OBJECTIVES: To explore the mechanisms of Qingre Lidan Jiedu Recipe (QLJR) for improving cognitive dysfunction in rats with high copper load. METHODS: Seventy-five male SD rats were randomized into normal control group, model group, QLJR group, penicillamine (PCA) group, and QLJR+ PCA group. Except for those in the control group, all the rats were fed a high-copper diet for 12 weeks. The effects of the treatments on cognitive function of the rats were assessed using the Barnes maze and passive avoidance tests. Hippocampal expressions of NIX, FUNDC1 and LC3 of the rats were detected using Western blotting and immunofluorescence staining, and changes in mitochondrial morphology were observed with transmission electron microscopy. RESULTS: Behavioral tests showed prolonged target hole latency, shortened latency to enter the dark chamber, and increased error counts of the rats in the model group, which were significantly improved in QLJR+PCA group; the error counts were significantly lower in QLJR+PCA group than in either QLJR or PCA group. Among all the groups, the hippocampal expressions of NIX and FUNDC1 were the lowest and LC3 I/II expression the highest in the model group; NIX and FUNDC1 expressions were significantly higher and LC3 I expression was lower in QLJR+PCA group than in QLJR group and PCA group. Immunofluorescence staining revealed weakened NIX and FUNDC1 expressions and enhanced LC3 expression in the hippocampus of the rats in the model group as compared with those in the normal control and QLJR+PCA groups, but their expressions did not differ significantly between QLJR and PCA groups. The rats in the model group showed obvious structural disarray of the mitochondria, which were improved in all the treatment groups. CONCLUSIONS QLJR improves cognitive dysfunction in rats with high copper load possibly by regulating mitophagy.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Drugs, Chinese Herbal/therapeutic use* ; Copper/toxicity* ; Mitophagy/drug effects* ; Hippocampus/drug effects* ; Cognition Disorders/drug therapy* ; Cognitive Dysfunction/chemically induced*

PURPOSE: This study was to identify changes in cognitive function and fatigue following chemotherapy in patients with stomach or colorectal cancer. METHODS: Of the participants, 67 underwent adjuvant chemotherapy, while 66 healthy participants made up the comparison group. Three assessment tools were used: 1) the Korean Mini-Mental State Examination; 2) Everyday Cognition; 3) Functional Assessment of Chronic Illness Therapy-Fatigue. The questionnaires were administered in three stages, before chemotherapy, towards the end of chemotherapy, and 6 months after the final chemotherapy session. Data were analyzed using descriptive statistics and repeated measures analysis of variance (RM ANOVA). RESULTS: At the post-chemotherapy stage, 38.8% of the patients who underwent adjuvant chemotherapy complained of subjective cognitive impairment and reported greater difficulty in the cognitive domains of attention and concentration, memory, and executive function. RM ANOVA revealed a significant decline in cognitive function after chemotherapy. However, improvement was observed six months after the completion of chemotherapy (F=42.68, p< .001). Cancer-related fatigue also showed similar patterns as observed in the case of cognitive function (F=44.76, p< .001). CONCLUSION: Chemotherapy was associated with increased cognitive decline and fatigue in cancer patients with cancer. Nursing intervention programs need to be developed to counteract cognitive decline and fatigue in patients undergoing chemotherapy.
Chemotherapy, Adjuvant ; Chronic Disease ; Cognition Disorders ; Cognition ; Colorectal Neoplasms ; Drug Therapy ; Executive Function ; Fatigue ; Gastrointestinal Neoplasms ; Healthy Volunteers ; Humans ; Longitudinal Studies ; Memory ; Nursing ; Prospective Studies ; Stomach

