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Retinal Levels of Amyloid Beta Correlate with Cerebral Levels of Amyloid Beta in Young APPswe/PS1dE9 Transgenic Mice before Onset of Alzheimer’s Disease
Objectives. Retina abnormalities are related to cognitive disorders in patients with Alzheimer’s disease (AD). Retinal amyloid beta (Aβ) can be labeled by curcumin. We measured Aβ content in the cerebrum and retina of APPswe/PS1dE9 (APP) transgenic mice with early age to investigate the correlation between cerebrum and retina. Methods. APP mice and age-matched wild-type mice were investigated every month from age 2 months to 6 months to assess changes in Aβ content in the retina and cerebrum. At the beginning of each month, mice were fed a curcumin diet (50 mg/kg/day) for 7 consecutive days. The Aβ levels in the retina and cerebrum were measured by ELISAs. Correlations were identified between retinal and cerebral Aβ contents using Pearson’s correlation. Results. In the absence of curcumin, there was a significant correlation between Aβ contents in the retina and cerebrum of APP mice (, ). With increasing age, Aβ-mediated degenerative change in the cerebrum ( in 5 months) and retina ( in 5 months) increased significantly. The inhibitory effect of curcumin on the Aβ level was significant in the cerebrum () and retina () of older APP mice in the early stage of life. Conclusion. We observed a significant correlation between the Aβ content in the retina and Aβ content in the cerebrum of APP mice. Our data suggest an appropriate time to measure retinal Aβ. Although curcumin can label Aβ in the retina, it also suppresses Aβ levels and weakens the degree of correlation between Aβ in cerebrum and retina tissues.
Comparison of Performance on the Clock Drawing Test Using Three Different Scales in Dialysis Patients
Background. The clock drawing test (CDT) is frequently used to detect changes in cognition. Multiple scales of varying length have been published to assess performance. The aim of this study is to compare the CDT performance measured by three scales among a sample of nondemented patients on renal dialysis and identify the variables that affect performance. Methodology. This is a cross-sectional study performed at the dialysis unit at King Saud University Medical City. Eighty-nine dialysis patients performed the CDT. The CDT was scored by the methods of Rouleau et al. (RCS 10-point), Babins et al. (BCS 18-point), and the MoCA (MCS 3-point). Regression models were used to determine influencing demographic and dialysis variables. Scores were then correlated, and a combined factor analysis of scale components was done. Results. Females represented 44.6%, the mean (SD) age was 49.99 (15.49) years, and education duration was 10.29 (5.5) years. Dialysis vintage was 55.81 (62.91) months. The scores for the MCS, RCS, and BCS were 2.18 (1.08), 6.67 (3.07), and 11.8 (5.5), respectively, with significant correlation (). In all scales, increasing age was associated with a lower score (each ). The scores increased with increasing education (each ). Diabetics had a lower score on both the BCS and MCS by 2.56 (SE 1.2) () and 0.71 () points, respectively. However, only age and years of education were significant in the multivariable analysis. In factor analysis, two shared factors appeared between the three scales: hand and number placement and the clock face. Conclusion. Age and education influence the performance on the CDT, and factors diverged into executive and visuospatial components. The MCS is likely to yield useful information but should be interpreted as part of the MoCA.
Evaluating Executive Functions in Patients with Juvenile Myoclonic Epilepsy Using Frontal Assessment Battery
Objective. In this study, we aimed to evaluate the executive profile of juvenile myoclonic epilepsy (JME) patients using the Frontal Assessment Battery (FAB) as a bedside screening tool and investigate its association with seizure proximity, family history of epilepsy, and polytherapy/monotherapy with antiepileptic drugs (AEDs). Background. JME patients have deficits in various aspects of executive functions. FAB has proved to be a useful tool for evaluating executive functions in clinical settings. Methods. Thirty-one JME patients and 110 healthy controls (HCs) were enrolled in this study. The participants were assessed using six subsets of FAB, including conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. Results. Compared to HCs, JME patients showed lower scores in conceptualization, mental flexibility, programming, sensitivity to interference, and total FAB. The number of AEDs (polytherapy versus monotherapy) and duration of time since the last seizure had no significant effect on FAB scores in JME patients. We found significant associations between disease duration and conceptualization, mental flexibility, inhibitory control, and total FAB score only in JME patients with recent seizure. Finally, receiver operating characteristic (ROC) analysis showed area under the curve (AUC) of 0.971 (95% confidence interval (CI): 0.947–0.994) for FAB total score, 0.933 for conceptualization (95% CI: 0.973-894), and 0.836 for mental flexibility (95% CI: 0.921-751). Conclusions. In summary, JME patients had deficits in different aspects of executive functions. FAB is a useful clinical tool for evaluation of executive functions in JME patients.
