Melatonin is a hormone secreted by the pineal gland, it can be associated with circadian rhythms, aging and neuroprotection. Melatonin levels are decreased in sporadic Alzheimer\'s disease (sAD) patients, which suggests a relationship between the melatonergic system and sAD. Melatonin may reduce inflammation, oxidative stress, TAU protein hyperphosphorylation, and the formation of β-amyloid (Aβ) aggregates. Therefore, the objective of this work was to investigate the impact of treatment with 10 mg/kg of melatonin (i.p) in the animal model of sAD induced by the intracerebroventricular (ICV) infusion of 3 mg/kg of streptozotocin (STZ). ICV-STZ causes changes in the brain of rats similar to those found in patients with sAD. These changes include; progressive memory decline, the formation of neurofibrillary tangles, senile plaques, disturbances in glucose metabolism, insulin resistance and even reactive astrogliosis characterized by the upregulation of glucose levels and glial fibrillary acidic protein (GFAP). The results show that ICV-STZ caused short-term spatial memory impairment in rats after 30 days of STZ infusion without locomotor impairment which was evaluated on day 27 post-injury. Furthermore, we observed that a prolonged 30-day treatment with melatonin can improve the cognitive impairment of animals in the Y-maze test, but not in the object location test. Finally, we demonstrated that animals receiving ICV-STZ have high levels of Aβ and GFAP in the hippocampus and that treatment with melatonin reduces Aβ levels but does not reduce GFAP levels, concluding that melatonin may be useful to control the progression of amyloid pathology in the brain.

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Early to intermediate AMD is characterized by the accumulation of lipid- and protein-rich drusen. Late stages of the disease are characterized by the development of choroidal neovascularization, termed \"exudative\" or \"neovascular AMD,\" or retinal pigment epithelium (RPE) cell and photoreceptor death, termed \"geographic atrophy\" (GA) in advanced nonexudative AMD. Although we have effective treatments for exudative AMD in the form of anti-VEGF agents, they have no role for patients with GA. Neuroprotection strategies have emerged as a possible way to slow photoreceptor degeneration and vision loss in patients with GA. These approaches include reduction of oxidative stress, modulation of the visual cycle, reduction of toxic molecules, inhibition of pathologic protein activity, prevention of cellular apoptosis or programmed necrosis (necroptosis), inhibition of inflammation, direct activation of neurotrophic factors, delivery of umbilical tissue-derived cells, and RPE replacement. Despite active investigation in this area and significant promise based on preclinical studies, many clinical studies have not yielded successful results. We discuss selected past and current neuroprotection trials for AMD, highlight the lessons learned from these past studies, and discuss our perspective regarding remaining questions that must be answered before neuroprotection can be successfully applied in the field of AMD research.

UNASSIGNED: Whether the route of anaesthesia is an independent risk factor for dementia remains unclear. Therefore, we conducted a propensity score-matched (PSM) population-based cohort study to compare dementia incidence among surgical patients undergoing different routes of anaesthesia.
UNASSIGNED: The inclusion criteria were being an inpatient >20 years of age who underwent major elective surgery, defined as those requiring GA without or with inhalation anaesthetics or regional anaesthesia, and being hospitalised for >1 day between Jan 1, 2008 and Dec 31, 2019 in Taiwan. Patients undergoing major elective surgery were categorised into three groups according to the type of anaesthesia administered: noninhalation anaesthesia, inhalation anaesthesia, and regional anaesthesia, matched at a 1:1 ratio. The incidence rate (IR) of dementia was determined.
UNASSIGNED: PSM yielded 63,750 patients (21,250 in the noninhalation anaesthesia group, 21,250 in the inhalation anaesthesia group, and 21,250 in the regional anaesthesia group). In the multivariate Cox regression analysis, the adjusted hazard ratios (aHRs; 95% confidence intervals) of dementia for the inhalation and noninhalation anaesthesia groups compared with the regional anaesthesia group were 20.16 (15.40-26.35; p < 0.001) and 18.33 (14.03-24.04; p < 0.001), respectively. The aHR of dementia for inhalation anaesthesia compared with noninhalation anaesthesia was 1.13 (1.03-1.22; p = 0.028). The IRs of dementia for the inhalation, noninhalation, and regional anaesthesia groups were 3647.90, 3492.00, and 272.99 per 100,000 person-years, respectively.
UNASSIGNED: In this population based cohort study, the incidence of dementia among surgical patients undergoing general anaesthesia was higher than among those undergoing regional anaesthesia. Among patients undergoing general anaesthesia, inhalation anaesthesia was associated with a higher risk of dementia than noninhalation anaesthesia. Our results should be confirmed in a randomised controlled trial.
UNASSIGNED: The study was partially supported by Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital (Funding Number: 10908, 10909, 11001, 11002, 11003, 11006, and 11013).

