Early detection of Alzheimer's disease with a total score of the German CERAD

The goal of the present study was to evaluate the diagnostic discriminability of three different global scores for the German version of the Consortium to Establish a Registry on Alzheimer's Disease-Neuropsychological Assessment Battery (CERAD-NAB). The CERAD-NAB was administered to 1100 healthy control participants [NC; Mini-Mental State Examination (MMSE) mean = 28.9] and 352 patients with very mild Alzheimer's disease (AD; MMSE mean = 26.1) at baseline and subsets of participants at follow-up an average of 2.4 (NC) and 1.2 (AD) years later. We calculated the following global scores: Chandler et al.'s (2005) score (summed raw scores), logistic regression on principal components analysis scores (PCA-LR), and logistic regression on demographically corrected CERAD-NAB variables (LR). Correct classification rates (CCR) were compared with areas under the receiver operating characteristics curves (AUC). The CCR of the LR score (AUC = .976) exceeded that of the PCA-LR, while the PCA-LR (AUC = .968) and Chandler (AUC = .968) scores performed comparably. Retest data improved the CCR of the PCA-LR and Chandler (trend) scores. Thus, for the German CERAD-NAB, Chandler et al.'s total score provided an effective global measure of cognitive functioning, whereby the inclusion of retest data tended to improve correct classification of individual cases. (JINS, 2010, 16, 910-920.

Screening properties of the German IQCODE with a two-year time frame in MCI and early Alzheimer's disease

Background: The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) is a widely used screening tool for dementia. We aimed to determine the ability of the German version of the 16-item IQCODE with a two-year time frame to discriminate healthy mature control participants (NC) from mild cognitive impairment (MCI) and probable early Alzheimer's disease (AD) patients (all with Mini-mental State Examination (MMSE) scores ≥ 24/30) and to optimize diagnostic discriminability by shortening the IQCODE. Methods: 453 NC (49.7% women, age = 69.5 years ± 8.2, education = 12.2 ± 2.9), 172 MCI patients (41.9% women, age = 71.5 years ± 8.8, education = 12.3 ± 3.1) and 208 AD patients (59.1% women, age = 76.0 years ± 6.4, education = 11.4 ± 2.9) participated. Stepwise binary logistic regression analyses (LR) were used to shorten the test. Receiver operating characteristic curves (ROC) determined sensitivities, specificities, and correct classification rates (CCRs) for (a) NC vs. all patients; (b) NC vs. MCI; and (c) NC vs. AD patients. Results: The mean IQCODE was 3.00 for NC, 3.35 for MCI, and 3.73 for AD. CCRs were 85.5% (NC-patient group), 79.9% (NC-MCI), and 90.7% (NC-AD), respectively. The diagnostic discriminability of the shortened 7-item IQCODE (i.e. items 1, 2, 3, 5, 7, 10, 14) was comparable with the longer version (i.e. 7-item CCRs: NC-patient group: 85.3%; NC-MCI: 80.1%, NC-AD: 90.5%). Conclusions: The German 16-item IQCODE with two-year time frame showed excellent screening properties for MCI and early AD patients. An abbreviated 7-item version demonstrated equally high diagnostic discriminability, thus allowing for more economical screenin

The Extension of the German CERAD Neuropsychological Assessment Battery with Tests Assessing Subcortical, Executive and Frontal Functions Improves Accuracy in Dementia Diagnosis

Alzheimer's disease (AD) is the most common form of dementia. Neuropsychological assessment of individuals with AD primarily focuses on tests of cortical functioning. However, in clinical practice, the underlying pathologies of dementia are unknown, and a focus on cortical functioning may neglect other domains of cognition, including subcortical and executive functioning. The current study aimed to improve the diagnostic discrimination ability of the Consortium to Establish a Registry for Alzheimer's Disease - Neuropsychological Assessment Battery (CERAD-NAB) by adding three tests of executive functioning and mental speed (Trail Making Tests A and B, S-Words).; Logistic regression analyses of 594 normal controls (NC), 326 patients with mild AD and 224 patients with other types of dementia (OD) were carried out, and the area under the curve values were compared to those of CERAD-NAB alone.; All comparisons except AD-OD (65.5%) showed excellent classification rates (NC-AD: 92.7%; NC-OD: 89.0%; NC-all patients: 91.0%) and a superior diagnostic accuracy of the extended version.; Our findings suggest that these three tests provide a sensible addition to the CERAD-NAB and can improve neuropsychological diagnosis of dementia

Genomic factors that shape craniofacial outcome and neural crest vulnerability in FASD

