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1.
Changes in polyphenol serum levels and cognitive performance after dietary supplementation with Concord grape juice in veterans with Gulf War Illness.
Van Doren, WW, Iqbal, UH, Helmer, DA, Litke, DR, Simon, JE, Wu, Q, Zhao, D, Yin, Z, Ho, L, Osinubi, O, et al
Life sciences. 2022;:119797
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Abstract
AIMS: We investigated whether the consumption of Concord grape juice (CGJ) was associated with increased bioavailability of serum metabolites and their potential impact on cognitive performance in Veterans with Gulf War Illness (GWI). MAIN METHODS Twenty-six veterans were selected from a cohort of 36 enrolled in a 24-week randomized, double-blind, Phase I/IIA clinical trial exploring whether the consumption of Concord grape juice (CGJ) was tolerable and safe in Veterans with GWI and improved cognitive function and fatigue. These 26 veterans were selected based on their completion of the entire 24-week protocol and documented adherence to the study beverage ≥80%. Differences in serum metabolite levels between CGJ and placebo at midpoint and endpoint were evaluated using two-way repeated measures ANOVA with post hoc Sidak's multiple comparison test. Bivariate correlations to assess for possible relationships between change in serum metabolite levels and change in cognitive function as measured by the Halstead Category Test-Russell Revised Version (RCAT) were also conducted. KEY FINDINGS Seventy-six metabolites were identified and quantified in this study, with three (cyanidin-glucuronide, me-cyanidin-glucuronide, and me-malvidin-glucuronide) found to be significantly higher (p < 0.05) in the CGJ group compared to placebo at 24 weeks. Significant associations between changes in cognitive function and changes in serum levels of epicatechin-sulphate (r = 0.48, p = 0.01) and petunidin-glucuronide (r = 0.53, p < 0.01) from baseline to 24 weeks were also observed. SIGNIFICANCE Our data suggest that dietary supplementation with CGJ is associated with increased bioavailability of specific phenolic metabolites, some of which may be correlated with cognitive performance.
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The effects of psilocybin on cognitive and emotional functions in healthy participants: Results from a phase 1, randomised, placebo-controlled trial involving simultaneous psilocybin administration and preparation.
Rucker, JJ, Marwood, L, Ajantaival, RJ, Bird, C, Eriksson, H, Harrison, J, Lennard-Jones, M, Mistry, S, Saldarini, F, Stansfield, S, et al
Journal of psychopharmacology (Oxford, England). 2022;(1):114-125
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Abstract
BACKGROUND Psilocybin, a psychoactive serotonin receptor partial agonist, has been reported to acutely reduce clinical symptoms of depressive disorders. Psilocybin's effects on cognitive function have not been widely or systematically studied. AIM: The aim of this study was to explore the safety of simultaneous administration of psilocybin to healthy participants in the largest randomised controlled trial of psilocybin to date. Primary and secondary endpoints assessed the short- and longer-term change in cognitive functioning, as assessed by a Cambridge Neuropsychological Test Automated Battery (CANTAB) Panel, and emotional processing scales. Safety was assessed via endpoints which included cognitive function, assessed by CANTAB global composite score, and treatment-emergent adverse event (TEAE) monitoring. METHODS In this phase 1, randomised, double-blind, placebo-controlled study, healthy participants (n = 89; mean age 36.1 years; 41 females, 48 males) were randomised to receive a single oral dose of 10 or 25 mg psilocybin, or placebo, administered simultaneously to up to six participants, with one-to-one psychological support - each participant having an assigned, dedicated therapist available throughout the session. RESULTS In total, 511 TEAEs were reported, with a median duration of 1.0 day; 67% of all TEAEs started and resolved on the day of administration. There were no serious TEAEs, and none led to study withdrawal. There were no clinically relevant between-group differences in CANTAB global composite score, CANTAB cognitive domain scores, or emotional processing scale scores. CONCLUSIONS These results indicate that 10 mg and 25 mg doses of psilocybin were generally well tolerated when given to up to six participants simultaneously and did not have any detrimental short- or long-term effects on cognitive functioning or emotional processing. CLINICAL TRIAL REGISTRATION EudraCT (https://www.clinicaltrialsregister.eu/) number: 2018-000978-30.
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Cumulative life course adversity, mental health, and cognition in the UK biobank.
