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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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[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.
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Blood pressure and low-density lipoprotein-cholesterol lowering for prevention of strokes and cognitive decline: a review of available trial evidence.
Zanchetti, A, Liu, L, Mancia, G, Parati, G, Grassi, G, Stramba-Badiale, M, Silani, V, Bilo, G, Corrao, G, Zambon, A, et al
Journal of hypertension. 2014;(9):1741-50
Abstract
BACKGROUND AND OBJECTIVES It is well established by a large number of randomized controlled trials that lowering blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) by drugs are powerful means to reduce stroke incidence, but the optimal BP and LDL-C levels to be achieved are largely uncertain. Concerning BP targets, two hypotheses are being confronted: first, the lower the BP, the better the treatment outcome, and second, the hypothesis that too low BP values are accompanied by a lower benefit and even higher risk. It is also unknown whether BP lowering and LDL-C lowering have additive beneficial effects for the primary and secondary prevention of stroke, and whether these treatments can prevent cognitive decline after stroke. RESULTS A review of existing data from randomized controlled trials confirms that solid evidence on optimal BP and LDL-C targets is missing, possible interactions between BP and LDL-C lowering treatments have never been directly investigated, and evidence in favour of a beneficial effect of BP or LDL-C lowering on cognitive decline is, at best, very weak. CONCLUSION A new, large randomized controlled trial is needed to determine the optimal level of BP and LDL-C for the prevention of recurrent stroke and cognitive decline.
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Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient: design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial.
Zanchetti, A, Liu, L, Mancia, G, Parati, G, Grassi, G, Stramba-Badiale, M, Silani, V, Bilo, G, Corrao, G, Zambon, A, et al
Journal of hypertension. 2014;(9):1888-97
Abstract
BACKGROUND AND OBJECTIVES The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown; neither is it clear whether in patients with a previous cardiovascular event, the optimal values are lower than in the low-to-moderate risk hypertensive patients, or a more cautious blood pressure (BP) reduction should be obtained. Because of the uncertainty whether 'the lower the better' or the 'J-curve' hypothesis is correct, the European Society of Hypertension and the Chinese Hypertension League have promoted a randomized trial comparing antihypertensive treatment strategies aiming at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack. As the optimal level of low-density lipoprotein cholesterol (LDL-C) level is also unknown in these patients, LDL-C-lowering has been included in the design. PROTOCOL DESIGN The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospective multinational, randomized trial with a 3 × 2 factorial design comparing: three different SBP targets (1, <145-135; 2, <135-125; 3, <125 mmHg); two different LDL-C targets (target A, 2.8-1.8; target B, <1.8 mmol/l). The trial is to be conducted on 7500 patients aged at least 65 years (2500 in Europe, 5000 in China) with hypertension and a stroke or transient ischaemic attack 1-6 months before randomization. Antihypertensive and statin treatments will be initiated or modified using suitable registered agents chosen by the investigators, in order to maintain patients within the randomized SBP and LDL-C windows. All patients will be followed up every 3 months for BP and every 6 months for LDL-C. Ambulatory BP will be measured yearly. OUTCOMES Primary outcome is time to stroke (fatal and non-fatal). Important secondary outcomes are: time to first major cardiovascular event; cognitive decline (Montreal Cognitive Assessment) and dementia. All major outcomes will be adjudicated by committees blind to randomized allocation. A Data and Safety Monitoring Board has open access to data and can recommend trial interruption for safety. SAMPLE SIZE CALCULATION It has been calculated that 925 patients would reach the primary outcome after a mean 4-year follow-up, and this should provide at least 80% power to detect a 25% stroke difference between SBP targets and a 20% difference between LDL-C targets.
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Effects of quetiapine on cognitive functions in schizophrenic patients: a preliminary single-trial ERP analysis.
Zhang, Y, Lehmann, M, Shobeiry, A, Höfer, D, Johannes, S, Emrich, HM, Dietrich, DE
Pharmacopsychiatry. 2009;(4):129-34
Abstract
AIM: The study aimed to explore by means of single-trial event-related potentials (ERPs), whether and how the medication change from older neuroleptics to quetiapine in schizophrenic patients led to a significant cognitive enhancement. This single-trial ERP analysis helps to investigate attention and memory processes in the single patient before and after treatment. PATIENTS AND METHODS Thirteen schizophrenic patients (mean age: 40.1+/-13.5 years) were followed up for 16 weeks and assessed for changes of clinical symptoms and ERP components P300 representing target detection processes and N400 indexing context integration in word recognition processes. Three subjects had to be excluded from the ERP recording sessions because of excessive blink artefacts and movements. RESULTS Regarding the P300 components of the target detection, there were significant increases of amplitudes in 5 of 10 patients (50%) at week 16 comparing with week 0. Regarding the N400 components of the word recognition, there were significant increases of amplitudes in 4 of 10 patients (40%) at week 16 comparing with week 0. DISCUSSION The mean scores of PANSS, MADRS, Bf-S, SCL-90 and CGI-S at the end of study (week 16) showed significant improvements compared to the baselines (week 0) (p<0.05). During the study, no extrapyramidal symptoms as well as akathisia were reported after quetiapine treatment. These preliminary data suggest that quetiapine might partially improve the cognitive functions in the context integration and target detection processing in these patients. This technical procedure (single-trial ERP) may help to differentially assess cognitive enhancements in each single patient under treatment.