scholarly journals Chemotherapy-Induced Cognitive Impairment and Hippocampal Neurogenesis: A Review of Physiological Mechanisms and Interventions

2021 ◽  
Vol 22 (23) ◽  
pp. 12697
Author(s):  
Melanie J. Sekeres ◽  
Meenakshie Bradley-Garcia ◽  
Alonso Martinez-Canabal ◽  
Gordon Winocur

A wide range of cognitive deficits, including memory loss associated with hippocampal dysfunction, have been widely reported in cancer survivors who received chemotherapy. Changes in both white matter and gray matter volume have been observed following chemotherapy treatment, with reduced volume in the medial temporal lobe thought to be due in part to reductions in hippocampal neurogenesis. Pre-clinical rodent models confirm that common chemotherapeutic agents used to treat various forms of non-CNS cancers reduce rates of hippocampal neurogenesis and impair performance on hippocampally-mediated learning and memory tasks. We review the pre-clinical rodent literature to identify how various chemotherapeutic drugs affect hippocampal neurogenesis and induce cognitive impairment. We also review factors such as physical exercise and environmental stimulation that may protect against chemotherapy-induced neurogenic suppression and hippocampal neurotoxicity. Finally, we review pharmacological interventions that target the hippocampus and are designed to prevent or reduce the cognitive and neurotoxic side effects of chemotherapy.

2021 ◽  
Vol 10 (16) ◽  
pp. e443101622316
Author(s):  
Murilo Bastos ◽  
Kelby Cavalheiro de Mendonça ◽  
Valquiria Camargo Lins ◽  
Eduardo Muzzolon ◽  
Deise Mara Soares ◽  
...  

Alzheimer's disease (AD) is characterized by cognitive impairment and progressive memory loss and drug treatments have limited efficacy. Thus, non-pharmacological interventions, such as music therapy, have shown to be promising as supporting pharmacological treatment and, therefore, may arouse commercial interest regarding the development of this type of product. Thus, this study aims to carry out a patentometric survey on patent registrations with music therapy in the treatment of AD. A systematic search was carried out from 2000 to 2020 on the Orbti-Questel website, searching for documents referring to music therapies in AD. The terms “Alzheimer music methodology active therapy” and “Alzheimer music methodology passive therapy” were used. After searching, reading, and excluding duplicate results, we found four patent families referring to music therapy in AD and all were selected as a result, which was considered little compared to the number of studies published on the subject.


2021 ◽  
Author(s):  
Letícia Requião ◽  
Murilo De Souza

Background: Cognitive vascular impairment (CCV) is a frequent, but overlooked, possible consequence of stroke. The most relevant markers in Magnetic Resonance Imaging (MRI) seem to be, among others, strategic location, severity of white matter changes, as well as the degree of atrophy of the medial temporal lobe. Objective: To assess the relationship between stroke and CCV using markers from MRI. Methods: Systematic review of observational studies published between 2005 and 2020. The search was carried out in the PubMed and SciELO databases with the keywords “stroke”, “MRI”, “Vascular cognitive impairment”. The PRISMA check-list was used to guide this review. Results: 8 studies were selected. “Event location” was the marker in MRI of the skull most frequently considered (7 studies). It proved to be a statistically significant marker (p <0.05) for the prediction of CCV in 6 out 7 studies. 75% of the studies included in this review evaluated the relationship between the presence of “hyperintensity in the white matter” at MRI and CCV. However, this marker was shown to be statistically significant in 50% of these studies. Conclusion: A review that brought together the assessment of a wide range of possible neuroradiological predictors of CVD after stroke had not been carried out so far. Yet it would be particularly useful to evaluate the markers in a more homogeneous way in a study with a larger sample size.


2019 ◽  
Author(s):  
Qingyang Luo ◽  
Xianghong Wu ◽  
Wen Huang

Abstract Background: Autoimmune encephalitis (AE) is a newly recognized autoimmune disorders in which the targets are proteins or receptors involved in synaptic transmission and neuronal excitability. α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is a subtype of glutamate receptor that mediates most of the fast excitatory neurotransmission in the brain. Case presentation: A 50-year-old woman presented with subacute onset of memory loss and behavioral changes. High levels of serum (1:1000) and CSF (1:32) antibodies against the AMPAR GluR2 were detected. A wide range of abnormalities in 6-8 Hz low to middle slow waves was found by electroencephalographs, and high-intensity signals on fluid-attenuated inversion recovery in both the medial temporal lobe and hippocampus were identified on brain magnetic resonance images. This patient presented with myasthenia gravis and type B2 thymoma (World Health Organization Thymoma Classification) at age 48. This case was unique in that the patient initiated with the symptom of myasthenia gravis and thymoma two years prior to encephalitis, and a complete thymectomy was performed before AE onset without recurrence of the thymoma when encephalitis occurred. Conclusions: Thymoma was reported to be associated with paraneoplastic neurological disease. This is the first time a thymectomy has been applied in a myasthenia gravis patient with thymoma two years prior to the onset of anti-AMPAR2 encephalitis. This case highlights the complexity of autoimmune encephalitis associated with thymoma. Keywords: Autoimmune encephalitis, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, thymoma, myasthenia gravis.


