an inactivated allele of the schizophrenia associated Brd1 gene display selective cognitive deficits with translational relevance to schizophrenia

Schizophrenia is a debilitating brain disorder characterized by disturbances of emotion, perception and cognition. Cognitive impairments predict functional outcome in schizophrenia and are detectable even in the prodromal stage of the disorder. However, our understanding of the underlying neurobiology is limited and procognitive treatments remain elusive. We recently demonstrated that mice heterozygous for an inactivated allele of the schizophrenia-associated Brd1 gene (Brd1+/− mice) display behaviors reminiscent of schizophrenia, including impaired social cognition and long-term memory. Here, we further characterize performance of these mice by following the preclinical guidelines recommended by the ‘Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)’ and ‘Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS)’ initiatives to maximize translational value. Brd1+/− mice exhibit relational encoding deficits, compromised working and long term memory, as well as impaired executive cognitive functioning with cognitive behaviors relying on medial prefrontal cortex being particularly affected. Akin to patients with schizophrenia, the cognitive deficits displayed by Brd1+/− mice are not global, but selective. Our results underline the value of Brd1+/− mice as a promising tool for studying the neurobiology of cognitive deficits in schizophrenia.

Impairment of executive cognitive control in type 2 diabetes, and its effects on health-related behavior and use of health services

We evaluated whether, among persons with type 2 diabetes: (1) impaired executive cognitive functioning (ECF) is more common than among people without diabetes; (2) ECF is associated with the capacity to engage in instrumental health-related behaviors; and (3) worse ECF is associated with increased health services utilization. A population-based sample of 1,063 older people was interviewed regarding medical history and health services utilization; participants were administered the Mini Mental State Exam and the Behavioral Dyscontrol Scale, a measure of ECF. Participants with diabetes performed more poorly on cognitive measures than those without diabetes. Among those with diabetes, lower ECF was associated with more outpatient care and with ever having been in a nursing home. Impaired behavioral self-regulation may affect the capacity to engage in behaviors that could improve clinical status, resulting in greater health services use. The findings suggest the possibility of a positive feedback loop, with ECF deficits adversely affecting adherence, in turn leading to greater cognitive impairment-an issue for future research.

Fetal growth restriction and developmental delay: current understanding and future possibilities

Fetal growth restriction and developmental delay: current understanding and future possibilities

P02-179 - Acquired brain injury and violent offending: prevalence and risk factors

IntroductionAcquired brain injury has been reported to be associated with violence.ObjectivesTo determine whether an association exists between acquired brain injury and violent offendingAimsStudy an association between brain injury and crime and identify associated risk factors.MethodsSystematic search of Medline, Embase, PsychInfo, CINAHL, TRIP, using terms, Acquired brain injury, traumatic brain injury (TBI), head injury, frontal lobe, crime, offending, violent offending, sexual offending, prison.ResultsA:Multiple studies reported higher life time history of head injury in prison or offender populations in comparison to control groups. Sampling bias and case definition problems have influenced reported prevalence of head injury in offender population ranging from 3.3% to 82%. Reports from secure psychiatric services identify that patients with history of head injury may be more difficult to discharge. Community based studies report cognitive damage as significant risk factor for domestic violence.B:Large scale population and military cohorts have reported a higher relative risk for criminal conviction in mild traumatic brain injury (TBI) group. TBI increases the risk of mental disorder by two-folds but also that TBI is significantly related to mental disorder with co-existing criminality.C:Childhood conduct problems, loss of a parent, substance misuse, maternal drug use in pregnancy, impaired executive cognitive functioning, structural damage to orbito-frontal and ventromedial areas, amygdala, and hippocampus are reported as risk factors for violent offending in this population group.ConclusionsThe review provides evidence for an association between brain injury and violent offending and also identifies associated risk factors.

Sam68 sequestration and partial loss of function are associated with splicing alterations in FXTAS patients

Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is a neurodegenerative disorder caused by expansion of 55-200 CGG repeats in the 5'-UTR of the FMR1 gene. FXTAS is characterized by action tremor, gait ataxia and impaired executive cognitive functioning. It has been proposed that FXTAS is caused by titration of RNA-binding proteins by the expanded CGG repeats. Sam68 is an RNA-binding protein involved in alternative splicing regulation and its ablation in mouse leads to motor coordination defects. Here, we report that mRNAs containing expanded CGG repeats form large and dynamic intranuclear RNA aggregates that recruit several RNA-binding proteins sequentially, first Sam68, then hnRNP-G and MBNL1. Importantly, Sam68 is sequestered by expanded CGG repeats and thereby loses its splicing-regulatory function. Consequently, Sam68-responsive splicing is altered in FXTAS patients. Finally, we found that regulation of Sam68 tyrosine phosphorylation modulates its localization within CGG aggregates and that tautomycin prevents both Sam68 and CGG RNA aggregate formation. Overall, these data support an RNA gain-of-function mechanism for FXTAS neuropathology, and suggest possible target routes for treatment options.

