Review: Diagnosis and treatment of dementia: 3. Mild cognitive impairment and cognitive impairment without dementia

Background

Mild cognitive impairment and cognitive impairment, no dementia, are emerging terms that encompass the clinical state between normal cognition and dementia in elderly people. Controversy surrounds their characterization, definition and application in clinical practice. In this article, we provide physicians with practical guidance on the definition, diagnosis and treatment of mild cognitive impairment and cognitive impairment, no dementia, based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, held in March 2006.

Methods

We developed evidence-based guidelines using systematic literature searches, with specific criteria for study selection and quality assessment, and a clear and transparent decision-making process. We selected studies published from January 1996 to December 2005 that had mild cognitive impairment or cognitive impairment, no dementia, as the outcome. Subsequent to the conference, we searched for additional articles published between January 2006 and January 2008. We graded the strength of evidence using the criteria of the Canadian Task Force on Preventive Health Care.

Results

We identified 2483 articles, of which 314 were considered to be relevant and of good or fair quality. From a synthesis of the evidence in these studies, we made 16 recommendations. In brief, family physicians should be aware that most types of dementia are preceded by a recognizable phase of mild cognitive decline. They should be familiar with the concepts of mild cognitive impairment and of cognitive impairment, no dementia. Patients with these conditions should be closely monitored because of their increased risk for dementia. Leisure activities, cognitive stimulation and physical activity could be promoted as part of a healthy lifestyle in elderly people and those with mild cognitive impairment. Vascular risk factors should be treated optimally. No other specific therapies can yet be recommended.

Interpretation

Physicians will increasingly see elderly patients with mild memory loss, and learning an approach to diagnosing states such as mild cognitive impairment is now warranted. Close monitoring for progression to dementia, promotion of a healthy lifestyle and treatment of vascular risk factors are recommended for the management of patients with mild cognitive impairment.

Articles to date in this series

• Chertkow H. Diagnosis and treatment of dementia: Introduction. Introducing a series based on the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. CMAJ 2008;178:316-21.
• Patterson C, Feightner JW, Garcia A, et al. Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease. CMAJ 2008;178:548-56.
• Feldman HH, Jacova C, Robillard A, et al. Diagnosis and treatment of dementia: 2. Diagnosis. CMAJ 2008;178:825-36.

     

Photo oxidation of rice starch II. Using a water soluble photo initiator

A new photo oxidation system was established when rice starch was oxidized using UV irradiation and 4-(trimethyl ammoniummethyl) benzophenone chloride (BP2) as a photo initiator. BP2 is a water soluble photo initiator. The slurry prepared for photo oxidation contained rice starch, water and BP2 only. No oxidizing agents were added. Parameters affecting the photo oxidation process, i.e. temperature, concentration of BP2, material:liquor ratio and irradiation time were determined. The produced oxidized starch was evaluated by measuring the carboxyl content, carbonyl content and apparent viscosity. The produced photo oxidized rice starch showed sound increase in the carboxyl and carbonyl contents and sharp decrease in the apparent viscosity. The produced photo oxidized starch was tested for its suitability as a sizing agent for cotton yarns. Native starch and oxidized starch, used as a sizing agent by Misr Company of Spinning and Weaving in El-Mahalla El-Kubra (Egypt), were used for comparison. Sized cotton yarns were evaluated by measuring the tensile strength, elongation at break and percent of size removal. Cotton yarns sized using the prepared photo oxidized rice starch showed higher tensile strength, elongation at break and percent of size removal compared with native starch and oxidized starch used by Misr Company of Spinning and Weaving.     

Chemical characteristics and antioxidant activity of exopolysaccharide fractions from Microbacterium terregens

The Gram-positive bacterial strain isolated from soil was identified as the non-pathogenic Microbacterium terregens. The exopolysaccharide (CPS) produced from M. terregens was obtained by isopropanol precipitation (13.72 g L^?1 growth medium), The resulted exopolysaccharide was purified by chromatography on DEAE-cellulose and Sephacryl S-200 columns, when two polysaccharide fractions termed CPSI and CPSII were obtained. Structure features of CPSI and CPSII were investigated by a combination of chemical and chromatographic analyses, such as acid hydrolysis, methylation analysis, periodate oxidation–Smith degradation, HPLC, GC–MS, and IR. The results indicated that CPSI and CPSII were composed of glucose: mannose in a ratio of 2.7:1 and 3.2:1 with molecular weights 80 and 150 kDa, respectively. It has a backbone of (1 → 4)-linked β-glucose residues, which occasionally branches at O-6. The branches were composed of (1 → 4)-linked β-mannose residues. The antioxidant activity of the CPS, CPSI and CPSII was evaluated in-vitro by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay (RSA). CPSI fraction showed the highest antioxidant activity among the three fractions, with an IC₅₀ value of 230 μg mL^?1. The effect of molecular weight of the polysaccharide on the improvement of the antioxidant potential seems to be significant.     

