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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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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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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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Impact of baseline vitamin B12 status on the effect of vitamin B12 supplementation on neurologic function in older people: secondary analysis of data from the OPEN randomised controlled trial.
Miles, LM, Allen, E, Clarke, R, Mills, K, Uauy, R, Dangour, AD
European journal of clinical nutrition. 2017;(10):1166-1172
Abstract
BACKGROUND/OBJECTIVES The available evidence from randomised controlled trials suggests that vitamin B12 supplementation does not improve neurologic function in older people with marginal but not deficient Vitamin B12 status. This secondary analysis used data from the Older People and Enhanced Neurological function (OPEN) randomised controlled trial to assess whether baseline vitamin B12 status or change in vitamin B12 status over 12 months altered the effectiveness of dietary vitamin B12 supplementation on neurologic function in asymptomatic older people with depleted vitamin B12 status at study entry. SUBJECTS/METHODS Vitamin B12 status was measured as serum concentrations of vitamin B12, holotranscobalamin, homocysteine and via a composite indicator (cB12). Neurological function outcomes included eleven electrophysiological measures of sensory and motor components of peripheral and central nerve function. Linear regression analyses were restricted to participants randomised into the intervention arm of the OPEN trial (n=91). RESULTS Analyses revealed an inconsistent pattern of moderate associations between some measures of baseline vitamin B12 status and some neurological responses to supplementation. The directions of effect varied and heterogeneity in effect across outcomes could not be explained according to type of neurological outcome. There was no evidence of differences in the neurological response to vitamin B12 supplementation according to change from baseline over 12 months in any indicator of B12 status. CONCLUSIONS This secondary analysis of high-quality data from the OPEN trial provides no evidence that baseline (or change from baseline) vitamin B12 status modifies the effect of vitamin B12 supplementation on peripheral or central nerve conduction among older people with marginal vitamin B12 status. There is currently insufficient evidence of efficacy for neurological function to support population-wide recommendations for vitamin B12 supplementation in healthy asymptomatic older people with marginal vitamin B12 status.
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Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial.
Liu, G, Weinger, JG, Lu, ZL, Xue, F, Sadeghpour, S
Journal of Alzheimer's disease : JAD. 2016;(4):971-90
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Abstract
BACKGROUND Cognitive impairment is a major problem in elderly, affecting quality of life. Pre-clinical studies show that MMFS-01, a synapse density enhancer, is effective at reversing cognitive decline in aging rodents. OBJECTIVE Since brain atrophy during aging is strongly associated with both cognitive decline and sleep disorder, we evaluated the efficacy of MMFS-01 in its ability to reverse cognitive impairment and improve sleep. METHODS We conducted a randomized, double-blind, placebo-controlled, parallel-designed trial in older adult subjects (age 50-70) with cognitive impairment. Subjects were treated with MMFS-01 (n = 23) or placebo (n = 21) for 12 weeks and cognitive ability, sleep quality, and emotion were evaluated. Overall cognitive ability was determined by a composite score of tests in four major cognitive domains. RESULTS With MMFS-01 treatment, overall cognitive ability improved significantly relative to placebo (p = 0.003; Cohen's d = 0.91). Cognitive fluctuation was also reduced. The study population had more severe executive function deficits than age-matched controls from normative data and MMFS-01 treatment nearly restored their impaired executive function, demonstrating that MMFS-01 may be clinically significant. Due to the strong placebo effects on sleep and anxiety, the effects of MMFS-01 on sleep and anxiety could not be determined. CONCLUSIONS The current study demonstrates the potential of MMFS-01 for treating cognitive impairment in older adults.
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Lidocaine Did Not Reduce Neuropsychological-Cognitive Decline in Patients 6 Months After Supratentorial Tumor Surgery: A Randomized, Controlled Trial.
Peng, Y, Zhang, W, Zhou, X, Ji, Y, Kass, IS, Han, R
Journal of neurosurgical anesthesiology. 2016;(1):6-13
Abstract
UNLABELLED : There is equivocal evidence examining cognitive improvement in response to lidocaine during cardiac surgery; however, no study has examined its effect on postoperative neuropsychological-cognitive decline after supratentorial tumor surgery. METHODS Ninety-four patients scheduled for supratentorial craniotomy were enrolled. Patients received either a dose of lidocaine (2%) via an intravenous bolus (1.5 mg/kg) after induction followed by an infusion at a rate of 2 mg/kg/h until the end of surgery (Lidocaine group) or the same volume of normal saline. The neuropsychological-cognitive decline was evaluated using the following tests: the Mini-Mental State Examination, the Information-Memory-Concentration test, the Hamilton Rating Scale for Depression, and the Hamilton Rating Scale for Anxiety. The cerebral oxygen extraction ratio and the difference in lactic acid levels between the bulb of the jugular vein and a peripheral artery were measured. RESULTS Eighty patients completed the neuropsychological tests, with 40 patients in each group. The incidence of postoperative decline at up to 6 months in the Lidocaine group was not significantly different than that in the Normal saline group. When the 2 cognitive tests were examined independent of the other tests, there was no difference between groups at 6 months. The cerebral oxygen extraction ratio was significantly lower in the Lidocaine group after surgery (P<0.05), and the arteriovenous difference of lactic acid was lower in the Lidocaine group (P<0.05). CONCLUSIONS Intraoperative infusion of lidocaine does not significantly decrease the incidence of postoperative neuropsychological-cognitive decline in patients 6 months after supratentorial tumor surgery.
