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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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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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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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Brain Hemodynamic Intermediate Phenotype Links Vitamin B12 to Cognitive Profile of Healthy and Mild Cognitive Impaired Subjects.
Cecchetti, L, Lettieri, G, Handjaras, G, Leo, A, Ricciardi, E, Pietrini, P, Pellegrini, S, ,
Neural plasticity. 2019;:6874805
Abstract
Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0.05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0.0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype.
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Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)-study protocol for a randomized controlled trial.
Wirth, M, Schwarz, C, Benson, G, Horn, N, Buchert, R, Lange, C, Köbe, T, Hetzer, S, Maglione, M, Michael, E, et al
Alzheimer's research & therapy. 2019;(1):36
Abstract
BACKGROUND Given the global increase in the aging population and age-related diseases, the promotion of healthy aging is one of the most crucial public health issues. This trial aims to contribute to the establishment of effective approaches to promote cognitive and brain health in older individuals with subjective cognitive decline (SCD). Presence of SCD is known to increase the risk of objective cognitive decline and progression to dementia due to Alzheimer's disease. Therefore, it is our primary goal to determine whether spermidine supplementation has a positive impact on memory performance in this at-risk group, as compared with placebo. The secondary goal is to examine the effects of spermidine intake on other neuropsychological, behavioral, and physiological parameters. METHODS The SmartAge trial is a monocentric, randomized, double-blind, placebo-controlled phase IIb trial. The study will investigate 12 months of intervention with spermidine-based nutritional supplementation (target intervention) compared with 12 months of placebo intake (control intervention). We plan to recruit 100 cognitively normal older individuals with SCD from memory clinics, neurologists and general practitioners in private practice, and the general population. Participants will be allocated to one of the two study arms using blockwise randomization stratified by age and sex with a 1:1 allocation ratio. The primary outcome is the change in memory performance between baseline and post-intervention visits (12 months after baseline). Secondary outcomes include the change in memory performance from baseline to follow-up assessment (18 months after baseline), as well as changes in neurocognitive, behavioral, and physiological parameters (including blood and neuroimaging biomarkers), assessed at baseline and post-intervention. DISCUSSION The SmartAge trial aims to provide evidence of the impact of spermidine supplementation on memory performance in older individuals with SCD. In addition, we will identify possible neurophysiological mechanisms of action underlying the anticipated cognitive benefits. Overall, this trial will contribute to the establishment of nutrition intervention in the prevention of Alzheimer's disease. TRIAL REGISTRATION ClinicalTrials.gov, NCT03094546 . Registered 29 March 2017-retrospectively registered. PROTOCOL VERSION Based on EA1/250/16 version 1.5.
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Safety and feasibility of estrogen receptor-β targeted phytoSERM formulation for menopausal symptoms: phase 1b/2a randomized clinical trial.
Schneider, LS, Hernandez, G, Zhao, L, Franke, AA, Chen, YL, Pawluczyk, S, Mack, WJ, Brinton, RD
Menopause (New York, N.Y.). 2019;(8):874-884
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OBJECTIVE PhytoSERM is a formulation of genistein, daidzein, and S-equol that has an 83-fold selective affinity for estrogen receptor-β (ERβ); and may enhance neuron function and estrogenic mechanisms in the brain without having peripheral estrogenic activity. METHODS We conducted an overarching, two-stage, dose-ranging, double-blinded, randomized, placebo-controlled trial of 12 weeks duration comparing 50 and 100 mg/d of phytoSERM with placebo for noncognitively impaired, perimenopausal women aged 45 to 60, with intact uteri and ovaries, with at least one cognitive complaint, and one vasomotor-related symptom. Primary objectives were to assess safety and tolerability of a 50 and 100 mg daily dose; and, secondly, to evaluate potential indicators of efficacy on cognition and vasomotor symptoms over 4 and 12 weeks, and using an embedded, 4-week, 2-period, placebo-controlled crossover trial for a subset of participants. RESULTS Seventy-one women were randomized to treatment; 70 were evaluated at 4 weeks; 12 were entered into the crossover study; 5 did not complete 12 weeks. Reasons for discontinuation were withdrawal of consent (n = 1) and lost to follow-up (n = 4). Adverse events occurred in 16.7% (n = 4) placebo, 39.1% (n = 9) 50 mg/d, and 29.2% (n = 7) 100 mg/d treated participants; 85% were mild and none was severe. Vaginal bleeding occurred in 0, placebo; 1, 50 mg; and 3, 100 mg/d participants. CONCLUSIONS The phytoSERM formulation was well tolerated at 50 and 100 mg daily doses. Based on safety outcomes, vaginal bleeding at the 100 mg dose, and vasomotor symptoms and cognitive outcomes at 12 weeks, a daily dose of 50 mg was considered preferable for a phase 2 efficacy trial.
