scholarly journals Genetic and Environmental Influences on Self-Reported Cognitive Functioning: Associations of Diverse Measures of Stress across the FMR1 CGG Repeat Range

2020 ◽  
Author(s):  
Nell Maltman ◽  
Leann Smith DaWalt ◽  
Jinkuk Hong ◽  
Mei Wang Baker ◽  
Elizabeth M Berry-Kravis ◽  
...  
Keyword(s):  
Executive Function ◽  
Cognitive Function ◽  
Executive Functioning ◽  
Life Events ◽  
Perceived Stress ◽  
Repeat Length ◽  
Repeat Number ◽  
Cgg Repeat ◽  
Memory Problems ◽  
Cgg Repeats

Abstract Background : The FMR1 gene is essential for neural development and healthy synaptic function. The modal number of CGG repeats in FMR1 is 30, but the range is large with the reported copy number extending down to as few as 6 CGGs and up to over 200 CGGs, conferring fragile X syndrome. Prior work suggests that behavioral phenotypes, including cognitive function, may vary along the continuum of the FMR1 CGG repeat range. Stress may negatively influence cognitive function; however, it is not known whether FMR1 -related variability (i.e., CGG repeat length), in addition to stress, independently influences cognitive function across the CGG range. Methods : Participants included 1275 mothers who had CGGs ranging from 18 to 123 repeats. Participants completed self-report measures of executive function (BRIEF-A), memory, subjective stress (i.e., perceived stress), and objective stress (i.e., number of life events, parenting a child with a disability). Stress and FMR1 -related variability (i.e., CGG repeat length) were examined as predictors of self-reported executive function and memory difficulty. Results : Each measure of stress (i.e., perceived stress, life events, and parenting a child with a disability) significantly predicted greater self-reported difficulties in executive function and the likelihood of memory problems, net of age and level of education. Additionally, above and beyond stress effects, CGG repeat number significantly predicted executive functioning and memory difficulties. There was a linear association of CGG repeat number with executive functioning limitations. The association of CGGs with memory difficulties was curvilinear, with participants in the premutation range having the greatest likelihood of reporting such difficulties. Conclusions : These findings suggest that CGG repeat length confers independent contributions to self-reported executive function difficulty and memory problems over and above indices of stress, suggesting additive effects of genetic variation and environmental exposure. Keywords : Stress, Cognitive Function, Executive Function, Memory, FMR1 , CGG Repeats

scholarly journals Genetic and Environmental Influences on Self-Reported Cognitive Functioning: Associations of Diverse Measures of Stress across the FMR1 CGG Repeat Range

2020 ◽  
Author(s):  
Nell Maltman ◽  
Leann Smith DaWalt ◽  
Jinkuk Hong ◽  
Mei Wang Baker ◽  
Elizabeth M Berry-Kravis ◽  
...  
Keyword(s):  
Executive Function ◽  
Cognitive Function ◽  
Life Events ◽  
Perceived Stress ◽  
Synaptic Function ◽  
Repeat Length ◽  
Cgg Repeat ◽  
Memory Problems ◽  
Cgg Repeats ◽  
Child With A Disability

Abstract Background: The FMR1 gene is essential for neural development and healthy synaptic function. The modal number of CGG repeats in FMR1 is 30, but the range is large with the reported copy number extending down to as few as 6 CGGs and up to over 200 CGGs. Prior work suggests that behavioral phenotypes, including cognitive function, may vary along the continuum of the FMR1 CGG repeat range. Stress also negatively influences cognitive function; however, it is not known whether FMR1-related variability (i.e., CGG repeat length), in addition to stress, independently influences cognitive function across the CGG range. Methods: Participants included 1275 mothers who had between 18 and 123 CGG repeats. Participants completed self-report measures of executive function (BRIEF-A), memory, subjective stress (i.e., perceived stress), and objective stress (i.e., number of life events, parenting a child with a disability). Stress and CGG repeat length were examined as predictors of self-reported executive function and memory difficulty. Results: Each measure of stress (i.e., perceived stress, life events, and parenting a child with a disability) significantly predicted greater self-reported difficulties in executive function and the likelihood of memory problems, net of age and level of education. Additionally, above and beyond stress effects, CGG repeat number significantly predicted executive functioning and memory difficulties. Conclusions: These findings suggest that CGG repeat length confers independent contributions to self-reported executive function difficulty and memory problems over and above indices of stress, suggesting additive effects of genetic variation and environmental exposure.

