Dataset Information

NCOG-11. COGNITIVE FUNCTIONS AND VARIANTS IN GENES ASSOCIATED WITH AGING AND INFLAMMATION IN BRAIN TUMOR PATIENTS

ABSTRACT: Abstract BACKGROUND Cognitive dysfunction is common in patients with brain tumors treated with radiotherapy (RT) and chemotherapy (CT). We reported previously that single nucleotide polymorphisms (SNPs) in the APOE, COMT and BDNF genes may influence cognitive outcome in this clinical population. In this study, we assessed whether additional genes with known associations with aging, Alzheimer’s disease and inflammation may contribute to cognitive dysfunction in brain tumor survivors. METHODS One hundred and fifty patients with brain tumors participated in the study: ninety had been treated with RT ± CT, fifty-seven had CT alone, and three had no therapy. All patients completed neuropsychological tests of attention, executive functions and memory, and provided a blood sample for genotyping. We used a Bayesian penalized multivariate regression approach to estimate the associations between the SNPs and cognitive outcome, adjusting for age, education, tumor location, treatment with RT ± CT, time since treatment completion, and APOE epsilon ?-4 allele. We quantified the strength of association between a SNP and a cognitive test score using a novel measure referred to as the posterior association summary (PAS) that takes value between 0 (= no association) and 1 (= very strong association). RESULTS Several SNPs previously reported in association with age-related cognitive decline and Alzheimer’s disease (PDE7A rs10808746, CD2AP rs9349407, ABCC1 rs8187858, APOE rs405697) and inflammation (IL-1A rs1800587, IL-1 rs1143634, IL-6 rs1474348) were strongly associated with tests of attention, executive functions and memory (PAS ? 0.95). Several additional SNPs that mapped to the ABCA7, CD33, COMT, IL-6, MS4A4E, PDE7A, PICALM, SERPINA3 and SORC1 genes were also associated with tests of attention and executive functions with PAS ? 0.90. CONCLUSION The findings provide new evidence that polymorphisms in genes associated with aging, Alzheimer’s disease and inflammation may be functionally relevant and influence cognitive outcome in patients with brain tumors.

SUBMITTER: Correa D

PROVIDER: S-EPMC5691884 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Project description:A fundamental set of cognitive abilities enable humans to efficiently process goal-relevant information, suppress irrelevant distractions, maintain information in working memory, and act flexibly in different behavioral contexts. Yet, studies of human cognition and their underlying neural mechanisms usually evaluate these cognitive constructs in silos, instead of comprehensively in-tandem within the same individual. Here, we developed a scalable, mobile platform, "BrainE" (short for Brain Engagement), to rapidly assay several essential aspects of cognition simultaneous with wireless electroencephalography (EEG) recordings. Using BrainE, we rapidly assessed five aspects of cognition including (1) selective attention, (2) response inhibition, (3) working memory, (4) flanker interference and (5) emotion interference processing, in 102 healthy young adults. We evaluated stimulus encoding in all tasks using the EEG neural recordings, and isolated the cortical sources of the spectrotemporal EEG dynamics. Additionally, we used BrainE in a two-visit study in 24 young adults to investigate the reliability of the neuro-cognitive data as well as its plasticity to transcranial magnetic stimulation (TMS). We found that stimulus encoding on multiple cognitive tasks could be rapidly assessed, identifying common as well as distinct task processes in both sensory and cognitive control brain regions. Event related synchronization (ERS) in the theta (3-7 Hz) and alpha (8-12 Hz) frequencies as well as event related desynchronization (ERD) in the beta frequencies (13-30 Hz) were distinctly observed in each task. The observed ERS/ERD effects were overall anticorrelated. The two-visit study confirmed high test-retest reliability for both cognitive and neural data, and neural responses showed specific TMS protocol driven modulation. We also show that the global cognitive neural responses are sensitive to mental health symptom self-reports. This first study with the BrainE platform showcases its utility in studying neuro-cognitive dynamics in a rapid and scalable fashion.

Project description:Background: Neuroscience lacks a reliable method of screening the early stages of dementia. Objective: To improve the diagnostics of age-related cognitive functions by developing insight into the proportionality of age-related changes in cognitive subdomains. Materials and Methods: We composed a battery of psychophysiological tests and collected an open-access psychophysiological outcomes of brain atrophy (POBA) dataset by testing individuals without dementia. To extend the utility of machine learning (ML) classification in cognitive studies, we proposed estimates of the disproportional changes in cognitive functions: an index of simple reaction time to decision-making time (ISD), ISD with the accuracy performance (ISDA), and an index of performance in simple and complex visual-motor reaction with account for accuracy (ISCA). Studying the distribution of the values of the indices over age allowed us to verify whether diverse cognitive functions decline equally throughout life or there is a divergence in age-related cognitive changes. Results: Unsupervised ML clustering shows that the optimal number of homogeneous age groups is four. The sample is segregated into the following age-groups: Adolescents ∈ [0, 20), Young adults ∈ [20, 40), Midlife adults ∈ [40, 60) and Older adults ≥60 year of age. For ISD, ISDA, and ISCA values, only the median of the Adolescents group is different from that of the other three age-groups sharing a similar distribution pattern (p > 0.01). After neurodevelopment and maturation, the indices preserve almost constant values with a slight trend toward functional decline. The reaction to a moving object (RMO) test results (RMO_mean) follow another tendency. The Midlife adults group's median significantly differs from the remaining three age subsamples (p < 0.01). No general trend in age-related changes of this dependent variable is observed. For all the data (ISD, ISDA, ISCA, and RMO_mean), Levene's test reveals no significant changes of the variances in age-groups (p > 0.05). Homoscedasticity also supports our assumption about a linear dependency between the observed features and age. Conclusion: In healthy brain aging, there are proportional age-related changes in the time estimates of information processing speed and inhibitory control in task switching. Future studies should test patients with dementia to determine whether the changes of the aforementioned indicators follow different patterns.

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NCOG-11. COGNITIVE FUNCTIONS AND VARIANTS IN GENES ASSOCIATED WITH AGING AND INFLAMMATION IN BRAIN TUMOR PATIENTS

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