Künzi, M, Gheorghe, DA, Kliegel, M, Ballhausen, N, Gallacher, J, Bauermeister, S
Scientific reports. 2022;(1):14700
Abstract
The association between adversity and cognition varies according to the specific adversity, when the adversity was experienced, and the cognitive domains investigated. Disentangling the effect of adversity and the underlying mechanistic pathway is therefore difficult. The association between adversity (i.e., maltreatment) accumulated over the life course and cognitive flexibility, as well as two potential mediators (i.e., intra-individual variability in reaction time and depression) of this association, were investigated. Data stem from the baseline population of the UK Biobank study (N = 73,489, Mdnage = 56, SDage = 7.628, 55.740% of women). Cumulative life course adversity (specifically maltreatment) was measured with items based on the Childhood Trauma Questionnaire (CTS-5) and items adapted from the British Crime Survey. Depression was assessed with the Patient Health Questionnaire-9 (PHQ-9). Intra-individual variability in reaction time was measured with a reaction time test "snap game" and the Trail Making Test A and B were used as a measure of cognitive flexibility. A path analysis was performed on these data. Higher cumulative adverse experiences were associated with lower performance in cognitive flexibility (β = .016, p < .001, 95% CI [0.009, 0.024]), and this effect was partly mediated by the level of depression (22.727% of the total effect of cumulative life course adversity on cognitive flexibility was mediated by depression (β = .005, p < .001, 95% CI [0.004, 0.007])). No association between cumulative life course adverse experiences and intra-individual variability in reaction time was found, nor was any indirect association between cumulative life course adversity and performance in cognitive flexibility via intra-individual variability in reaction time. The association between cumulative life course adversity, depression, and performance in cognitive flexibility has been highlighted. In contrast, no indirect effect between cumulative life course adversity and performance in cognitive flexibility via intra-individual variability in reaction time was found, suggesting that it is not a potential mechanism underlying the association between cumulative life course adversity and executive function.
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Effects of dual-task interference on swallowing in healthy aging adults.
Krishnamurthy, R, Philip, R, Balasubramanium, RK, Rangarathnam, B
PloS one. 2021;(6):e0253550
Abstract
A wide body of literature has demonstrated that the neural representation of healthy swallowing is mostly bilateral, with one hemisphere dominant over the other. While several studies have demonstrated the presence of laterality for swallowing related functions among young adults, the data on older adults are still growing. The purpose of this paper is to investigate potential changes in hemispheric dominance in healthy aging adults for swallowing related tasks using a behavioral dual-task paradigm. A modified dual-task paradigm was designed to investigate the potential reduction in hemispherical specialization for swallowing function. Eighty healthy right-handed participants in the study were divided into two groups [Group 1: young adults (18-40 years) and Group 2: older adults (65 and above)]. All the participants performed a timed water swallow test at baseline and with two interference conditions (silent word repetition, and facial recognition). The results of the study revealed the following 1) a statistically significant effect of age on swallow performance; 2) statistically significant effect of each of the interference tasks on two of the swallow measures (VPS and VPT) in younger adults; and 3) no significant effect of the interference tasks on the swallowing performance of older adults. These findings suggest that aging substantially affects swallowing in older individuals, and this potentially accompanies a reduction in the hemispheric specialization for swallowing related tasks.
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Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression.
Markun, S, Gravestock, I, Jäger, L, Rosemann, T, Pichierri, G, Burgstaller, JM
Nutrients. 2021;(3)
Abstract
Vitamin B12 is often used to improve cognitive function, depressive symptoms, and fatigue. In most cases, such complaints are not associated with overt vitamin B12 deficiency or advanced neurological disorders and the effectiveness of vitamin B12 supplementation in such cases is uncertain. The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to assess the effects of vitamin B12 alone (B12 alone), in addition to vitamin B12 and folic acid with or without vitamin B6 (B complex) on cognitive function, depressive symptoms, and idiopathic fatigue in patients without advanced neurological disorders or overt vitamin B12 deficiency. Medline, Embase, PsycInfo, Cochrane Library, and Scopus were searched. A total of 16 RCTs with 6276 participants were included. Regarding cognitive function outcomes, we found no evidence for an effect of B12 alone or B complex supplementation on any subdomain of cognitive function outcomes. Further, meta-regression showed no significant associations of treatment effects with any of the potential predictors. We also found no overall effect of vitamin supplementation on measures of depression. Further, only one study reported effects on idiopathic fatigue, and therefore, no analysis was possible. Vitamin B12 supplementation is likely ineffective for improving cognitive function and depressive symptoms in patients without advanced neurological disorders.
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Effect of Early High-Dose Vitamin D3 Repletion on Cognitive Outcomes in Critically Ill Adults.