Executive Cognitive Function and Cessation of Smoking Among Older Smokers

Evaluation of: Brega AG, Grigsby J, Kooken R, Hamman RF, Baxter J: The impact of executive cognitive functioning on rates of smoking cessation in the San Luis Valley Health and Aging Study. Age Ageing 37, 521–525 (2008). The prevalence of smoking among the elderly is lower than in the general population, but aging populations in many countries mean that smoking-related diseases will increase as a health burden in the future. Executive cognitive functioning (ECF) allows people to plan and regulate behavior in order to achieve future goals. Impaired ECF is prevalent in those aged over 65 years and may be a factor in continued smoking among the elderly. Initial studies suggest that current ECF predicts successful cessation of smoking. Among ever smokers, 74% of those with unimpaired ECF had successfully quit compared with 65% of those with some level of ECF impairment. However, a general measure of cognition did not predict cessation. These findings have implications for how cessation of smoking programs can be improved in order to help older smokers quit smoking by providing more social support as well as the removal of smoking cues.

Age at First Drink and the First Incidence of Adult‐Onset DSM‐IV Alcohol Use Disorders

Existing studies of the association between age at first drink (AFD) and the risk of alcohol use disorders (AUD) suffer from inconsistent levels of control and designs that may inflate associations by failure to control for duration of exposure to risk. This study examined associations between AFD (ages <15 and 15-17 vs. 18+ years) and first incidence of DSM-IV alcohol dependence, abuse, and specific AUD criteria over a 3-year follow-up in a longitudinal study of U.S. drinkers 18 years of age and older at baseline (n = 22,316), controlling for duration of exposure, family history, and a wide range of baseline and childhood risk factors. After adjusting for all risk factors, the incidence of dependence was increased for AFD <15 years (OR = 1.38) and for women only with AFD at ages 15 to 17 (OR = 1.54). The incidence of abuse was increased at AFD <15 and 15 to 17 years (OR = 1.52 and 1.30, respectively). Most dependence criteria showed significant associations with AFD, but hazardous drinking and continued drinking despite interpersonal problems were the only abuse criteria to do so. All associations were nonsignificant after controlling for volume of consumption, except that AFD at all ages <18 combined was associated with a reduced likelihood of impaired control, and AFD at ages 15 to 17 was associated with lower odds of drinking more/longer than intended among heavy-volume drinkers. In a population of low-risk drinkers that excluded those with positive family histories, personality disorders, and childhood risk factors, there were strong associations between early AFD (<18) and the incidence of dependence (OR = 3.79) and continued drinking despite physical/psychological problems (OR = 2.71), but no association with incidence of abuse. There is a robust association between AFD and the risk of AUD that appears to reflect willful rather than uncontrolled heavy drinking, consistent with misuse governed by poor decision-making and/or reward-processing skills associated with impaired executive cognitive function (ECF). Additional research is needed to determine causality in the role of impaired ECF, including longitudinal studies with samples of low-risk adolescents.

Cognitive function in young adults following intrauterine growth restriction with abnormal fetal aortic blood flow

Intrauterine growth restriction (IUGR) is a recognized risk factor for neurological deficits later in life. Abnormal fetal blood flow in the presence of IUGR helps to distinguish fetuses with true growth impairment from those that are small but normally grown. This study aimed to evaluate the influence of IUGR with abnormal fetal blood flow on cognitive function and psychological development in young adults. Cognitive capacity (Wechsler adult intelligence scale-III (WAIS-III)) and psychological development (symptom check-list and Wender Utah rating scale) were evaluated at 18 years of age in 19 subjects who had had IUGR (abnormal fetal blood flow in the descending aorta and birth weight small-for-gestational age) and in 23 control subjects who had had normal fetal aortic blood flow and birth weight appropriate-for-gestational age (AGA). School grades at 16 years of age were also recorded. The IUGR subjects had significantly lower results at 18 years of age in the combined subtests of the WAIS-III measuring executive cognitive functions (P = 0.03) and lower school grades at 16 years of age (P = 0.03) compared with the AGA group. IUGR subjects did not exhibit significantly more psychological distress symptoms. IUGR with abnormal fetal blood flow is associated with impaired executive cognitive function in young adults.

