Oroxylum Indicum ameliorates chemotherapy induced cognitive impairment

While chemotherapy is the most effective therapeutic approach for treating a variety of cancer patients, commonly used chemotherapeutic agents, often induce several adverse effects. Escalating evidence indicates that chemotherapeutics, particularly doxorubicin (DOX) and cyclophosphamide (CPS), induce cognitive impairment associated with central nervous system toxicity. This study was performed to determine neuroprotective effects of Oroxylum indicum extract (OIE) in regard to preventing chemotherapy induced cognitive impairment (CICI) occurring after 4 cycles of DOX (2mg/kg) and CPS (50mg/kg) combination chemotherapy in male C57BL/6J mice. OIE significantly prevented the chemotherapy impaired short-term cognitive performance, exploratory behavior associated with cognitive performance, cognitive performance, and spatial learning and memory in the Y-maze, Open-Field, Novel Object Recognition, and Morris Water Maze tests, respectively. These data suggest that OIE protects from the CICI. OIE decreased the reactive oxygen species and lipid peroxide generated by the chemotherapy treatment in the brain, while also blocking the chemotherapy-induced glutathione depletion. These results establish that OIE exhibits potent antioxidant activity in chemotherapy treated mice. Notably, OIE significantly increased the Complex-I and Complex-IV activities in the brain, indicating that OIE enhances mitochondrial function in the brain. In silico analysis of the major active chemical constituents (Oroxylin A, Baicalein and Chrysin) of OIE indicated that OIE has a favorable absorption, distribution, metabolism and excretion (ADME) profile. Taken together, our results are consistent with the conclusion that OIE prevents CICI by counteracting oxidative stress and perhaps by improving mitochondrial function.

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Cerebral Mitochondrial Function and Cognitive Performance during Aging: A Longitudinal Study in NMRI Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/4060769 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12 ◽

Cited By ~ 7

Author(s):

Martina Reutzel ◽

Rekha Grewal ◽

Benjamin Dilberger ◽

Carmina Silaidos ◽

Aljoscha Joppe ◽

...

Keyword(s):

Longitudinal Data ◽

Cognitive Performance ◽

Mitochondrial Biogenesis ◽

Mitochondrial Function ◽

Aging Process ◽

Brain Aging ◽

Model Organisms ◽

Nmri Mice ◽

Aged Mice ◽

The Brain

Brain aging is one of the major risk factors for the development of several neurodegenerative diseases. Therefore, mitochondrial dysfunction plays an important role in processes of both, brain aging and neurodegeneration. Aged mice including NMRI mice are established model organisms to study physiological and molecular mechanisms of brain aging. However, longitudinal data evaluated in one cohort are rare but are important to understand the aging process of the brain throughout life, especially since pathological changes early in life might pave the way to neurodegeneration in advanced age. To assess the longitudinal course of brain aging, we used a cohort of female NMRI mice and measured brain mitochondrial function, cognitive performance, and molecular markers every 6 months until mice reached the age of 24 months. Furthermore, we measured citrate synthase activity and respiration of isolated brain mitochondria. Mice at the age of three months served as young controls. At six months of age, mitochondria-related genes (complex IV, creb-1, β-AMPK, and Tfam) were significantly elevated. Brain ATP levels were significantly reduced at an age of 18 months while mitochondria respiration was already reduced in middle-aged mice which is in accordance with the monitored impairments in cognitive tests. mRNA expression of genes involved in mitochondrial biogenesis (cAMP response element-binding protein 1 (creb-1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), nuclear respiratory factor-1 (Nrf-1), mitochondrial transcription factor A (Tfam), growth-associated protein 43 (GAP43), and synaptophysin 1 (SYP1)) and the antioxidative defense system (catalase (Cat) and superoxide dismutase 2 (SOD2)) was measured and showed significantly decreased expression patterns in the brain starting at an age of 18 months. BDNF expression reached, a maximum after 6 months. On the basis of longitudinal data, our results demonstrate a close connection between the age-related decline of cognitive performance, energy metabolism, and mitochondrial biogenesis during the physiological brain aging process.

