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Superoxide Dismutase, BDNF, and Cognitive Improvement in Drug-Naive First-Episode Patients With Schizophrenia: A 12-Week Longitudinal Study.
Wu, Z, Liu, Q, Zhang, Y, Guan, X, Xiu, M, Zhang, X
The international journal of neuropsychopharmacology. 2022;(2):128-135
Abstract
OBJECTIVE Cognitive improvement after antipsychotic agents in patients with schizophrenia (SCZ) appears to involve redox regulation through neurotrophins such as brain derived neurotropic factor (BDNF). This study examined whether cognitive improvement was associated with the increase in superoxide dismutase (SOD) and whether higher levels of BDNF could have a permissive role in allowing SOD to improve cognition. METHODS We examined this hypothesis in 183 drug-naïve first-episode SCZ patients taking risperidone monotherapy for 12 weeks. We measured total copper-zinc SOD (CuZn-SOD), manganese SOD (Mn-SOD), and SOD activities and BDNF levels in these patients and compared their levels with 152 healthy controls. We assessed cognitive functioning and clinical symptoms at baseline and 12-week follow-up. RESULTS After treatment with risperidone, CuZn-SOD activity was significantly increased, and BDNF levels were slightly increased. Increased CuZn-SOD activity was associated with the cognitive effectiveness of risperidone monotherapy. The BDNF levels and SOD activities were correlated at baseline but not after 12-week treatment. Furthermore, baseline CuZn-SOD activity positively correlated with improvement on the delayed memory subscale of the Repeatable Battery for the Assessment of Neuropsychological Status only in the high BDNF subgroup. CONCLUSIONS Our longitudinal study suggests that risperidone can enhance SOD activity and that, in combination with higher baseline BDNF levels acting in a permissive role, can improve cognitive impairments in SCZ. Greater baseline CuZn-SOD activity also may have predictive value for cognitive improvement of delayed memory in SCZ patients receiving risperidone treatment.
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Brain functions and cognition on transient insulin deprivation in type 1 diabetes.
Creo, AL, Cortes, TM, Jo, HJ, Huebner, AR, Dasari, S, Tillema, JM, Lteif, AN, Klaus, KA, Ruegsegger, GN, Kudva, YC, et al
JCI insight. 2021;(5)
Abstract
BACKGROUNDType 1 diabetes (T1D) is a risk factor for dementia and structural brain changes. It remains to be determined whether transient insulin deprivation that frequently occurs in insulin-treated individuals with T1D alters brain function.METHODSWe therefore performed functional and structural magnetic resonance imaging, magnetic resonance spectroscopy, and neuropsychological testing at baseline and following 5.4 ± 0.6 hours of insulin deprivation in 14 individuals with T1D and compared results with those from 14 age-, sex-, and BMI-matched nondiabetic (ND) participants with no interventions.RESULTSInsulin deprivation in T1D increased blood glucose, and β-hydroxybutyrate, while reducing bicarbonate levels. Participants with T1D showed lower baseline brain N-acetyl aspartate and myo-inositol levels but higher cortical fractional anisotropy, suggesting unhealthy neurons and brain microstructure. Although cognitive functions did not differ between participants with T1D and ND participants at baseline, significant changes in fine motor speed as well as attention and short-term memory occurred following insulin deprivation in participants with T1D. Insulin deprivation also reduced brain adenosine triphosphate levels and altered the phosphocreatine/adenosine triphosphate ratio. Baseline differences in functional connectivity in brain regions between participants with T1D and ND participants were noted, and on insulin deprivation further alterations in functional connectivity between regions, especially cortical and hippocampus-caudate regions, were observed. These alterations in functional connectivity correlated to brain metabolites and to changes in cognition.CONCLUSIONTransient insulin deprivation therefore caused alterations in executive aspects of cognitive function concurrent with functional connectivity between memory regions and the sensory cortex. These findings have important clinical implications, as many patients with T1D inadvertently have periods of transient insulin deprivation.TRIAL REGISTRATIONClinicalTrials.gov NCT03392441.FUNDINGClinical and Translational Science Award (UL1 TR002377) from the National Center for Advancing Translational Science; NIH grants (R21 AG60139 and R01 AG62859); the Mayo Foundation.
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Effectiveness and Safety Profile of Ginkgo biloba Standardized Extract (EGb761®) in Patients with Amnestic Mild Cognitive Impairment.