UNASSIGNED: To assess the repeatability of peripapillary OCT angiography (OCTA) in those with Alzheimer disease (AD), mild cognitive impairment (MCI), Parkinson disease (PD), or normal cognition.
UNASSIGNED: Cross-sectional.
UNASSIGNED: Patients with a clinical diagnosis of AD, MCI, PD, or normal cognition were imaged. Those with glaucoma, diabetes mellitus, vitreoretinal pathology, and poor-quality images were excluded.
UNASSIGNED: Each eligible eye of each participant underwent 2 OCTA 4.5 × 4.5-mm peripapillary scans in a single session using a Zeiss Cirrus HD-OCT 5000 with AngioPlex (Carl Zeiss Meditec). The Zeiss software (v11.0.0.29946) quantified measures of perfusion in the radial peripapillary capillary (RPC) plexus in 4 sectors (superior, nasal, inferior, temporal). The average of these sectors was calculated and reported.
UNASSIGNED: Radial peripapillary capillary plexus perfusion was quantified using 2 parameters: capillary perfusion density (CPD) and capillary flux index (CFI). Intraclass correlation coefficients (ICCs) were used to quantify repeatability. For subjects who had both eyes included, the average values of each scan pair were used to assess interocular symmetry of CPD and CFI.
UNASSIGNED: Of 374 eyes, 46 were from participants who had AD, 85 were from participants who had MCI, 87 were from participants who had PD, and 156 were from participants who had normal cognition. Capillary perfusion density ICC in AD = 0.88 (95% confidence interval [CI], 0.79-0.93), MCI = 0.95 (0.92-0.96), PD = 0.91 (0.87-0.94), and controls = 0.90 (0.87-0.93). Capillary flux index ICC in AD = 0.82 (0.70-0.90), MCI = 0.87 (0.80-0.91), PD = 0.91 (0.87-0.94) and controls = 0.85 (0.79-0.89). There were no significant differences in interocular variation in average CPD and CFI in AD, MCI, or PD (all P > 0.05). Isolated interocular sectoral CPD differences were noted in AD (nasal, P = 0.049; temporal, P = 0.024), PD (nasal, P = 0.036), and controls (nasal, P = 0.016). Interocular differences in CFI in the superior sector in MCI (P = 0.028) and in average CFI for controls (P = 0.035) were observed.
UNASSIGNED: Peripapillary OCTA repeatability in AD, MCI, and PD is good-excellent and similar to those with normal cognition. Insignificant interocular asymmetry in peripapillary OCTA suggests neurodegeneration may proceed uniformly; future studies may reveal the appropriateness of single-eye imaging.