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Investigating Associations Between Inflammatory Biomarkers, Gray Matter, Neurofilament Light and Cognitive Performance in Healthy Older Adults

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.719553 ◽

2021 ◽

Vol 13 ◽

Author(s):

Hollis C. Karoly ◽

Carillon J. Skrzynski ◽

Erin Moe ◽

Angela D. Bryan ◽

Kent E. Hutchison

Keyword(s):

Older Adults ◽

Cognitive Impairment ◽

Cognitive Performance ◽

Gray Matter ◽

Regression Models ◽

Normal Aging ◽

Neurofilament Light ◽

Healthy Older Adults ◽

Analytic Models ◽

The Brain

Background: Exploring biological variables that may serve as indicators of the development and progression of cognitive decline is currently a high-priority research area. Recent studies have demonstrated that during normal aging, individuals experience increased inflammation throughout the brain and body, which may be linked to cognitive impairment and reduced gray matter volume in the brain. Neurofilament light polypeptide (NfL), which is released into the circulation following neuronal damage, has been proposed as a biomarker for neurodegenerative diseases, and may also have utility in the context of normal aging. The present study tested associations between age, peripheral levels of the pro-inflammatory cytokine IL-6, peripheral NfL, brain volume, and cognitive performance in a sample of healthy adults over 60 years old.Methods: Of the 273 individuals who participated in this study, 173 had useable neuroimaging data, a subset of whom had useable blood data (used for quantifying IL-6 and NfL) and completed a cognitive task. Gray matter (GM) thickness values were extracted from brain areas of interest using Freesurfer. Regression models were used to test relationships between IL-6, NfL, GM, and cognitive performance. To test putative functional relationships between these variables, exploratory path analytic models were estimated, in which the relationship between age, IL-6, and working memory performance were linked via four different operationalizations of brain health: (1) a latent GM variable composed of several regions linked to cognitive impairment, (2) NfL alone, (3) NfL combined with the GM latent variable, and (4) the hippocampus alone.Results: Regression models showed that IL-6 and NfL were significantly negatively associated with GM volume and that GM was positively associated with cognitive performance. The path analytic models indicated that age and cognitive performance are linked by GM in the hippocampus as well as several other regions previously associated with cognitive impairment, but not by NfL alone. Peripheral IL-6 was not associated with age in any of the path models.Conclusions: Results suggest that among healthy older adults, there are several GM regions that link age and cognitive performance. Notably, NfL alone is not a sufficient marker of brain changes associated with aging, inflammation, and cognitive performance.

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No evidence that footedness in pheasants influences cognitive performance in tasks assessing colour discrimination and spatial ability

Learning & Behavior ◽

10.3758/s13420-019-00402-8 ◽

2020 ◽

Vol 48 (1) ◽

pp. 84-95 ◽

Cited By ~ 1

Author(s):

Mark A. Whiteside ◽

Mackenzie M. Bess ◽

Elisa Frasnelli ◽

Christine E. Beardsworth ◽

Ellis J.G. Langley ◽

...

Keyword(s):

Cognitive Ability ◽

Cognitive Performance ◽

Individual Performance ◽

Phasianus Colchicus ◽

Spatial Learning And Memory ◽

Stabilizing Selection ◽

Human Species ◽

Wide Range ◽

Population Bias ◽

The Brain

ABSTRACTThe differential specialization of each side of the brain facilitates the parallel processing of information and has been documented in a wide range of animals. Animals that are more lateralized as indicated by consistent preferential limb use are commonly reported to exhibit superior cognitive ability as well as other behavioural advantages. We assayed the lateralization of 135 young pheasants (Phasianus colchicus), indicated by their footedness in a spontaneous stepping task, and related this measure to individual performance in either 3 assays of visual or spatial learning and memory. We found no evidence that pronounced footedness enhances cognitive ability in any of the tasks. We also found no evidence that an intermediate footedness relates to better cognitive performance. This lack of relationship is surprising because previous work revealed that pheasants have a slight population bias towards right footedness, and when released into the wild, individuals with higher degrees of footedness were more likely to die. One explanation for why extreme lateralization is constrained was that it led to poorer cognitive performance, or that optimal cognitive performance was associated with some intermediate level of lateralization. This stabilizing selection could explain the pattern of moderate lateralization that is seen in most non-human species that have been studied. However, we found no evidence in this study to support this explanation.