From the fetus at risk to intelligence, educational attainment and psychological distress in the young adult

Objective Intrauterine growth restriction (IUGR) is a recognized risk factor for neurological deficits later in life. Abnormal fetal blood flow in the presence of IUGR helps to distinguish fetuses with true growth impairment from those that are small but normally grown. This study aimed to evaluate the influence of IUGR with abnormal fetal blood flow on cognitive function and psychological development in young adults. Methods Cognitive capacity (Wechsler adult intelligence scale-III (WAIS-III)) and psychological development (symptom check-list and Wender Utah rating scale) were evaluated at 18 years of age in 19 subjects who had had IUGR (abnormal fetal blood flow in the descending aorta and birth weight small-for-gestational age) and in 23 control subjects who had had normal fetal aortic blood flow and birth weight appropriate-for-gestational age (AGA). School grades at 16 years of age were also recorded. Results The IUGR subjects had significantly lower results at 18 years of age in the combined subtests of the WAIS-III measuring executive cognitive functions (P = 0.03) and lower school grades at 16 years of age (P = 0.03) compared with the AGA group. IUGR subjects did not exhibit significantly more psychological distress symptoms. Conclusion IUGR with abnormal fetal blood flow is associated with impaired executive cognitive function in young adults.

Discovering endophenotypes for major depression.

The limited success of genetic studies of major depression has raised questions concerning the definition of genetically relevant phenotypes. This paper presents strategies to improve the phenotypic definition of major depression by proposing endophenotypes at two levels: First, dissecting the depressive phenotype into key components results in narrow definitions of putative psychopathological endophenotypes: mood bias toward negative emotions, impaired reward function, impaired learning and memory, neurovegetative signs, impaired diurnal variation, impaired executive cognitive function, psychomotor change, and increased stress sensitivity. A review of the recent literature on neurobiological and genetic findings associated with these components is given. Second, the most consistent heritable biological markers of major depression are proposed as biological endophenotypes for genetic studies: REM sleep abnormalities, functional and structural brain abnormalities, dysfunctions in serotonergic, catecholaminergic, hypothalamic-pituitary-adrenocortical axis, and CRH systems, and intracellular signal transduction endophenotypes. The associations among the psychopathological and biological endophenotypes are discussed with respect to specificity, temporal stability, heritability, familiality, and clinical and biological plausibility. Finally, the case is made for the development of a new classification system in order to reduce the heterogeneity of depression representing a major impediment to elucidating the genetic and neurobiological basis of this common, severe, and often life-threatening illness.

Prevalence of Disorders of Executive Cognitive Functioning among the Elderly: Findings from the San Luis Valley Health and Aging Study

The San Luis Valley Health and Aging Study is a population-based epidemiologic study of chronic illness and disability among Hispanic and non-Hispanic white persons over the age of 60 in two counties in rural southern Colorado, USA. Between 1993 and 1995, we examined the prevalence of impaired executive cognitive functioning in a sample of 1,313 individuals living both in the community and in nursing homes. Overall, 1 person in 3 was found to have at least mild impairment, while 1 in 6 had moderate to severe deficits. Increasing levels of executive functioning impairment were associated with lower education, advancing age, and Hispanic ethnicity. After controlling for education and acculturation, the differences by ethnic group were no longer significant.

Relation between executive cognitive functioning and the adverse consequences of alcohol use in social drinkers.

The purpose of this study was to assess the relation between Executive Cognitive Functioning (ECF) and the adverse consequences of alcohol consumption. ECF encompasses "higher order" cognitive abilities involved in goal-directed behavior, such as attentional control, mental flexibility, planning, and self-monitoring. Impaired ECF has been shown to result in a variety of negative consequences, including excessive drug and alcohol use. Subjects were 79 nonalcoholic male social drinkers between 17 to 30 years of age. ECF was measured using three neuropsychological tests: the Wisconsin Card Sorting Test (WCST), the Conditional Associative Learning Test (CAT), and the Sequential Matching Memory Test (SMMT). Adverse drinking consequences were measured using the Drinker Inventory of Consequences (DrInC). The DrInC assesses drinking consequences in five domains: Physical, Intrapersonal, Interpersonal, Social Responsibility, and Impulse Control. Scores from the neuropsychological tests were reduced into two latent variables: one representing the WCST and the other representing the CAT and SMMT. The results indicated that errors on the CAT/SMMT variable were positively related to adverse consequences in each domain, except for physical consequences. A similar association was found between the WCST variable and impulse control consequences. These findings indicate that performance on tests measuring ECF is related to the severity of drinking consequences. Therefore, prevention and treatment outcomes may be improved by incorporating cognitive habilitation into current interventions.

The significance of frontal system disorders for medical practice and health policy.

In major chronic diseases, apathy or impaired executive cognitive function (ECF) can reduce the patient's ability to cope with the disease and its treatment and to maintain personal safety, dignity, and goal-directed activity. Psychometric and imaging studies support a causal role for frontal system dysfunction. The view that frontal system dysfunction mediates or aggravates disability in a wide range of psychiatric and nonpsychiatric disorders 1) motivates further research on how ECF deficits interact with specific physical impairments to produce disability; 2) supports policies that base entitlements to care on ECF impairments; and 3) suggests the need for a vigorous search for drugs that prevent or palliate prefrontal dysfunction, especially the syndromes of apathy and impaired ECF.