Abnormal Homocysteine Metabolism: An Insight of Alzheimer’s Disease from DNA Methylation
Alzheimer’s disease (AD) is a chronic neurodegenerative disease in the central nervous system that has complex pathogenesis in the elderly. The current review focuses on the epigenetic mechanisms of AD, according to the latest findings. One of the best-characterized chromatin modifications in epigenetic mechanisms is DNA methylation. Highly replicable data shows that AD occurrence is often accompanied by methylation level changes of the AD-related gene. Homocysteine (Hcy) is not only an intermediate product of one-carbon metabolism but also an important independent risk factor of AD; it can affect the cognitive function of the brain by changing the one-carbon metabolism and interfering with the DNA methylation process, resulting in cerebrovascular disease. In general, Hcy may be an environmental factor that affects AD via the DNA methylation pathway with a series of changes in AD-related substance. This review will concentrate on the relation between DNA methylation and Hcy and try to figure out their rule in the pathophysiology of AD.
A Novel Metabolic Connectome Method to Predict Progression to Mild Cognitive Impairment
Objective. Glucose-based positron emission tomography (PET) imaging has been widely used to predict the progression of mild cognitive impairment (MCI) into Alzheimer’s disease (AD) clinically. However, existing discriminant methods are unsubtle to reveal pathophysiological changes. Therefore, we present a novel metabolic connectome-based predictive modeling to predict progression from MCI to AD accurately. Methods. In this study, we acquired fluorodeoxyglucose PET images and clinical assessments from 420 MCI patients with 36 months follow-up. Individual metabolic network based on connectome analysis was constructed, and the metabolic connectivity in this network was extracted as predictive features. Three different classification strategies were implemented to interrogate the predictive performance. To verify the effectivity of selected features, specific brain regions associated with MCI conversion were identified based on these features and compared with prior knowledge. Results. As a result, 4005 connectome features were obtained, and 153 in which were selected as efficient features. Our proposed feature extraction method had achieved 85.2% accuracy for MCI conversion prediction (sensitivity: 88.1%; specificity: 81.2%; and AUC: 0.933). The discriminative brain regions associated with MCI conversion were mainly located in the precentral gyrus, precuneus, lingual, and inferior frontal gyrus. Conclusion. Overall, the results suggest that our proposed individual metabolic connectome method has great potential to predict whether MCI patients will progress to AD. The metabolic connectome may help to identify brain metabolic dysfunction and build a clinically applicable biomarker to predict the MCI progression.
Neuropsychological and Emotional Functioning in Patients with Cushing’s Syndrome
Patients with Cushing’s syndrome (CS) frequently report impairments in cognitive and emotional functioning. Given neuroimaging research that implicates alterations in structure and function in the brain in this population, goals of this study were to investigate neuropsychological and emotional functioning, with particular emphasis on complex attention and memory. In a clinical sample of 18 adults with CS referred for neuropsychological evaluation (age , 72% Caucasian), patients’ most common subjective complaints were in attention and increased irritability. On objective testing, patients exhibited significant declines in the consistency of their sustained attention and visual-spatial functioning compared to normative peers. Patients exhibited on average significantly reduced initial learning following first exposure to visual and verbal stimuli but intact retention of information learned. Patients with CS endorsed highly elevated levels of somatization, depression, and anxiety, and 59% of them scored in the clinically elevated range for somatization and depressive symptomatology. Exploratory analyses suggested that the 11 patients with active Cushing’s exhibited lower processing speed, poorer sustained attention, naming, and cognitive flexibility compared to the 7 patients who achieved biochemical remission. Patients with active Cushing’s also reported higher levels of somatization and anxiety compared to patients in biochemical remission. Overall, this study provides new insights into complex attention and memory deficits in patients with CS and concern regarding cognitive and emotional issues despite resolution of hypercortisolism. Our study opens several avenues for further exploration.