scholarly journals Effects of Cyclophosphamide and/or Doxorubicin in a Murine Model of Postchemotherapy Cognitive Impairment

2017 ◽  
Vol 162 (2) ◽  
pp. 462-474 ◽  
Author(s):  
Timothy J Flanigan ◽  
Julie E Anderson ◽  
Ikram Elayan ◽  
Antiño R Allen ◽  
Sherry A Ferguson
Keyword(s):  
Cognitive Impairment ◽  
Dentate Gyrus ◽  
Test Performance ◽  
Motor Coordination ◽  
Human Condition ◽  
Spatial Learning And Memory ◽  
Exact Nature ◽  
Spine Density ◽  
Breast Cancer Patients ◽  
Route Of Exposure

Abstract Postchemotherapy cognitive impairment, or PCCI, is a common complaint, particularly among breast cancer patients. However, the exact nature of PCCI appears complex. To model the human condition, ovariectomized C57BL/6J mice were treated intravenous weekly for 4 weeks with saline, 2 mg/kg doxorubicin (DOX), 50 mg/kg cyclophosphamide (CYP), or DOX + CYP. For the subsequent 10 weeks, mice were assessed on several behavioral tests, including those measuring spatial learning and memory. After sacrifice, hippocampal spine density and morphology in the dentate gyrus, CA1, and CA3 regions were measured. Additionally, hippocampal levels of total glutathione, glutathione disulfide, MnSOD, CuZnSOD, and cytokines were measured. Body weight decreased in all groups during treatment, but recovered post-treatment. Most behaviors were unaffected by drug treatment: Open field activity, motor coordination, grip strength, water maze and Barnes maze performance, buried food test performance, and novel object and object location recognition tests. There were some significant effects of CYP and DOX + CYP treatment during the initial test of home cage behavior, but these did not persist into the second and third test times. Density of stubby spines, but not mushroom or thin spines, in the dentate gyrus was significantly decreased in the DOX, CYP, and DOX + CYP treatment groups. There were no significant effects in the CA1 or CA3 regions. CuZnSOD levels were significantly increased in DOX + CYP-treated mice; other hippocampal antioxidant levels were unaffected. Most cytokines showed no treatment-related effects, but IL-1β, IL-6, and IL-12 were slightly reduced in mice treated with DOX + CYP. Although the animal model, route of exposure, and DOX and CYP doses used here were reflective of human exposure, there were only sporadic effects due to chemotherapeutic treatment.

scholarly journals SAT-285 TSH/TSHR Signaling Deficiency Impairs Spatial Learning and Memory

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sisi Luan ◽  
He Zhao ◽  
Jiajun Zhao
Keyword(s):  
Cognitive Impairment ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Dendritic Spine ◽  
Spatial Learning And Memory ◽  
Mrna Levels ◽  
Subclinical Hyperthyroidism ◽  
Spine Density ◽  
Cross Sectional ◽  
Synaptic Density

Abstract Background: Subclinical hyperthyroidism is associated with cognitive impairment, but the mechanism has remained unclear. As subclinical hyperthyroidism is characterized by significantly decreased TSH levels, this study aimed to investigate whether TSH regulates cognitive function. Methods: The correlation between TSH and cognitive impairment was investigated in a cross-sectional population study. The role of TSH/TSH receptor (TSHR) signaling in spatial learning and memory was further examined by behavior tests in Tshr-/- mice. Dendritic spine, synaptic density and structure of hippocampal CA1 pyramidal neurons were detected by Golgi’s method and electron microscopy. The mRNA and protein expression levels of learning and memory-related genes were assessed by RNA sequencing, real-time PCR, immunoblotting and immunofluorescence approaches. Results: Serum TSH level correlated negatively with cognitive impairment in the current population. Consistently, Tshr deletion in mice led to significantly compromised performance in hippocampus-dependent tasks, reduced dendritic spine density and excitatory synaptic density as well as altered synaptic structure in CA1 subfield of the hippocampus. Furthermore, the mRNA levels of learning and memory-related genes were altered, and protein levels of CREB-regulated genes were downregulated in the hippocampus of Tshr-/- mice. Conclusions: These findings reveal that TSH/TSHR signaling ablation impairs spatial learning and memory, indicating a decline in TSH level might contribute to the increased prevalence of cognitive impairment in subclinical hyperthyroidism patients.

scholarly journals An Evaluation of DNA Methyltransferase 1 (DNMT1) Single Nucleotide Polymorphisms and Chemotherapy-Associated Cognitive Impairment: A Prospective, Longitudinal Study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alexandre Chan ◽  
Angie Yeo ◽  
Maung Shwe ◽  
Chia Jie Tan ◽  
Koon Mian Foo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Cancer Patients ◽  
Dna Methyltransferase ◽  
Dna Methyltransferases ◽  
Breast Cancer Patients ◽  
Prospective Longitudinal Study ◽  
Cognitive Domains ◽  
Prospective Longitudinal

