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Concept: Neurocognitive

219

Observational studies in humans have found associations between overstimulation in infancy via excessive television viewing and subsequent deficits in cognition and attention. We developed and tested a mouse model of overstimulation whereby p10 mice were subjected to audio (70 db) and visual stimulation (flashing lights) for six hours per day for a total of 42 days. 10 days later cognition and behavior were tested using the following tests: Light Dark Latency, Elevated Plus Maze, Novel Object Recognition, and Barnes Maze. In all tests, overstimulated mice performed significantly worse compared to controls suggesting increased activity and risk taking, diminished short term memory, and decreased cognitive function. These findings suggest that excessive non-normative stimulation during critical periods of brain development can have demonstrable untoward effects on subsequent neurocognitive function.

Concepts: Brain, Cognitive neuroscience, Cognitive psychology, Behaviorism, Memory, Neurocognitive, Cognition, Psychology

175

Recent reports show that fewer adolescents believe that regular cannabis use is harmful to health. Concomitantly, adolescents are initiating cannabis use at younger ages, and more adolescents are using cannabis on a daily basis. The purpose of the present study was to test the association between persistent cannabis use and neuropsychological decline and determine whether decline is concentrated among adolescent-onset cannabis users. Participants were members of the Dunedin Study, a prospective study of a birth cohort of 1,037 individuals followed from birth (1972/1973) to age 38 y. Cannabis use was ascertained in interviews at ages 18, 21, 26, 32, and 38 y. Neuropsychological testing was conducted at age 13 y, before initiation of cannabis use, and again at age 38 y, after a pattern of persistent cannabis use had developed. Persistent cannabis use was associated with neuropsychological decline broadly across domains of functioning, even after controlling for years of education. Informants also reported noticing more cognitive problems for persistent cannabis users. Impairment was concentrated among adolescent-onset cannabis users, with more persistent use associated with greater decline. Further, cessation of cannabis use did not fully restore neuropsychological functioning among adolescent-onset cannabis users. Findings are suggestive of a neurotoxic effect of cannabis on the adolescent brain and highlight the importance of prevention and policy efforts targeting adolescents.

Concepts: Neuropsychology, The Adolescents, Cohort study, Neuropsychological test, Initiation, Age, Neurocognitive, Adolescence

151

The aim of this research was to study semantic abilities and their loss in mild cognitive impairment (MCI) and in dementia, while analyzing efficiency in the use of associative relations, within verbal and visuoperceptual modalities. Participants were split into 4 groups: 19 participants with amnestic MCI, 16 patients with mild Alzheimer disease (AD), 20 patients with moderate AD, and 20 healthy controls (HCs). All participants performed standardized neuropsychological tests and experimental (naming and semantic associations) tasks to evaluate verbal and visuoperceptual semantic abilities. We analyzed 4 associative relations (part/whole, function, superordinate, and contiguity) in both verbal and visuoperceptual code. Our results suggest a progressive impairment in semantic categorization knowledge, with worse performance in the AD groups relative to the MCI and HC groups. Our data show a different pattern in the 4 associative relations and the involvement of associative semantic relations already in the early stage of disease, as well as a different pattern of deterioration between verbal and visuoperceptual modalities. Our data indicate that the visuoperceptual semantic network appears to be less deteriorated than the verbal network in AD. The verbal semantic network may be more sensitive in detecting patients at an early stage of the disease.

Concepts: Caregiving and dementia, Donepezil, Semantics, Neurocognitive, Dementia, Semantic memory, Mild cognitive impairment, Alzheimer's disease

74

Chocolate and cocoa flavanols have been associated with improvements in a range of health complaints dating from ancient times, and has established cardiovascular benefits. Less is known about the effects of chocolate on neurocognition and behavior. The aim of this study was to investigate whether chocolate intake was associated with cognitive function, with adjustment for cardiovascular, lifestyle and dietary factors. Cross-sectional analyses were undertaken on 968 community-dwelling participants, aged 23-98 years, from the Maine-Syracuse Longitudinal Study (MSLS). Habitual chocolate intake was related to cognitive performance, measured with an extensive battery of neuropsychological tests. More frequent chocolate consumption was significantly associated with better performance on the Global Composite score, Visual-Spatial Memory and Organization, Working Memory, Scanning and Tracking, Abstract Reasoning, and the Mini-Mental State Examination. With the exception of Working Memory, these relations were not attenuated with statistical control for cardiovascular, lifestyle and dietary factors. Prospective analyses revealed no association between cognitive function and chocolate intake measured up to 18 years later. Further intervention trials and longitudinal studies are needed to explore relations between chocolate, cocoa flavanols and cognition, and the underlying causal mechanisms.