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Mood and neuropsychological effects of different doses of ketamine in electroconvulsive therapy for treatment-resistant depression.
Zhong, X, He, H, Zhang, C, Wang, Z, Jiang, M, Li, Q, Zhang, M, Huang, X
Journal of affective disorders. 2016;:124-30
Abstract
BACKGROUND Treatment-resistant depression (TRD) is a growing clinical challenge. Electroconvulsive therapy (ECT) is an effective tool for TRD treatment. However, there remains a subset of patients who do not respond to this treatment with common anesthetic agent. Ketamine, a noteworthy anesthetic agent, has emerged as an augmentation to enhance the antidepressant efficacy of ECT. Trials of i.v. ketamine in TRD indicated dose-related mood enhancing efficacy. We aimed to explore anesthetic and subanesthetic concentrations of ketamine in ECT for TRD with respect to their impact on mood and neuropsychological effects. METHODS Ninety TRD patients (36 males, 54 females; average age, 30.6 years old) were randomly assigned to receive either ketamine (0.8mg/kg) (n=30), subanesthetic ketamine (0.5mg/kg) plus propofol (0.5mg/kg) (n=30) or propofol (0.8mg/kg) (n=30) as an anesthetic and underwent 8 ECT sessions. The primary outcome measures were the 17-item Hamilton Depression Rating Scale (HDRS-17), cognitive assessments and seizure parameters. RESULTS The ketamine group had an earlier improvement in HDRS-17, longer seizure duration, lower electric quantity, a higher remission rate, and a lower degree of executive cognitive impairment compared to the ketamine+propofol and propofol groups. The ketamine+propofol group showed earlier improvement in the HDRS-17, a longer seizure duration and a different seizure energy index when compared to the propofol group. LIMITATIONS The postoperative dissociative side effect was not assessed. CONCLUSIONS Both anesthetic and subanesthetic concentrations of ketamine have rapid mood enhancing actions in ECT for TRD, while anesthetic concentrations results in larger magnitudes of antidepression and cognitive protection. ECT with ketamine anesthesia might be an optimized therapy for patients with TRD.
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Higher Visit-to-Visit Low-Density Lipoprotein Cholesterol Variability Is Associated With Lower Cognitive Performance, Lower Cerebral Blood Flow, and Greater White Matter Hyperintensity Load in Older Subjects.
Smit, RA, Trompet, S, Sabayan, B, le Cessie, S, van der Grond, J, van Buchem, MA, de Craen, AJ, Jukema, JW
Circulation. 2016;(3):212-21
Abstract
BACKGROUND Recently, it was shown that intraindividual variation in low-density lipoprotein cholesterol (LDL-C) predicts both cerebrovascular and cardiovascular events. We aimed to examine whether this extends to cognitive function and examined possible pathways using a magnetic resonance imaging substudy. METHODS We investigated the association between LDL-C variability and 4 cognitive domains at month 30 in 4428 participants of PROSPER (PROspective Study of Pravastatin in the Elderly at Risk). Additionally, we assessed the association of LDL-C variability with neuroimaging outcomes in a subset of 535 participants. LDL-C variability was defined as the intraindividual standard deviation over 4 postbaseline LDL-C measurements, and all analyses were adjusted for mean LDL-C levels and cardiovascular risk factors. RESULTS Higher LDL-C variability was associated with lower cognitive function in both the placebo and pravastatin treatment arms. Associations were present for selective attention (P=0.017 and P=0.11, respectively), processing speed (P=0.20 and P=0.029), and memory (immediate recall, P=0.002 and P=0.006; delayed recall, P=0.001 and P≤0.001). Furthermore, higher LDL-C variability was associated with lower cerebral blood flow in both trial arms (P=0.031 and P=0.050) and with greater white matter hyperintensity load in the pravastatin arm (P=0.046). No evidence was found for interaction between LDL-C variability and pravastatin treatment for both cognitive and magnetic resonance imaging outcomes. CONCLUSIONS We found that higher visit-to-visit variability in LDL-C, independently of mean LDL-C levels and statin treatment, is associated with lower cognitive performance, lower cerebral blood flow, and greater white matter hyperintensity load.
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[Effect of Dexmedetomidine Combined Electrical Stimulation on Coanitive Function of Patients Receiving Extracerebral Intervention].
