Search

Abstract Background Blood-brain barrier (BBB) alterations may contribute to AD pathology through various mechanisms, including impaired amyloid-β (Aβ) clearance and neuroinflammation. Soluble platelet-derived growth factor receptor beta (sPDGFRβ) has emerged as a potential biomarker for BBB integrity. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers a direct assessment of BBB permeability. However, the relationship between BBB dysfunction, cognitive impairment, and AD pathology remains unclear, with inconsistent findings in the literature. Methods We conducted a cross-sectional study using data from the DELCODE and DESCRIBE cohorts to investigate BBB dysfunction in participants with normal cognition (NC), mild cognitive impairment (MCI), and AD dementia. BBB function was assessed using DCE-MRI and sPDGFRβ levels in cerebrospinal fluid and AD biomarkers Aβ and tau were measured. In a subset of patients, the CSF/plasma-ratio of albumin (QAlb) as a standard marker of BBB integrity and markers of neuroinflammation were analyzed. Results 91 participants (NC: 44, MCI: 21, AD: 26) were included in the analysis. The average age was 74.4 years, 42% were female. Increased hippocampal BBB disruption was observed in the AD-group (Ktrans: 0.55 × 10− 3 min− 1 ± 0.74 × 10− 3 min− 1) but not the MCI-group (Ktrans: 0.177 × 10− 3 min− 1 ± 0.22 × 10− 3 min− 1), compared to the NC group (Ktrans: 0.19 × 10− 3 min− 1 ± 0.37 × 10− 3 min− 1, p

Summary: Background: Blood-based biomarkers offer a promising, less invasive, and more cost-effective alternative for Alzheimer's disease screening compared to cerebrospinal fluid or imaging biomarkers. However, they have been extensively studied only in memory clinic-based cohorts. We aimed to validate them in a more heterogeneous, older patient population from primary care. Methods: We measured plasma Aβ42/Aβ40, P-tau181, NfL, and GFAP in 1007 individuals without dementia, aged 79–94 years, from the longitudinal, primary care-based German AgeCoDe study. We assessed the association with cognitive decline, disease progression, and the capacity to predict future dementia of the Alzheimer's type (DAT). We also evaluated biomarker dynamics in 305 individuals with a follow-up sample (∼8 years later). Findings: Higher levels of P-tau181 (HR = 1.32 [95% CI: 1.17–1.51]), NfL (HR = 1.19 [95% CI: 1.03–1.36]), and GFAP (HR = 1.36 [95% CI: 1.22–1.52]), and a lower Aβ42/Aβ40 ratio (HR = 0.80 [95% CI: 0.68–0.95]) were associated with an increased risk of progressing to clinically-diagnosed DAT. Additionally, higher levels of P-tau181 (β = −0.49 [95% CI: −0.71 to 0.26]), NfL (β = −0.29 [95% CI: −0.52 to 0.06]), and GFAP (β = −0.60 [95% CI: −0.83 to 0.38]) were linked to faster cognitive decline. A two-step DAT prediction strategy combining initial MMSE with biomarkers improved the identification of individuals in the prodromal stage for potential treatment eligibility. Biomarker levels changed over time, with increases in P-tau181 (β = 0.19 [95% CI: 0.14–0.25]), NfL (β = 2.88 [95% CI: 2.18–3.59]), and GFAP (β = 8.23 [95% CI: 6.71–9.75]). NfL (β = 2.47 [95% CI: 1.04–3.89]) and GFAP (β = 4.45 [95% CI: 1.38–7.51]) exhibited a faster increase in individuals progressing to DAT. Interpretation: Evaluating plasma biomarkers, alongside brief cognitive assessments, might enhance the precision of risk assessment for DAT progression in primary care. Funding: Alzheimer Forschung Initiative, Bundesministerium für Bildung und Forschung.

The present study investigated the association of genetic predisposition for white matter hyperintensities (WMHs) with incident amnestic mild cognitive impairment (aMCI) or Alzheimer’s disease (AD), as well as whether such an association was influenced by age, sex, and cognitive reserve. Overall, 537 individuals without aMCI or dementia at baseline were included. Among them, 62 individuals developed aMCI/AD at follow up. Genetic propensity to WMH was estimated using a polygenic risk score for WMHs (PRS WMH). The association of PRS WMH with aMCI/AD incidence was examined using COX models. A higher PRS WMH was associated with a 47.2% higher aMCI/AD incidence (p = 0.015) in the fully adjusted model. Subgroup analyses showed significant results in the older age group, in which individuals with a higher genetic predisposition for WMHs had a 3.4-fold higher risk for developing aMCI/AD at follow up (p < 0.001), as well as in the lower cognitive reserve (CR, proxied by education years) group, in which individuals with a higher genetic predisposition for WMHs had an over 2-fold higher risk (p = 0.013). Genetic predisposition for WMHs was associated with aMCI/AD incidence, particularly in the group of participants with a low CR. Thus, CR might be a modifier in the relationship between genetic predisposition for WMHs and incident aMCI/AD.