Concepts: Longitudinal study, Cognitive neuroscience, Sociology, Causality, Cognitive psychology, Neurocognitive, Cognition, Psychology

51

Shift work has been proposed to promote cognitive disturbances in humans; however, conflicting evidence is also present. By using data from 7143 middle-aged and elderly humans (45-75 years) who participated in the Swedish EpiHealth cohort study, the present analysis sought to investigate whether self-reported shift work history would be associated with performance on the trail making test (TMT). The TMT has been proposed to be a useful neuropsychological tool to evaluate humans' executive cognitive function, which is known to decrease with age. After adjustment for potential confounders (e.g., age, education, and sleep duration), it was observed that current and recent former shift workers (worked shifts during the past 5 years) performed worse on the TMT than nonshift workers. In contrast, performance on the TMT did not differ between past shift workers (off from shift work for more than 5 years) and nonshift workers. Collectively, our results indicate that shift work history is linked to poorer performance on the TMT in a cohort of middle-aged and elderly humans.

Concepts: Neurocognitive, Present, Cognition, Knowledge, Past, Psychology, Time, Shift work

48

Alzheimer’s disease is one of the most significant healthcare problems nationally and globally. Recently, the first description of the reversal of cognitive decline in patients with early Alzheimer’s disease or its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment), was published [1]. The therapeutic approach used was programmatic and personalized rather than monotherapeutic and invariant, and was dubbed metabolic enhancement for neurodegeneration (MEND). Patients who had had to discontinue work were able to return to work, and those struggling at work were able to improve their performance. The patients, their spouses, and their co-workers all reported clear improvements. Here we report the results from quantitative MRI and neuropsychological testing in ten patients with cognitive decline, nine ApoE4+ (five homozygous and four heterozygous) and one ApoE4-, who were treated with the MEND protocol for 5-24 months. The magnitude of the improvement is unprecedented, providing additional objective evidence that this programmatic approach to cognitive decline is highly effective. These results have far-reaching implications for the treatment of Alzheimer’s disease, MCI, and SCI; for personalized programs that may enhance pharmaceutical efficacy; and for personal identification of ApoE genotype.

Concepts: Neurocognitive, Mild cognitive impairment, Better, Zygosity, Medicine, Improve, Alzheimer's disease, Apolipoprotein E

44

Hearing impairment (HI) is prevalent, is modifiable, and has been associated with cognitive decline. We tested the hypothesis that audiometric HI measured in 2013 is associated with poorer cognitive function in 253 men and women from Washington County, Maryland (mean age = 76.9 years) in a pilot study carried out within the Atherosclerosis Risk in Communities Neurocognitive Study. Three cognitive tests were administered in 1990-1992, 1996-1998, and 2013, and a full neuropsychological battery was administered in 2013. Multivariable-adjusted differences in standardized cognitive scores (cross-sectional analysis) and trajectories of 20-year change (longitudinal analysis) were modeled using linear regression and generalized estimating equations, respectively. Hearing thresholds for pure tone frequencies of 0.5-4 kHz were averaged to obtain a pure tone average in the better-hearing ear. Hearing was categorized as follows: ≤25 dB, no HI; 26-40 dB, mild HI; and >40 dB, moderate/severe HI. Comparing participants with moderate/severe HI to participants with no HI, 20-year rates of decline in memory and global function differed by -0.47 standard deviations (P = 0.02) and -0.29 standard deviations (P = 0.02), respectively. Estimated declines were greatest in participants who did not wear a hearing aid. These findings add to the limited literature on cognitive impairments associated with HI, and they support future research on whether HI treatment may reduce risk of cognitive decline.