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CSF and Plasma Cholinergic Markers in Patients With Cognitive Impairment

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.704583 ◽

2021 ◽

Vol 13 ◽

Author(s):

Azadeh Karami ◽

Taher Darreh-Shori ◽

Marianne Schultzberg ◽

Maria Eriksdotter

Keyword(s):

Cognitive Impairment ◽

Cognitive Performance ◽

Protein Concentration ◽

Memory Loss ◽

Chat Activity ◽

Protein Levels ◽

Cholinergic Signaling ◽

Hydrolysis Of ◽

The Brain ◽

Prevalent Form

IntroductionAlzheimer’s disease (AD) is the most prevalent form of dementia with symptoms of deteriorating cognitive functions and memory loss, partially as a result of a decrease in cholinergic neurotransmission. The disease is incurable and treatment with cholinesterase inhibitors (ChEIs) is symptomatic. Choline acetyltransferase (ChAT), the enzyme that synthesizes acetylcholine (ACh), has been proven recently to be present in both cerebrospinal fluid (CSF) and plasma. As ChAT plays a role in regulating the extracellular ACh levels, it may have an impact on prognosis and cognitive performance in AD patients.ObjectivesTo measure ChAT activity and its protein concentration in CSF and plasma from patients with AD, mild cognitive impairment (MCI), or Subjective cognitive impairment (SCI).MethodsPlasma and CSF samples were obtained from 21 AD, 32 MCI, and 30 SCI patients. The activity and protein levels of ChAT and acetylcholinesterase (AChE), the enzyme catalyzing the hydrolysis of ACh, were analyzed using an integrated activity and protein concentration ELISA-like assay. A Cholinergic Index was calculated as the ratio of ChAT to AChE activities in CSF. The data were analyzed in relation to dementia biomarkers and cognitive performance of the patients.ResultsThe CSF ChAT activity was significantly higher (55–67%) in MCI patients compared to AD and SCI cases. The CSF Cholinergic Index was 41 and 22% lower in AD patients than in MCI and SCI subjects, respectively. This index correlated positively with the Aβ42/p-tau ratio in CSF in SCI but negatively with that in AD and MCI. The ChAT activity and protein levels in plasma exhibited significant differences with the pattern of AD>>MCI>SCI.ConclusionThis is the first study investigating soluble levels of the key cholinergic enzyme, ChAT, in both plasma and CSF of individuals at different clinical stages of dementia. Although further validation is needed, the overall pattern of the results suggests that in the continuum of AD, the cholinergic signaling exhibits an inverse U-shape dynamic of changes in the brain that greatly differs from the changes observed in the plasma compartment.

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Mild cognitive impairment: when nutrition helps brain energy rescue—a report from the EuGMS 2020 Congress

European Geriatric Medicine ◽

10.1007/s41999-021-00534-z ◽

2021 ◽

Author(s):

Stephen C. Cunnane ◽

Cornel C. Sieber ◽

Russell H. Swerdlow ◽

Alfonso J. Cruz-Jentoft

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Performance ◽

Alternative Energy ◽

Nutritional Intervention ◽

Older Individuals ◽

Nutritional Interventions ◽

The Brain ◽

Brain Energy

Abstract Background Mild cognitive impairment (MCI) is characterized by a decline in cognition and mainly affects older individuals above the age of 60. The global incidence of MCI varies, but it is often underdiagnosed and untreated. There is a distinct lack of approved pharmacologic options to treat MCI. There is, however, evidence to support the efficacy of nutritional interventions, such as ketogenic supplements/diets, which offer ketones as an alternative energy source to brain cells. This article explores the effect of ketones on metabolic activity in the brain and the mechanisms by which ketogenic medium-chain triglycerides (kMCTs) induce ketosis in patients with MCI. Key takeaways This article reviews the effect of ketogenic supplements/diets on brain metabolism, including evidence supporting the efficacy of ketones as an efficient fuel for the brain. It discusses the use of oral nutritional ketogenic supplements, with particular reference to the 6-month randomized controlled BENEFIC trial, which showed that consumption of a kMCT drink, BrainXpert Energy Complex, improved cognitive performance in individuals with MCI compared with placebo. Conclusion While there is a need for more long-term studies, results from the BENEFIC trial revealed the benefits of a brain-specific ketogenic supplement, as a nutritional intervention, on cognitive performance in individuals with MCI.

