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Perilla seed oil in combination with nobiletin-rich ponkan powder enhances cognitive function in healthy elderly Japanese individuals: a possible supplement for brain health in the elderly.
Hashimoto, M, Matsuzaki, K, Maruyama, K, Hossain, S, Sumiyoshi, E, Wakatsuki, H, Kato, S, Ohno, M, Tanabe, Y, Kuroda, Y, et al
Food & function. 2022;(5):2768-2781
Abstract
Perilla (Perilla frutescens) seed oil (PO), rich in α-linolenic acid (ALA), can improve cognitive function in healthy elderly Japanese people. Here, supplements containing either PO alone or PO with nobiletin-rich air-dried immature ponkan powder were examined for their effects on cognitive function in 49 healthy elderly Japanese individuals. Patients were enrolled in a 12-month randomized, double-blind, parallel-armed study. Randomized participants in the PO group received soft gelatin capsules containing 1.47 mL (0.88 g of ALA) of PO daily, and those in the PO + ponkan powder (POPP) group received soft gelatin capsules containing both 1.47 mL of PO and 1.12 g ponkan powder (2.91 mg of nobiletin) daily. At the end of intervention, the POPP group showed significantly higher cognitive index scores than the PO group. The pro-cognitive effects of POPP treatment were accompanied by increases in ALA and docosahexaenoic acid levels in red blood cell plasma membranes, serum brain-derived neurotropic factor (BDNF) levels, and biological antioxidant potential. We demonstrate that 12-month intervention with POPP enhances serum BDNF and antioxidant potential, and may improve age-related cognitive impairment in healthy elderly people by increasing red blood cell ω-3 fatty acid levels. Clinical Trial Registry, UMIN000040863.
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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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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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Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-β-Related Biomarkers in Older Adults with Mild Cognitive Impairment by a Randomized, Double Blind, Placebo-Controlled Trial.
Bai, D, Fan, J, Li, M, Dong, C, Gao, Y, Fu, M, Huang, G, Liu, H
Journal of Alzheimer's disease : JAD. 2021;(1):155-167
Abstract
BACKGROUND The neuroprotective benefits of combined folic acid and docosahexaenoic acid (DHA) on cognitive function in mild cognitive impairment (MCI) patients are suggested but unconfirmed. OBJECTIVE To explore the effects of 6-month folic acid + DHA on cognitive function in patients with MCI. METHODS Our randomized controlled trial (trial number ChiCTR-IOR-16008351) was conducted in Tianjin, China. We divided 160 MCI patients aged > 60 years into four regimen groups randomly: folic acid (0.8 mg/day) + DHA (800 mg/day), folic acid (0.8 mg/day), DHA (800 mg/day), and placebo, for 6 months. Cognitive function and blood amyloid-β peptide (Aβ) biomarker levels were measured at baseline and 6 months. Cognitive function was also measured at 12 months. RESULTS A total of 138 patients completed this trial. Folic acid improved the full-scale intelligence quotient (FSIQ), arithmetic, and picture complement scores; DHA improved the FSIQ, information, arithmetic, and digit span scores; folic acid + DHA improved the arithmetic (difference 1.67, 95% CI 1.02 to 2.31) and digital span (1.33, 0.24 to 2.43) scores compared to placebo. At 12 months, all scores declined in the intervention groups. Folic acid and folic acid + DHA increased blood folate (folic acid + DHA: 7.70, 3.81 to 11.59) and S-adenosylmethionine (23.93, 1.86 to 46.00) levels and reduced homocysteine levels (-6.51, -10.57 to -2.45) compared to placebo. DHA lower the Aβ40 levels (-40.57, -79.79 to -1.35) compared to placebo (p < 0.05), and folic acid + DHA reduced the Aβ42 (-95.59, -150.76 to -40.43) and Aβ40 levels (-45.75, -84.67 to -6.84) more than DHA (p < 0.05). CONCLUSION Folic acid and DHA improve cognitive function and reduce blood Aβ production in MCI patients. Combination therapy may be more beneficial in reducing blood Aβ-related biomarkers.
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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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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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Effect of Advanced Glycation End Products on Cognition in Older Adults with Type 2 Diabetes: Results from a Pilot Clinical Trial.