Han, JH, Ginde, AA, Brown, SM, Baughman, A, Collar, EM, Ely, EW, Gong, MN, Hope, AA, Hou, PC, Hough, CL, et al
Chest. 2021;(3):909-918
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Abstract
BACKGROUND Long-term cognitive impairment frequently occurs after critical illness; no treatments are known to improve long-term cognition. RESEARCH QUESTION Does a single high-dose (540,000 International Units) enteral treatment of vitamin D3 given shortly after hospital admission in critically ill patients who are vitamin D deficient improve long-term global cognition or executive function? STUDY DESIGN AND METHODS This study evaluated long-term cognitive outcomes among patients enrolled in a multicenter, blinded, randomized clinical trial comparing vitamin D3 treatment vs placebo in critically ill adults with vitamin D deficiency. Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Executive function was measured with a composite score derived from three Delis-Kaplan Executive Function System subscales. Outcomes were assessed at a median of 443 days (interquartile range, 390-482 days) after randomization and were compared using multivariate proportional odds regression. Adjusted ORs of > 1.0 would indicate better outcomes in the vitamin D3 group compared with the placebo group. RESULTS Ninety-five patients were enrolled, including 47 patients randomized to vitamin D3 treatment and 48 patients randomized to placebo. The adjusted median RBANS score at follow-up was 79.6 (95% CI, 73.0-84.0) in the vitamin D3 group and 82.1 (95% CI, 74.7-84.6) in the placebo group (adjusted OR, 0.83; 95% CI, 0.50-1.38). The adjusted median executive function composite scores were 8.1 (95% CI, 6.8-9.0) and 8.7 (95% CI, 7.4-9.3), respectively (adjusted OR, 0.72; 95% CI, 0.36-1.42). INTERPRETATION In vitamin D-deficient, critically-ill adults, a large dose of enteral vitamin D3 did not improve long-term global cognition or executive function. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT03733418; URL: www.clinicaltrials.gov.
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Dose-Response of Paraxanthine on Cognitive Function: A Double Blind, Placebo Controlled, Crossover Trial.
Xing, D, Yoo, C, Gonzalez, D, Jenkins, V, Nottingham, K, Dickerson, B, Leonard, M, Ko, J, Faries, M, Kephart, W, et al
Nutrients. 2021;(12)
Abstract
UNLABELLED Paraxanthine (PXN) is a metabolite of caffeine that has recently been reported to enhance cognition at a dose of 200 mg. OBJECTIVE To determine the acute and short-term (7-day) effects of varying doses of PXN on cognitive function and side effects. METHODS In a double blind, placebo-controlled, crossover, and counterbalanced manner, 12 healthy male and female volunteers (22.7 ± 4 years, 165 ± 7 cm, 66.5 ± 11 kg, 24.4 ± 3 kg/m2) ingested 200 mg of a placebo (PLA), 50 mg of PXN (ENFINITY™, Ingenious Ingredients, L.P.) + 150 mg PLA, 100 mg PXN + 100 mg PLA, or 200 mg of PXN. With each treatment experiment, participants completed side effect questionnaires and donated a fasting blood sample. Participants then performed a series of tests assessing cognition, executive function, memory, and reaction time. Participants then ingested one capsule of PLA or PXN treatments. Participants then completed side effects and cognitive function tests after 1, 2, 3, 4, 5, and 6 h of treatment ingestion. Participants continued ingesting one dose of the assigned treatment daily for 6-days and returned to the lab on day 7 to donate a fasting blood sample, assess side effects, and perform cognitive function tests. Participants repeated the experiment while ingesting remaining treatments in a counterbalanced manner after at least a 7-day washout period until all treatments were assessed. RESULTS The Sternberg Task Test (STT) 4-Letter Length Present Reaction Time tended to differ among groups (p = 0.06). Assessment of mean changes from baseline with 95% CI's revealed several significant differences among treatments in Berg-Wisconsin Card Sorting Correct Responses, Preservative Errors (PEBL), and Preservative Errors (PAR Rules). There was also evidence of significant differences among treatments in the Go/No-Go Task tests in Mean Accuracy as well as several time points of increasing complexity among STT variables. Finally, there was evidence from Psychomotor Vigilance Task Test assessment that response time improved over the series of 20 trials assessed as well as during the 6-h experiment in the PXN treatment. Acute and short-term benefits compared to PLA were seen with each dose studied but more consistent effects appeared to be at 100 mg and 200 mg doses. No significant differences were observed among treatments in clinical chemistry panels or the frequency or severity of reported side effects. Results provide evidence that acute ingestion of 100 mg and 200 mg of PXN may affect some measures of cognition, memory, reasoning, and response time as well as help sustain attention. Additionally, that acute and daily ingestion of PXN for 7 days is not associated with any clinically significant side effects. CONCLUSIONS PXN may serve as an effective nootropic agent at doses as low as 50 mg.
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Facility-based and home-based multidomain interventions including cognitive training, exercise, diet, vascular risk management, and motivation for older adults: a randomized controlled feasibility trial.