scholarly journals Is FMR1 CGG Repeat Number Polymorphism Associated With Phenotypic Variation in the General Population? Report From a Cohort of 5,499 Adults

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinkuk Hong ◽  
Leann DaWalt ◽  
Mei Wang Baker ◽  
Elizabeth M. Berry-Kravis ◽  
Marsha R. Mailick
Keyword(s):  
High School ◽  
General Population ◽  
Fragile X ◽  
Repeat Length ◽  
College Graduation ◽  
Repeat Number ◽  
Cgg Repeat ◽  
Age At Menopause ◽  
Cgg Repeats ◽  
Biological Children

FMR1 CGG repeat length was assayed in 5499 research participants (2637 men and 2862 women) in the Wisconsin Longitudinal Study (WLS), a population-based cohort. Most past research has focused on clinically-ascertained individuals with expansions in CGG repeats, either those with fragile X syndrome (> 200 CGG repeats), the FMR1 premutation (55–200 repeats), or in the gray zone (variously defined as 45–54 or 41–54 repeats). In contrast, the WLS is a unique source of data that was obtained from an unselected cohort of individuals from the general population for whom FMR1 CGG repeat length was assayed. The WLS is a random sample of one-third of all high school seniors in the state of Wisconsin in 1957. The most recent round of data collection was in 2011; thus, the study spanned over 50 years. Saliva samples were obtained from 69% of surviving members of the cohort in 2008 and 2011, from which CGG repeats were assayed. With one exception, the CGG repeat length of all members of this cohort was below 100 (ranging from 7 to 84). The present study evaluated the genotype-phenotype associations of CGG repeat number and IQ, college graduation, age at menopause, number of biological children, having a child with intellectual or developmental disabilities, and the likelihood of experiencing an episode of depression during adulthood. Linear and curvilinear effects were probed. Although effect sizes were small, significant associations were found between CGG repeat length and high school IQ score, college graduation, number of biological children, age at menopause, and the likelihood of having an episode of depression. However, there was no significant association between repeat length and having a child diagnosed with an IDD condition. This study demonstrates a continuum of phenotype effects with FMR1 repeat lengths and illustrates how research inspired by a rare genetic condition (such as fragile X syndrome) can be used to probe genotype-phenotype associations in the general population.

scholarly journals FMRP Levels in Human Peripheral Blood Leukocytes Correlates with Intellectual Disability

Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1780
Author(s):  
Mark Roth ◽  
Lucienne Ronco ◽  
Diego Cadavid ◽  
Blythe Durbin-Johnson ◽  
Randi J. Hagerman ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Intellectual Disability ◽  
Peripheral Blood ◽  
Fragile X ◽  
Repeat Expansion ◽  
Repeat Number ◽  
Cgg Repeat ◽  
Fragile X Mental Retardation ◽  
Cgg Repeats ◽  
Fmr1 Mrna

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. FXS is an X-linked, neurodevelopmental disorder caused by a CGG trinucleotide repeat expansion in the 5′ untranslated region (UTR) of the Fragile X Mental Retardation gene, FMR1. Greater than 200 CGG repeats results in epigenetic silencing of the gene leading to the deficiency or absence of Fragile X mental retardation protein (FMRP). The loss of FMRP is considered the root cause of FXS. The relationship between neurological function and FMRP expression in peripheral blood mononuclear cells (PBMCs) has not been well established. Assays to detect and measure FMR1 and FMRP have been described; however, none are sufficiently sensitive, precise, or quantitative to properly characterize the relationships between cognitive ability and CGG repeat number, FMR1 mRNA expression, or FMRP expression measured in PBMCs. To address these limitations, two novel immunoassays were developed and optimized, an electro-chemiluminescence immunoassay and a multiparameter flow cytometry assay. Both assays were performed on PMBCs isolated from 27 study participants with FMR1 CGG repeats ranging from normal to full mutation. After correcting for methylation, a significant positive correlation between CGG repeat number and FMR1 mRNA expression levels and a significant negative correlation between FMRP levels and CGG repeat expansion was observed. Importantly, a high positive correlation was observed between intellectual quotient (IQ) and FMRP expression measured in PBMCs.

