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Choline Pathway Nutrients and Metabolites and Cognitive Impairment After Acute Ischemic Stroke.
Zhong, C, Lu, Z, Che, B, Qian, S, Zheng, X, Wang, A, Bu, X, Zhang, J, Ju, Z, Xu, T, et al
Stroke. 2021;(3):887-895
Abstract
BACKGROUND AND PURPOSE Choline metabolism was suggested to play pathophysiological roles in nervous system and atherosclerosis development. However, little is known about the impacts of choline pathway nutrients and metabolites on poststroke cognitive impairment. We aimed to prospectively investigate the relationships between circulating choline, betaine, and trimethylamine N-oxide with cognitive impairment among acute ischemic stroke patients. METHODS We derived data from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). Plasma choline, betaine, and trimethylamine N-oxide concentrations at baseline were measured in 617 participants. Cognitive impairment was evaluated using the Mini-Mental State Examination and the Montreal Cognitive Assessment. Reclassification and calibration of models with choline-related biomarkers were evaluated. RESULTS Plasma choline and betaine were inversely associated with cognitive impairment. Compared with the lowest tertile, adjusted odds ratios of Mini-Mental State Examination-defined cognitive impairment for participants in the highest tertiles of choline and betaine were 0.59 (95% CI, 0.39-0.90) and 0.60 (95% CI, 0.39-0.92), respectively. In addition, both choline and betaine offered incremental predictive ability over the basic model with established risk factors, shown by increase in net reclassification improvement and integrated discrimination improvement. There were similar significant relationships between choline and betaine with cognitive impairment as defined by the Montreal Cognitive Assessment. However, plasma trimethylamine N-oxide was only associated with cognitive impairment evaluated using the Mini-Mental State Examination; the adjusted odds ratio was 1.33 (95% CI, 1.04-1.72) for each 1-SD increment of trimethylamine N-oxide. CONCLUSIONS Patients with higher choline and betaine levels had lower risk of cognitive impairment after ischemic stroke, supporting promising prognostic roles of choline pathway nutrients for poststroke cognitive impairment.
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Pre-Dementia Stages and Incident Dementia in the NuAge Study.
Beauchet, O, Sekhon, H, Launay, CP, Gaudreau, P, Morais, JA, Allali, G
Journal of Alzheimer's disease : JAD. 2021;(4):1465-1470
Abstract
BACKGROUND Motoric cognitive risk syndrome (MCR) and mild cognitive impairment (MCI) are two pre-dementia stages with an overlap, which may influence the risk for dementia. OBJECTIVE The study aims to examine the association of MCR, MCI, and their combination with incident dementia in Quebec community-dwelling older adults. METHODS 1,063 older adults (i.e., ≥65) were selected from a population-based observational cohort study known as the "Nutrition as a determinant of successful aging: The Quebec longitudinal study" (NuAge). Participants were separated into four groups at the baseline assessment: those without MCR and MCI (i.e., cognitively healthy individual; CHI), those with MCR alone, those with MCI alone, and those with MCR plus MCI. Incident dementia was recorded at each annual visit during a 3-year follow-up. RESULTS The prevalence of CHI was 87.2%, MCR 3.0%, MCI 8.8%, and MCR plus MCI 0.9%. The overall incidence of dementia was 2.4% and was significantly associated with MCR alone (Odd Ratio (OR) = 5.00 with 95% Confidence interval (CI) = [1.01;24.59] and p = 0.049), MCI alone (OR = 6.04 with 95% CI = [2.36;15.47] and p≤0.001), and the combination of MCR and MCI (OR = 25.75 with 95% CI = [5.32;124.66] and p≤0.001). CONCLUSION Combining MCR and MCI increased the risk for incident dementia. These results also demonstrated that this combination is a better predictor of dementia than MCI or MCR alone.
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Nutrition-Based Approaches in Clinical Trials Targeting Cognitive Function: Highlights of the CTAD 2020.
Giudici, KV
The journal of prevention of Alzheimer's disease. 2021;(2):118-122
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Abstract
The Clinical Trials on Alzheimer's Disease (CTAD) 2020 conference was the stage for researchers from all over the world to present their recent and ongoing research focused on potential Alzheimer's disease (AD) treatments and prevention of cognitive decline. Among a varied range of topics, nutritional aspects arose as possibilities of treatments towards the promotion of a healthy aging. Among the discussed themes, supplementation of omega-3 polyunsaturated fatty acids and multi-nutrient approaches were presented, suggesting that long-term supplementation (i.e., over 3 years) might be needed for observing positive effects on cognitive performance. Trials testing ketogenic agents and carbohydrate-restricted diet were also presented and showed promising effects on improving cognitive function of mild-cognitive impaired (MCI) and pre-diabetic individuals, respectively, in a short-term way (i.e. after 3 to 6 months). The combination of some of the nutritional approaches with physical activity interventions raises the question on whether they would individually perform in a similar way. Promising therapies involving nutrition appear to be safe and well tolerated by volunteers. Failures on achieving positive findings raise questions on whether they were driven by specific characteristics of the studied populations, insufficient doses or duration of treatment. Notwithstanding, current evidence on the applicability of nutrition-based approaches as AD treatments are encouraging but demand further research on the topic.