Băjenaru, O, Prada, G, Antochi, F, Jianu, C, Tudose, C, Cuciureanu, A, Docu, AA, Perrot, V, Avram, M, Tiu, C
CNS & neurological disorders drug targets. 2021;(4):378-384
Abstract
BACKGROUND Ginkgo biloba is a common symptomatic treatment for cognitive impairment, although data on its efficacy are controversial. OBJECTIVE The aim of the current study was to evaluate the effectiveness of standardized Ginkgo biloba extract EGb761® (Tanakan®) for the improvements of cognitive functions over 24 months in a local cohort of patients diagnosed with amnestic mild cognitive impairment (aMCI). METHODS This multicentre non-interventional study included 500 eligible patients with a MCI treated with 120 mg/day standardized Ginkgo biloba extract EGb761® (Tanakan®). Patients were evaluated using several scales for assessment of cognition, memory, activities of daily living, and depression (MMSE, FAQ, CGI, HAM-D) at baseline and every 6 months after that for a 24-month period. The median change in MMSE at the 24-month follow-up was the primary outcome of the study. RESULTS A statistically significant increase of 2 points in the median MMSE score was obtained. In patients with other concomitant cognitive disorders, the improvement in MMSE was less significant. Tanakan® improved memory impairment (using the delayed recall test) and the ability to accomplish activities of daily living (mean FAQ score, 1.7); it also decreased the severity of depression (mean HAM-D score, 2.4) at the end of the study. More than 80% of the patients showed minimal improvement of their condition as assessed by the CGI-Improvement Scale. CONCLUSION The administration of EGb761® (Tanakan®) led to a significant improvement of cognitive decline, memory, activities of daily living, and depression in subjects with aMCI over 24 months.
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A randomized phase II remote study to assess Bacopa for Gulf War Illness associated cognitive dysfunction: Design and methods of a national study.
Cheema, AK, Wiener, LE, McNeil, RB, Abreu, MM, Craddock, T, Fletcher, MA, Helmer, DA, Ashford, JW, Sullivan, K, Klimas, NG
Life sciences. 2021;:119819
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Abstract
AIMS: Gulf War Illness (GWI) is a chronic, debilitating, multi-symptom condition affecting as many as one-third of the nearly 700,000 U.S. troops deployed to the Middle East during the 1990-1991 Gulf War (GW). The treatment of GWI relies on symptom management. A common challenge in studying the efficacy of interventions for symptom management is participant recruitment related to factors such as the burden of travelling to study sites and the widespread dispersion of Veterans with GWI. The goal of this study is to assess the efficacy of a novel low-risk therapeutic agent, Bacopa monnieri, for cognitive function in Veterans with GWI and to evaluate the utility of a remote patient-centric study design developed to promote recruitment and minimize participant burden. MAIN METHODS To promote effective participant recruitment, we developed a remote patient-centric study design. Participants will be recruited online through social media and through a web-based research volunteer list of GW Veterans. An online assessment platform will be used, and laboratory blood draws will be performed at clinical laboratory sites that are local to participants. Furthermore, the assigned intervention will be mailed to each participant. SIGNIFICANCE These study design adaptations will open participation to Veterans nearly nationwide and reduce administrative costs while maintaining methodologic rigor and participant safety in a randomized, placebo-controlled phase II clinical trial.
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Preliminary Report on the Feasibility and Efficacy of the Modified Atkins Diet for Treatment of Mild Cognitive Impairment and Early Alzheimer's Disease.
Brandt, J, Buchholz, A, Henry-Barron, B, Vizthum, D, Avramopoulos, D, Cervenka, MC
Journal of Alzheimer's disease : JAD. 2019;(3):969-981
Abstract
Ketone bodies, the products of fat metabolism, are a source of energy for the brain and are available even when glucose supplies are inadequate (such as with severe carbohydrate deprivation) or its metabolism is faulty (as it is in Alzheimer's disease). This phase I/II randomized clinical trial examined the feasibility of using a modified Atkins diet (MAD) to induce ketogenesis in persons with mild cognitive impairment (MCI) or early AD, and the effect of this diet on memory and other clinical outcomes. In the first 2.5 years of active recruitment, only 27 eligible and willing patients enrolled. After extensive assessment and education, they and their study partners were randomly assigned for 12 weeks to either the MAD or the National Institute on Aging (NIA) recommended diet for seniors. As of April 2018, 9 patients in the MAD arm and 5 in the NIA arm have completed the trial. In spite of extensive teaching, coaching, and monitoring, adherence to both diets was only fair. Among those in the MAD arm who generated at least trace amounts of urinary ketones, there was a large (effect size = 0.53) and statistically significant (p = 0.03) increase in Memory Composite Score between the baseline and week-6 assessment. MAD participants also reported increased energy between baseline and week-6 assessment. Despite challenges to implementing this trial, resulting in a small sample, our preliminary data suggest that the generation of even trace ketones might enhance episodic memory and patient-reported vitality in very early AD.