Examining the Moderating Role of a Mediterranean Diet in the Relationship Between Perceived Stress and Cognitive Function in Older Adults

2020 ◽  
Author(s):  
Danielle D’Amico ◽  
Vivian Huang ◽  
Alexandra J Fiocco
Keyword(s):  
Older Adults ◽  
Cognitive Function ◽  
Executive Functioning ◽  
Episodic Memory ◽  
Mediterranean Diet ◽  
Perceived Stress ◽  
Verbal Learning ◽  
Diet Adherence ◽  
Mediterranean Diet Adherence ◽  
Diet Pattern

Abstract Objectives Perceived stress and adherence to a Mediterranean diet pattern have been identified as independent predictors of cognitive function in older adulthood; however, no studies to date have examined the interaction between perceived stress and diet adherence on cognitive health. This cross-sectional study investigated the synergistic effect of perceived stress and adherence to a Mediterranean diet pattern on cognitive function in 192 nondemented older adults aged 60–95 years. Method Participants completed a Food Frequency Questionnaire (FFQ) and the Perceived Stress Scale (PSS-10). Executive functioning was assessed using the Trail Making Test-Part B (TMT-B) and episodic memory was assessed using the immediate and delayed free recall subscales from the California Verbal Learning Test (CVLT-II). Results Moderation analyses revealed that higher perceived stress was associated with worse executive functioning at low levels of Mediterranean diet adherence (B = 1.75, SE = 0.67, p = .009), but not at moderate and high levels of Mediterranean diet adherence (ps > .05). Perceived stress was not associated with episodic memory, irrespective of Mediterranean diet adherence. Discussion Findings provide preliminary evidence that the association between higher perceived stress and poorer executive function may be dependent on diet intake. Additional research is needed to confirm these findings.

scholarly journals Effects of physical activity on cognitive function among patients with diabetes in China: a nationally longitudinal study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Anying Bai ◽  
Liyuan Tao ◽  
Jia Huang ◽  
Jing Tao ◽  
Jue Liu
Keyword(s):  
Physical Activity ◽  
Executive Function ◽  
Longitudinal Study ◽  
Cognitive Function ◽  
Episodic Memory ◽  
Age Groups ◽  
Screening Tools ◽  
Diabetic Patients ◽  
Patients With Diabetes ◽  
Lagged Dependent Variable

Abstract Background We aimed to examine the effect of physical activity on different cognitive domains among patients with diabetes. Methods We used two waves of data from the Chinese Health and Retirement Longitudinal Study (CHARLS, 2013–2015), a nationally representative dataset of Chinese population aged over 45. Total physical activity scores were calculated based on the International Physical Activity Questionnaire (IPAQ). Executive function and episodic memory were used as measures of cognitive function. We conducted lagged dependent variable models to explore the association between physical activity and cognitive function in full sample as well as two different age groups (45–65, ≥65). Results: 862 diabetic patients were included. We found that diabetic participants who had greater level of physical activity at baseline were associated with better episodic memory function in 2 years (p < 0.05). Moreover, physical activity was significantly associated with less decline in episodic memory in fully adjusted models, and the associations were stronger among patients aged 45–65 years (p < 0.05). No statistically significant association was found between physical activity and executive function in all age groups. Conclusions Physical activity may prevent some of the potential decline in episodic memory in diabetic patients. Clinicians and public health departments should strengthen the promotion of physical activity and develop early screening tools among diabetic participants to prevent the progression of cognitive impairment.

scholarly journals Mapping of long-term cognitive and motor deficits in pediatric cerebellar brain tumor survivors into a cerebellar white matter atlas