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Phosphodiesterase as a Target for Cognition Enhancement in Schizophrenia.
Al-Nema, MY, Gaurav, A
Current topics in medicinal chemistry. 2020;(26):2404-2421
Abstract
Schizophrenia is a severe mental disorder that affects more than 1% of the population worldwide. Dopamine system dysfunction and alterations in glutamatergic neurotransmission are strongly implicated in the aetiology of schizophrenia. To date, antipsychotic drugs are the only available treatment for the symptoms of schizophrenia. These medications, which act as D2-receptor antagonist, adequately address the positive symptoms of the disease, but they fail to improve the negative symptoms and cognitive impairment. In schizophrenia, cognitive impairment is a core feature of the disorder. Therefore, the treatment of cognitive impairment and the other symptoms related to schizophrenia remains a significant unmet medical need. Currently, phosphodiesterases (PDEs) are considered the best drug target for the treatment of schizophrenia since many PDE subfamilies are abundant in the brain regions that are relevant to cognition. Thus, this review aims to illustrate the mechanism of PDEs in treating the symptoms of schizophrenia and summarises the encouraging results of PDE inhibitors as anti-schizophrenic drugs in preclinical and clinical studies.
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Effects of Rice Wine Lees on Cognitive Function in Community-Dwelling Physically Active Older Adults: A Pilot Randomized Controlled Trial.
Nagai, N, Shindo, N, Wada, A, Izu, H, Fujii, T, Matsubara, K, Wada, Y, Sakane, N
The journal of prevention of Alzheimer's disease. 2020;(2):95-103
Abstract
BACKGROUND Rice wine lees (RWL), a Japanese traditional fermented product, is a rich source of one-carbon metabolism-related nutrients, which may have beneficial effects on cognitive function. OBJECTIVES We aimed to examine the effect of the RWL on cognitive function in community-dwelling physically active older adults. DESIGN Double-blind, randomized, placebo-controlled study (clinical trial number: UMIN 000027158). SETTING Community-based intervention including assessments conducted at the University of Hyogo and a public liberal arts school in Himeji City, Japan. PARTICIPANTS A total of 35 community-dwelling older adults (68-80 years) who performed mild exercise before and during the trial were assigned to either the RWL (n=17) or the placebo group (n=18). INTERVENTION Daily consumption of 50 g RWL powder, which contained one-carbon metabolism-related nutrients, or the placebo powder (made from soy protein and dextrin) for 12 weeks. Both supplements included equivalent amounts of energy and protein. MEASUREMENTS Montreal Cognitive Assessment, computerized cognitive function test, and measurements of serum predictive biomarkers (transthyretin, apolipoprotein A1, and complement C3) were conducted at baseline and follow-up. RESULTS Visual selective attention and serum transthyretin significantly improved in the RWL group, whereas there was no significant change in the placebo group. No significant group difference was observed in the remaining cognitive performance tests. CONCLUSIONS RWL supplements seem to have a few effects on cognitive function in community-dwelling physically active older adults. However, the impact was limited; therefore, further studies with sufficient sample size are warranted to elucidate this issue.
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Potential effect of herbal antidepressants on cognitive deficit: Pharmacological activity and possible molecular mechanism.