PURPOSE: This study aimed to develop and test a structural model for chemotherapy-related cognitive impairment of breast cancer patients based on a literature review and Hess and Insel's chemotherapy-related cognitive change model. METHODS: The Participants consisted of 250 patients who were ≥19 years of age. The assessment tools included the Menopause Rating Scale, Symptom Experience Scale, Hospital Anxiety and Depression Scale, Everyday Cognition, and Functional Assessment of Cancer Therapy-Breast Cancer. Data were analyzed using the SPSS 21.0 and AMOS 21.0 programs. RESULTS: The modified model was a good fit for the data. The model fit indices were χ2=423.18 (p<.001), χ2/df=3.38, CFI=.91, NFI=.91, TLI=.89, SRMR=.05, RMSEA=.09, and AIC=515.18. Chemotherapy-related cognitive impairment was directly influenced by menopausal symptoms (β=.38, p=.002), depression and anxiety (β=.25, p=.002), and symptom experiences (β=.19, p=.012). These predictors explained 47.7% of the variance in chemotherapy-related cognitive impairment. Depression and anxiety mediated the relations among menopausal symptoms, symptom experiences, and with chemotherapy related cognitive impairment. Depression and anxiety (β=−.51, p=.001), symptom experiences (β=−.27, p=.001), menopausal symptoms (β=−.22, p=.008), and chemotherapy-related cognitive impairment (β=−.15, p=.024) had direct effects on the quality of life and these variables explained 91.3%. CONCLUSION: These results suggest that chemotherapy-related toxicity is highly associated with cognitive decline and quality of life in women with breast cancer. Depression and anxiety increased vulnerability to cognitive impairment after chemotherapy. Nursing intervention is needed to relieve chemotherapy-related toxicity and psychological factor as well as cognitive decline for quality of life in patients undergoing chemotherapy.
Anxiety ; Breast Neoplasms ; Breast ; Cognition ; Cognition Disorders ; Depression ; Drug Therapy ; Female ; Humans ; Menopause ; Models, Structural ; Nursing ; Psychology ; Quality of Life

Multiple Sclerosis (MS) is a chronic disabling neuroinflammatory disease. Psychiatric manifestations have a high prevalence in MS patients and may worsen the illness progression and the patients’ quality of life (QoL). Depression is a highly prevalent condition in MS patients, associated with poorer adherence to treatment, decreased functional status and QoL, and increased suicide risk. Diagnosis and treatment of this disorder is challenging because of symptom overlap. Other prevalent psychiatric comorbidities are anxiety disorders, bipolar disorder, psychotic disorders, substance misuse and personality disorders. As the illness progresses, personality changes can happen, as well as affect abnormalities. Cognitive changes occur frequently in MS patients, and affect features like processing speed, attention, learning, memory, visual spatial capabilities, and some language deficits. Disease-modifying treatments may reduce cognitive impairment because of their container action on the brain’s lesion burden. Other QoL determinants such as fatigue, pain, sexual dysfunction, exercise, resilience and social support should be taken into account, in order to promote the individuals’ well-being. Further studies are needed in order to elucidate the effectiveness of pharmacotherapy and more neuroimaging studies are required to clarify the relationship between structural changes and psychiatric comorbidities.
Anxiety Disorders ; Bipolar Disorder ; Cognition ; Cognition Disorders ; Comorbidity ; Depression ; Diagnosis ; Drug Therapy ; Fatigue ; Humans ; Learning ; Memory ; Multiple Sclerosis ; Neuroimaging ; Personality Disorders ; Prevalence ; Psychotic Disorders ; Quality of Life ; Suicide

Valproic acid (VPA), an agent that is used to treat epileptic seizures, can cause spatial memory impairment in adults and children. This effect is thought to be due to the ability of VPA to inhibit neurogenesis in the hippocampus, which is required for learning. We have previously used an animal model to show that VPA significantly impairs hippocampal-spatial working memory and inhibits neuronal generation in the sub-granular zone of the dentate gyrus. As there are patient reports of improvements in memory after discontinuing VPA treatment, the present study investigated the recovery of both spatial memory and hippocampal neurogenesis at two time points after withdrawal of VPA. Male Wistar rats were given intraperitoneal injections of 0.9% normal saline or VPA (300 mg/kg) twice a day for 10 d. At 1, 30, or 45 d after the drug treatment, the novel object location (NOL) test was used to examine spatial memory; hippocampal cell division was counted using Ki67 immunohistochemistry, and levels of brain-derived neurotrophic factor (BDNF) and Notch1 were measured using western immunoblotting. Spatial working memory was impaired 1 and 30 d after the final administration, but was restored to control levels by 45 d. Cell proliferation had increased to control levels at 30 and 45 d. Both markers of neurogenesis (BDNF and Notch1 levels) had returned to control levels at 45 d. These results demonstrate that memory recovery occurs over a period of six weeks after discontinuing VPA treatment and is preceded by a return of hippocampal neurogenesis to control levels.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Cell Proliferation ; Cognition/drug effects* ; Dentate Gyrus/drug effects* ; Enzyme Inhibitors/pharmacology* ; Hippocampus/metabolism* ; Immunohistochemistry ; Male ; Memory Disorders/therapy* ; Memory, Short-Term/drug effects* ; Neurogenesis/drug effects* ; Neurons/metabolism* ; Rats ; Rats, Wistar ; Receptor, Notch1/metabolism* ; Spatial Memory/drug effects* ; Valproic Acid/pharmacology*