New development for combined bioscouring and bleaching of cotton-based fabrics

A thorough investigation into conditions appropriate for effecting combined eco-friendly bioscouring and/or bleaching of cotton-based fabrics was undertaken. Fabrics used include cotton, grey mercerized cotton, cotton/polyester blend 50/50 and cotton/polyester blend 35/65. The four cotton-based fabric were subjected to bioscouring by single use of alkaline pectinase enzymes or by using binary mixtures of alkaline pectinase and cellulase enzymes under a variety of conditions. Results of bioscouring show that, the bioscoured substrates exhibit fabrics performances which are comparable with these of the conventional alkali scouring. It has been also found that, incorporation of ethylenediaminetetraacetic acid (EDTA) in the bioscouring with mixture from alkaline pectinase and cellulase improves the performance of the bioscoured fabrics. Addition of β-cyclodextrin to the bioscouring solution using alkaline pectinase in admixtures with cellulase acts in favor of technical properties and performance of the bioscoured fabrics. Concurrent bioscouring and bleaching by in situ formed peracetic acid using tetraacetylethylenediamine (TAED) and H₂O₂ was also investigated. The results reveal unequivocally that the environmentally sound technology brought about by current development is by far the best. The new development involves a single-stage process for full purification/preparation of cotton textiles. The new development at its optimal comprises treatment of the fabric with an aqueous formulation consisting of alkaline pectinase enzyme (2 g/L), TAED (15 g/L), H₂O₂ (5 g/L), nonionic wetting agent (0.5 g/L) and sodium silicate (2 g/L). The treatment is carried out at 60 °C for 60 min. Beside the advantages of the new development with respect to major technical fabric properties, it is eco-friendly and reproducible. This advocates the new development for mill trials.     

Importance of Proteins Controlling Initiation of DNA Replication in the Growth of the High-Pressure-Loving Bacterium Photobacterium profundum SS9