Yuan, J, Wu, Y, Li, JY, Chen, X, Zhang, L, Liu, YF, Tong, SX, Deng, FF
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine. 2016;(3):285-8
Abstract
OBJECTIVE To explore the effect of dexmedetomidine combined electrical stimulation on cognitive function of neurosurgical diseases patients treated by extracerebral intervention. METHODS Totally 122 patients with neurosurgical diseases who underwent selective intervention were randomly assigned to the observation group and the control group, 61 cases in each group. Patients in the control group recieved anesthesia by dexmedetomidine. Those in the observation group received electrical stimulation at Baihui (DU20), Yintang ( EX-HN3), and Neiguan (PC6) before dexmedetomidine anesthesia. The cognitive function of patients at preoperative day 1 and postoperative day 1 was respectively evaluated by Mini-Mental State Examinations (MMSE). Serum NSE, S-100β, IL-1β, IL-6, and TNF-α levels were detected in the two groups before intervention and immediately after intervention using ELISA. RESULTS MMSE scores of two groups were significantly reduced at post-intervention day 1, as compared with one day before intervention. MMSE score of the observation group at post-intervention day 1 was (23.15 ± 1.87) points, significantly higher than that of the control group [ (19.34 ± 1.64) points , (P < 0.05)]. The postoperative cognitive dysfunction (POCD) incidence rate of the observation group was 16.4% (10/61), significantly lower than that of the control group [39.3% (24/61); P < 0.05]. Compared with before intervention, NSE and S-100β protein levels, IL-1β, IL-6 and α-TNF levels of the two groups increased (P < 0.05). Post-intervention NSE and S-100β protein levels, IL-1β, IL-6 and α-TNF levels were significantly lower in the observation group than in the control group (P < 0.05). CONCLUSION Dexmedetomidine combied electrical stimulation could effectively prevent the occurrence of postoperative cognition, and reduce levels of NSA, S-100β, IL-1β, IL-6 and TNF-α.
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[Correlative study of the metabolic disorder of hippocampus and cerebral cortex and cognitive impairment in moderate to severe OSAHS patients].
Wang, B, Xu, X, Liang, G, Zhang, Y, Liu, L, Zhang, J
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery. 2015;(7):607-11
Abstract
OBJECTIVE To research the serum levels of BDNF, H2S and S-100β as metabolic product of hippocampus and cerebral cortex in moderate to severe obstructive sleep apnea hypopnea syndrome(OSAHS) patients before and after surgery, and to analyze their correlations with cognitive impairment. METHOD Forty-four randomly selected diagnosed OSAHS patients were divided into two groups according to Montreal Cognitive Assessment (MoCA), 19 cases in cognitively normal group and 25 cases in cognitive dysfunction group. Cases in cognitive dysfunction group underwent UPPP oriented surgery, and received 6 months follow-up, 21 cases were remained as treament group, 4 cases lost. 19 cases of healthy subjects were randomly selected as the normal control group. All groups were detected for the serum BDNF, H2S and S-100β levels to analyze the correlations between the biochemical indexes and sleep disorders indexes, hypoxia levels and cognitive function scores. RESULT (1) In the comparison between the treatment group and the normal control group regarding PSG monitoring results, the AHI, I + II, LA/HT and SLT90% indexes of OSAHS patients increased, and the III + IV phase, REM phase, MSaO2 and LSaO2 decreased. In the comparison between the cognitive dysfunction group and the cognitively normal group, the III + IV, REM and LSaO2 indexes of the cognitive dysfunction group decreased. (2) In the comparison between cognitive dysfunction group and cognitively normal group, and between the treatment group and the normal control group, BDNF and H2S levels increased and S-100β levels decreased, and the MoCA total scores, attention, memory/delayed recall scores decreased. (3) The correlation between biochemical indexes with PSG indexes was as follows. The serum BNDF and H2S levels were negatively correlated with AHI index. The serum BNDF and H2S levels were positively correlated with III + IV stage, REM stage and MSaO2 indexes. The S-100β level was positively correlated with AHI index, and S-100β levels were negatively correlated with III + IV stage, REM stage, MSaO2 and LSaO2 indexes. (4) The correlation between biochemical indexes and MoCA scores was as follows. The serum BNDF and H2S levels were positively correlated with MoCA total scores, attention, and memory/delayed recall scores. The serum S-100β levels were negatively correlated with MoCA total scores, attention and memory/ delayed recall scores. (5) The linear regression equation between MoCA total scores in cognitive dysfunction group of OSAHS patients and the serum BNDF, H2S and S-100β levels was as follows: Y(MoCA) = 40.131 + 0.22 X(BDNF) + 0.012 X(H2S)-0.647X(S-100β) (R2 = 0.461). CONCLUSION OSAHS patients with sleep disorder and nocturnal hypoxemia might suffer from cognitive dysfunction in which attention and memory predominates. Serum BNDF, H2S and S-100β levels, which could indirectly reflect the metabolic abnormalities degree of hippocampus and cerebral cortex, are sensitive indicators of early cognitive dysfunction in OSAHS patients.