Abstract INTRODUCTION We investigated the association of inflammatory mechanisms with markers of Alzheimer's disease (AD) pathology and rates of cognitive decline in the AD spectrum. METHODS We studied 296 cases from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study (DELCODE) cohort, and an extension cohort of 276 cases of the Alzheimer's Disease Neuroimaging Initiative study. Using Bayesian confirmatory factor analysis, we constructed latent factors for synaptic integrity, microglia, cerebrovascular endothelial function, cytokine/chemokine, and complement components of the inflammatory response using a set of inflammatory markers in cerebrospinal fluid. RESULTS We found strong evidence for an association of synaptic integrity, microglia response, and cerebrovascular endothelial function with a latent factor of AD pathology and with rates of cognitive decline. We found evidence against an association of complement and cytokine/chemokine factors with AD pathology and rates of cognitive decline. DISCUSSION Latent factors provided access to directly unobservable components of the neuroinflammatory response and their association with AD pathology and cognitive decline.

Placental-site trophoblastic tumor (PSTT) is a rare pathological entity included in the spectrum of gestational trophoblastic neoplasia (GTN). It is a neoplasia with metastatic potential that, once metastasized, has poor prognosis because the tumor tends to be less sensitive to chemotherapy. We present a rare case of gestational trophoblastic neoplasia, in which hysterectomy for persistent gestational trophoblastic disease after hydatidiform mole, revealed a primary PSTT in the uterus. Subsequently, a slight persistent elevation of the beta fraction of human chorionic gonadotropin hormone (B-hCG) during follow-up revealed the presence of bone metastases. This location is not usual from this tumor, being even more rare the case of PSTT with isolated bone metastases. Metastasic foci were only identified with PET-CT since the usual diagnostic resources were not able to do it. Finally, it is also remarkable in our case that the treatment required the confluence of chemotherapy together with immunotherapy to achieve a favorable response.

The possible relationship between Subjective Cognitive Decline (SCD) and dementia needs further investigation. In the present study, we explored the association between specific biomarkers of Alzheimer’s Disease (AD), amyloid-beta 42 (Aβ42) and Tau with the odds of SCD using data from two ongoing studies. In total, 849 cognitively normal (CN) individuals were included in our analyses. Among the participants, 107 had available results regarding cerebrospinal fluid (CSF) Aβ42 and Tau, while 742 had available genetic data to construct polygenic risk scores (PRSs) reflecting their genetic predisposition for CSF Aβ42 and plasma total Tau levels. The associations between AD biomarkers and SCD were tested using logistic regression models adjusted for possible confounders such as age, sex, education, depression, and baseline cognitive test scores. Abnormal values of CSF Aβ42 were related to 2.5-fold higher odds of SCD, while higher polygenic loading for Aβ42 was associated with 1.6-fold higher odds of SCD. CSF Tau, as well as polygenic loading for total Tau, were not associated with SCD. Thus, only cerebral amyloidosis appears to be related to SCD status, either in the form of polygenic risk or actual CSF measurements. The temporal sequence of amyloidosis being followed by tauopathy may partially explain our findings.

Abstract Background In preclinical Alzheimer’s disease, it is unclear why some individuals with amyloid pathologic change are asymptomatic (stage 1), whereas others experience subjective cognitive decline (SCD, stage 2). Here, we examined the association of stage 1 vs. stage 2 with structural brain reserve in memory-related brain regions. Methods We tested whether the volumes of hippocampal subfields and parahippocampal regions were larger in individuals at stage 1 compared to asymptomatic amyloid-negative older adults (healthy controls, HCs). We also tested whether individuals with stage 2 would show the opposite pattern, namely smaller brain volumes than in amyloid-negative individuals with SCD. Participants with cerebrospinal fluid (CSF) biomarker data and bilateral volumetric MRI data from the observational, multi-centric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study were included. The sample comprised 95 amyloid-negative and 26 amyloid-positive asymptomatic participants as well as 104 amyloid-negative and 47 amyloid-positive individuals with SCD. Volumes were based on high-resolution T2-weighted images and automatic segmentation with manual correction according to a recently established high-resolution segmentation protocol. Results In asymptomatic individuals, brain volumes of hippocampal subfields and of the parahippocampal cortex were numerically larger in stage 1 compared to HCs, whereas the opposite was the case in individuals with SCD. MANOVAs with volumes as dependent data and age, sex, years of education, and DELCODE site as covariates showed a significant interaction between diagnosis (asymptomatic versus SCD) and amyloid status (Aß42/40 negative versus positive) for hippocampal subfields. Post hoc paired comparisons taking into account the same covariates showed that dentate gyrus and CA1 volumes in SCD were significantly smaller in amyloid-positive than negative individuals. In contrast, CA1 volumes were significantly (p = 0.014) larger in stage 1 compared with HCs. Conclusions These data indicate that HCs and stages 1 and 2 do not correspond to linear brain volume reduction. Instead, stage 1 is associated with larger than expected volumes of hippocampal subfields in the face of amyloid pathology. This indicates a brain reserve mechanism in stage 1 that enables individuals with amyloid pathologic change to be cognitively normal and asymptomatic without subjective cognitive decline.