2021 ◽  
Author(s):  
Letícia Escorse Requião ◽  
Murilo Santos de Souza

Background: Cognitive vascular impairment (CCV) is a frequent, but overlooked, possible consequence of stroke. Neuroimaging is essential for the evaluation of these patients with cognitive deficits supposedly secondary to vascular lesions, with Nuclear Magnetic Resonance (NMR) of the skull being the most sensitive method for identifying markers associated with CCV. The most relevant markers seem to be, among others, strategic location, severity of white matter changes, as well as the degree of atrophy of the medial temporal lobe. Objective: To assess the relationship between stroke and CCV using markers from skull MRI. Methodology: This is a systematic review of observational studies published between 2005 and 2020. The search was carried out in the PubMed and SciELO databases with the keywords consulted by the following MeSH and DeCS sites: “stroke”, “MRI”, “Vascular cognitive impairment”, using the boolean operator “and”. The PRISMA check-list was used to guide this review. Results: According to the eligibility criteria, eight studies were selected. “Event location” was the marker in MRI of the skull most frequently considered, being the object of evaluation in seven of the eight studies analyzed and proving to be a statistically significant marker (p <0.05) for the prediction of CCV in six of them. 75% of the studies included in this review evaluated the relationship between the presence of “hyperintensity in the white matter” at MRI and CCV. However, this marker was shown to be statistically significant in 50% of these studies. Conclusion: A review that brought together the assessment of a wide range of possible neuroradiological predictors of CVD after stroke had not been carried out so far. It would be particularly useful to evaluate the markers in a more homogeneous way in a study with a larger sample size, which would allow quantitative analysis to measure the influence of each predictor.


2019 ◽  
Author(s):  
Qingyang Luo ◽  
Xianghong Wu ◽  
wen huang

Abstract Background Autoimmune encephalitis (AE) is a newly recognized autoimmune disorders in which the targets are proteins or receptors involved in synaptic transmission and neuronal excitability. α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is a subtype of glutamate receptor that mediates most of the fast excitatory neurotransmission in the brain. Case presentation A 50-year-old woman presented with subacute onset of memory loss and behavioral changes. High levels of serum (1:1000) and CSF (1:32) antibodies against the AMPAR GluR2 were detected. A wide range of abnormalities in 6-8 Hz low to middle slow waves was found by electroencephalographs, and high-intensity signals on fluid-attenuated inversion recovery in both the medial temporal lobe and hippocampus were identified on brain magnetic resonance images. This patient presented with myasthenia gravis and type B2 thymoma (World Health Organization Thymoma Classification) at age 48. This case was unique in that the patient initiated with the symptom of myasthenia gravis and thymoma two years prior to encephalitis, and a complete thymectomy was performed before AE onset without recurrence of the thymoma when encephalitis occurred. Conclusions Thymoma was reported to be associated with paraneoplastic neurological disease. This is the first time a thymectomy has been applied in a myasthenia gravis patient with thymoma two years prior to the onset of anti-AMPAR2 encephalitis. This case highlights the complexity of autoimmune encephalitis associated with thymoma.


BMJ Open ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. e035980 ◽  
Author(s):  
Elyse Couch ◽  
Vanessa Lawrence ◽  
Melissa Co ◽  
Matthew Prina

ObjectivesNon-pharmacological treatments are an important aspect of dementia care. A wide range of interventions have been trialled for mild dementia and mild cognitive impairment (MCI). However, the variety of outcome measures used in these trials makes it difficult to make meaningful comparisons. The objective of this study is to map trends in which outcome measures are used in trials of non-pharmacological treatments in MCI and mild dementia.DesignScoping review.Data sourcesEMBASE, PsychINFO, Medline and the Cochrane Register of Controlled Trials were searched from inception until February 2018. An additional search was conducted in April 2019EligibilityWe included randomised controlled trials (RCTs) testing non-pharmacological interventions for people diagnosed with MCI or mild dementia. Studies were restricted to full RCTs; observational, feasibility and pilot studies were not included.Charting methodsAll outcome measures used by included studies were extracted and grouped thematically. Trends in the types of outcome measures used were explored by type of intervention, country and year of publication.Results91 studies were included in this review. We extracted 358 individual outcome measures, of which 78 (22%) were used more than once. Cognitive measures were the most frequently used, with the Mini-Mental State Examination being the most popular.ConclusionsOur findings highlight an inconsistency in the use of outcome measures. Cognition has been prioritised over other domains, despite previous research highlighting the importance of quality of life and caregiver measures. To ensure a robust evidence base, more research is needed to highlight which outcome measures should be used over others.PROSPERO registration numberCRD42018102649.