Li, JM, Zhao, Y, Sun, Y, Kong, LD
Journal of ethnopharmacology. 2020;:112830
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cognitive symptom is a "core" symptom of major depressive disorder (MDD) patients with clear deficit in memory, social and occupational function, and may persist during the remitting phase. Therefore, the remission of cognitive symptom has been considered as one of the main objectives in the treatment of MDD. Herbal antidepressants have been used to treat MDD, and there has been great advances in the understanding of the ability of these herbs to improve cognitive deficit linked to brain injury and various diseases including depression, Alzheimer disease, diabetes and age-related disorders. This systematic review summarizes the evidence from preclinical studies and clinical trials of herbal antidepressants with positive effects on cognitive deficit. The potential mechanisms by which herbal antidepressants prevent cognitive deficit are also reviewed. This review will facilitate further research and applications. MATERIALS AND METHODS We conducted an open-ended, English restricted search of MEDLINE (PubMed), Web of Science and Scopus for all available articles published or online before 31 December 2019, using terms pertaining to medical herb/phytomedicine/phytochemical/Chinese medicine and depression/major depressive disorder/antidepressant and/or cognitive impairment/cognitive deficit/cognitive dysfunction. RESULTS 7 prescriptions, more than 30 individual herbs and 50 phytochemicals from China, Japan, Korea and India with positive effects on the depressive state and cognitive deficit are reviewed herein. The evidence from preclinical studies and clinical trials proves that these herbal antidepressants exhibit positive effects on one or more aspects of cognitive defect including spatial, episodic, aversive, and short- and long-term memory. The action mode of the improvement of cognitive deficit by these herbal antidepressants is mediated mainly through two pathways. One pathway is to promote hippocampal neurogenesis through activating brain derived neurotrophic factor-tropomyosin-related kinase B signaling. The other pathway is to prevent neuronal apoptosis through the inhibition of neuro-inflammation and neuro-oxidation. CONCLUSION These herbal antidepressants, having potential therapy for cognitive deficit, may prevent pathological processes of neurodegenerative diseases. Furthermore, these herbal medicines should provide a treasure trove, which will accelerate the development of new antidepressants that can effectively improve cognitive symptom in MDD. Studies on their molecular mechanisms may provide more potential targets and therapeutic approaches for new drug discovery.
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Cerebrovascular risk factors impact frontoparietal network integrity and executive function in healthy ageing.
Veldsman, M, Tai, XY, Nichols, T, Smith, S, Peixoto, J, Manohar, S, Husain, M
Nature communications. 2020;(1):4340
Abstract
Healthy cognitive ageing is a societal and public health priority. Cerebrovascular risk factors increase the likelihood of dementia in older people but their impact on cognitive ageing in younger, healthy brains is less clear. The UK Biobank provides cognition and brain imaging measures in the largest population cohort studied to date. Here we show that cognitive abilities of healthy individuals (N = 22,059) in this sample are detrimentally affected by cerebrovascular risk factors. Structural equation modelling revealed that cerebrovascular risk is associated with reduced cerebral grey matter and white matter integrity within a fronto-parietal brain network underlying executive function. Notably, higher systolic blood pressure was associated with worse executive cognitive function in mid-life (44-69 years), but not in late-life (>70 years). During mid-life this association did not occur in the systolic range of 110-140 mmHg. These findings suggest cerebrovascular risk factors impact on brain structure and cognitive function in healthy people.
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Effects of Liberal vs Restrictive Transfusion Thresholds on Survival and Neurocognitive Outcomes in Extremely Low-Birth-Weight Infants: The ETTNO Randomized Clinical Trial.
Franz, AR, Engel, C, Bassler, D, Rüdiger, M, Thome, UH, Maier, RF, Krägeloh-Mann, I, Kron, M, Essers, J, Bührer, C, et al
JAMA. 2020;(6):560-570
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Abstract
IMPORTANCE Red blood cell transfusions are commonly administered to infants weighing less than 1000 g at birth. Evidence-based transfusion thresholds have not been established. Previous studies have suggested higher rates of cognitive impairment with restrictive transfusion thresholds. OBJECTIVE To compare the effect of liberal vs restrictive red blood cell transfusion strategies on death or disability. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial conducted in 36 level III/IV neonatal intensive care units in Europe among 1013 infants with birth weights of 400 g to 999 g at less than 72 hours after birth; enrollment took place between July 14, 2011, and November 14, 2014, and follow-up was completed by January 15, 2018. INTERVENTIONS Infants were randomly assigned to liberal (n = 492) or restrictive (n = 521) red blood cell transfusion thresholds based on infants' postnatal age and current health state. MAIN OUTCOME AND MEASURES The primary outcome, measured at 24 months of corrected age, was death or disability, defined as any of cognitive deficit, cerebral palsy, or severe visual or hearing impairment. Secondary outcome measures included individual components of the primary outcome, complications of prematurity, and growth. RESULTS Among 1013 patients randomized (median gestational age at birth, 26.3 [interquartile range {IQR}, 24.9-27.6] weeks; 509 [50.2%] females), 928 (91.6%) completed the trial. Among infants in the liberal vs restrictive transfusion thresholds groups, respectively, incidence of any transfusion was 400/492 (81.3%) vs 315/521 (60.5%); median volume transfused was 40 mL (IQR, 16-73 mL) vs 19 mL (IQR, 0-46 mL); and weekly mean hematocrit was 3 percentage points higher with liberal thresholds. Among infants in the liberal vs restrictive thresholds groups, the primary outcome occurred in 200/450 (44.4%) vs 205/478 (42.9%), respectively, for a difference of 1.6% (95% CI, -4.8% to 7.9%; P = .72). Death by 24 months occurred in 38/460 (8.3%) vs 44/491 (9.0%), for a difference of -0.7% (95% CI, -4.3% to 2.9%; P = .70), cognitive deficit was observed in 154/410 (37.6%) vs 148/430 (34.4%), for a difference of 3.2% (95% CI, -3.3% to 9.6%; P = .47), and cerebral palsy occurred in 18/419 (4.3%) vs 25/443 (5.6%), for a difference of -1.3% (95% CI, -4.2% to 1.5%; P = .37), in the liberal vs the restrictive thresholds groups, respectively. In the liberal vs restrictive thresholds groups, necrotizing enterocolitis requiring surgical intervention occurred in 20/492 (4.1%) vs 28/518 (5.4%); bronchopulmonary dysplasia occurred in 130/458 (28.4%) vs 126/485 (26.0%); and treatment for retinopathy of prematurity was required in 41/472 (8.7%) vs 38/492 (7.7%). Growth at follow-up was also not significantly different between groups. CONCLUSIONS AND RELEVANCE Among infants with birth weights of less than 1000 g, a strategy of liberal blood transfusions compared with restrictive transfusions did not reduce the likelihood of death or disability at 24 months of corrected age. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01393496.