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Microbial functional change is linked with clinical outcomes after capsular fecal transplant in cirrhosis.
Bajaj, JS, Salzman, N, Acharya, C, Takei, H, Kakiyama, G, Fagan, A, White, MB, Gavis, EA, Holtz, ML, Hayward, M, et al
JCI insight. 2019;(24)
Abstract
BACKGROUNDHepatic encephalopathy (HE) is associated with poor outcomes. A prior randomized, pilot trial demonstrated safety after oral capsular fecal microbial transplant (FMT) in HE, with favorable changes in microbial composition and cognition. However, microbial functional changes are unclear. The aim of this study was to determine the effect of FMT on the gut-brain axis compared with placebo, using microbial function based on bile acids (BAs), inflammation (serum IL-6, LPS-binding protein [LBP]), and their association with EncephalApp.METHODSTwenty cirrhotic patients were randomized 1:1 into groups that received 1-time FMT capsules from a donor enriched in Lachnospiraceae and Ruminococcaceae or placebo capsules, with 5-month follow-up for safety outcomes. Stool microbiota and BA; serum IL-6, BA, and LBP; and EncephalApp were analyzed at baseline and 4 weeks after FMT/placebo. Correlation networks among microbiota, BAs, EncephalApp, IL-6, and LBP were performed before/after FMT.RESULTSFMT-assigned participants had 1 HE recurrence and 2 unrelated infections. Six placebo-assigned participants developed negative outcomes. FMT, but not placebo, was associated with reduced serum IL-6 and LBP and improved EncephalApp. FMT-assigned participants demonstrated higher deconjugation and secondary BA formation in feces and serum compared with baseline. No change was seen in placebo. Correlation networks showed greater complexity after FMT compared with baseline. Beneficial taxa, such as Ruminococcaceae, Verrucomicrobiaceae, and Lachnospiraceae, were correlated with cognitive improvement and decrease in inflammation after FMT. Fecal/serum secondary/primary ratios and PiCRUST secondary BA pathways did not increase in participants who developed poor outcomes.CONCLUSIONGut microbial function in cirrhosis is beneficially affected by capsular FMT, with improved inflammation and cognition. Lower secondary BAs in FMT recipients could select for participants who develop negative outcomes.TRIAL REGISTRATIONClinicaltrials.gov NCT03152188.FUNDINGNational Center for Advancing Translational Sciences NIH grant R21TR002024, VA Merit Review grant 2I0CX001076, the United Kingdom National Institute for Health Research Biomedical Facility at Imperial College London, the British Heart Foundation, Wellcome Trust, and King's College London.
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Imprinting methylation in SNRPN and MEST1 in adult blood predicts cognitive ability.
Lorgen-Ritchie, M, Murray, AD, Ferguson-Smith, AC, Richards, M, Horgan, GW, Phillips, LH, Hoad, G, Gall, I, Harrison, K, McNeill, G, et al
PloS one. 2019;(2):e0211799
Abstract
Genomic imprinting is important for normal brain development and aberrant imprinting has been associated with impaired cognition. We studied the imprinting status in selected imprints (H19, IGF2, SNRPN, PEG3, MEST1, NESPAS, KvDMR, IG-DMR and ZAC1) by pyrosequencing in blood samples from longitudinal cohorts born in 1936 (n = 485) and 1921 (n = 223), and anterior hippocampus, posterior hippocampus, periventricular white matter, and thalamus from brains donated to the Aberdeen Brain Bank (n = 4). MEST1 imprint methylation was related to childhood cognitive ability score (-0.416 95% CI -0.792,-0.041; p = 0.030), with the strongest effect evident in males (-0.929 95% CI -1.531,-0.326; p = 0.003). SNRPN imprint methylation was also related to childhood cognitive ability (+0.335 95%CI 0.008,0.663; p = 0.045). A significant association was also observed for SNRPN methylation and adult crystallised cognitive ability (+0.262 95%CI 0.007,0.517; p = 0.044). Further testing of significant findings in a second cohort from the same region, but born in 1921, resulted in similar effect sizes and greater significance when the cohorts were combined (MEST1; -0.371 95% CI -0.677,-0.065; p = 0.017; SNRPN; +0.361 95% CI 0.079,0.643; p = 0.012). For SNRPN and MEST1 and four other imprints the methylation levels in blood and in the five brain regions were similar. Methylation of the paternally expressed, maternally methylated genes SNRPN and MEST1 in adult blood was associated with cognitive ability in childhood. This is consistent with the known importance of the SNRPN containing 15q11-q13 and the MEST1 containing 7q31-34 regions in cognitive function. These findings, and their sex specific nature in MEST1, point to new mechanisms through which complex phenotypes such as cognitive ability may be inherited. These mechanisms are potentially relevant to both the heritable and non-heritable components of cognitive ability. The process of epigenetic imprinting-within SNRPN and MEST1 in particular-and the factors that influence it, are worthy of further study in relation to the determinants of cognitive ability.