Abstract Strong evidence suggests that genetic variations in DNA methyltransferases (DNMTs) may alter the downstream expression and DNA methylation patterns of neuronal genes and influence cognition. This study investigates the association between a DNMT1 polymorphism, rs2162560, and chemotherapy-associated cognitive impairment (CACI) in a cohort of breast cancer patients. This is a prospective, longitudinal cohort study. From 2011 to 2017, 351 early-stage breast cancer patients receiving chemotherapy were assessed at baseline, the midpoint, and the end of chemotherapy. DNA was extracted from whole blood, and genotyping was performed using Sanger sequencing. Patients’ self-perceived cognitive function and cognitive performance were assessed at three different time points using FACT-Cog (v.3) and a neuropsychological battery, respectively. The association between DNMT1 rs2162560 and cognitive function was evaluated using logistic regression analyses. Overall, 33.3% of the patients reported impairment relative to baseline in one or more cognitive domains. Cognitive impairment was observed in various objective cognitive domains, with incidences ranging from 7.2% to 36.9%. The DNMT1 rs2162560 A allele was observed in 21.8% of patients and this was associated with lower odds of self-reported cognitive decline in the concentration (OR = 0.45, 95% CI: 0.25–0.82, P = 0.01) and functional interference (OR = 0.48, 95% CI: 0.24–0.95, P = 0.03) domains. No significant association was observed between DNMT1 rs2162560 and objective cognitive impairment. This is the first study to show a significant association between the DNMT1 rs2162560 polymorphism and CACI. Our data suggest that epigenetic processes could contribute to CACI, and further studies are needed to validate these findings.

scholarly journals “The Dichotic Digit Test” as an Index Indicator for Hearing Problem in Dementia: Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Nattawan Utoomprurkporn ◽  
Chris J.D. Hardy ◽  
Joshua Stott ◽  
Sergi G. Costafreda ◽  
Jason Warren ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cognitive Impairment ◽  
Speech Processing ◽  
Test Performance ◽  
Meta Analysis ◽  
Control Group ◽  
People With Dementia ◽  
Ear Advantage ◽  
Right Ear Advantage ◽  
Dementia Onset

Abstract Background Patients with dementia commonly have problems processing speech in the presence of competing background speech or noise. This difficulty can be present from the very early stages of dementia, and may be a preclinical feature of Alzheimer's disease. Purpose This study investigates whether people with dementia perform worse on the dichotic digit test (DDT), an experimental probe of speech processing in the presence of competing speech, and whether test performance may predict dementia onset. Research Design Systematic review and meta-analysis. Data Collection and Analysis A literature search was conducted in Medline, Embase, Scopus, and Psycinfo. We included (1) studies that included people with a diagnosis of dementia and a healthy control group with no cognitive impairment; (2) studies that reported results from a DDT in a free-recall response task; and (3) studies that had the dichotic digit mean correct percentage score or right-ear advantage, as outcome measurements. Results People with dementia had a lower DDT total score, with a pooled mean difference of 18.6% (95% confidence interval [CI]: 21.2–15.9). Patients with dementia had an increased right-ear advantage relative to controls with a pooled difference of 24.4% (95% CI: 21.8–27.0). Conclusion The DDT total scores are lower and the right-ear advantage increased in cognitively impaired versus normal control participants. The findings also suggest that the reduction of dichotic digit total score and increase of right-ear advantage progress as cognitive impairment increases. Whether abnormalities in dichotic digit scores could predict subsequent dementia onset should be examined in further longitudinal studies.

scholarly journals The Clock Drawing Test: Performance differences between the free-drawn and incomplete-copy versions in patients with MCI and dementia

2016 ◽  
Vol 10 (3) ◽  
pp. 227-231 ◽  
Author(s):  
Bárbara Costa Beber ◽  
Renata Kochhann ◽  
Bruna Matias ◽  
Márcia Lorena Fagundes Chaves
Keyword(s):  
Cognitive Impairment ◽  
Test Performance ◽  
Diagnostic Value ◽  
Control Group ◽  
Cognitive Screening ◽  
Scoring Method ◽  
Clock Drawing Test ◽  
Clock Drawing ◽  
Healthy Elderly ◽  
Drawing Test

ABSTRACT Background: The Clock Drawing Test (CDT) is a brief cognitive screening tool for dementia. Several different presentation formats and scoring methods for the CDT are available in the literature. Objective: In this study we aimed to compare performance on the free-drawn and "incomplete-copy" versions of the CDT using the same short scoring method in Mild Cognitive Impairment (MCI) and dementia patients, and healthy elderly participants. Methods: 90 participants (controlled for age, sex and education) subdivided into control group (n=20), MCI group (n=30) and dementia group (n=40) (Alzheimer's disease - AD=20; Vascular Dementia - VD=20) were recruited for this study. The participants performed the two CDT versions at different times and a blinded neuropsychologist scored the CDTs using the same scoring system. Results: The scores on the free-drawn version were significantly lower than the incomplete-copy version for all groups. The dementia group had significantly lower scores on the incomplete-copy version of the CDT than the control group. MCI patients did not differ significantly from the dementia or control groups. Performance on the free-drawn copy differed significantly among all groups. Conclusion: The free-drawn CDT version is more cognitively demanding and sensitive for detecting mild/early cognitive impairment. Further evaluation of the diagnostic value (accuracy) of the free-drawn CDT in Brazilian MCI patients is needed.

Long-term cognitive impairment of breast cancer patients after chemotherapy: A functional MRI study

2016 ◽  
Vol 85 (6) ◽  
pp. 1053-1057 ◽  
Author(s):  
Hui Miao ◽  
Jingjing Li ◽  
Sheng Hu ◽  
Xiaoxuan He ◽  
Savannah C. Partridge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cognitive Impairment ◽  
Cancer Patients ◽  
Functional Mri ◽  
Breast Cancer Patients ◽  
Mri Study
Sign in / Sign up

Export Citation Format

Share Document