Search

BACKGROUND: Studies have suggested a connection between a decrease in the levels of polyunsaturated fatty acids (PUFAs) and Alzheimer's disease (AD). We aimed to assess the effect of supplementation with omega-3 fatty acids (n-3 FAs) on biomarkers analyzed in the cerebrospinal fluid (CSF) of patients diagnosed with AD. OBJECTIVE: To investigate the effects of daily supplementation with 2.3 g of PUFAs in AD patients on the biomarkers in CSF described below. We also explored the possible correlation between these biomarkers and the performance in the cognitive test Mini-Mental State Examination (MMSE). METHODS: Thirty-three patients diagnosed with AD were randomized to either treatment with a daily intake of 2.3 g of n-3 FAs (n = 18) or placebo (n = 15). CSF samples were collected at baseline and after six months of treatment, and the following biomarkers were analyzed: Aβ 38, Aβ 40, Aβ 42, t-tau, p-tau, neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), soluble IL-1 receptor type II (sIL-1RII), and IL-6. RESULTS: There were no significant differences between the groups concerning the level of the different biomarkers in the CSF at baseline. Within the treatment group, there was a small but significant increase in both YKL-40 (p = 0.04) and NfL (p = 0.03), while the other CSF biomarkers remained stable. CONCLUSION: Supplementation with n-3 FAs had a statistically significant effect on NfL and YKL-40, resulting in an increase of both biomarkers, indicating a possible increase of inflammatory response and axonal damage. This increase in biomarkers did not correlate with MMSE score., Funding agencies:Pronova Biocare A/SFunds of CapioOdd FellowSwedish Society of PhysiciansLion's SwedenStohne's FoundationAlzheimer Drug Discovery Foundation (ADDF), USA RDAPB-201 809-2016615 2018092016862ALF ALFGBG-715986European Union Joint Program for Neurodegenerative Disorders JPND2019466-236European Research Council (ERC) 681712 Swedish State Support for Clinical Research ALFGBG-720931UK Dementia Research Institute at UCLSarfond 31 Forskning Senil demensRegion Auvergne-Rhone-AlpesRegion Bourgogne-Franche-ComteRegion Hauts-de-FranceRegion Nouvelle-Aquitaine

Background: Trials of supplementation with omega-3 fatty acids (omega 3-FAs) in patients with mild cognitive impairment or Alzheimer's disease (AD) have produced inconsistent effects on cognitive decline. There is evidence of an interaction between B vitamin status and omega 3-FAs in relation to brain atrophy and cognitive decline. Objective: We investigated whether baseline levels of plasma total homocysteine (tHcy), a marker of B vitamin status, modify the effects of omega 3-FAs supplementation on cognitive performance in moderate AD. Methods: This post hoc analysis of the OmegAD trial included 171 community-based patients with AD (MMSE >= 15): 88 patients received daily doses of 1.7 g docosahexaenoic acid and 0.6 g eicosapentaenoic acid for 6 months. Treatment outcome on cognition was analyzed according to baseline levels of tHcy using a general linear model and ANCOVA. Results: We found significant interactions between omega 3-FA supplementation and tHcy on cognition and clinical stage assessed by MMSE (p = 0.040), global CDR (p = 0.059), and CDRsob (p = 0.023), but not on ADAS-cog (p = 0.649). In patients with tHcy levels <11.7 mu mol/L, omega 3-FA supplementation improved cognitive performance as measured by MMSE (+7.1%, 95% CI: 0.59 to 13.7%, p = 0.033) and clinical status as measured by CDRsob (-22.3%, 95% CI: -5.8 to -38.7%, p = 0.009) compared with placebo. Conclusion: The effect of omega 3-FA supplementation on MMSE and CDR appears to be influenced by baseline tHcy, suggesting that adequate B vitamin status is required to obtain beneficial effects of omega 3-FA on cognition.

Low tissue levels of the major marine ω3 fatty acids (FAs) DHA and EPA are found in Alzheimer’s disease (AD). We investigated if healthy proxies to AD patients have higher levels of these ω3 FAs. We observed lower levels of EPA and DHA in subcutaneous adipose tissue biopsies from 64 AD patients compared with 16 cognitively healthy proxies. No significant difference was observed when pairwise comparisons were made between a subset of 16 AD patients and their co-habiting proxies. Larger studies are needed to replicate these findings and to determine if they could depend on FA intake or differences in metabolism.

