Intrusion Errors and Progression of Cognitive Deficits in Older Adults with Mild Cognitive Impairment and PreMCI States.

INTRODUCTION: Among persons with amnestic mild cognitive impairment (aMCI), intrusion errors on subscales that measure proactive semantic interference (PSI) may be among the earliest behavioral markers of elevated Alzheimer's disease brain pathology. While there has been considerable cross-sectional work in the area, it is presently unknown whether semantic intrusion errors are predictive of progression of cognitive impairment in aMCI or PreMCI (not cognitively normal but not meeting full criteria for MCI). METHODS: This study examined the extent to which the percentage of semantic intrusion errors (PIE) based on total responses on a novel cognitive stress test, the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L), could predict clinical/cognitive outcomes over an average 26-month period in older adults initially diagnosed with aMCI, PreMCI, and normal cognition. RESULTS: On the LASSI-L subscale sensitive to PSI, a PIE cut point of 44% intrusion errors distinguished between those at-risk individuals with PreMCI who progressed to MCI over time compared to individuals with PreMCI who reverted to normal on longitudinal follow-up. Importantly, PIE was able to accurately predict 83.3% of aMCI individuals who later progressed to dementia. DISCUSSION: These preliminary findings indicate that PIE on LASSI-L subscales that measure PSI may be a useful predictor of clinical progression overtime in at-risk older adults.

Total Synthesis of Nominal Cyclocinamide B and Investigation into the Identity of the Cyclocinamides.

The total synthesis of nominal cyclocinamide B, a cyclic peptide marine natural product, is reported together with an isomer of nominal cyclocinamide A. Initial attempts at the synthesis of the title compounds by inclusion of a turn inducer failed. However, direct synthesis succeeded in formation of the 14-membered cyclic peptide structure. Comparison of the data from all synthetic cyclocinamide A and B compounds with those of the natural products leads to the conclusion that the two natural products possess the same relative stereochemistry and that the true structures have not been defined.

A novel method of evaluating semantic intrusion errors to distinguish between amyloid positive and negative groups on the Alzheimer's disease continuum.

BACKGROUND: The development and validation of clinical outcome measures to detect early cognitive decline associated with Alzheimer's disease (AD) biomarkers is imperative. Semantic intrusions on the Loewenstein Acevedo Scales of Semantic Interference and Learning (LASSI-L) has outperformed widely used cognitive measures as an early correlate of elevated brain amyloid in prodromal AD and has distinguished those with amnestic mild cognitive impairment (aMCI) and high amyloid load from aMCI attributable to other non-AD conditions. METHODS: Since intrusion errors on memory tasks vary widely, we employed a novel method that accounts for the percentage of intrusion errors (PIE) in relation to total responses. Individuals with either high or low amyloid load across the spectrum of aMCI and dementia and amyloid negative cognitively normal older adults (CN) were studied. RESULTS: Mean PIE on indices sensitive to proactive semantic interference (PSI) and failure to recover from proactive semantic interference (frPSI) could distinguish amyloid positive from amyloid negative aMCI and dementia groups. Number of correct responses alone, while able to differentiate the different diagnostic groups, did not differentiate amyloid positive aMCI from their counterparts without amyloid pathology. CONCLUSIONS: PIE, a novel and sensitive index of early memory dysfunction, demonstrated high levels of sensitivity and specificity in differentiating CN from amyloid positive persons with preclinical AD. Mean levels of PIE are higher for amyloid positive aMCI and dementia participants relative to their amyloid negative counterparts.

Early-onset group B streptococcal disease in the United States: potential for further reduction.

OBJECTIVE: To describe lapses in adherence to group B streptococcus (GBS) prevention guidelines among cases of early-onset GBS disease in term and preterm neonates and to estimate the potential for further reduction in disease burden under current prevention strategies. METHODS: We reviewed labor and delivery and prenatal records of mothers of neonates with early-onset GBS disease (aged younger than 7 days with GBS isolated from a normally sterile site) identified at population-based surveillance sites in 2008-2009. We interviewed prenatal care providers about GBS screening practices and obtained relevant laboratory records. We evaluated the data for errors in prenatal screening, laboratory methods, communication of results, and intrapartum antibiotic prophylaxis. Using published data on screening sensitivity and intrapartum prophylaxis effectiveness, we estimated the potential reduction in cases under optimal prevention implementation. RESULTS: Among 309 cases, 179 (57.9%) had one or more implementation errors. The most common error type in term and preterm case-patients was prenatal screening (80 of 222 [36.0%]) and intrapartum prophylaxis (46 of 85 [54.1%]), respectively. We estimated that under optimal implementation, cases of early-onset GBS disease could be reduced by 26-59% with the largest benefit from a single intervention coming from improved use of intrapartum prophylaxis (16% decrease). CONCLUSION: Further reduction of early-onset GBS disease burden is possible under current prevention strategies, particularly with improved implementation of antibiotic prophylaxis. However, even with perfect adherence to recommended practices, the decline in cases may be modest. Therefore, novel prevention approaches such as improved intrapartum assays and vaccines are also needed.

Total synthesis of nominal (11S)- and (11R)-cyclocinamide A.

The cyclocinamides possess a unique ß(2)αß(2)α 14-membered tetrapeptide core. The initially reported biological data and intriguing structure, which was without full stereochemical identification, necessitated synthesis of both nominal (all-S) cyclocinamide A and the 11R isomer. The completed synthesis is highlighted by the use of a (cyclo)asparagine-containing dipeptide as a turn inducing fragment. Due to inconsistencies in analytical data between natural and synthetic samples, a re-evaluation of the natural product stereochemistry appears necessary.