2021 ◽  
Author(s):  
Frederik Grosse ◽  
Stefan Mark Rueckriegel ◽  
Ulrich-Wilhelm Thomale ◽  
Pablo Hernáiz Driever
Keyword(s):  
Brain Tumor ◽  
Executive Function ◽  
Cognitive Function ◽  
White Matter ◽  
Cerebellar Nuclei ◽  
Motor Deficits ◽  
Deep Cerebellar Nuclei ◽  
Cerebellar White Matter ◽  
Lesion Symptom Mapping

Abstract Purpose Diaschisis of cerebrocerebellar loops contributes to cognitive and motor deficits in pediatric cerebellar brain tumor survivors. We used a cerebellar white matter atlas and hypothesized that lesion symptom mapping may reveal the critical lesions of cerebellar tracts. Methods We examined 31 long-term survivors of pediatric posterior fossa tumors (13 pilocytic astrocytoma, 18 medulloblastoma). Patients underwent neuronal imaging, examination for ataxia, fine motor and cognitive function, planning abilities, and executive function. Individual consolidated cerebellar lesions were drawn manually onto patients’ individual MRI and normalized into Montreal Neurologic Institute (MNI) space for further analysis with voxel-based lesion symptom mapping. Results Lesion symptom mapping linked deficits of motor function to the superior cerebellar peduncle (SCP), deep cerebellar nuclei (interposed nucleus (IN), fastigial nucleus (FN), ventromedial dentate nucleus (DN)), and inferior vermis (VIIIa, VIIIb, IX, X). Statistical maps of deficits of intelligence and executive function mapped with minor variations to the same cerebellar structures. Conclusion We identified lesions to the SCP next to deep cerebellar nuclei as critical for limiting both motor and cognitive function in pediatric cerebellar tumor survivors. Future strategies safeguarding motor and cognitive function will have to identify patients preoperatively at risk for damage to these critical structures and adapt multimodal therapeutic options accordingly.

scholarly journals Racial Disparities in Cognitive Function: The Roles of Cumulative Stress Exposures Across the Life Course

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 504-504
Author(s):  
Ruijia Chen ◽  
Jennifer Weuve ◽  
Laura Kubzansky ◽  
David Williams
Keyword(s):  
Executive Function ◽  
Cognitive Function ◽  
Episodic Memory ◽  
Life Course ◽  
Racial Disparities ◽  
The United States ◽  
Coping Resources ◽  
Age Group ◽  
Cumulative Stress ◽  
The Life Course

Abstract Introduction: Racial disparities in cognitive function have been well-documented in the literature, but factors driving the disparities remain under explored. This study aims to quantify the extent to which cumulative stress exposures across the life course explain Black–White disparities in executive function and episodic memory. Method: Data were drawn from the 2004–2006 wave of the Midlife Development in the United States (MIDUS) and the MIDUS refresher study (N=5,967, 5,277 White, 690 Black). Cumulative stress exposures were assessed by using 10 domains of stressors (e.g., financial stress, childhood adversity). Cognitive function was assessed using the Brief Test of Adult Cognition by Telephone. Marginal structural models were conducted to quantify the proportion of the effect of race/ethnicity status on cognitive function that can be explained by cumulative stress exposures. Result: Blacks reported higher levels of cumulative stress exposures and lower average levels of executive function and episodic memory than Whites. Cumulative stress exposures explained 8.43% of the disparities in executive function and 13.21 % of the disparities in episodic memory. Cumulative stress exposures had stronger effects on racial disparities in cognitive function in the older age group (age≥ 55 years old) than in the younger age group (age &lt; 55 years old). Conclusion: Cumulative stress exposures explain modest proportions of racial disparities in levels of cognitive function. Interventions that focus on reducing stress exposures or improving coping resources among Blacks may help lessen racial disparities in cognitive function at the population level.

scholarly journals Slow Wave Sleep and EEG Delta Spectral Power are Associated with Cognitive Function in Parkinson’s Disease

2020 ◽  
pp. 1-12
Author(s):  
Kimberly H. Wood ◽  
Adeel A. Memon ◽  
Raima A. Memon ◽  
Allen Joop ◽  
Jennifer Pilkington ◽  
...  
Keyword(s):  
Executive Function ◽  
Cognitive Function ◽  
Cognitive Performance ◽  
Slow Wave ◽  
Effect Size ◽  
Processing Speed ◽  
Slow Wave Sleep ◽  
Spectral Power ◽  
Z Scores ◽  
Domain Scores