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Plasma metabolomics in early Alzheimer's disease patients diagnosed with amyloid biomarker.
Peña-Bautista, C, Roca, M, Hervás, D, Cuevas, A, López-Cuevas, R, Vento, M, Baquero, M, García-Blanco, A, Cháfer-Pericás, C
Journal of proteomics. 2019;:144-152
Abstract
An untargeted metabolomics study has been carried out using plasma samples from patients with Mild Cognitive Impairment due to Alzheimer's disease patients (MCI-AD, n = 29) and healthy people (n = 29)). They have been classified following the National Institute on Aging and Alzheimer's Association (NIA-AA) recommendations and cerebrospinal fluid biomarkers. The analytical method was based on liquid chromatography coupled to high resolution mass spectrometry. The data process from the corresponding metabolic profiles retained 1158 molecular features in positive and 424 in negative ionization mode. Differences between metabolomic profiles from MCI-AD patients and healthy participants were investigated using a penalized logistic regression analysis (ElasticNet), and being able to select automatically the most informative variables (53 molecular features). From the molecular features selected for the elastic net models, 16 variables were preliminarily identified by The Human Metabolome Database (amino acids, lipids…). However, only 4 of these variables were tentatively identified by MS/MS and all ions fragmentation modes, being choline the only confirmed metabolite. Regarding their metabolic pathways, they could be involved in cholinergic system, energy metabolism, amino acids and lipids pathways. To conclude, this is a reliable approach to early AD mechanisms, and choline has been identified as a promising AD diagnosis metabolite. SIGNIFICANCE The untargeted analysis carried out in human plasma samples from early Alzheimer's disease patients and healthy individuals, and the use of sophisticated statistical tools, identified some metabolic pathways and plasma biomarkers. Preliminarily, cholinergic system, energy metabolism, and aminoacids and lipids pathways may be involved in early Alzheimer's disease development.
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Chronic consumption of flavanone-rich orange juice is associated with cognitive benefits: an 8-wk, randomized, double-blind, placebo-controlled trial in healthy older adults.
Kean, RJ, Lamport, DJ, Dodd, GF, Freeman, JE, Williams, CM, Ellis, JA, Butler, LT, Spencer, JP
The American journal of clinical nutrition. 2015;(3):506-14
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Abstract
BACKGROUND Research indicates that the chronic consumption of flavonoids is associated with cognitive benefits in adults with mild cognitive impairment and neurodegenerative disease, although to our knowledge, there have been no such studies in healthy older adults. Furthermore, the effects of commonly consumed orange juice flavanones on cognitive function remain unexplored. OBJECTIVE We investigated whether 8 wk of daily flavanone-rich orange juice consumption was beneficial for cognitive function in healthy older adults. DESIGN High-flavanone (305 mg) 100% orange juice and an equicaloric low-flavanone (37 mg) orange-flavored cordial (500 mL) were consumed daily for 8 wk by 37 healthy older adults (mean age: 67 y) according to a crossover, double-blind, randomized design separated by a 4-wk washout. Cognitive function, mood, and blood pressure were assessed at baseline and follow-up by using standardized validated tests. RESULTS Global cognitive function was significantly better after 8-wk consumption of flavanone-rich juice than after 8-wk consumption of the low-flavanone control. No significant effects on mood or blood pressure were observed. CONCLUSIONS Chronic daily consumption of flavanone-rich 100% orange juice over 8 wk is beneficial for cognitive function in healthy older adults. The potential for flavanone-rich foods and drinks to attenuate cognitive decline in aging and the mechanisms that underlie these effects should be investigated.