Chemotherapeutic agents induce long-term side effects, including cognitive impairment and mood disorders, particularly in breast cancer survivors who have undergone chemotherapy. However, the precise mechanisms underpinning chemotherapy-induced hippocampal dysfunction remain unknown. In this study, we investigated the detrimental effects of chronic treatment with a combination of adriamycin and cyclophosphamide (AC) on the neuronal architecture and functions of the hippocampi of female C57BL/6 mice. After chronic AC administration, mice showed memory impairment (measured using a novel object recognition memory task) and depression-like behavior (measured using the tail suspension test and forced swim test). According to Golgi staining, chronic AC treatment significantly reduced the total dendritic length, ramification, and complexity as well as spine density and maturation in hippocampal neurons in a sub-region-specific manner. Additionally, the AC combination significantly reduced adult neurogenesis, the extent of the vascular network, and the levels of hippocampal angiogenesis-related factors. However, chronic AC treatment did not increase the levels of inflammation-related signals (microglial or astrocytic distribution, or the levels of pro-inflammatory cytokines or M1/M2 macrophage markers). Thus, chronic AC treatment changed the neuronal architecture of the adult hippocampus, possibly by reducing neurogenesis and the extent of the vasculature, independently of neuroinflammation. Such detrimental changes in micromorphometric parameters may explain the hippocampal dysfunction observed after cancer chemotherapy.
Adult ; Animals ; Breast Neoplasms ; Cognition Disorders ; Cyclophosphamide ; Cytokines ; Doxorubicin ; Drug Therapy ; Female ; Hindlimb Suspension ; Hippocampus ; Humans ; Macrophages ; Memory ; Mice* ; Mood Disorders ; Neurogenesis ; Neurons ; Spine ; Survivors

BACKGROUND/OBJECTIVES: Fermented Laminaria japonica (FL), a type sea tangle used as a functional food ingredient, has been reported to possess cognitive improving properties that may aid in the treatment of common neurodegenerative disorders, such as dementia. MATERIALS/METHODS: We examined the effects of FL on scopolamine (Sco)- and ethanol (EtOH)-induced hippocampus-dependent memory impairment, using the Passive avoidance (PA) and Morris water maze (MWM) tests. To examine the underlying mechanisms associated with neuroprotective effects, we analyzed acetylcholine (ACh) and acetylcholinesterase (AChE) activity, brain tissue expression of muscarinic acetylcholine receptor (mAChR), cAMP response element binding protein (CREB) and extracellular signal-regulated kinases 1/2 (ERK1/2), and immunohistochemical analysis, in the hippocampus of mice, compared to current drug therapy intervention. Biochemical blood analysis was carried out to determine the effects of FL on alanine transaminase (ALT), aspartate transaminase (AST), and triglyceride (TG) and total cholesterol (TC) levels. 7 groups (n = 10) consisted of a control (CON), 3 Sco-induced dementia and 3 EtOH-induced dementia groups, with both dementia group types containing an untreated group (Sco and EtOH); a positive control, orally administered donepezil (Dpz) (4mg/kg) (Sco + Dpz and EtOH + Dpz); and an FL (50 mg/kg) treatment group (Sco + FL50 and EtOH + FL50), orally administered over the 4-week experimental period. RESULTS: FL50 significantly reduced EtOH-induced increase in AST and ALT levels. FL50 treatment reduced EtOH-impaired step-through latency time in the PA test, and Sco- and EtOH-induced dementia escape latency times in the MWM test. Moreover, anticholinergic effects of Sco and EtOH on the brain were reversed by FL50, through the attenuation of AChE activity and elevation of ACh concentration. FL50 elevated ERK1/2 protein expression and increased p-CREB (ser133) in hippocampus brain tissue, according to Western blot and immunohistochemistry analysis, respectively. CONCLUSION: Overall, these results suggest that FL may be considered an efficacious intervention for Sco- and EtOH-induced dementia, in terms of reversing cognitive impairment and neuroplastic dysfunction.
Acetylcholine ; Acetylcholinesterase ; Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Blotting, Western ; Brain ; Cholesterol ; Cognition Disorders* ; Cyclic AMP Response Element-Binding Protein ; Dementia* ; Drug Therapy ; Ethanol ; Extracellular Signal-Regulated MAP Kinases ; Functional Food ; Hippocampus ; Immunohistochemistry ; Laminaria* ; Memory ; Mice* ; Neurodegenerative Diseases ; Neuronal Plasticity* ; Neuroprotective Agents ; Receptors, Muscarinic ; Scopolamine Hydrobromide ; Triglycerides ; United Nations ; Water