The molecular mechanism(s) by which deep-sea bacteria grow optimally under high hydrostatic pressure at low temperatures is poorly understood. To gain further insight into the mechanism(s), a previous study screened transposon mutant libraries of the deep-sea bacterium Photobacterium profundum SS9 and identified mutants which exhibited alterations in growth at high pressure relative to that of the parent strain. Two of these mutants, FL23 (PBPRA3229::mini-Tn10) and FL28 (PBPRA1039::mini-Tn10), were found to have high-pressure sensitivity and enhanced-growth phenotypes, respectively. The PBPRA3229 and PBPRA1039 genes encode proteins which are highly similar to Escherichia coli DiaA, a positive regulator, and SeqA, a negative regulator, respectively, of the initiation of DNA replication. In this study, we investigated the hypothesis that PBPRA3229 and PBPRA1039 encode DiaA and SeqA homologs, respectively. Consistent with this, we determined that the plasmid-carried PBPRA3229 and PBPRA1039 genes restored synchrony to the initiation of DNA replication in E. coli mutants lacking DiaA and SeqA, respectively. Additionally, PBPRA3229 restored the cold sensitivity phenotype of an E. coli dnaA(Cs) diaA double mutant whereas PBPRA1039 suppressed the cold sensitivity phenotype of an E. coli dnaA(Cs) single mutant. Taken together, these findings show that the genes disrupted in FL23 and FL28 encode DiaA and SeqA homologs, respectively. Consequently, our findings add support to a model whereby high pressure affects the initiation of DNA replication in P. profundum SS9 and either the presence of a positive regulator (DiaA) or the removal of a negative regulator (SeqA) promotes growth under these conditions.Despite the fact that more than 70% of the earth''s surface is covered by oceans, which have an average temperature of 3°C and exert an average hydrostatic pressure of 38 MPa (atmospheric pressure is ∼0.1 MPa), little is understood about the molecular basis of cold- and high-pressure-adapted deep-ocean life. The discovery and isolation of the pyschrotolerant facultative piezophile (high-pressure-loving organism) Photobacterium profundum SS9 (8) have made it possible to more readily address the mechanisms of piezophilic growth at cold temperatures (for a recent review, see reference 3). P. profundum SS9 is a gammaproteobacterium originally isolated from an amphipod homogenate obtained from the Sulu Sea in the Philippines at a depth of 2.5 km and a temperature of 9°C (8). Although it grows optimally at 28 MPa and 15°C, P. profundum SS9 can also grow over a wide range of pressures (0.1 to 90 MPa) and temperatures (2 to 20°C). The ability to grow at atmospheric pressure has made P. profundum SS9 more amenable to genetic manipulation than obligate piezophiles. The P. profundum SS9 genome has been sequenced and annotated (26) and consists of two chromosomes and an 80-kb plasmid. It was determined that the 80-kb plasmid is nonessential for the piezophilic growth of P. profundum SS9 (26).To gain insights into the genetic basis of high-pressure-adapted growth, transposon mutant libraries of P. profundum SS9R (a rifampin [rifampicin]-resistant derivative of SS9) were screened in liquid culture for mutants with defects in the ability to grow at high pressure (45 MPa, 15°C) (19). One of the putative high-pressure-sensitive mutants (FL23) isolated from these screens had a mini-Tn10 insertion in the gene PBPRA3229, which encodes a protein with 75% identity (85% similarity) to Escherichia coli DiaA (DnaA initiator-associating factor) (14). Although FL23 shows growth defects at 0.1 MPa (15°C) relative to the parent strain, the ratio of growth at 45 MPa to growth at 0.1 MPa and 15°C is substantially reduced compared to that of the parent strain, confirming that disruption of PBPRA3229 results in a high-pressure sensitivity growth phenotype (19).In E. coli, DiaA is necessary to ensure the timely initiation of DNA replication (14). DiaA forms a tetramer and binds to multiple molecules of DnaA, promoting (i) the binding of DnaA to the origin of replication in E. coli (known as oriC), (ii) ATP-DnaA-specific conformational changes in the oriC complex, and (iii) the unwinding of oriC DNA (17). Consequently, E. coli DiaA acts as a positive regulator of the initiation of DNA replication. In the absence of DiaA, initiation of DNA replication is delayed and in E. coli cells with two oriC copies, it only occurs from one of these, resulting in cells with three copies of their chromosome (14). In contrast, this is an extremely rare occurrence in wild-type E. coli cells. Although disruption of diaA in E. coli results in an asynchronous DNA replication phenotype, it does not appear to affect growth or morphology at atmospheric pressure at 37°C in a genetic background with a wild-type dnaA gene. However, disruption of the diaA gene suppresses the cold sensitivity phenotype of an E. coli dnaA(Cs) mutant at 30°C.Even though PBPRA3229 is highly similar to E. coli DiaA, it also shows 45% identity (65% similarity) to a phosphoheptose isomerase in E. coli known as GmhA (4). GmhA is involved in lipopolysaccharide (LPS) biosynthesis and catalyzes the isomerization of d-sedoheptulose 7-phosphate into d-glycero-d-manno-heptose 7-phosphate, which is the first step in the biosynthesis of ADP-glycero-manno-heptose, a subunit of the LPS inner core. The LPS forms the outermost leaflet of the outer membrane of gram-negative bacterial cells, and in E. coli K-12 strains, the LPS is composed of inner and outer sugar cores and lipid A (25). E. coli K-12 mutants lacking GmhA produce truncated LPS species relative to that of the parent strain due to the absence of the inner core, which can be easily visualized by gel electrophoresis followed by silver staining (4). Due to the high degree of sequence similarity between PBPRA3229 and GmhA, it is also possible that FL23 has an alteration in its LPS relative to that of the parent strain.In contrast to DiaA, SeqA is a negative regulator of the initiation of DNA replication in E. coli (20). E. coli SeqA binds to hemimethylated oriC and prevents the binding of ATP-DnaA. Disruption of seqA in E. coli also results in an asynchronous-replication phenotype. However, the effect of DiaA on the timing of DNA replication initiation appears to be SeqA independent (14). Interestingly, a putative P. profundum SS9R seqA transposon insertion mutant (PBPRA1039::Tn10) was identified as having high-pressure-enhanced growth at 45 MPa and 15°C relative to its growth at atmospheric pressure (19). Therefore, this preliminary finding suggests that the removal of a negative regulator of the initiation of DNA replication could promote the growth of P. profundum SS9R at high pressure.In this study, we investigated the hypothesis that proteins that regulate the initiation of DNA replication play a key role in the piezophilic growth of P. profundum SS9. We determined that PBPRA3229 and PBPRA1039 encode functional DiaA and SeqA homologs, respectively, and we propose a model whereby the initiation of DNA replication is sensitive to high pressure and either the production of a positive regulator (DiaA) or the removal of a negative regulator (SeqA) can promote growth under these conditions.     

