ABSTRACT
Alzheimer's disease (AD) is the most common cause of dementia worldwide. Although, many putative biomarkers are reported for AD, only a few have been validated in the clinical setting. Ubiquitin levels increase in cerebrospinal fluid (CSF) of patients with AD, but its diagnostic value is not clear. In this present study we evaluate the performance of ubiquitin as a diagnostic marker and deduce a statistical association with disease pathology in AD. Ubiquitin levels were estimated in subjects with AD, other forms of dementias, neurological disorders and healthy age matched population. The levels of ubiquitin were significantly higher in subjects with AD when compared with other groups (p<0.0001). A significant positive correlation was observed between ubiquitin, tau and apolipoprotein Eε4 genotype; with Aß42 the correlation was negative. By comparing the effect size of the association between ubiquitin and a diagnosis of AD, we find that high ubiquitin levels are specific for AD. We obtained an odds ratio of 5.6 (95% CI 5.0-7.7) for ubiquitin, towards a diagnosis of AD based on clinical criteria, CSF biomarker signature (Aß42+tau) and apolipoprotein Eε4 genotype. Hence, all our findings taken together provide a strong statistical association linking ubiquitin to the pathology in AD. We also find that, the performance of ubiquitin as a diagnostic marker is comparable to that of CSF Aß42 or tau or apolipoprotein Eε4 genotype considered individually.
Subject(s)
Alzheimer Disease/cerebrospinal fluid , Ubiquitin/cerebrospinal fluid , Adult , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Alzheimer Disease/genetics , Amyloid beta-Peptides/cerebrospinal fluid , Apolipoproteins E/genetics , Biomarkers/cerebrospinal fluid , Dementia/cerebrospinal fluid , Female , Humans , Male , Mental Status Schedule , Middle Aged , Nervous System Diseases/cerebrospinal fluid , Odds Ratio , Peptide Fragments/cerebrospinal fluid , ROC Curve , Sensitivity and Specificity , tau Proteins/cerebrospinal fluidABSTRACT
The etiology of Alzheimer's disease (AD) is multifactorial involving both genetic and environmental factors. Apolipoprotein E (ApoE) gene plays a pivotal role in risk and age of onset of AD. Although it is broadly accepted that ApoE genotype is linked to the pathogenesis of AD, there are still controversial results regarding the association of ApoE levels in cerebrospinal fluid (CSF) with the occurrence of AD. Some studies have shown a positive correlation between CSF ApoE levels and AD, whereas others showed no link. In this study, we measured ApoE levels to assess the usefulness of CSF ApoE as a diagnostic marker of AD by comparing the levels in 3 patient groups and in control participants. No significant difference was observed in CSF ApoE concentrations between the patients with AD and the controls. So, it appears that CSF ApoE measurement does not offer any diagnostic advantage for AD.
Subject(s)
Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/diagnosis , Apolipoprotein E4/cerebrospinal fluid , Apolipoproteins E/cerebrospinal fluid , Aged , Alzheimer Disease/epidemiology , Alzheimer Disease/genetics , Apolipoprotein E4/genetics , Apolipoproteins E/genetics , Biomarkers/cerebrospinal fluid , Female , Gene Frequency , Genotype , Humans , India/epidemiology , Male , Middle Aged , Risk FactorsABSTRACT
OBJECTIVE: To determine the efficacy of a combination of ondansetron and dexamethasone in preventing postoperative nausea and vomiting after middle ear surgery compared with ondansetron alone. DESIGN: A prospective, randomized, double-blind study with prestudy power analysis performed to determine the sample size. SETTING: A tertiary teaching hospital. METHOD: One hundred patients undergoing tympanomastoidectomy under general anesthesia were included in the study. Patients in group O (n = 50) received ondansetron 4 mg and those in group OD (n = 50) received ondansetron 4 mg with dexamethasone 8 mg 30 minutes before the end of surgery. All patients were monitored for nausea score, episodes of vomiting, and rescue antiemetic requirement in 48 hours after surgery. The total number of complete responders was calculated. Patients' satisfaction at the end of the study period was also estimated. RESULTS: In patients receiving combination antiemetic (group OD), the nausea score was significantly less (p < .01) at 6, 12, and 24 hours after surgery. The total incidence of vomiting was reduced from 28% in group O to 6% in group OD. Rescue antiemetic requirement was significantly less (p < .01) in group OD. The number of complete responders significantly improved in the combination group (92% vs 62%). The patients were also found to be more satisfied in this group. CONCLUSION: Prophylaxis with a combination of ondansetron and dexamethasone decreased the incidence of nausea and vomiting after middle ear surgery to a minimum and improved patients' satisfaction significantly in the postoperative period.
