Neuropsychiatric features in a multi-ethnic population with Alzheimer disease and mild cognitive impairment.

BACKGROUND: Alzheimer disease (AD) is more prevalent in African American (AA) and Hispanic White (HIW) compared to Non-Hispanic White (NHW) individuals. Similarly, neuropsychiatric symptoms (NPS) vary by population in AD. This is likely the result of both sociocultural and genetic ancestral differences. However, the impact of these NPS on AD in different groups is not well understood. METHODS: Self-declared AA, HIW, and NHW individuals were ascertained as part of ongoing AD genetics studies. Participants who scored higher than 0.5 on the Clinical Dementia Rating (CDR) Scale (CDR) were included. Group similarities and differences on Neuropsychiatric Inventory Questionnaire (NPI-Q) outcomes (NPI-Q total score, NPI-Q items) were evaluated using univariate ANOVAs and post hoc comparisons after controlling for sex and CDR stage. RESULTS: Our sample consisted of 498 participants (26% AA; 30% HIW; 44% NHW). Overall, NPI-Q total scores differed significantly between our groups, with HIW having the highest NPI-Q total scores, and by AD stage as measured by CDR. We found no significant difference in NPI-Q total score by sex. There were six NPI-Q items with comparable prevalence in all groups and six items that significantly differed between the groups (Anxiety, Apathy, Depression, Disinhibition, Elation, and Irritability). Further, within the HIW group, differences were found between Puerto Rican and Cuban American Hispanics across several NPI-Q items. Finally, Six NPI-Q items were more prevalent in the later stages of AD including Agitation, Appetite, Hallucinations, Irritability, Motor Disturbance, and Nighttime Behavior. CONCLUSIONS: We identified differences in NPS among HIW, AA, and NHW individuals. Most striking was the high burden of NPS in HIW, particularly for mood and anxiety symptoms. We suggest that NPS differences may represent the impact of sociocultural influences on symptom presentation as well as potential genetic factors rooted in ancestral background. Given the complex relationship between AD and NPS it is crucial to discern the presence of NPS to ensure appropriate interventions.

Genome-wide association analysis and admixture mapping in a Puerto Rican cohort supports an Alzheimer disease risk locus on chromosome 12.

Introduction: Hispanic/Latino populations are underrepresented in Alzheimer Disease (AD) genetic studies. Puerto Ricans (PR), a three-way admixed (European, African, and Amerindian) population is the second-largest Hispanic group in the continental US. We aimed to conduct a genome-wide association study (GWAS) and comprehensive analyses to identify novel AD susceptibility loci and characterize known AD genetic risk loci in the PR population. Materials and methods: Our study included Whole Genome Sequencing (WGS) and phenotype data from 648 PR individuals (345 AD, 303 cognitively unimpaired). We used a generalized linear-mixed model adjusting for sex, age, population substructure, and genetic relationship matrix. To infer local ancestry, we merged the dataset with the HGDP/1000G reference panel. Subsequently, we conducted univariate admixture mapping (AM) analysis. Results: We identified suggestive signals within the SLC38A1 and SCN8A genes on chromosome 12q13. This region overlaps with an area of linkage of AD in previous studies (12q13) in independent data sets further supporting. Univariate African AM analysis identified one suggestive ancestral block (p = 7.2×10-6) located in the same region. The ancestry-aware approach showed that this region has both European and African ancestral backgrounds and both contributing to the risk in this region. We also replicated 11 different known AD loci -including APOE- identified in mostly European studies, which is likely due to the high European background of the PR population. Conclusion: PR GWAS and AM analysis identified a suggestive AD risk locus on chromosome 12, which includes the SLC38A1 and SCN8A genes. Our findings demonstrate the importance of designing GWAS and ancestry-aware approaches and including underrepresented populations in genetic studies of AD.

Linkage of Alzheimer disease families with Puerto Rican ancestry identifies a chromosome 9 locus.

The genetic admixture of Caribbean Hispanics provides an opportunity to discover novel genetic factors in Alzheimer disease (AD). We sought to identify genetic variants for AD through a family-based design using the Puerto Rican (PR) Alzheimer Disease Initiative (PRADI). Whole-genome sequencing (WGS) and parametric linkage analysis were performed for 100 individuals from 23 multiplex PRADI families. Variants were prioritized by minor allele frequency (<0.01), functional potential [combined annotation dependent depletion score (CADD) >10], and co-segregation with AD. Variants were further ranked using an independent PR case-control WGS dataset (PR10/66). A genome-wide significant linkage peak was found in 9p21 with a heterogeneity logarithm of the odds score (HLOD) >5.1, which overlaps with an AD linkage region from two published independent studies. The region harbors C9orf72, but no expanded repeats were observed in the families. Seven variants prioritized by the PRADI families also displayed evidence for association in the PR10/66 (p < 0.05), including a missense variant in UNC13B. Our study demonstrated the importance of family-based design and WGS in genetic study of AD.

Determination of organochlorine pesticides in complex matrices by single-drop microextraction coupled to gas chromatography-mass spectrometry.

A rapid and simple single-drop microextraction method (SDME) has been used to preconcentrate eighteen organochlorine pesticides (OCPs) from water samples with a complex matrix. Exposing two microlitre toluene drop to an aqueous sample contaminated with OCPs proved an excellent preconcentration method prior to analysis by gas chromatography-mass spectrometry (GC-MS). A Plackett-Burman design was used for screening and a central composite design for optimizing the significant variables in order to evaluate several possibly influential and/or interacting factors. The studied variables were drop volume, aqueous sample volume, agitation speed, ionic strength and extraction time. The optimum experimental conditions of the proposed SDME method were: 2 microL toluene microdrop exposed for 37 min to 10 mL of the aqueous sample containing 0% w/v NaCl and stirred at 380 rpm. The calculated calibration curves gave high-level linearity for all target analytes with correlation coefficients ranging between 0.9991 and 0.9999. The repeatability of the proposed method, expressed as relative standard deviation, varied between 5.9 and 9.9% (n=8). The detection limits were in the range of 0.022-0.101 microg L(-1) using GC-MS with selective ion monitoring. The LOD values obtained are able to detect these OCPs in aqueous matrices as required by EPA Method 625. Analysis of spiked effluent wastewater samples revealed that the matrix had no effect on extraction for eleven of the analytes but exerted notable effect for the other analytes.

Informe preliminar de avances en el Proyecto Visión de Primera Línea en la Región Sudamericana

En el siguiente informe se presentan los resultados del proyecto ôVisión de Primera Líneaö, cuyo propósito fue medir el avance hacia la implementación del Marco de Acción de Hyogo (MAH) en la región de Sudamérica, con referencia específica en los cuatro países piloto participantes en esta primera fase: Bolivia, Perú, Uruguay, Venezuela