2019 ◽  
Vol 16 (7) ◽  
pp. 808-817 ◽  
Author(s):  
Laxmi Banjare ◽  
Sant Kumar Verma ◽  
Akhlesh Kumar Jain ◽  
Suresh Thareja

Background: In spite of the availability of various treatment approaches including surgery, radiotherapy, and hormonal therapy, the steroidal aromatase inhibitors (SAIs) play a significant role as chemotherapeutic agents for the treatment of estrogen-dependent breast cancer with the benefit of reduced risk of recurrence. However, due to greater toxicity and side effects associated with currently available anti-breast cancer agents, there is emergent requirement to develop target-specific AIs with safer anti-breast cancer profile. Methods: It is challenging task to design target-specific and less toxic SAIs, though the molecular modeling tools viz. molecular docking simulations and QSAR have been continuing for more than two decades for the fast and efficient designing of novel, selective, potent and safe molecules against various biological targets to fight the number of dreaded diseases/disorders. In order to design novel and selective SAIs, structure guided molecular docking assisted alignment dependent 3D-QSAR studies was performed on a data set comprises of 22 molecules bearing steroidal scaffold with wide range of aromatase inhibitory activity. Results: 3D-QSAR model developed using molecular weighted (MW) extent alignment approach showed good statistical quality and predictive ability when compared to model developed using moments of inertia (MI) alignment approach. Conclusion: The explored binding interactions and generated pharmacophoric features (steric and electrostatic) of steroidal molecules could be exploited for further design, direct synthesis and development of new potential safer SAIs, that can be effective to reduce the mortality and morbidity associated with breast cancer.


2019 ◽  
Vol 19 (5) ◽  
pp. 599-609 ◽  
Author(s):  
Sumathi Sundaravadivelu ◽  
Sonia K. Raj ◽  
Banupriya S. Kumar ◽  
Poornima Arumugamand ◽  
Padma P. Ragunathan

Background: Functional foods, neutraceuticals and natural antioxidants have established their potential roles in the protection of human health and diseases. Thymoquinone (TQ), the main bioactive component of Nigella sativa seeds (black cumin seeds), a plant derived neutraceutical was used by ancient Egyptians because of their ability to cure a variety of health conditions and used as a dietary food supplement. Owing to its multi targeting nature, TQ interferes with a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Additionally, TQ can specifically sensitize tumor cells towards conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy) and simultaneously minimize therapy-associated toxic effects in normal cells besides being cost effective and safe. TQ was found to play a protective role when given along with chemotherapeutic agents to normal cells. Methods: In the present study, reverse in silico docking approach was used to search for potential molecular targets for cancer therapy. Various metastatic and apoptotic targets were docked with the target ligand. TQ was also tested for its anticancer activities for its ability to cause cell death, arrest cell cycle and ability to inhibit PARP gene expression. Results: In silico docking studies showed that TQ effectively docked metastatic targets MMPs and other apoptotic and cell proliferation targets EGFR. They were able to bring about cell death mediated by apoptosis, cell cycle arrest in the late apoptotic stage and induce DNA damage too. TQ effectively down regulated PARP gene expression which can lead to enhanced cancer cell death. Conclusion: Thymoquinone a neutraceutical can be employed as a new therapeutic agent to target triple negative breast cancer which is otherwise difficult to treat as there are no receptors on them. Can be employed along with standard chemotherapeutic drugs to treat breast cancer as a combinatorial therapy.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 817-817
Author(s):  
Shana Stites

Abstract Many studies find gender differences in how older adults’ report on their memory, perform on cognitive testing, and manage functional impairments that can accompany cognitive impairment. Thus, understanding gender’s effects in aging and Alzheimer’s research is key for advancing methods to prevent, slow, manage, and diagnosis cognitive impairment. Our study, CoGenT3 – The study of Cognition and Gender in Three Generations – seeks to disambiguate the effects of gender on cognition in order to inform a conceptual model, guide innovations in measurement, and support future study. To accomplish this ambitious goal, we have gathered an interdisciplinary team with expertise in psychology, cognition, sexual and gender minorities, library science, measurement, quantitative methods, qualitative methods, and gender and women’s studies. The team benefits from the intersections of expertise in being able to build new research ideas, gain novel insights, and evaluate a wide-range of actions and re-actions but this novelty can also raise challenges.


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