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Starving the brain: Structural abnormalities and cognitive impairment in adolescents with anorexia nervosa

Seminars in Clinical Neuropsychiatry ◽

10.1053/scnp.2001.22263 ◽

2001 ◽

Vol 6 (2) ◽

pp. 146-152 ◽

Cited By ~ 57

Author(s):

Debra K. Katzman ◽

Bruce Christensen ◽

Arlene R. Young ◽

Robert B. Zipursky

Keyword(s):

Anorexia Nervosa ◽

Cognitive Impairment ◽

Structural Abnormalities ◽

The Brain

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Brain FDG PET for the Etiological Diagnosis of Clinically Uncertain Cognitive Impairment During Delirium in Remission

Journal of Alzheimer s Disease ◽

10.3233/jad-200530 ◽

2020 ◽

Vol 77 (4) ◽

pp. 1609-1622

Author(s):

Franziska Mathies ◽

Catharina Lange ◽

Anja Mäurer ◽

Ivayla Apostolova ◽

Susanne Klutmann ◽

...

Keyword(s):

Cognitive Impairment ◽

Fdg Pet ◽

False Negative ◽

Ground Truth ◽

Etiological Diagnosis ◽

Geriatric Unit ◽

Positron Emission ◽

The Brain ◽

Hospitalized Geriatric Patients

Background: Positron emission tomography (PET) of the brain with 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG) is widely used for the etiological diagnosis of clinically uncertain cognitive impairment (CUCI). Acute full-blown delirium can cause reversible alterations of FDG uptake that mimic neurodegenerative disease. Objective: This study tested whether delirium in remission affects the performance of FDG PET for differentiation between neurodegenerative and non-neurodegenerative etiology of CUCI. Methods: The study included 88 patients (82.0±5.7 y) with newly detected CUCI during hospitalization in a geriatric unit. Twenty-seven (31%) of the patients were diagnosed with delirium during their current hospital stay, which, however, at time of enrollment was in remission so that delirium was not considered the primary cause of the CUCI. Cases were categorized as neurodegenerative or non-neurodegenerative etiology based on visual inspection of FDG PET. The diagnosis at clinical follow-up after ≥12 months served as ground truth to evaluate the diagnostic performance of FDG PET. Results: FDG PET was categorized as neurodegenerative in 51 (58%) of the patients. Follow-up after 16±3 months was obtained in 68 (77%) of the patients. The clinical follow-up diagnosis confirmed the FDG PET-based categorization in 60 patients (88%, 4 false negative and 4 false positive cases with respect to detection of neurodegeneration). The fraction of correct PET-based categorization did not differ between patients with delirium in remission and patients without delirium (86% versus 89%, p = 0.666). Conclusion: Brain FDG PET is useful for the etiological diagnosis of CUCI in hospitalized geriatric patients, as well as in patients with delirium in remission.

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Exploring the Role of Remote Ischemic Preconditioning In Long Term Cognitive Impairment after Global Ischemia-Reperfusion-Induced Vascular Dementia in Mice

Journal of Clinical and Medical Research ◽

10.37191/mapsci-2582-4333-2(5)-045 ◽

2020 ◽

Author(s):

Amteshwar Singh Jaggi

Keyword(s):

Cognitive Impairment ◽

Cerebral Ischemia ◽

Vascular Dementia ◽

Ischemic Preconditioning ◽

Ischemia Reperfusion ◽

Remote Ischemic Preconditioning ◽

Global Cerebral Ischemia ◽

Cerebral Ischemic ◽

The Brain

Aim: The aim of the present study is to explore the neuroprotective effects of remote ischemic preconditioning in long term cognitive impairment after global cerebral ischemia induced-vascular dementia in mice. Material and methods: The mice were subjected to global cerebral ischemia by occluding the bilateral common carotid arteries for 12 minutes followed by the 24 hours of the reperfusion. The remote ischemic preconditioning stimulus was delivered in the form of 4 cycles of ischemia/reperfusion for 5 minutes each. The cerebral ischemic injury induced-long term cognitive impairment-related learning and memory alterations was assessed using morris water maze, the motor performances of the animals were evaluated using rota-rod test and neurological severity score. The cerebral infract size of the brain were quantified using triphenyltetrazolium chloride staining. Results: Global cerebral ischemia causes long term memory impairment, decreases motor performances and increases the brain infract size in animals. The delivery of remote ischemic preconditioning stimulus significantly abolished the long-term cognitive impairment and ameliorates the motor performances as well as cerebral infract size in brain. Conclusion: The remote ischemic preconditioning mediates neuro protection against global cerebral ischemic injury induced long-term cognitive impairment.