Abstract Background Neuroinflammation constitutes a pathological hallmark of Alzheimer’s disease (AD). Still, it remains unresolved if peripheral inflammatory markers can be utilized for research purposes similar to blood-based beta-amyloid and neurodegeneration measures. We investigated experimental inflammation markers in serum and analyzed interrelations towards AD pathology features in a cohort with a focus on at-risk stages of AD. Methods Data of 74 healthy controls (HC), 99 subjective cognitive decline (SCD), 75 mild cognitive impairment (MCI), 23 AD relatives, and 38 AD subjects were obtained from the DELCODE cohort. A panel of 20 serum biomarkers was determined using immunoassays. Analyses were adjusted for age, sex, APOE status, and body mass index and included correlations between serum and CSF marker levels and AD biomarker levels. Group-wise comparisons were based on screening diagnosis and routine AD biomarker-based schematics. Structural imaging data were combined into composite scores representing Braak stage regions and related to serum biomarker levels. The Preclinical Alzheimer’s Cognitive Composite (PACC5) score was used to test for associations between the biomarkers and cognitive performance. Results Each experimental marker displayed an individual profile of interrelations to AD biomarkers, imaging, or cognition features. Serum-soluble AXL (sAXL), IL-6, and YKL-40 showed the most striking associations. Soluble AXL was significantly elevated in AD subjects with pathological CSF beta-amyloid/tau profile and negatively related to structural imaging and cognitive function. Serum IL-6 was negatively correlated to structural measures of Braak regions, without associations to corresponding IL-6 CSF levels or other AD features. Serum YKL-40 correlated most consistently to CSF AD biomarker profiles and showed the strongest negative relations to structure, but none to cognitive outcomes. Conclusions Serum sAXL, IL-6, and YKL-40 relate to different AD features, including the degree of neuropathology and cognitive functioning. This may suggest that peripheral blood signatures correspond to specific stages of the disease. As serum markers did not reflect the corresponding CSF protein levels, our data highlight the need to interpret serum inflammatory markers depending on the respective protein’s specific biology and cellular origin. These marker-specific differences will have to be considered to further define and interpret blood-based inflammatory profiles for AD research.

Summary: Alzheimer disease (AD) is the most common form of senile dementia, with high incidence late in life in many populations including Caribbean Hispanic (CH) populations. Such admixed populations, descended from more than one ancestral population, can present challenges for genetic studies, including limited sample sizes and unique analytical constraints. Therefore, CH populations and other admixed populations have not been well represented in studies of AD, and much of the genetic variation contributing to AD risk in these populations remains unknown. Here, we conduct genome-wide analysis of AD in multiplex CH families from the Alzheimer Disease Sequencing Project (ADSP). We developed, validated, and applied an implementation of a logistic mixed model for admixture mapping with binary traits that leverages genetic ancestry to identify ancestry-of-origin loci contributing to AD. We identified three loci on chromosome 13q33.3 associated with reduced risk of AD, where associations were driven by Native American (NAM) ancestry. This AD admixture mapping signal spans the FAM155A, ABHD13, TNFSF13B, LIG4, and MYO16 genes and was supported by evidence for association in an independent sample from the Alzheimer’s Genetics in Argentina—Alzheimer Argentina consortium (AGA-ALZAR) study with considerable NAM ancestry. We also provide evidence of NAM haplotypes and key variants within 13q33.3 that segregate with AD in the ADSP whole-genome sequencing data. Interestingly, the widely used genome-wide association study approach failed to identify associations in this region. Our findings underscore the potential of leveraging genetic ancestry diversity in recently admixed populations to improve genetic mapping, in this case for AD-relevant loci.