Concepts: Arithmetic mean, Regression analysis, Statistics, Cognitive neuroscience, Sound, Neurocognitive, Standard deviation, Cognition

40

Background Previously, we reported that there was no significant difference at 30 days in the rate of a primary composite outcome of death, myocardial infarction, stroke, or new renal failure requiring dialysis between patients who underwent coronary-artery bypass grafting (CABG) performed with a beating-heart technique (off-pump) and those who underwent CABG performed with cardiopulmonary bypass (on-pump). We now report results on quality of life and cognitive function and on clinical outcomes at 1 year. Methods We enrolled 4752 patients with coronary artery disease who were scheduled to undergo CABG and randomly assigned them to undergo the procedure off-pump or on-pump. Patients were enrolled at 79 centers in 19 countries. We assessed quality of life and cognitive function at discharge, at 30 days, and at 1 year and clinical outcomes at 1 year. Results At 1 year, there was no significant difference in the rate of the primary composite outcome between off-pump and on-pump CABG (12.1% and 13.3%, respectively; hazard ratio with off-pump CABG, 0.91; 95% confidence interval [CI], 0.77 to 1.07; P=0.24). The rate of the primary outcome was also similar in the two groups in the period between 31 days and 1 year (hazard ratio, 0.79; 95% CI, 0.55 to 1.13; P=0.19). The rate of repeat coronary revascularization at 1 year was 1.4% in the off-pump group and 0.8% in the on-pump group (hazard ratio, 1.66; 95% CI, 0.95 to 2.89; P=0.07). There were no significant differences between the two groups at 1 year in measures of quality of life or neurocognitive function. Conclusions At 1 year after CABG, there was no significant difference between off-pump and on-pump CABG with respect to the primary composite outcome, the rate of repeat coronary revascularization, quality of life, or neurocognitive function. (Funded by the Canadian Institutes of Health Research; CORONARY ClinicalTrials.gov number, NCT00463294 .).

Concepts: Neurocognitive, Atheroma, Artery, Angina pectoris, Myocardial infarction, Atherosclerosis, Coronary artery bypass surgery, Coronary artery disease

38

Stimulants and caffeine have been proposed for cognitive enhancement by healthy subjects. This study investigated whether performance in chess - a competitive mind game requiring highly complex cognitive skills - can be enhanced by methylphenidate, modafinil or caffeine. In a phase IV, randomized, double-blind, placebo-controlled trial, 39 male chess players received 2×200mg modafinil, 2×20mg methylphenidate, and 2×200mg caffeine or placebo in a 4×4 crossover design. They played twenty 15-minute games during two sessions against a chess program (Fritz 12; adapted to players' strength) and completed several neuropsychological tests. Marked substance effects were observed since all three substances significantly increased average reflection time per game compared to placebo resulting in a significantly increased number of games lost on time with all three treatments. Treatment effects on chess performance were not seen if all games (n=3059) were analysed. Only when controlling for game duration as well as when excluding those games lost on time, both modafinil and methylphenidate enhanced chess performance as demonstrated by significantly higher scores in the remaining 2876 games compared to placebo. In conjunction with results from neuropsychological testing we conclude that modifying effects of stimulants on complex cognitive tasks may in particular result from more reflective decision making processes. When not under time pressure, such effects may result in enhanced performance. Yet, under time constraints more reflective decision making may not improve or even have detrimental effects on complex task performance.

Concepts: Clinical trial, Neuropsychological test, Chess, Neurocognitive, Decision making, Neuropsychological assessment, Randomized controlled trial, Cognition

36

Auditory verbal hallucinations have attracted a great deal of scientific interest, but despite the fact that they are fundamentally a social experience-in essence, a form of hallucinated communication-current theories remain firmly rooted in an individualistic account and have largely avoided engagement with social cognition. Nevertheless, there is mounting evidence for the role of social cognitive and social neurocognitive processes in auditory verbal hallucinations, and, consequently, it is proposed that problems with the internalisation of social models may be key to the experience.

Concepts: Fact, Theory, Face perception, Neurocognitive, Sociology, Science, Psychology, Cognition