Results Tolcapone was well tolerated and no patients dropped out. The most frequent treatment-related adverse event during tolcapone treatment was elevated liver enzymes (21%). There were no significant differences between tolcapone treatment and placebo in the primary or imaging outcomes. However, there were significant differences between RBANS total scores (p less then 0.01), NPI-Q total scores (p = 0.04), and CGI total scores (p = 0.035) between treatment conditions which were driven by differences between baseline and tolcapone conditions. Further, there was a trend toward significance between tolcapone and placebo on the CGI (p = 0.078). Conclusions Further study of COMT inhibition and related approaches with longer duration of treatment and larger sample sizes in frontotemporal lobar degeneration-spectrum disorders may be warranted.Background Advanced glycation end products (AGEs) are an important risk factor for the development of cognitive decline in aging and late-onset neurodegenerative diseases including Alzheimer's disease. However, whether and how dietary AGEs exacerbate cognitive impairment and brain mitochondrial dysfunction in the aging process remains largely unknown. Objective We investigated the direct effects of dietary AGEs on AGE adducts accumulation, mitochondrial function, and cognitive performance in mice. Methods Mice were fed the AGE+ diet or AGE-diet. We examined levels of AGE adducts in serum and cerebral cortexes by immunodetection and immunohistochemistry, determined levels of reactive oxygen species by biochemical analysis, detected enzyme activity associated with mitochondrial respiratory chain complexes I & IV and ATP levels, and assessed learning and memory ability with Morris Water Maze and Nesting Behavior study. Results Levels of AGE adducts (MG-H1 and CEL) were robustly increased in the serum and brain of AGE+ diet fed mice compared to AGE-group. Furthermore, greatly elevated levels of reactive oxygen species, decreased activities of mitochondrial respiratory chain complexes I & IV, reduced ATP levels, and impaired learning and memory were evident in AGE+ diet fed mice compared to AGE-group. Conclusion These results indicate that dietary AGEs are important sources of AGE accumulation in vivo, resulting in mitochondrial dysfunction, impairment of energy metabolism, and subsequent cognitive impairment. Thus, reducing AGEs intake to lower accumulation of AGEs could hold therapeutic potential for the prevention and treatment of AGEs-induced mitochondrial dysfunction linked to cognitive decline.Background There is an urgent need to develop feasible biomarkers for diagnosis and prognosis of Alzheimer's disease (AD). Mounting evidence implicates that dysregulation of energy metabolism is a key and early event in AD pathogenesis. AMP-activated protein kinase (AMPK) is a central molecular sensor that plays a critical role in maintaining cellular energy homeostasis, and aberrant brain AMPK activities are linked to AD pathophysiology. Objective We aimed to investigated protein levels of AMPKα isoforms, AMPKα1 and AMPKα2, in plasma samples from patients clinically diagnosed with mild cognitive impairment (MCI) or AD, along with age-matched healthy controls. Methods 30 participants (10 MCI, 10 AD, and 10 controls) were included in our pilot study. Plasma levels of AMPKα1 and AMPKα2 were determined by ELISA. Receiver operating characteristic (ROC) analysis was used to assess sensitivity and specificity. Linear regression was used to assess the correlation between levels of AMPKα isoforms and other biomarkers. Results Plasma levels of AMPKα1 were decreased in MCI and AD patients, while levels of AMPKα2 were unaltered as compared to controls. ROC analysis showed relatively high sensitivity and specificity for AMPKα1 to distinguish MCI and AD from controls. Linear regression analysis showed that plasma levels of AMPKα1 were correlated with a brain imaging biomarker (AD signature cortical thicknesses). Conclusion Plasma levels of AMPKα1 were decreased in MCI and AD patients. Future endeavor to explore whether blood AMPKα1 protein expression has the value as a potential biomarker for AD and MCI diagnosis shall be encouraged.Background The environment of patients with Alzheimer's disease and related disorders (ADRD) intensifies the consequences of cognitive impairment and exacerbates behavioral problems if inappropriate or, conversely, mitigate these problems if its design is tailored to the needs of these persons. Objective We evaluate the impacts of hospitalization and of a specific healing garden on self-consciousness which represent a central impairment in ADRD. The self-consciousness questionnaire (SCQ), validated for its assessment at mild to moderate phases of the disease, explores the dimensions of personal identity, awareness of cognitive deficiencies, self-assessment of affective state, awareness of body representation, prospective memory, capacity for introspection, and moral judgments. Methods After having verified, by means of a preliminary study, its feasibility to the more advanced stages of the disease, this questionnaire allowed assessment of the impact of the environment by comparing, in routine care, patients hospitalized in a cognitive-behavioral unit who solely remain indoors with others who use the Art, Memory and Life healing garden. Results A significant decrease in SCQ due to an increase in anosognosia during hospitalization was observed in the group that remained indoors. For the group using the garden, a positive effect on overall SCQ score was observed, as a result of a significant improvement in body representation as the driving parameter. Conclusion Factors that are grounded in the hypotheses that spearheaded its conception, such as sensory enrichment, familiarity, contact with nature, scaffolding role for cognitive functions, supportive effect for social interactions, and the "Nancy hypotheses of beauty", thus contribute to their validation.Background Calcium and vitamin D deficiency is common among Iranian women of childbearing age and poses adverse effects on pregnancy outcomes. The aim of the current study was to determine the prevalence of vitamin D and calcium in a sample of Iranian pregnant women and to assess its correlation with the feto-maternal outcomes. With this aim. Methods In this prospective cross-sectional study, a sample of pregnant women between 15 to 45 years who were in the third trimester were recruited from a number of hospitals in Tehran. Data were collected by the means of a self-developed questionnaire, interviews, physical examination, and paraclinical tests including measuring the serum level of calcium, vitamin D, parathormone (PTH) and phosphorous (Pi). The questionnaire obtained information on age, level of education, socio-economic status, parity, gravidity, calcium intake during pregnancy, as well as feto-maternal outcomes. Results We included a total number of 233 singleton pregnancies. selleck products Most of the subjects (58.4%) had vitamin D deficiency and 12.