Obsessive-compulsive disorder (OCD) has recently been linked to increased methylation levels in the oxytocin receptor (OXTR) gene, and OXTR hypermethylation has predicted a worse treatment response to cognitive-behavioural therapy (CBT). Furthermore, OCD is associated with childhood trauma and stressful life events, which have both been shown to affect OXTR methylation. Here, we aimed to replicate findings of increased OXTR methylation as a predictor of disease and worse treatment response in an independent sample that received treatment within the public health care system. In addition, we aimed to extend previous findings by examining associations between OXTR hypermethylation, environmental stressors, OCD diagnosis, and treatment response. Methylation levels at two CpGs within OXTR exon III were compared between n = 181 OCD patients and n = 199 healthy controls using linear regression analysis. In a subsample of OCD patients (n = 98) with documented treatment data, we examined associations between methylation and treatment response to CBT. Childhood adversity and stressful life events were assessed using Childhood Trauma Questionnaire and Life Experience Survey, respectively. OCD patients exhibited significant hypermethylation at CpG site cg04523291 compared to controls, and increased methylation was associated with impaired treatment response. Moreover, hypermethylation at cg04523291 was associated with stressful life events in OCD patients, and with childhood adversity in controls. Yet, there were no significant mediation effects. In conclusion, we replicated the association between OXTR hypermethylation and OCD in the largest sample, so far. Furthermore, our findings support the role of OXTR methylation as a promising biomarker for treatment response in OCD.

Abstract Background Genetic variants within the APOE locus may modulate Alzheimer’s disease (AD) risk independently or in conjunction with APOE*2/3/4 genotypes. Identifying such variants and mechanisms would importantly advance our understanding of APOE pathophysiology and provide critical guidance for AD therapies aimed at APOE. The APOE locus however remains relatively poorly understood in AD, owing to multiple challenges that include its complex linkage structure and uncertainty in APOE*2/3/4 genotype quality. Here, we present a novel APOE*2/3/4 filtering approach and showcase its relevance on AD risk association analyses for the rs439401 variant, which is located 1801 base pairs downstream of APOE and has been associated with a potential regulatory effect on APOE. Methods We used thirty-two AD-related cohorts, with genetic data from various high-density single-nucleotide polymorphism microarrays, whole-genome sequencing, and whole-exome sequencing. Study participants were filtered to be ages 60 and older, non-Hispanic, of European ancestry, and diagnosed as cognitively normal or AD (n = 65,701). Primary analyses investigated AD risk in APOE*4/4 carriers. Additional supporting analyses were performed in APOE*3/4 and 3/3 strata. Outcomes were compared under two different APOE*2/3/4 filtering approaches. Results Using more conventional APOE*2/3/4 filtering criteria (approach 1), we showed that, when in-phase with APOE*4, rs439401 was variably associated with protective effects on AD case-control status. However, when applying a novel filter that increases the certainty of the APOE*2/3/4 genotypes by applying more stringent criteria for concordance between the provided APOE genotype and imputed APOE genotype (approach 2), we observed that all significant effects were lost. Conclusions We showed that careful consideration of APOE genotype and appropriate sample filtering were crucial to robustly interrogate the role of the APOE locus on AD risk. Our study presents a novel APOE filtering approach and provides important guidelines for research into the APOE locus, as well as for elucidating genetic interaction effects with APOE*2/3/4.

Introduction: The metabolic routes altered in Alzheimer's disease (AD) brain are poorly understood. As the metabolic pathways are evolutionarily conserved, the metabolic profiles carried out in animal models of AD could be directly translated into human studies.Methods: We performed untargeted Nuclear Magnetic Resonance metabolomics in hippocampus of McGill-R-Thy1-APP transgenic (Tg) rats, a model of AD-like cerebral amyloidosis and the translational potential of these findings was assessed by targeted Gas Chromatography-Electron Impact-Mass Spectrometry in plasma of participants in the German longitudinal cohort AgeCoDe.Results: In rat hippocampus 26 metabolites were identified. Of these 26 metabolites, nine showed differences between rat genotypes that were nominally significant. Two of them presented partial least square-discriminant analysis (PLS-DA) loadings with the larger absolute weights and the highest Variable Importance in Projection (VIP) scores and were specifically assigned to nicotinamide adenine dinucleotide (NAD) and nicotinamide (Nam). NAD levels were significantly decreased in Tg rat brains as compared to controls. In agreement with these results, plasma of AD patients showed significantly reduced levels of Nam in respect to cognitively normal participants. In addition, high plasma levels of Nam showed a 27% risk reduction of progressing to AD dementia within the following 2.5 years, this hazard ratio is lost afterwards.Discussion: To our knowledge, this is the first report showing that a decrease of Nam plasma levels is observed couple of years before conversion to AD, thereby suggesting its potential use as biomarker for AD progression.