UNASSIGNED: Many neurodegenerative such as Alzheimer\'s disease (AD) are characterized by cholinergic dysfunction and oxidative stress which is a key event in neuronal death process. Thus, anticholinesterase and anti-oxidation compounds are two promising strategies in the development of AD drugs. Beyond their culinary use, spices are today studies for health purpose. In this study, some spices consumed in Cameroon were evaluated for their anticholinesterase and neuroprotective effects.
UNASSIGNED: Colorimetric methods were used to determine total flavonoid and alkaloid content of a combinated extract (hydroethanolic + ethanolic extracts) of different selected spices. Aftermaths, anti-cholinesterase activity of spice extract was carried out using Ellman\'s method. Finally, neuroprotective effects performed on human SK-N-SH cells stressed with H2O2 by assessing neuronal survival ( resazurin assay) and neuronal death (LDH assay).
UNASSIGNED: Flavonoid content of spices extract were ranged from 22.94 to 32.01 mg EQ/g DM and alkaloid content were ranged from 320 to 896 mg EQu/g DM. Among the spices studied, Xylopia parviflora presented the greatest acetylcholinesterase inhibition with an IC50 = 14 µg/mL. In Cell culture experiments, pre-incubation of SK-N-SH cell with the selected spices at different concentrations were improved neuronal survival and reduced the percentage of neuronal cells dead.
UNASSIGNED: The present results reveal that selected spices consumed in Cameroon have good anticholinesterase activity as well as neuroprotective effect on SK-N-SH which may provide new natural compounds that could help in the management of Alzheimer\'s disease.

Compounds that selectively modulate multiple targets can provide clinical benefits and are an alternative to traditional highly selective agents for unique targets. High-throughput screening (HTS) for multitarget-directed ligands (MTDLs) using approved drugs, and fragment-based drug design has become a regular strategy to achieve an ideal multitarget combination. However, the unexpected presence of pan-assay interference compounds (PAINS) suspects in the development of MTDLs frequently results in nonspecific interactions or other undesirable effects leading to artefacts or false-positive data of biological assays. Publicly available filters can help to identify PAINS suspects; however, these filters cannot comprehensively conclude whether these suspects are \"bad\" or innocent. Additionally, these in silico approaches may inappropriately label a ligand as PAINS. More than 80% of the initial hits can be identified as PAINS by the filters if appropriate biochemical tests are not used resulting in false positive data that are unacceptable for medicinal chemists in manuscript peer review and future studies. Therefore, extensive offline experiments should be used after online filtering to discriminate \"bad\" PAINS and avoid incorrect evaluation of good scaffolds. We suggest that the use of \"Fair Trial Strategy\" to identify interesting molecules in PAINS suspects to provide certain structure‒function insight in MTDL development.

Aging is a naturally biological process with adverse effects. The continuous accumulation of reactive oxygen species (ROS) trigger cellular and tissue damage by activating several aging enzymes. The antioxidant properties of traditional medicinal plants used by Jakun aborigine\'s community are a promising approach to alleviate aging process and prevent Alzheimer. The aim of the current investigation was to optimize a novel anti-aging formulation from traditional plants (Cnestis palala stem, Urceola micrantha stem, Marantodes pumilum stem and Microporus xanthopus fruiting bodies) using simplex centroid mixture design (SCMD). After selecting the optimal formulations based on desirability function of antioxidant activity (DPPḢ, ABTS ˙ + and FRAP), they were further examined against the activity of aging-related-enzymes (collagenase, tyrosinase, acetyl- and butyrylcholinesterase). The single extracts of C. palala, U. micrantha and the binary mixture of C. palala and U. micrantha were the optimal formulations with high antioxidant activities. Single extract of U. micrantha showed the highest inhibition towards matrix metalloproteinase-1 (49.44 ± 4.11 %), while C. palala water extract showed highest inhibitions towards tyrosinase (14.06 ± 0.31%), acetylcholinesterase (32.92 ± 2.13%) and butyrylcholinesterase (34.89 ± 2.84%) enzymes. The single extracts of C. palala and U. micrantha displayed better activity as compared to the binary mixture formulation. In conclusion, these findings could be a baseline for further exploration of novel anti-aging agents from natural resources.