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Analysis of Functional and Cognitive Impairment in Institutionalized Individuals with Movement Disorders

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190311104247 ◽

2019 ◽

Vol 19 (7) ◽

pp. 1022-1031 ◽

Cited By ~ 2

Author(s):

Paula D. Cebrián ◽

Omar Cauli

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Activities Of Daily Living ◽

Cognitive Performance ◽

Functional Impairment ◽

Movement Disorders ◽

Neurological Disorders ◽

Daily Living ◽

Severe Cognitive Impairment

Background: Many neurological disorders lead to institutionalization and can be accompanied in their advanced stages by functional impairment, and progressive loss of mobility, and cognitive alterations. Objective: We analyzed the relationship between functional impairment and cognitive performance and its related subdomains in individuals with Parkinson’s disease, Alzheimer’s disease accompanied by motor dysfunction, and with other neurological disorders characterized by both motor and cognitive problems. Methods: All participants lived in nursing homes (Valencia, Spain) and underwent cognitive evaluation with the Mini-Mental State Examination; functional assessment of independence in activities of daily living using the Barthel score and Katz index; and assessment of mobility with the elderly mobility scale. Results: The mean age of the subjects was 82.8 ± 0.6 years, 47% of the sample included individuals with Parkinson’s disease, and 48 % of the sample presented severe cognitive impairment. Direct significant relationships were found between the level of cognitive impairment and functional capacity (p < 0.01) and mobility (p < 0.05). Among the different domains, memory impairment was not associated with altered activities of daily living or mobility. The functional impairment and the risk of severe cognitive impairment were significantly (p<0.05) higher in female compared to male patients. Among comorbidities, overweight/obesity and diabetes were significantly (p < 0.05) associated with poor cognitive performance in those individuals with mild/moderate cognitive impairment. Conclusion: In institutionalized individuals with movement disorders there is an association between functional and cognitive impairment. Reduction of over-weight and proper control of diabetes may represent novel targets for improving cognitive function at such early stages.

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Using historical data to facilitate clinical prevention trials in Alzheimer disease? An analysis of longitudinal MCI (mild cognitive impairment) data sets

Alzheimer s Research & Therapy ◽

10.1186/s13195-021-00832-5 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Manfred Berres ◽

Andreas U. Monsch ◽

René Spiegel

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Performance ◽

Placebo Treatment ◽

Drug Trial ◽

The Other ◽

Data Sets ◽

Control Groups ◽

Community Needs ◽

Clinical Prevention

Abstract Background The Placebo Group Simulation Approach (PGSA) aims at partially replacing randomized placebo-controlled trials (RPCTs), making use of data from historical control groups in order to decrease the needed number of study participants exposed to lengthy placebo treatment. PGSA algorithms to create virtual control groups were originally derived from mild cognitive impairment (MCI) data of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. To produce more generalizable algorithms, we aimed to compile five different MCI databases in a heuristic manner to create a “standard control algorithm” for use in future clinical trials. Methods We compared data from two North American cohort studies (n=395 and 4328, respectively), one company-sponsored international clinical drug trial (n=831) and two convenience patient samples, one from Germany (n=726), and one from Switzerland (n=1558). Results Despite differences between the five MCI samples regarding inclusion and exclusion criteria, their baseline demographic and cognitive performance data varied less than expected. However, the five samples differed markedly with regard to their subsequent cognitive performance and clinical development: (1) MCI patients from the drug trial did not deteriorate on verbal fluency over 3 years, whereas patients in the other samples did; (2) relatively few patients from the drug trial progressed from MCI to dementia (about 10% after 4 years), in contrast to the other four samples with progression rates over 30%. Conclusion Conventional MCI criteria were insufficient to allow for the creation of well-defined and internationally comparable samples of MCI patients. More recently published criteria for MCI or “MCI due to AD” are unlikely to remedy this situation. The Alzheimer scientific community needs to agree on a standard set of neuropsychological tests including appropriate selection criteria to make MCI a scientifically more useful concept. Patient data from different sources would then be comparable, and the scientific merits of algorithm-based study designs such as the PGSA could be properly assessed.

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