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Effects of 90 Days of Resveratrol Supplementation on Cognitive Function in Elders: A Pilot Study.
Anton, SD, Ebner, N, Dzierzewski, JM, Zlatar, ZZ, Gurka, MJ, Dotson, VM, Kirton, J, Mankowski, RT, Marsiske, M, Manini, TM
Journal of alternative and complementary medicine (New York, N.Y.). 2018;(7):725-732
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OBJECTIVE The purpose of this trial was to study the effects of chronic resveratrol use on cognitive function in humans. DESIGN The authors conducted a double-blind, Phase IIa randomized, placebo-controlled trial to obtain preliminary estimates of the effects of resveratrol supplementation on cognitive function over a 90-day period in older adults. LOCATION University of Florida in Gainesville, FL. SUBJECTS Sedentary, overweight older adults (N = 32; age range: 65-93 years, M age = 73.34 years, SD age = 7.02 years). INTERVENTION Participants were randomized to one of three treatment groups (placebo, 300 mg/day resveratrol, 1000 mg/day resveratrol) for 90 days. OUTCOME MEASURES Cognitive function was assessed before and after treatment using a well-characterized test battery: Trail Making, Digits Forward and Backward, Erikson-Flanker, Controlled Oral Word Association, Hopkins Verbal Learning Test-Revised, and Task Switching. RESULTS Psychomotor speed improved on the Trail Making Test part A in participants taking 1000 mg/day of resveratrol compared with participants in both the 300 mg/day condition and the placebo condition (p = 0.02). CONCLUSION This pilot study suggests that 90 days of resveratrol supplementation at a dose of 1000/mg per day selectively improves psychomotor speed but does not significantly affect other domains of cognitive function in older adults. These findings provide modest support to further study the effects of resveratrol on cognitive function in older adults.
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Cognitively-Based Compassion Training (CBCT®) in Breast Cancer Survivors: A Randomized Clinical Trial Study.
Gonzalez-Hernandez, E, Romero, R, Campos, D, Burychka, D, Diego-Pedro, R, Baños, R, Negi, LT, Cebolla, A
Integrative cancer therapies. 2018;(3):684-696
Abstract
CONTEXT Breast cancer (BC) requires a significant psychological adaptation once treatment is finished. There is growing evidence of how compassion training enhances psychological and physical well-being, however, there are very few studies analyzing the efficacy of compassion-based Interventions on BC survivors. OBJECTIVE To study the efficacy of the Cognitively-Based Compassion Training (CBCT) protocol in a BC survivor sample on quality of life, psychological well-being, fear of cancer recurrence, self-compassion, and compassion domains and mindfulness facets. Furthermore, enrollment, adherence, and satisfaction with the intervention were also analyzed. METHODS A randomized clinical trial was designed. Participants (n = 56) were randomly assigned to CBCT (n = 28) or a treatment-as-usual control group (TAU; n = 28). Pre-post intervention and 6-month follow-up measures took place to evaluate health-related quality of life, psychological well-being; psychological stress, coping strategies, and triggering cognitions; self-compassion and compassion; and mindfulness in both intervention and wait-list groups. RESULTS Accrual of eligible participants was high (77%), and the drop-out rate was 16%. Attendance to CBCT sessions was high and practice off sessions exceeded expectations). CBCT was effective in diminishing stress caused by FCR, fostering self-kindness and common humanity, and increasing overall self-compassion scores, mindful observation, and acting with awareness skillsets. CONCLUSION CBCT could be considered a promising and potentially useful intervention to diminish stress caused by FCR and enhance self-kindness, common humanity, overall self-compassion, mindful observation, and acting with awareness skillsets. Nevertheless, future randomized trials are needed and a process of deeper cultural adaptation required.