IntroductionSeveral lifestyle factors promote protection against Alzheimer's disease (AD) throughout a person's lifespan. Although such protective effects have been described for occupational cognitive requirements (OCR) in midlife, it is currently unknown whether they are conveyed by brain maintenance (BM), brain reserve (BR), or cognitive reserve (CR) or a combination of them.MethodsWe systematically derived hypotheses for these resilience concepts and tested them in the population-based AgeCoDe cohort and memory clinic-based AD high-risk DELCODE study. The OCR score (OCRS) was measured using job activities based on the O*NET occupational classification system. Four sets of analyses were conducted: (1) the interaction of OCR and APOE-ε4 with regard to cognitive decline (N = 2,369, AgeCoDe), (2) association with differentially shaped retrospective trajectories before the onset of dementia of the Alzheimer's type (DAT; N = 474, AgeCoDe), (3) cross-sectional interaction of the OCR and cerebrospinal fluid (CSF) AD biomarkers and brain structural measures regarding memory function (N = 873, DELCODE), and (4) cross-sectional and longitudinal association of OCR with CSF AD biomarkers and brain structural measures (N = 873, DELCODE).ResultsRegarding (1), higher OCRS was associated with a reduced association of APOE-ε4 with cognitive decline (mean follow-up = 6.03 years), consistent with CR and BR. Regarding (2), high OCRS was associated with a later onset but subsequently stronger cognitive decline in individuals converting to DAT, consistent with CR. Regarding (3), higher OCRS was associated with a weaker association of the CSF Aβ42/40 ratio and hippocampal volume with memory function, consistent with CR. Regarding (4), OCR was not associated with the levels or changes in CSF AD biomarkers (mean follow-up = 2.61 years). We found a cross-sectional, age-independent association of OCRS with some MRI markers, but no association with 1-year-change. OCR was not associated with the intracranial volume. These results are not completely consistent with those of BR or BM.DiscussionOur results support the link between OCR and CR. Promoting and seeking complex and stimulating work conditions in midlife could therefore contribute to increased resistance to pathologies in old age and might complement prevention measures aimed at reducing pathology.

Abstract Alterations in frontal and parietal neural activations during working memory task performance have been suggested as a candidate endophenotype of obsessive-compulsive disorder (OCD) in studies involving first-degree relatives. However, the direct link between genetic risk for OCD and neuro-functional alterations during working memory performance has not been investigated to date. Thus, the aim of the current functional magnetic resonance imaging (fMRI) study was to test the direct association between polygenic risk for OCD and neural activity during the performance of a numeric n-back task with four working memory load conditions in 128 participants, including patients with OCD, unaffected first-degree relatives of OCD patients, and healthy controls. Behavioral results show a significant performance deficit at high working memory load in both patients with OCD and first-degree relatives (p

ObjectiveEvidence supports the important role of neuroinflammation in some types of dementia. This study aimed to evaluate the effect of epistasis of gene cytokines such as interleukin (IL)-α, IL-6, tumor necrosis factor (TNFα), and interferon-gamma (IFN-γ) on the susceptibility to the development of dementia.Materials and methodsIn the study, 221 patients diagnosed with dementia and 710 controls were included. The multifactor-dimensionality reduction (MDR) analysis was performed to identify the epistasis between SNP located in genes of IL-α (rs1800587), IL-6 (rs1800796), TNFα (rs361525 and rs1800629), and IFNγ (rs2069705). The best risk prediction model was identified based on precision and cross-validation consistency.ResultsMultifactor-dimensionality reduction analysis detected a significant model with the genes TNFα, IFNγ, IL1α, and IL6 (prediction success: 72%, p < 0.0001). When risk factors were analyzed with these polymorphisms, the model achieved a similar prediction for dementia as the genes-only model.ConclusionThese data indicate that gene–gene interactions form significant models to identify populations susceptible to dementia.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Background and purpose: Vascular risk factors may influence cognitive function and thus represent possible targets for preventive approaches against dementia. Yet it remains unknown, if they associate with cognition independently of the individual genetic risk for dementia. Methods: In a population-based study of 1172 community-dwelling individuals aged ≥65 years in Greece, we constructed a vascular burden score (VBS; based on presence of hypertension, diabetes, hyperlipidemia, heart disease, and cerebrovascular disease, range 0–5) and a polygenic risk score (PRS) for clinically-diagnosed Alzheimer's disease (AD) based on 23 genetic variants. We then explored in joint models the associations of the PRS for AD and VBS with global cognitive performance, cognitive performance across multiple cognitive domains, and odds of dementia. Results: The mean age of study participants was 73.9 ± 5.2 years (57.1% females). Both the PRS for AD and VBS were associated with worse global cognitive performance (beta per-SD-increment in PRS: -0.06, 95%CI: -0.10 to -0.02, beta per-point-increment in VBS: -0.05, 95%CI: -0.09 to -0.02), worse performance across individual cognitive domains (memory, executive function, attention, language, visuospatial ability), and higher odds of dementia (OR per-SD increment in PRS: 1.56, 95%CI: 1.17–2.09, OR per-point increment in VBS: 1.38, 95%CI: 1.05–1.81). There was no evidence of an interaction between the two scores. Higher VBS was associated with worse cognitive performance equally across tertiles of the PRS for AD, even among individuals at the highest tertile. Conclusions: Both genetic risk and vascular burden are independently and additively associated with worse cognitive performance and higher odds of dementia.

