Explore the vast range of titles available.

To compare alterations of mitochondria DNA (mtDNA) copy number, single nucleotide polymorphisms (SNPs), and oxidative damage of mtDNA in clinically stable patients with major depressive disorder (MDD). Patients met DSM-IV diagnostic criteria for MDD were recruited from the psychiatric outpatient clinic at Changhua Christian Hospital, Taiwan. They were clinically stable and their medications had not changed for at least the preceding two months. Exclusion criteria were substance-induced psychotic disorder, eating disorder, anxiety disorder or illicit substance abuse. Comparison subjects did not have any major psychiatric disorder and they were medically healthy. Peripheral blood leukocytes were analyzed to compare copy number, SNPs and oxidative damage of mtDNA between the two groups. 40 MDD patients and 70 comparison subjects were collected. The median age of the subjects was 42 years and 38 years in MDD and comparison groups, respectively. Leukocyte mtDNA copy number of MDD patients was significantly lower than that of the comparison group (p = 0.037). MDD patients had significantly higher mitochondrial oxidative damage than the comparison group (6.44 vs. 3.90, p<0.001). After generalized linear model adjusted for age, sex, smoking, family history, and psychotropic use, mtDNA copy number was still significantly lower in the MDD group (p<0.001). MtDNA oxidative damage was positively correlated with age (p<0.001) and MDD (p<0.001). Antipsychotic use was negatively associated with mtDNA copy number (p = 0.036). The study is cross-sectional with no longitudinal follow up. The cohort is clinically stable and generalizability of our result to other cohort should be considered. Our study suggests that oxidative stress and mitochondria may play a role in the pathophysiology of MDD. More large-scale studies are warranted to assess the interplay between oxidative stress, mitochondria dysfunction and MDD.

Depression is highly associated with dementia, and this study will compare the frequencies, severity, and symptoms of depression between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Frequency of depression was determined according to the DSM-IV criteria for major depression or the National Institute of Mental Health criteria for depression in AD (NIMH-dAD). Severity of depression were assessed using the Hamilton Depression Rating Scale, the Cornell Scale for Depression in Dementia, and the depression subscale in Neuropsychiatric Inventory. The rates of depressive symptoms were compared between AD and DLB. A total of 312 patients were investigated (AD/DLB = 241/71). The frequency of major depression was significantly higher (p = 0.017) in DLB (19.7%) than in AD (8.7%). The higher frequency of depression in DLB was not reproduced by using the NIMH-dAD criteria (DLB: AD = 43.7%: 33.2%; p = 0.105). The severity of depression was higher in DLB than in AD according to the Hamilton Depression Rating Scale (p < 0.001) and the Cornell Scale for Depression in Dementia (p < 0.001). Among depressive symptoms, pervasive anhedonia had the highest odds ratio in DLB compared with AD. This is the first study using the NIMH-dAD criteria to investigate the frequency of depression in DLB. Our study shows that co-morbid major depression is more frequent in DLB than in AD. Pervasive anhedonia had the greatest value for the differential diagnosis of depression between DLB and AD.

Previous studies on the clinical and pathological manifestations of Parkinson's disease dementia (PDD) have reported findings more similar to dementia with Lewy bodies (DLB) than to Alzheimer's disease (AD). The aim of this study was to investigate the neuropsychiatric symptoms of PDD compared to DLB and AD. We conducted a retrospective case-control study on 125 newly diagnosed consecutive PDD patients and age- and dementia stage-matched controls with either DLB (N = 250) or AD (N = 500) who visited the same hospital over the same period. For each case and control, neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory (NPI). Overall, 513 (58.6%) patients were female and 362 (41.4%) were male. Comparisons of clinical data revealed that the PDD group, similar to the AD group, had a lower NPI total score, NPI caregiver burden score, and rate of antipsychotic use (all p < 0.001) than the DLB group. One or more psychiatric symptoms were reported in 95.2% of the PDD, 99.2% of the DLB, and 96.8% of the AD patients. The PDD group had lower subscores in the items of delusions, hallucinations, agitation, anxiety, irritation, aberrant motor behavior compared to the DLB group. Severe neuropsychiatric symptoms among all dementia patients were associated with younger age, more advanced stage, and a diagnosis of DLB. Neuropsychiatric symptoms in PDD were more like those in AD than in DLB. Severe neuropsychiatric symptoms in degenerative dementia were associated with younger age, more advanced stage of dementia, and a diagnosis of DLB.