Amine functional polymers, especially cationically charged, are interesting biomacromolecules for several reasons, including easy cell membrane entrance, their ability to escape endosomes through the proton sponge effect, spontaneous complexation and delivery of drugs and siRNA, and simple functionalization in aqueous solutions. Dendrimers, a subclass of precision polymers, are monodisperse and exhibit a large and exact number of peripheral end groups in relation to their size and have shown promise in drug delivery, biomedical imaging and as antiviral agents. In this work, hydroxyl functional dendrimers of generation 1 to 5 based on 2,2-bis(methylol)propionic acid (bis-MPA) were modified to bear 6 to 96 peripheral amino groups through esterification reactions with beta-alanine. All dendrimers were isolated in high yields and with remarkable monodispersity. This was successfully accomplished utilizing the present advantages of fluoride-promoted esterification (FPE) with imidazole-activated monomers. Straightforward postfunctionalization was conducted on a second generation amino functional dendrimer with tetraethylene glycol through NHS-amidation and carbonyl diimidazole (CDI) activation to full conversion with short reaction times. Fast biodegradation of the dendrimers through loss of peripheral beta-alanine groups was observed and generational- and dose-dependent cytotoxicity was evaluated with a set of cell lines. An increase. in neurotoxicity compared to hydroxyl-functional dendrimers was shown in neuronal cells, however, the dendrimers were slightly less neurotoxic than commercially available poly(amidoamine) dendrimers (PAMAMs). Additionally, their effect on bacteria was evaluated and the second generation dendrimer was found unique inhibiting the growth of Escherichia coli at physiological conditions while being nontoxic toward human cells. Finally, these results cement a robust and sustainable synthetic route to amino-functional polyester dendrimers with int, QC 20180112

With an increasing usage of photovoltaic panels also in urban context the cases of glare caused by photovoltaic systems are raising. Many countries have low or no regulations regarding outdoor glare caused by daylight, therefore legal cases can be complicated. Even though there are thresholds agreed upon for glare indoors there are no thresholds determined for outdoor daylight glare situations, therefore the thresholds suggested so far are compared. Due to the lack of an approved assessment method the aim of this study is to create a method which can be used to assess glare from photovoltaic panels. A comparison study based on the method of the Daylight Glare Potential and a study to determine thresholds for the sun disk luminance were performed to evaluate the functionality of the suggested method. It can be concluded that with additional verifying studies the method can be a way to decrease the cases of glare caused by photovoltaic systems and raise the awareness of this problem already during the planning phase., Developing an assessment method in order to determine glare caused by reflections of solar panels The increased usage of solar energy does not only have positive effects. Unfortunately, the amount of glare caused by reflections occurs with increased frequency. The awareness that measures must be taken against the human-caused climate change is increasing and results in an increase in the installation of renewable energy sources. One of the renewable energy sources is the usage of photovoltaic panels, which transfer the energy of the sun into electrical energy. Consequently, problems caused by reflections of photovoltaic panels onto neighbouring buildings are rising. In order to determine the time, place and strength of these undesired reflections, the assessment method described in this thesis was developed. Even though glare is not a new phenomenon it is mostly considered within indoor situations like offices with artificial lighting. Glare caused by the reflection of a photovoltaic panel is however caused by the sun itself and since existing methods are usually focused on indoor situations they could not be applied here. With the developed assessment method, it is possible to determine glare without a particular indoor situation. Therefore, it can already be used in an early planning process or when there is a legal case between neighbours. Even though it is proposed for photovoltaic panels the assessment method can be used for all kind of surfaces, for example windows or metal facades. Currently, photovoltaic systems are planned according to the need of the owner without regards to the impact on third parties. The reason for this is that there are no regulations stating that studies about the impact on third parties must be done. Only few countries have regulations considering the reflections of photovoltaic panels, however, these regulations are lacking a legally binding status. A study on legal cases showed that in some of the cases the guidelines were mentione

Background: omega 3 fatty acids (omega 3 FAs) may slow the rate of decline in cognitive performance in mild forms of cognitive impairment and Alzheimer's disease (AD). However, the relationship between changes of plasma omega 3 FA levels and cognitive performance, as well as effects of gender, are poorly known. Objective: To study the effect of 6-month administration of DHA-rich omega 3 FA supplementation on plasma FA profiles in patients with mild to moderate AD in relation to cognitive performance and gender. This investigation is part of the OmegAD Study. Methods: 174 AD patients (74 +/- 9 years) were randomized to a daily intake of 2.3g omega 3 FA or placebo for 6 months; subsequently all received the omega 3 FA preparation for the next 6 months. Baseline as well as changes in plasma levels of the main omega 3 FAs in 165 patients, while receiving omega 3 FA supplementation for 6 months, were analyzed for association to cognitive performance (assessed by ADAS-cog and MMSE scores) as well as to gender. Results: Preservation of cognitive functioning, assessed by ADAS-cog or its sub-items (but not MMSE) scores, was significantly associated to increasing plasma omega 3 FA levels over time. Thus, the higher omega 3 FA plasma levels rose, the lower was the rate of cognitive deterioration. This effect was not related to gender; since although females displayed higher omega 3 FA plasma levels than did males after 6 months of supplementation, this difference disappeared when adjusted for body weight. Conclusions: Since our study suggests dose-response relationships between plasma levels of omega 3 FA and preservation of cognition, future omega 3 FA trials in patients with mild AD should consider exploring graded (and body weight adjusted) doses of omega 3 FA.