Prenatal alcohol exposure (PAE) causes distinctive facial characteristics in some pregnancies and not others; genetic factors may contribute to this differential vulnerability. Ethanol disrupts multiple events of neural crest development including induction, survival, migration, and differentiation. Animal models and genomic approaches have substantially advanced our understanding of the mechanisms underlying these facial changes. PAE during gastrulation produces craniofacial changes corresponding with human fetal alcohol syndrome. These result because PAE reduces prechordal plate extension and suppresses sonic hedgehog, leading to holoprosencephaly and malpositioned facial primordia. Haploinsufficiency in sonic hedgehog signaling increases vulnerability to facial deficits and may influence some PAE pregnancies. In contrast, PAE during early neurogenesis produces facial hypoplasia, preceded by neural crest reductions due to significant apoptosis. Factors mediating this apoptosis include intracellular calcium mobilization, elevated reactive oxygen species, and loss of trophic support from β-catenin/calcium, sonic hedgehog, and mTOR signaling. Genomewide SNP analysis links PDGF receptor genes with facial outcomes in human PAE. Multiple genomic-level comparisons of ethanol-sensitive and –resistant early embryos, in both mouse and chick, independently identify common candidate genes that may potentially modify craniofacial vulnerability, including ribosomal proteins, proteosome, RNA splicing, and focal adhesion. In summary, research using animal models with genome-level differences in ethanol vulnerability, as well as targeted loss- and gain-of-function mutants, has clarified the mechanisms mediating craniofacial change in PAE. The findings additionally suggest that craniofacial deficits may represent a gene-ethanol interaction for some affected individuals. Genetic-level changes may prime individuals toward greater sensitivity or resistance to ethanol's neurotoxicity

A high-density SNP panel reveals extensive diversity, frequent recombination and multiple recombination hotspots within the chicken major histocompatibility complex B region between BG2 and CD1A1

Background: The major histocompatibility complex (MHC) is present within the genomes of all jawed vertebrates. MHC genes are especially important in regulating immune responses, but even after over 80 years of research on the MHC, much remains to be learned about how it influences adaptive and innate immune responses. In most species, the MHC is highly polymorphic and polygenic. Strong and highly reproducible associations are established for chicken MHC-B haplotypes in a number of infectious diseases. Here, we report (1) the development of a high-density SNP (single nucleotide polymorphism) panel for MHC-B typing that encompasses a 209,296 bp region in which 45 MHC-B genes are located, (2) how this panel was used to define chicken MHC-B haplotypes within a large number of lines/breeds and (3) the detection of recombinants which contributes to the observed diversity. Methods: A SNP panel was developed for the MHC-B region between the BG2 and CD1A1 genes. To construct this panel, each SNP was tested in end-point read assays on more than 7500 DNA samples obtained from inbred and commercially used egg-layer lines that carry known and novel MHC-B haplotypes. One hundred and one SNPs were selected for the panel. Additional breeds and experimentally-derived lines, including lines that carry MHC-B recombinant haplotypes, were then genotyped. Results: MHC-B haplotypes based on SNP genotyping were consistent with the MHC-B haplotypes that were assigned previously in experimental lines that carry B2, B5, B12, B13, B15, B19, B21, and B24 haplotypes. SNP genotyping resulted in the identification of 122 MHC-B haplotypes including a number of recombinant haplotypes, which indicate that crossing-over events at multiple locations within the region lead to the production of new MHC-B haplotypes. Furthermore, evidence of gene duplication and deletion was found. Conclusions: The chicken MHC-B region is highly polymorphic across the surveyed 209-kb region that contains 45 genes. Our results expand the number of identified haplotypes and provide insights into the contribution of recombination events to MHC-B diversity including the identification of recombination hotspots and an estimation of recombination frequency

Identifying Archaeological Bone via Non-Destructive ZooMS and the Materiality of Symbolic Expression: Examples from Iroquoian Bone Points.

Today, practical, functional and symbolic choices inform the selection of raw materials for worked objects. In cases where we can discern the origin of worked bone, tooth, ivory and antler objects in the past, we assume that similar choices are being made. However, morphological species identification of worked objects is often impossible due to the loss of identifying characteristics during manufacture. Here, we describe a novel non-destructive ZooMS (Zooarchaeology by Mass Spectrometry) method which was applied to bone points from Pre-Contact St. Lawrence Iroquoian village sites in southern Quebec, Canada. The traditional ZooMS technique requires destructive analysis of a sample, which can be problematic when dealing with artefacts. Here we instead extracted proteins from the plastic bags in which the points had been stored. ZooMS analysis revealed hitherto unexpected species, notably black bear (Ursus americanus) and human (Homo sapiens sapiens), used in point manufacture. These surprising results (confirmed through genomic sequencing) highlight the importance of advancing biomolecular research in artefact studies. Furthermore, they unexpectedly and exceptionally allow us to identify and explore the tangible, material traces of the symbolic relationship between bears and humans, central to past and present Iroquoian cosmology and mythology