The purpose of this study was to investigate the nutritional status of dementia patients and examine the correlation with sarcopenia, frailty, depression, and quality of life. We enrolled patients aged 60 years and over with Mini Mental State Examination (MMSE) scores ≤ 26 (Taiwan), and dementia diagnosed by a neurologist or psychiatrist. Nutritional status was assessed with the Mini Nutritional Assessment (MNA). Muscle mass was measured by dual-energy X-ray absorptiometry. Muscle strength and endurance were evaluated by handgrip, leg-back strength, dumbbell curls, sit to stand test, and gait speed. Quality of life, frailty, and depression status were measured by questionnaires. Patients with moderate dementia (MMSE ≤ 20) had a significantly lower MNA score, muscle function, and quality of life than patients with mild dementia (p < 0.01). A lower MNA score was significantly associated with the risk of frailty (odds ratio: 4.76, p < 0.01), depression (odds ratio: 3.17, p = 0.03), and poor quality of life (odds ratio: 2.73, p < 0.05), and sarcopenia (odds ratio: 3.97, p = 0.03) after adjusting for potential confounders. In conclusion, patients with dementia were at risk of malnutrition, and nutritional status was associated to the risk of sarcopenia, frailty, depression, and quality of life.

Huntington’s disease (HD) is a progressive and fatal neurodegenerative disease caused by CAG repeat expansion in the coding region of huntingtin (HTT) protein. The accumulation of mutant HTT (mHTT) contributes to neurotoxicity by causing autophagy defects and oxidative stress that ultimately lead to neuronal death. Interestingly, epidemiologic studies have demonstrated that the prevalence of type-2 diabetes, a metabolic disease mainly caused by defective insulin signaling, is higher in patients with HD than in healthy controls. Although the precise mechanisms of mHTT-mediated toxicity remain unclear, the blockade of brain insulin signaling may initiate or exacerbate mHTT-induced neurodegeneration. In this study, we used an in vitro HD model to investigate whether neuronal insulin signaling is involved in mHTT-mediated neurotoxicity. Our results demonstrated that mHTT overexpression significantly impairs insulin signaling and causes apoptosis in neuronal cells. However, treatment with liraglutide, a GLP-1 analogue, markedly restores insulin sensitivity and enhances cell viability. This neuroprotective effect may be attributed to the contribution of the upregulated expression of genes associated with endogenous antioxidant pathways to oxidative stress reduction. In addition, liraglutide stimulates autophagy through AMPK activation, which attenuates the accumulation of HTT aggregates within neuronal cells. Our findings collectively suggest that liraglutide can rescue impaired insulin signaling caused by mHTT and that GLP-1 may potentially reduce mHTT-induced neurotoxicity in the pathogenesis of HD.

Objectives: Dementia is an oxidative stress-related disease. Coenzyme Q10 is a nutrient that occurs naturally in the human body and acts as an antioxidant. The purpose of this study was to investigate the relationships of coenzyme Q10 status, biomarkers for dementia (amyloid β and tau protein), and antioxidant capacity in patients with dementia. Methods: Eighty dementia patients aged ≥ 60 years and with a Mini Mental State Examination (MMSE) score ≤ 26 were enrolled. The levels of coenzyme Q10, total antioxidant capacity (TAC), amyloid β, and tau protein were measured. Results: A total of 73% of patients had a low coenzyme Q10 status. Patients with low coenzyme Q10 status had a significantly higher level of serum amyloid β-42 and amyloid β-42/40 ratio (p < 0.05). Coenzyme Q10 status was significantly correlated with the values of TAC, MMSE score, amyloid β-42, and amyloid β-42/40 ratio (p < 0.05) but not with tau protein. Additionally, a high proportion of moderate dementia patients were found to have low coenzyme Q10 status (p = 0.07). Conclusion: Patients with dementia suffered from coenzyme Q10 deficiency, and the degree of deficiency was related to the level of amyloid-β and antioxidant capacity. Since adequate level of coenzyme Q10 may delay the progression of dementia, monitoring coenzyme Q10 status in patients with dementia is necessary.