Lotan, R, Ganmore, I, Livny, A, Itzhaki, N, Waserman, M, Shelly, S, Zacharia, M, Moshier, E, Uribarri, J, Beisswenger, P, et al
Journal of Alzheimer's disease : JAD. 2021;(4):1785-1795
Abstract
BACKGROUND Dietary advanced glycation end-products (AGEs) are linked to cognitive decline. However, clinical trials have not tested the effect of AGEs on cognition in older adults. OBJECTIVE The aim of the current pilot trial was to examine the feasibility of an intervention to reduce dietary AGEs on cognition and on cerebral blood flow (CBF). METHODS The design is a pilot randomized controlled trial of dietary AGEs reduction in older adults with type 2 diabetes. Seventy-five participants were randomized to two arms. The control arm received standard of care (SOC) guidelines for good glycemic control; the intervention arm, in addition to SOC guidelines, were instructed to reduce their dietary AGEs intake. Global cognition and CBF were assessed at baseline and after 6 months of intervention. RESULTS At baseline, we found a reverse association between AGEs and cognitive functioning, possibly reflecting the long-term toxicity of AGEs on the brain. There was a significant improvement in global cognition at 6 months in both the intervention and SOC groups which was more prominent in participants with mild cognitive impairment. We also found that at baseline, higher AGEs were associated with increased CBF in the left inferior parietal cortex; however, 6 months of the AGEs lowering intervention did not affect CBF levels, despite lowering AGEs exposure in blood. CONCLUSION The current pilot trial focused on the feasibility and methodology of intervening through diet to reduce AGEs in older adults with type 2 diabetes. Our results suggest that participants with mild cognitive impairment may benefit from an intensive dietary intervention.
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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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Trait Energy and Fatigue Modify the Effects of Caffeine on Mood, Cognitive and Fine-Motor Task Performance: A Post-Hoc Study.
Fuller, DT, Smith, ML, Boolani, A
Nutrients. 2021;(2)
Abstract
Multiple studies suggest that genetic polymorphisms influence the neurocognitive effects of caffeine. Using data collected from a double-blinded, within-participants, randomized, cross-over design, this study examined the effects of trait (long-standing pre-disposition) mental and physical energy and fatigue to changes in moods (Profile of Mood Survey-Short Form (POMS-SF), state mental and physical energy and fatigue survey), cognitive (serial subtractions of 3 (SS3) and 7 (SS7)), and fine-motor task (nine-hole peg test) performance after consuming a caffeinated beverage and a non-caffeinated placebo. Results indicate that trait mental and physical fatigue and mental energy modified the effects of caffeine on vigor, tension-anxiety, physical, and mental fatigue. Additionally, we report that those who were high trait physical and mental fatigue and low-trait mental energy reported the greatest benefit of caffeine on the SS3 and SS7, while those who were high trait mental and physical fatigue reported the greatest benefit of consuming caffeine on fine-motor task performance. The results of our study suggest that trait mental and physical fatigue and mental energy modify the acute effects of caffeine among a group of healthy, young adults and should be measured and controlled for by researchers who choose to study the effects of caffeine on acute moods and cognitive and fine-motor task performance.
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Effects of Daily Matcha and Caffeine Intake on Mild Acute Psychological Stress-Related Cognitive Function in Middle-Aged and Older Adults: A Randomized Placebo-Controlled Study.
Baba, Y, Inagaki, S, Nakagawa, S, Kobayashi, M, Kaneko, T, Takihara, T
Nutrients. 2021;(5)
Abstract
Matcha, a type of green tea, has a higher amino acid content than other types of tea. We previously examined the ability of matcha to improve cognitive function in older adults and determined that continuous matcha intake improves attention and executive function. This study aimed to compare the effects of matcha and caffeine and clarify the differences between these effects. The study was registered at the University Hospital Medical Information Network (UMIN000036578). The effect of single and continuous intake was compared, and the usefulness of continuous intake was evaluated under the stress condition. The Uchida-Kraepelin test (UKT) was used to induce mild acute stress, and the Cognitrax was used to evaluate cognitive function. A single dose of caffeine improved attentional function during or after stress loading. The reduced reaction time in the Cognitrax, observed following a single dose of matcha, was likely due to caffeine. The matcha group showed an increase in the amount of work after continuous intake, whereas the caffeine group only showed an increase in the amount of work for the UKT after a single dose. Ingesting matcha with caffeine improves both attention and work performance when suffering from psychological stress compared with caffeine alone.