Background: Oxidative stress and inflammation are two key mechanisms suggested to be involved in the pathogenesis of Alzheimer's disease (AD). Omega-3 fatty acids (omega-3 FAs) found in fish and fish oil have several biological properties that may be beneficial in AD. However, they may also auto-oxidize and induce in vivo lipid peroxidation. Objective: The objective of this study was to evaluate systemic oxidative stress and inflammatory biomarkers following oral supplementation of dietary omega-3 FA. Methods: Forty patients with moderate AD were randomized to receive 1.7 g DHA (22:6) and 0.6 g EPA (20:5) or placebo for 6 months. Urinary samples were collected before and after supplementation. The levels of the major F-2-isoprostane, 8-iso-PGF(2 alpha) a consistent in vivo biomarker of oxidative stress, and 15-keto-dihydro-PGF(2 alpha), a major metabolite of PGF(2 alpha) and biomarker of inflammatory response, were measured. Results: F-2-isoprostane in urine increased in the placebo group after 6 months, but therewas no clear difference in treatment effect between supplemented and non-supplemented patients on the urinary levels of F-2-isoprostanes and 15-keto-dihydro-PGF(2 alpha). At baseline, the levels of 15-keto-dihydro-PGF(2 alpha) showed negative correlative relationships to omega-3 FAs, and a positive correlation to linoleic acid. 8-iso-PGF(2 alpha) correlated negatively to the omega-6 FA arachidonic acid. Conclusion: The findings indicate that supplementation of omega-3 FAs to patients with AD for 6 months does not have a clear effect on free radical-mediated formation of F-2-isoprostane or cyclooxygenase-mediated formation of prostaglandin F-2 alpha. The correlative relationships to FAs indicate a potential role of FAs in immunoregulation.

Dementia is characterized by a progressive cognitive decline and neuropsychiatric symptoms (NPSD) such as agitation, apathy and sleeping problems. There is some evidence of activation of inflammatory pathways in the brain in dementia, but little research has been performed regarding the role of neuroinflammation in NPSD, which might represent a potential novel target for treatment. The aim of this study was to examine the possible association between NPSD and cerebrospinal fluid (CSF) levels of the cytokines IL-6, TNF-α and IL-10, and the cytokine receptor sIL-1RII, in patients with dementia and NPSD. Ninety-four patients (mean age 79±8; 67% female) with a score on the neuropsychiatric inventory (NPI) ≥10 points, were included. Clinical assessment included administration of NPI, the mini-mental state examination (MMSE) and the Cohen-Mansfield agitation inventory (CMAI). The cytokine levels in CSF samples were analysed by enzyme-linked immunosorbent assay. Correlations were statistically examined using Spearman's rank correlation coefficient (r), and simple- and multiple-linear regression. The anti-inflammatory cytokine IL-10 showed reverse correlations with total NPI score (NPI-total=-0.001, t(90)= 8.50, p=0.004) and NPI sub-items agitation (agitation=-0.007, t(90)=7.02, p=0.009) and night-time behaviour (night time behaviour=-0.006, t(90)=6.34, p=0.01). There was a trend towards reverse correlation between IL-10 and depression (depression=-0.004, t(90)=2.96, p=0.09). Also, the soluble cytokine receptor sIL-1RII showed a trend towards correlation with apathy (apathy=0.82, t(82)=3.62, p=0.06). The levels of IL-6 showed no significant correlations with NPSD. Levels of TNF-α were non-detectable. In Alzheimer's disease (AD) subjects (n=33), IL-6 showed reverse correlation with anxiety (r=-0.35, p=0.049). In mixed AD subjects (n=26), IL-10 showed reverse correlations with the total NPI score (r=-0.46, p=0.02) and depression (r=-0.45, p=0.02). The findings indicate a rela, Funding Agencies:Janssen Pharmaceuticals, Stockholm, Sweden Petrus and Augusta Hedlunds Foundation Loo and Hans Osterman Foundation