The association between smoking and suicide is still controversial, particular for early life cigarette smoking exposure. Few studies have investigated this association in adolescents using population-based cohorts, and the relationship with second hand smoking (SHS) exposure has not been addressed. In this study, we followed a large population-based sample of younger people to investigate the association between smoking, SHS exposure and suicide mortality. Between October 1995 and June 1996, 162,682 junior high school students ages 11 to 16 years old living in a geographic catchment area in Taiwan were enrolled and then followed till December 2007 (1,948,432 person-years) through linkage to the National Death Certification System. Participants who were currently smoking at baseline had a greater than six-fold higher suicide mortality than those who did not smoke (29.5 vs. 4.8 per 100,000 person-years, p<0.001) as well as higher natural mortality (33.7 vs. 10.3 per 100,000 person-years, p<0.001). After controlling for gender, age, parental education, asthma, allergic rhinitis, and alcohol consumption, the adjusted hazard ratios for suicide were 3.69 (95% CI 1.85-7.39) in current smokers, and 1.47 (95% CI 0.94-2.30) and 2.83 (95% CI 1.54-5.20) respectively in adolescents exposed to SHS of 1-20 cigarettes and >20 cigarettes/per day. The estimated depression-adjusted odds ratio did not change substantially. The population attributable fractions for suicide associated with smoking and heavy SHS exposure (>20 cigarettes/per day) were 9.6% and 10.6%, respectively. This study showed evidence of excess suicide mortality among young adults exposed to active or passive early life cigarette smoking.

The effective dose (HE) and organ or tissue equivalent dose (HT) for use in brain computed tomography (CT) examinations with various body weights were evaluated. Thermoluminescent dosimeters (TLD-100H) were inserted into Rando and five anthropomorphic phantoms. These phantoms were made of polymethylmethacrylate (PMMA), according to the specifications of ICRU 48, with masses from 10 to 90 kg. Brain CT examinations were conducted, scanning the maxillae from the external auditory meatus to the parietal bone using a 128-slice multi-detector CT (MDCT) scanner. To reduce errors, three independent trials were conducted. Calculated HE,TLD, based on the weighting factor recommended by ICRP 103, was 1.72 ± 0.28 mSv, which slightly exceeds the HE,DLP of 1.70 mSv, that was calculated from the dose–length product (DLP) of the Rando phantom. This experiment yielded HE,TLD values of ICRP 103 from the highest 1.85 ± 0.28 (90 kg) to the lowest 1.47 ± 0.22 (10 kg) mSv. HE,TLD (mSv) = 5.45×10−3 W(kg) + 1.361, with an R2 of 0.87667. Using the DLP protocol, HE,DLP was estimated from CTDIvol that was recorded directly from the console display of the CT unit and multiplied by the conversion coefficient (k) recommended by the ICRP 103. Finally, the experimental results obtained herein are compared with those in the literature. Physicians should choose and adjust protocols to prevent the exposure of patients to unnecessary radiation, satisfying the as low as reasonably achievable (ALARA) principle. These findings will be valuable to patients, physicians, radiologists and the public.

When studying the range of toxic substances triggering dementia, special attention should be paid to the materials used in dental practice, particularly to dental fillings containing amalgam. This necessitated conducting large-scale epidemiologic studies. The aim of our research was to determine the risk factors for developing dementia when filling materials containing amalgam are used in dental practice. In order to achieve the set goals, the following tasks were undertaken: (1) The social and demographic characteristics of the examined patients were studied; (2) the spectrum of concomitant somatic diseases was determined in patients of different gender and age; and (3) the relationship between dementia incidence and the volume of dental filling material containing amalgam was identified in patients with different somatic diseases. In general, the research conducted did not reveal any direct relationship between the development of dementia and the volume of filling material containing amalgam. However, among the people with dementia, there were persons for whom its progression was accelerated in cases where a large volume of dental filling material containing amalgam was present.

Chondroitin sulfate synthases, a family of enzyme involved in chondroitin sulfate (CS) polymerization, are dysregulated in various human malignancies, but their roles in glioma remain unclear. We performed database analysis and immunohistochemistry on human glioma tissue, to demonstrate that the expression of CHSY1 was frequently upregulated in glioma, and that it was associated with adverse clinicopathologic features, including high tumor grade and poor survival. Using a chondroitin sulfate-specific antibody, we showed that the expression of CHSY1 was significantly associated with CS formation in glioma tissue and cells. In addition, overexpression of CHSY1 in glioma cells enhanced cell viability and orthotopic tumor growth, whereas CHSY1 silencing suppressed malignant growth. Mechanistic investigations revealed that CHSY1 selectively regulates PDGFRA activation and PDGF-induced signaling in glioma cells by stabilizing PDGFRA protein levels. Inhibiting PDGFR activity with crenolanib decreased CHSY1-induced malignant characteristics of GL261 cells and prolonged survival in an orthotopic mouse model of glioma, which underlines the critical role of PDGFRA in mediating the effects of CHSY1. Taken together, these results provide information on CHSY1 expression and its role in glioma progression, and highlight novel insights into the significance of CHSY1 in PDGFRA signaling. Thus, our findings point to new molecular targets for glioma treatment.