Background: Cognitive and sleep dysfunction are common non-motor symptoms in Parkinson’s disease (PD). Objective: Determine the relationship between slow wave sleep (SWS) and cognitive performance in PD. Methods: Thirty-two PD participants were evaluated with polysomnography and a comprehensive level II neurocognitive battery, as defined by the Movement Disorders Society Task Force for diagnosis of PD-mild cognitive impairment. Raw scores for each test were transformed into z-scores using normative data. Z-scores were averaged to obtain domain scores, and domain scores were averaged to determine the Composite Cognitive Score (CCS), the primary outcome. Participants were grouped by percent of SWS into High SWS and Low SWS groups and compared on CCS and other outcomes using 2-sided t-tests or Mann-Whitney U. Correlations of cognitive outcomes with sleep architecture and EEG spectral power were performed. Results: Participants in the High SWS group demonstrated better global cognitive function (CCS) (p = 0.01, effect size: r = 0.45). In exploratory analyses, the High SWS group showed better performance in domains of executive function (effect size: Cohen’s d = 1.05), language (d = 0.95), and processing speed (d = 1.12). Percentage of SWS was correlated with global cognition and executive function, language, and processing speed. Frontal EEG delta power during N3 was correlated with the CCS and executive function. Cognition was not correlated with subjective sleep quality. Conclusion: Increased SWS and higher delta spectral power are associated with better cognitive performance in PD. This demonstrates the significant relationship between sleep and cognitive function and suggests that interventions to improve sleep might improve cognition in individuals with PD.

scholarly journals The Relationship of Psychiatric Symptoms with Performance-Based and Self-Reported Cognitive Function After Ischemic Stroke

2021 ◽  
pp. 1-13
Author(s):  
Elisabeth Kliem ◽  
Elise Gjestad ◽  
Truls Ryum ◽  
Alexander Olsen ◽  
Bente Thommessen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Executive Function ◽  
Depressive Symptoms ◽  
Cognitive Function ◽  
Psychiatric Symptoms ◽  
Post Stroke ◽  
Cognitive Difficulties ◽  
Memory And Attention ◽  
Relationship Of ◽  
The Relationship

Abstract Objective: Findings on the relationship of psychiatric symptoms with performance-based and self-reported cognitive function post-stroke are inconclusive. We aimed to (1) study the relation of depression and anxiety to performance-based cognitive function and (2) explore a broader spectrum of psychiatric symptoms and their association with performance-based versus self-reported cognitive function. Method: Individuals with supratentorial ischemic stroke performed neuropsychological examination 3 months after stroke. For primary analyses, composite scores for memory and attention/executive function were calculated based on selected neuropsychological tests, and the Hospital Anxiety and Depression Scale (HADS) was used. Psychiatric symptoms and self-reported cognitive function for secondary aims were assessed using the Symptom-Checklist-90 – Revised (SCL-90-R). Results: In a sample of 86 patients [mean (M) age: 64.6 ± 9.2; Mini-Mental State Examination (MMSE), 3–7 days post-stroke: M = 28.4 ± 1.7; National Institutes of Health Stroke Scale (NIHSS) after 3 months: M = 0.7 ± 1.6] depressive symptoms (HADS) were associated with poorer memory performance after controlling for age, sex, and education (p ≤ .01). In a subsample (n = 41; Age: M = 65.7 ± 8.1; MMSE: M = 28.4 ± 1.8; NIHSS: M = 1.0 ± 1.9), symptoms of phobic anxiety (SCL-90-R) were associated with poorer performance-based memory and attention/executive function, and symptoms of anxiety (SCL-90-R) with lower attention/executive function. Higher levels of self-reported cognitive difficulties were associated with higher scores in all psychiatric domains (p ≤ .05). Conclusion: Even in relatively well-functioning stroke patients, depressive symptoms are associated with poorer memory. The results also suggest that various psychiatric symptoms are more related to self-reported rather than to performance-based cognitive function. Screening for self-reported cognitive difficulties may not only help to identify patients with cognitive impairment, but also those who need psychological treatment.

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