Abstract Background Late-life depression (LLD) is one of the most prevalent mental disorders in old age. It is associated with various adverse outcomes and frequent use of health care services thereby remaining a serious public health concern. Compared with depression in early adulthood, most treatment options of LLD are less effective. Psychotherapy may be particularly beneficial for LLD due to specific psychological conditions in old age and a low risk of side effects. Although cognitive behavioural therapy (CBT) is highly established and effective in depression in young and mid-life there is only a limited number of small studies on CBT in LLD. An LLD-specific CBT has not yet been compared to an active, but unspecific supportive psychological intervention in a multicentre trial. Methods Here we present the design of the CBTlate trial, which is a multicentre, randomized, observer-blinded, active-controlled, parallel group trial. CBTlate aims at including 248 patients with LLD of both genders at 7 sites in Germany. The purpose of the study is to test the hypothesis that a 15-session individually-delivered CBT specific for LLD is of superior efficacy in reducing symptoms of depression in comparison with a supportive unspecific intervention (SUI) of the same quantity. The intervention includes 8 weeks of individual treatment sessions twice per week and a follow-up period of 6 months after randomization. The primary end point is the severity of depression at the end of treatment measured by the self-rated 30-item Geriatric Depression Scale (GDS). Secondary endpoints include depressive symptoms at week 5 and at follow-up (6 months after randomization). Additional secondary endpoints include the change of depressive symptoms assessed with a clinician-rating-scale and a patient reported outcome instrument for major depressive disorder, anxiety symptoms, sleep, cognition, quality of life, and overall health status from baseline to end-of treatment and to end of follow-up. Add-on protocols include MRI and the collection of blood samples. Discussion This study is the first multicentre trial of a specific CBT intervention for LLD compared to an unspecific supportive psychological intervention administered in a specialist setting. It has important implications for developing and implementing efficient psychotherapeutic strategies for LLD and may be a significant step to broaden treatment options for people suffering from LLD. Trial registration ClinicalTrials.gov (NCT03735576, registered on 24 October 2018); DRKS (DRKS00013769, registered on 28 June 2018).

Several studies have investigated the association of the Parkinson’s disease (PD) polygenic risk score (PRS) with several aspects of well-established PD. We sought to evaluate the association of PRS with the prodromal stage of PD. We calculated PRS in a longitudinal sample (n = 1120) of community dwelling individuals ≥ 65 years from the HELIAD (The Hellenic Longitudinal Investigation of Aging and Diet) study in order to evaluate the association of this score with the probability of prodromal PD or any of the established risk and prodromal markers in MDS research criteria, using regression multi-adjusted models. Increases in PRS estimated from GWAS summary statistics’ ninety top SNPS with p < 5 × 10–8 was associated with increased odds of having probable/possible prodromal PD (i.e., ≥ 30% probability, OR = 1.033, 95%CI: 1.009–1.057 p = 0.006). From the prodromal PD risk markers, significant association was found between PRS and global cognitive deficit exclusively (p = 0.003). To our knowledge, our study is the first population based study investigating the association between PRS scores and prodromal markers of Parkinson’s disease. Our results suggest a strong relationship between the accumulation of many common genetic variants, as measured by PRS, and cognitive deficits.