A few patients with Hashimoto\'s thyroiditis or Graves\' disease develop a multiform syndrome of the central nervous system (CNS) termed Hashimoto\'s encephalopathy or steroid-responsive encephalopathy associated with autoimmune thyroid disease (HE/SREAT). They have high levels of thyroid autoantibodies (TgAb, TPOAb and/or TSH-R-Ab) in blood and cerebrospinal fluid. Autoantibodies against alpha-enolase, aldehyde reductase-I (AKRIA) and/or dimethylargininase-I (DDAHI), proteins expressed in the CNS among other tissues, were detected in the blood and, when searched, in the cerebrospinal fluid of HE/SREAT patients. Recently, we reported that alpha-enolase, AKRIA and DDAHI share local sequence homology with each of the three autoantigens (TgAb, TPOAb, TSH-R-Ab), often in epitope-containing segments of the thyroid autoantigens. We hypothesized that there might be additional CNS-expressed proteins homologous to thyroid autoantigens, possibly overlapping known epitopes of the thyroid autoantigens. We used bioinformatic methods to address this hypothesis. Six, 27 and 47 of 46,809 CNS-expressed proteins share homology with TSH-R, Tg and TPO, respectively. The homologous regions often contain epitopes, and some match regions of thyroid autoantigens which have homology with alpha-enolase, AKRIA and/or DDAHI. Several of the aforementioned proteins are present in CNS areas that show abnormalities at neuroimaging in HE/SREAT patients. Furthermore, autoantibodies against some of the said six, 27 and 47 proteins were reported to be associated with a number of autoimmune diseases. Not only we validated our hypothesis, but we think that such a variety of potential CNS targets for thyroid Ab against epitopes contained in regions that have local homology with CNS proteins may explain the polymorphic phenotypes of HE/SREAT. Only when elevated amounts of these Ab are synthesized and trespass the blood-brain barrier, HE/SREAT appears. This might explain why HE/SREAT is so relatively rare.

BACKGROUND: Metabolic syndrome is a cluster of metabolic risk factors. The clear causes of its development are not known yet and there is no comprehensive treatment of this disease. There is a trend to use natural substances in the treatment of various diseases, but their effects need to be well explored. We decided to test effect of rutin compared to the effect of the standard drug atorvastatin.
METHODS: As a model of metabolic syndrome we used males of hypertriacylglycerolemic rats in combination with high-fat-high-fructose diet. Rutin (100 mg/kg) and atorvastatin (50 mg/kg) were administered orally daily for 5 weeks.
RESULTS: We determined biochemical parameters from blood: HDL-cholesterol, LDL-cholesterol, total cholesterol, triacylglycerols. Relaxation and contraction response of aorta was measured to determine vessel dysfunctions and possible predisposition to cardiovascular disease. The negative influence on cognitive functions could be associated with the development of metabolic cognitive syndrome. Therefore we aimed to monitor spatial memory by Morris water maze test. Both rutin and atorvastatin had a tendency to decrease levels of serum triacylglycerols, but only atorvastatin significantly reduced levels od LDL-cholesterol and increased HDL-cholesterol levels. Both compounds significantly reduced the phenylephrine-induced contractile response of the aorta and improved the relaxation response. Further, treated animals learned better compared to untreated rats in the Morris water maze.
CONCLUSIONS: Based on our results we can assume that atorvastatin and rutin had positive effect on spatial memory and vessel reactivity. Atorvastatin optimized lipid profile of blood serum.

BACKGROUND: Staging vascular cognitive impairment (VCI) might be useful for sample selection in clinical trials and for guiding clinical decision-making. Clinical dementia rating (CDR) has been applied for staging cognitive impairments of different etiologies, but it may underestimate severity of non-Alzheimer\'s disease cognitive deficits.
METHODS: Out of a total of 147 elderly subjects, 23 (mean age: 72.95 ± 7.51 years; 56% female; mean schooling: 9.52 ± 5.11 years) fulfilled clinical and neuroimaging criteria for VCI. Correlations among cognitive and functional status and scores in CDR and its subsums (CDR Sum of Boxes - CDR-SoB - and CDR Functional Subsum - CDR-FUNC) were performed.
RESULTS: Both CDR-SoB and CDR-FUNC correlated with global cognitive performance, functional status, CLOX 2, working memory and abstraction tests. CDR global score only correlated with functional status.
CONCLUSIONS: CDR-FUNC, as well as CDR-SoB, appear to be better indexes of severity in VCI than CDR global score.