Biomarkers are very useful in the diagnosis and identification of neurocognitive impairments (NCIs) or disorders (NCDs) in HIV-infected individuals, and in particular, blood biomarkers have become more promising because they are cheap and easy to obtain or accept. A systematically literature retrieval was conducted by using PubMed, CNKI, Wanfang and VIP databases for studies about blood biomarkers of neurocognitive impairment of HIV-infected individuals in 2008-2017, according to the inclusion and exclusion criteria. Finally, a total of 43 related articles were included for this systematic review for the purpose of providing scientific evidence for further research and clinical practices.
Adult ; Anti-Retroviral Agents/therapeutic use* ; Biomarkers/blood* ; Cognition Disorders/diagnosis* ; Female ; HIV Infections/drug therapy* ; Humans ; Neurocognitive Disorders/diagnosis*

PURPOSE: The purpose of this study was to test a hypothetical model of chemotherapy-related cognitive impairment (CRCI) and depression in people with gastrointestinal cancer. METHODS: A purposive sample of 198 patients undergoing chemotherapy was recruited from November 2014 to July 2015. The instruments were Everyday Cognition (ECog), Hospital Anxiety Depression Scale (HADS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and M. D. Anderson Symptom Inventory-Gastrointestinal Cancer Module. Data were analyzed using descriptive statistics, correlation, and path analysis. RESULTS: CRCI was directly affected by cancer symptoms (β=.19, p=.004) and fatigue (β=.56, p<.001)(R²=47.2%). Depression was directly affected by fatigue (β=.48, p<.001) and CRCI (β=.27, p<.001). However, The impact of cancer symptoms on depression was confirmed through the mediating effect of CRCI. CONCLUSION: Results indicate that in patients with gastrointestinal cancer undergoing chemotherapy along with the direct physiologic effects (fatigue, symptoms) of cancer treatment may have altered cognitive function leading to depression.
Anxiety ; Chronic Disease ; Cognition ; Cognition Disorders* ; Depression* ; Drug Therapy ; Fatigue* ; Gastrointestinal Neoplasms* ; Humans ; Mild Cognitive Impairment ; Negotiating

The neurocognitive function and quality of life of 58 Korean survivors of childhood medulloblastoma were assessed after surgery, cranial radiation and chemotherapy. All patients were evaluated with a battery of neurocognitive function tests and the Pediatric Functional Assessment of Cancer Therapy-Brain Tumor Survivors, which consists of self-report questionnaires on quality of life. The mean full-scale intelligence quotient (IQ), verbal IQ, and performance IQ scores were 90.2, 97.1, and 84.16, respectively. The mean memory quotient (MQ) score was 86.78, which was within 1 standard deviation of the average score of 100. Processing speed, attention, and executive function showed mild to moderate deficits. Intelligence, memory, executive function, visuospatial function, and simple motor function were significantly lower in the patients diagnosed before 8 years of age compared with those diagnosed after 8. The cognitive deficits in the patients diagnosed at younger ages might be related to earlier exposure to craniospinal irradiation and chemotherapy. The patient and parent proxy evaluations of attention, fine motor function, and quality of life did not differ. We found significant neurocognitive changes in a wide range of neurocognitive functional domains in Korean survivors of childhood medulloblastoma. Long-term follow-up studies of survivors of childhood medulloblastoma beginning at the time of their first diagnosis are required to better understand the deficits exhibited by survivors of childhood medulloblastoma, so that intervention strategies and treatment refinements that reduce the long-term neurocognitive decline can be developed.
Cognition ; Cognition Disorders ; Craniospinal Irradiation ; Diagnosis ; Drug Therapy ; Executive Function ; Follow-Up Studies ; Humans ; Intelligence ; Korea ; Medulloblastoma* ; Memory ; Parents ; Proxy ; Quality of Life* ; Survivors*