Characterization of bacterial proteases with a panel of fluorescent peptide substrates

Bacteria produce a range of proteolytic enzymes. In an attempt to detect and identify bacteria on the basis of their protease activity, a panel of protease substrates was investigated. Peptides conjugated to the fluorophore 7-amino-4-methylcoumarin (AMC) are well-established substrates for measuring protease activity. Although peptide-AMC substrates are generally not specific for a single protease, a unique pattern can be achieved for both highly specific enzymes and those with a broader substrate range by comparing different peptide substrates. The panel of 7 peptide-AMC substrates chosen exhibited a unique pattern for nine microbial proteases. The selected peptides were used to determine protease activity in cultured strains of Pseudomonas aeruginosa and Staphylococcus aureus. A signal pattern obtained with peptides with arginine, lysine, and tyrosine in the P1 position characterized the bacterial protease activities in these samples. The kinetic parameters for the three best substrates for the P. aeruginosa sample were calculated. Further information about substrate specificity was gained by the selective use of protease inhibitors. The results presented show that peptide-AMC substrates provide a simple and sensitive tool to characterize protease activity in microbiological samples and that they have the potential to identify and distinguish different bacterial species.     

An integrated microfluidic platform for magnetic microbeads separation and confinement

An innovative microfluidic platform for magnetic beads manipulation is introduced, consisting of novel microfabricated 3D magnetic devices positioned in a microfluidic chamber. Each magnetic device comprises of an embedded actuation micro-coil in various design versions, a ferromagnetic pillar, a magnetic backside plate and a sensing micro-coil. The various designs of the micro-coils enable efficient magnetic beads trapping and concentration in different patterns. The finite element analysis (FEA) results show a significant increase of the developed force on suspended magnetic beads when the magnetic pillar and backside plate were integrated into the device structure. These simulation results were confirmed experimentally by measuring the magnetic beads trapping ratios for the different designs and structures of the devices under continuous flow conditions. The trapping ratios and profiles were studied using beads counting, measuring the change of inductance with the sensing micro-coil and by image processing. The devices have efficiently demonstrated a controlled and localized magnetic beads trapping and concentration at small spatial locations for the first time. The new results shown in this study demonstrate the feasibility of efficiently using these original devices as key elements in complex bio-analysis systems.     

Biology, immature and adult morphology, and molecular characterization of a new species of the genus Entedon (Hymenoptera: Eulophidae) associated with the invasive pest Specularius impressithorax (Coleoptera: Chrysomelidae, Bruchinae) on Erythrina plants

Entedon erythrinae sp. n. (Hymenoptera: Eulophidae), a gregarious egg-larval endoparasitoid of the Erythrina bruchine Specularius impressithorax, an invasive pest of the coral tree seeds (Erythrina spp.), is described from the Hawaiian Islands and Africa (South Africa, Tanzania and Mozambique). The biology and morphology of preimaginal stages of this new species are described in details.It is remarkable that the early embryo of the parasitoid represents a mass of undifferentiated cells surrounded by a peculiar membrane formed by the peripheral enlarged polygonal cells. The young larva developing inside this membrane corresponds morphologically to the second instar of congeneric species. Various peculiarities of the parasitoid-host relationships in gregarious and solitary Entedon parasitoids are discussed. The DNA sequences of 28S D2 (nuclear), Cytochrome Oxidase I (COI, mitochondrial) and Cytochrome B (CytB, mitochondrial) genes are provided for this new species and compared with the sequences of some other Afrotropical and Palearctic species of the genus.     

Identification of a yolk sac cell population with hematopoietic activity in view of CD45/c-Kit expression

During murine embryonic development, primitive hematopoiesis occurs in the yolk sac (YS). Recent studies have shown that the YS also harbors definitive hematopoietic activity. However, the population of YS cells contributing to definitive hematopoiesis has not been identified. In this study, we characterized the hematopoietic cell populations in the YS of mouse embryos from E9.5 to E14.5 in view of the expression profiles of CD45 and c-Kit. The YS cells from E9.5 to E11.5 could be divided into six populations: CD45(-) c-Kit(-) , CD45(-) c-Kit(low) , CD45(-) c-Kit(high) , CD45(low) c-Kit(high) , CD45(high) c-Kit(high) and CD45(high) c-Kit(very low) . Among these populations, CD45(low) c-Kit(high) cells showed the highest multilineage hematopoietic colony-forming activity. Later in development, the YS cells from E12.5 to E14.5 lost the second and fourth populations (i.e., they retained CD45(-) c-Kit(-) , CD45(-) c-Kit(high) , CD45(high) c-Kit(high) and CD45(high) c-Kit(very low) cells), and concurrently with the disappearance of the CD45(low) c-Kit(high) population, no significant hematopoietic activity was found in any of the populations on and after E12.5. CD45(low) c-Kit(high) YS cells, which had a round morphology with a large nucleus, possessed the ability to differentiate into myeloid and B lymphoid cells when cultured with stromal cells. These findings suggest that CD45(low) c-Kit(high) YS cells include more undifferentiated cells than the other YS cell populations and possess in vitro potency to differentiate into multilineage hematopoietic cells. Furthermore, this cell population disappears from the YS at around E12.5, when the site of hematopoiesis has already shifted to the fetal liver and the placenta.