Abstract Background Subjective cognitive decline (SCD) has been proposed as a pre-MCI at-risk condition of Alzheimer’s disease (AD). Current research is focusing on a refined assessment of specific SCD features associated with increased risk for AD, as proposed in the SCD-plus criteria. We developed a structured interview (SCD-I) for the assessment of these features and tested their relationship with AD biomarkers. Methods We analyzed data of 205 cognitively normal participants of the DELCODE study (mean age = 68.9 years; 52% female) with available CSF AD biomarkers (Aß-42, p-Tau181, Aß-42/Tau ratio, total Tau). For each of five cognitive domains (including memory, language, attention, planning, others), a study physician asked participants about the following SCD-plus features: the presence of subjective decline, associated worries, onset of SCD, feeling of worse performance than others of the same age group, and informant confirmation. We compared AD biomarkers of subjects endorsing each of these questions with those who did not, controlling for age. SCD was also quantified by two summary scores: the number of fulfilled SCD-plus features, and the number of domains with experienced decline. Covariate-adjusted linear regression analyses were used to test whether these SCD scores predicted abnormality in AD biomarkers. Results Lower Aß-42 levels were associated with a reported decline in memory and language abilities, and with the following SCD-plus features: onset of subjective decline within 5 years, confirmation of cognitive decline by an informant, and decline-related worries. Furthermore, both quantitative SCD scores were associated with lower Aß42 and lower Aß42/Tau ratio, but not with total Tau or p-Tau181. Conclusions Findings support the usefulness of a criterion-based interview approach to assess and quantify SCD in the context of AD and validate the current SCD-plus features as predictors of AD pathology. While some features seem to be more closely associated with AD biomarkers than others, aggregated scores over several SCD-plus features or SCD domains may be the best predictors of AD pathology.

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

APOE genotype is the strongest genetic risk factor for Alzheimer’s Disease (AD). The low degree of homology between mouse and human APOE is a concerning issue in preclinical models currently used to study the role of this gene in AD pathophysiology. A key objective of ADAPTED (Alzheimer's Disease Apolipoprotein Pathology for Treatment Elucidation and Development) project was to generate in vitro models that better recapitulate human APOE biology. We describe a new set of induced pluripotent stem cells (iPSC) lines carrying common APOE variants (Ɛ2, Ɛ3, and Ɛ3/Ɛ4) and a knock-out isogenic to the parental APOE Ɛ4/Ɛ4 line (UKBi011-A).

Abstract Introduction Large studies on cognitive profiles of patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD‐MCI) compared to Parkinson's disease (PD‐MCI) are rare. Methods Data from two multicenter cohort studies in AD and PD were merged using a unified base rate approach for the MCI diagnosis. Cognitive profiles were compared using scores derived from the Consortium to Establish a Registry for Alzheimer's Disease battery. Results Patients with AD‐MCI showed lower standardized scores on all memory test scores and a language test. Patients with PD‐MCI showed lower standardized scores in a set‐shifting measure as an executive task. A cross‐validated logistic regression with test scores as predictors was able to classify 72% of patients correctly to AD‐MCI versus PD‐MCI. Discussion The applied test battery successfully discriminated between AD‐MCI and PD‐MCI. Neuropsychological test batteries in clinical practice should always include a broad spectrum of cognitive domains to capture any cognitive changes.

Neurodegenerative diseases (NDD) such as Alzheimer's (AD) and Parkinson's disease (PD) are distinct clinical entities, however, the aggregation of key neuronal proteins, presumably leading to neuronal demise appears to represent a common mechanism. It has become evident, that advanced glycation end products (AGEs) trigger the accumulation of such modified proteins, which eventually contributes to pathological aspect of NDDs. Increased levels of AGEs are found in amyloid plaques in AD brains and in both advanced and early PD (incidental Lewy body disease). The molecular mechanisms by which AGE dependent modifications may modulate the susceptibility towards NDDs, however, remain enigmatic and it is unclear, whether AGEs may serve as biomarker of NDD. In the present study, we examined AGEs (CML: Carboxymethyllysine and CEL: Carboxyethyllysine), markers of oxidative stress and micronutrients in the plasma of PD and AD patients and controls. As compared to healthy controls, AD females displayed lower levels of CEL while higher levels of CML were found in AD and PD patients. A somewhat similar pattern was observed for protein carbonyls (PC), revealing lower values exclusively in AD females, whereas AD males displayed significantly higher values compared to healthy controls and PD. Sex-specific differences were also observed for other relevant markers such as malondialdehyde, 3-nitrotyrosine, γ -tocopherols, retinol, plasma proteins and α-carotene, while α-tocopherols, β-carotene, lutein/zeaxanthin, β-cryptoxanthin and lycopene showed no relevant association. Taken together, our study suggests yet unappreciated differences of the distribution of AGEs among the sexes in NDD. We therefore suggest to make a clear distinction between sexes when analyzing oxidative (AGEs)-related stress and carbonyl-related stress and vitamins.