Moon, SY, Hong, CH, Jeong, JH, Park, YK, Na, HR, Song, HS, Kim, BC, Park, KW, Park, HK, Choi, M, et al
Aging. 2021;(12):15898-15916
Abstract
We aimed to evaluate the feasibility of multidomain intervention (MI) tailored to the Korean context. In an outcome assessor-blinded, randomized controlled trial, participants without dementia and with one or more modifiable dementia risk factors, aged 60-79 years, were randomly assigned to the facility-based MI (FMI; n=51), the home-based MI (HMI; n=51), or the control group receiving general health advice (n=50). The 24-week intervention comprised vascular risk management, cognitive training, social activity, physical exercise, nutrition guidance, and motivational enhancement. The FMI participants performed all intervention programs at a facility three times a week. The HMI participants performed some programs at a facility once every 1-2 weeks and performed others at home. The primary outcome was feasibility measured through retention, adherence, and at least no differences from the control group in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). In the FMI and HMI groups, the retention rates were 88.2% and 96.1%, and adherence to the intervention was 94.5% and 96.8%, respectively. The RBANS total scale index score improved significantly in the FMI (5.46 ± 7.50, P = 0.004) and HMI (5.50 ± 8.14, P = 0.004) groups compared to the control group (-0.74 ± 11.51). The FMI and HMI are feasible and there are indicators of efficacy.
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The Hunger Games: Homeostatic State-Dependent Fluctuations in Disinhibition Measured with a Novel Gamified Test Battery.
Voigt, K, Giddens, E, Stark, R, Frisch, E, Moskovsky, N, Kakoschke, N, Stout, JC, Bellgrove, MA, Andrews, ZB, Verdejo-Garcia, A
Nutrients. 2021;(6)
Abstract
Food homeostatic states (hunger and satiety) influence the cognitive systems regulating impulsive responses, but the direction and specific mechanisms involved in this effect remain elusive. We examined how fasting, and satiety, affect cognitive mechanisms underpinning disinhibition using a novel framework and a gamified test-battery. Thirty-four participants completed the test-battery measuring three cognitive facets of disinhibition: attentional control, information gathering and monitoring of feedback, across two experimental sessions: one after overnight fasting and another after a standardised meal. Homeostatic state was assessed using subjective self-reports and biological markers (i.e., blood-derived liver-expressed antimicrobial protein 2 (LEAP-2), insulin and leptin). We found that participants who experienced greater subjective hunger during the satiety session were more impulsive in the information gathering task; results were not confounded by changes in mood or anxiety. Homeostatic state did not significantly influence disinhibition mechanisms linked to attentional control or feedback monitoring. However, we found a significant interaction between homeostatic state and LEAP-2 on attentional control, with higher LEAP-2 associated with faster reaction times in the fasted condition only. Our findings indicate lingering hunger after eating increases impulsive behaviour via reduced information gathering. These findings identify a novel mechanism that may underpin the tendency to overeat and/or engage in broader impulsive behaviours.
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Factors determining cognitive, motor and language scores in low birth weight infants from North India.
Upadhyay, RP, Taneja, S, Ranjitkar, S, Mazumder, S, Bhandari, N, Dua, T, Shrestha, L, Strand, TA
PloS one. 2021;(5):e0251387
Abstract
BACKGROUND Children born with low birth weight (LBW) tend to have lower neurodevelopmental scores compared to term normal birth weight children. It is important to determine factors that influence neurodevelopment in these low birth weight children especially in the first 2-3 years of life that represents a period of substantial brain development. METHODS This secondary data analysis was conducted using data from LBW infants enrolled soon after birth in an individually randomized controlled trial (RCT) and followed up till end of 1st year. Neurodevelopmental assessment was done at 12 months of corrected age by trained psychologists using Bayley Scales of Infant and Toddler Development 3rd edition (Bayley-III). Factors influencing cognitive, motor and language scores were determined using multivariable linear regression model. RESULTS Linear growth (i.e., length for age z score, LAZ) [cognitive: Standardized ẞ-coefficient = 2.19, 95% CI; 1.29, 3.10; motor: 2.41, 95% CI; 1.59, 3.23; language: 1.37, 95% CI; 0.70, 2.04], stimulation at home [cognitive: 0.21, 95% CI; 0.15, 0.27; motor: 0.12, 95% CI; 0.07, 0.17; language: 0.21, 95% CI; 0.16, 0.25] and number of diarrhoeal episodes [cognitive: -2.87, 95% CI; -4.34, -1.39; motor: -2.62, 95% CI; -3.93, -1.29; language: -2.25, 95% CI; -3.32, -1.17] influenced the composite scores in all three domains i.e., cognitive, language and motor. While increase in LAZ score and stimulation led to increase in composite scores; an increase in number of diarrhoeal episodes was associated with decrease in scores. Weight for height z scores (WHZ) were associated with motor and language but not with cognitive scores. Additionally, a negative association of birth order with cognitive and language scores was noted. CONCLUSIONS The findings indicate the possible importance of promoting nutrition and preventing diarrhoea as well as ensuring optimal stimulation and nurturance at home for enhancing child development in LBW infants.