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Effect of glucose and sucrose on cognition in healthy humans: a systematic review and meta-analysis of interventional studies.
García, CR, Piernas, C, Martínez-Rodríguez, A, Hernández-Morante, JJ
Nutrition reviews. 2021;(2):171-187
Abstract
CONTEXT Evidence suggests that plasma glucose levels may influence cognitive performance, but this has not been systematically reviewed and quantified. OBJECTIVE The aim of this review was to investigate the potential effects of glucose and sucrose, compared with placebo, on cognition in healthy humans. DATA SOURCES The electronic databases PubMed and Web of Science were searched up to December 2019. Reference lists of selected articles were checked manually. STUDY SELECTION Randomized controlled trials or crossover trials that compared glucose or sucrose with placebo for effects on cognition were eligible. DATA EXTRACTION Potentially eligible articles were selected independently by 2 authors. Risk of bias was assessed through the Cochrane Collaboration tool. Standardized mean differences (SMDs) were obtained from random-effects meta-analyses for a subsample of studies that reported the same outcomes. RESULTS Thirty-seven trials were identified, of which 35 investigated the effect of glucose consumption compared with placebo on cognition. Two studies found no effect of glucose on cognition, while the others found mixed results. Only 3 of the 37 studies investigated the effects of sucrose intake, reporting mixed results. Meta-analyses revealed a significantly positive effect of glucose compared with control, but only when a verbal performance test (immediate word recall) was used in parallel-design studies (SMD = 0.61; 95%CI, 0.20-1.02; I2 = 0%). Twenty-four studies were classified as having high risk of bias for the selection procedure. CONCLUSIONS A limited body of evidence shows a beneficial effect of glucose in individuals performing immediate verbal tasks. High-quality trials with standardized cognitive measurements are needed to better establish the effect of glucose or sucrose on cognition. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration number CRD42019122939.
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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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The impact of dietary macronutrient intake on cognitive function and the brain.
Muth, AK, Park, SQ
Clinical nutrition (Edinburgh, Scotland). 2021;(6):3999-4010
Abstract
Macronutrients - carbohydrates, fats, and proteins - supply the nutrients required for optimal functioning. Inadequate intake compromises both physical and brain health. We synthesized research on macronutrients from whole meals on cognitive function in healthy adults and identified underlying mechanisms. Intake of simple carbohydrates ('sugars') is consistently associated with decreased global cognition whereas consumption of complex carbohydrates correlates with successful brain aging and improved memory both in the short- and long-term. Saturated fatty acid intake correlates with decreased memory and learning scores whereas omega-3 intake correlates positively with memory scores. Protein intake boosts executive function and working memory when task-demands are high. Individual differences affecting the macronutrient-cognition relationship are age, physical activity, and glucose metabolism. Neural correlates reflect findings on cognitive functions: cortical thickness and cerebral amyloid burden correlate with sugar intake, inflammatory status and cerebral glucose metabolism correlate with fatty acid intake. Key mechanisms by which dietary macronutrients affect the brain and cognition include glucose and insulin metabolism, neurotransmitter actions, and cerebral oxidation and inflammation. In conclusion, macronutrient intake affects cognitive function both acutely and in the long-term, involving peripheral and central mechanisms. A healthy diet supports brain integrity and functionality, whereas inadequate nutrition compromises it. Studying diet can be key to nutritional recommendations, thereby improving the landscape of mental health and healthy brain aging.
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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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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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Gut-brain axis: A matter of concern in neuropsychiatric disorders…!
Naveed, M, Zhou, QG, Xu, C, Taleb, A, Meng, F, Ahmed, B, Zhang, Y, Fukunaga, K, Han, F
Progress in neuro-psychopharmacology & biological psychiatry. 2021;:110051
Abstract
The gut microbiota is composed of a large number of microbes, usually regarded as commensal bacteria. It has become gradually clear that gastrointestinal microbiota affects gut pathophysiology and the central nervous system (CNS) function by modulating the signaling pathways of the microbiota-gut-brain (MGB) axis. This bidirectional MGB axis communication primarily acts through neuroendocrine, neuroimmune, and autonomic nervous systems (ANS) mechanisms. Accumulating evidence reveals that gut microbiota interacts with the host brain, and its modulation may play a critical role in the pathology of neuropsychiatric disorders. Recently, neuroscience research has established the significance of gut microbiota in the development of brain systems that are essential to stress-related behaviors, including depression and anxiety. Application of modulators of the MGB, such as psychobiotics (e.g., probiotics), prebiotics, and specific diets, may be a promising therapeutic approach for neuropsychiatric disorders. The present review article primarily focuses on the relevant features of the disturbances of the MGB axis in the pathophysiology of neuropsychiatric disorders and its potential mechanisms.
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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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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.