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Differential effects of cognitive training modules in healthy aging and mild cognitive impairment: A comprehensive meta-analysis of randomized controlled trials.
Basak, C, Qin, S, O'Connell, MA
Psychology and aging. 2020;(2):220-249
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Abstract
This meta-analysis was designed to compare the effectiveness of 2 cognitive training modules, single-component training, which targets 1 specific cognitive ability, versus multicomponent training, which trains multiple cognitive abilities, on both trained abilities (near transfer) and untrained abilities (far transfer) in older adults. The meta-analysis also assessed whether individual differences in mental status interacted with the extent of transfer. Eligible randomized controlled trials (215 training studies) examined the immediate effects of cognitive training in either healthy aging (HA) or mild cognitive impairment (MCI). Results yielded an overall net-gain effect size (g) for the cognitive training of 0.28 (p < .001). These effects were similar across mental status and training modules, and were significant for both near (g = 0.37) and far (g = 0.22) transfer. Although all training modules yielded significant near transfer, only a few yielded significant far transfer. Single-component training of executive functions was most effective on near and far transfer, with processing speed training improving everyday functioning. All modules of multicomponent training (specific and nonspecific) yielded significant near and far transfer, including everyday functioning. Training effects on cognition were moderated by educational attainment and number of cognitive outcomes, but only in HA. These findings suggest that, in older adults, all modules of multicomponent training are more effective in engendering near and far transfer, including everyday functioning, when compared with single-component training modules. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
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Homocysteine: A modifiable culprit of cognitive impairment for us to conquer?
Ji, Y, Lyu, P, Jin, W, Li, X, Li, X, Dong, Y
Journal of the neurological sciences. 2019;:128-136
Abstract
BACKGROUND Cognitive impairment, including mild cognitive impairment and its progressive deterioration to dementia, results in great hazards to the patient and the surrounding society. While some of the risk factors are unmodifiable, such as age, lower educational attainment, and genetic factors, another proposed one-homocysteine, an amino acid produced in the methylation cycle of protein metabolism is modifiable by cheap and easily accessible B-vitamins treatments in medical practice. OBJECTIVE AND METHODS To investigate the relationship between homocysteine and cognitive impairment, elucidate the underlying pathophysiological mechanisms and exploit any potential therapeutic values of homocysteine-lowering treatments in prevention and/or treatment in cognitive decline, we searched on the PUBMED databases surrounding around the physiological homocysteine metabolism, detrimental effects of abnormal homocysteine concentrations on the brain, and review observational and interventional experiments to date estimating the relationship between homocysteine and cognitive impairment with relatively powerful evidence. RESULTS Intrinsic and environmental factors help maintain the normal homocysteine concentrations, and pathological homocysteine concentrations exert adverse effects mediated by cellular and vascular pathways. Although many observational studies have suggested a causal link between hyperhomocysteinemia and cognitive impairment, the majority of randomized controlled trials failed to observe marked benefits on cognition by homocysteine-lowering treatments using B-vitamins, partly arising from some design limitations including: not identifying individuals at earlier stages of cognitive impairment who are most likely to benefit, overlooking any latent safety hazards of multiple vitamin supplementation, lack of sensitive and domain-specific cognitive tests, and interference of other underappreciated factors. CONCLUSION More studies are required to better explain the related pathophysiological mechanisms, improve experimental methods, and investigate the preventive or/and therapeutic effects of homocysteine-lowering strategies on cognitive impairment.