The accuracy of the MMSE in detecting cognitive impairment when administered by general practitioners: A prospective observational study

<p>Abstract</p> <p>Background</p> <p>The Mini-Mental State Examination (MMSE) has contributed to detecting cognitive impairment, yet few studies have evaluated its accuracy when used by general practitioners (GP) in an actual public-health setting.</p> <p>Objectives</p> <p>We evaluated the accuracy of MMSE scores obtained by GPs by comparing them to scores obtained by Alzheimer's Evaluation Units (UVA).</p> <p>Methods</p> <p>The study was observational in design and involved 59 voluntary GPs who, after having undergone training, administered the MMSE to patients with symptoms of cognitive disturbances. Individuals who scored ≤ 24 (adjusted by age and educational level) were referred to Alzheimer's Evaluation Units (UVA) for diagnosis (including the MMSE). UVAs were unblinded to the MMSE score of the GP. To measure interrater agreement, the weighted Kappa statistic was calculated. To evaluate factors associated with the magnitude of the difference between paired scores, a linear regression model was applied. To quantify the accuracy in discriminating no cognitive impairment from any cognitive impairment and from Alzheimer's disease (AD), the ROC curves (AUC) were calculated.</p> <p>Results</p> <p>For the 317 patients, the mean score obtained by GPs was significantly lower (15.8 vs. 17.4 for the UVAs; p < 0.01). However, overall concordance was good (Kappa = 0.86). Only the diagnosis made by the UVA was associated with the difference between paired scores: the adjusted mean difference was 3.1 for no cognitive impairment and 3.8 for mild cognitive impairment. The AUC of the scores for GPs was 0.80 (95%CI: 0.75–0.86) for discriminating between no impairment and any impairment and 0.89 (95%CI: 0.84–0.94) for distinguishing patients with AD, though the UVA scores discriminated better.</p> <p>Conclusion</p> <p>In a public-health setting involving patients with symptoms of cognitive disturbances, the MMSE used by the GPs was sufficiently accurate to detect patients with cognitive impairment, particularly those with dementia.</p

Synthesis of marmycin A and investigation into its cellular activity

Anthracyclines such as doxorubicin are used extensively in the treatment of cancers. Anthraquinone-related angucyclines also exhibit antiproliferative properties and have been proposed to operate via similar mechanisms, including direct genome targeting. Here, we report the chemical synthesis of marmycin A and the study of its cellular activity. The aromatic core was constructed by means of a one-pot multistep reaction comprising a regioselective Diels-Alder cycloaddition, and the complex sugar backbone was introduced through a copper-catalysed Ullmann cross-coupling, followed by a challenging Friedel-Crafts cyclization. Remarkably, fluorescence microscopy revealed that marmycin A does not target the nucleus but instead accumulates in lysosomes, thereby promoting cell death independently of genome targeting. Furthermore, a synthetic dimer of marmycin A and the lysosome-targeting agent artesunate exhibited a synergistic activity against the invasive MDA-MB-231 cancer cell line. These findings shed light on the elusive pathways through which anthraquinone derivatives act in cells, pointing towards unanticipated biological and therapeutic applications

Prevalence, Distribution, and Impact of Mild Cognitive Impairment in Latin America, China, and India: A 10/66 Population-Based Study

A set of cross-sectional surveys carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India reveal the prevalence and between-country variation in mild cognitive impairment at a population level

Interplay between n-3 and n-6 long-chain polyunsaturated fatty acids and the endocannabinoid system in brain protection and repair.

The brain is enriched in arachidonic acid (ARA) and docosahexaenoic acid (DHA), long-chain polyunsaturated fatty acids (LCPUFA) of the n-6 and n-3 series, respectively. Both are essential for optimal brain development and function. Dietary enrichment with DHA and other long-chain n-3 PUFA, such as eicosapentaenoic acid (EPA) have shown beneficial effects on learning and memory, neuroinflammatory processes and synaptic plasticity and neurogenesis. ARA, DHA and EPA are precursors to a diverse repertoire of bioactive lipid mediators, including endocannabinoids. The endocannabinoid system comprises cannabinoid receptors, their endogenous ligands, the endocannabinoids, and their biosynthetic and degradation enzymes. Anandamide (AEA) and 2-archidonoylglycerol (2-AG) are the most widely studied endocannabinoids, and are both derived from phospholipid-bound ARA. The endocannabinoid system also has well established roles in neuroinflammation, synaptic plasticity and neurogenesis, suggesting an overlap in the neuroprotective effects observed with these different classes of lipids. Indeed, growing evidence suggests a complex interplay between n-3 and n-6 LCPUFA and the endocannabinoid system. For example, long-term DHA and EPA supplementation reduces AEA and 2-AG levels, with reciprocal increases in levels of the analogous endocannabinoid-like DHA and EPA-derived molecules. This review summarises current evidence of this interplay and discusses the therapeutic potential for brain protection and repair