Lameness in dairy cows is an extremely painful multifactorial condition that affects the welfare of animals and economically impacts the dairy industry worldwide. The aim of this study was to determine the profile of cytokines in the spinal cord dorsal horn of dairy cows with painful chronic inflammatory lameness. Concentrations of 10 cytokines were measured in the spinal cord of seven adult dairy cows with chronic lameness and seven adult dairy cows with no lameness. In all cows lameness was evaluated using a mobility scoring system and registered accordingly. Immediately after euthanasia the spinal cord was removed and 20 cm of lumbar segments (L2–L5) were obtained. After dorsal horn removal and processing, cytokine quantification of tumor necrosis factor-alpha (TNF-α), interleukin-1alpha (IL-1α), interleukin 13 (IL-13), chemokine-10 (CXCL10/IP-10), chemokine-9 (CXCL9/MIG), interferon-alpha (IFN-α), interferon-gamma (IFN-γ), interleukin-21 (IL-21), interleukin-36ra (IL-36ra), and macrophage inflammatory protein-1 beta (MIP-1β) was performed using a multiplex array. Lame cows had higher concentrations of TNF-α, IL-1-α, IL-13, CXCL10, CXCL9, IFN-α, and IFN-γ in their dorsal horn compared to non-lame cows, while IL-21 concentration was decreased. No differences in IL-36ra and MIP-1β concentrations between lame and non-lame cows were observed. Painful chronic inflammation of the hoof in dairy cows leads to a marked increase in cytokine concentration in the dorsal horn of the spinal cord, which could represent a state of neuroinflammation of the Central Nervous System (CNS).

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

Alzheimer's disease (AD) is most the frequent neurodegenerative disease, and the APOE ε4 allele is the most prominent risk factor for late-onset AD. Here, we present an iPSC line generated from peripheral blood cells of a male AD patient employing Sendai virus vectors encoding the transcription factors OCT4, SOX2, KLF4 and c-MYC. The characterized iPSC line expresses typical human pluripotency markers and shows differentiation into all three germ layers, complete reprogramming vector clearance, a normal SNP genotype and maintenance of the APOE ε4/ε4 allele.

Abstract Background Deep phenotyping and longitudinal assessment of predementia at-risk states of Alzheimer’s disease (AD) are required to define populations and outcomes for dementia prevention trials. Subjective cognitive decline (SCD) is a pre-mild cognitive impairment (pre-MCI) at-risk state of dementia, which emerges as a highly promising target for AD prevention. Methods The German Center for Neurodegenerative Diseases (DZNE) is conducting the multicenter DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE), which focuses on the characterization of SCD in patients recruited from memory clinics. In addition, individuals with amnestic MCI, mild Alzheimer’s dementia patients, first-degree relatives of patients with Alzheimer’s dementia, and cognitively unimpaired control subjects are studied. The total number of subjects to be enrolled is 1000. Participants receive extensive clinical and neuropsychological assessments, magnetic resonance imaging, positron emission tomography, and biomaterial collection is perfomed. In this publication, we report cognitive and clinical data as well as apolipoprotein E (APOE) genotype and cerebrospinal fluid (CSF) biomarker results of the first 394 baseline data sets. Results In comparison with the control group, patients with SCD showed slightly poorer performance on cognitive and functional measures (Alzheimer’s Disease Assessment Scale—cognitive part, Clinical Dementia Rating, Functional Activities Questionnaire), with all mean scores in a range which would be considered unimpaired. APOE4 genotype was enriched in the SCD group in comparison to what would be expected in the population and the frequency was significantly higher in comparison to the control group. CSF Aβ42 was lower in the SCD group in comparison to the control group at a statistical trend with age as a covariate. There were no group differences in Tau or pTau concentrations between the SCD and the control groups. The differences in all measures between the MCI group and the AD group were as expected. Conclusions The initial baseline data for DELCODE support the approach of using SCD in patients recruited through memory clinics as an enrichment strategy for late-stage preclinical AD. This is indicated by slightly lower performance in a range of measures in SCD in comparison to the control subjects as well as by enriched APOE4 frequency and lower CSF Aβ42 concentration. Trial registration German Clinical Trials Register DRKS00007966. Registered 4 May 2015.

Abstract Introduction We examined the association between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, neural novelty responses, and brain volume in predementia old age. Methods We conducted a cross‐sectional analysis of the observational, multicentric DZNE‐Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Seventy‐six participants completed task functional magnetic resonance imaging and provided CSF (40 cognitively unimpaired, 21 experiencing subjective cognitive decline, and 15 with mild cognitive impairment). We assessed the correlation between CSF biomarkers and whole‐brain functional magnetic resonance imaging novelty responses to scene images. Results Total tau levels were specifically and negatively associated with novelty responses in the right amygdala and right hippocampus. Mediation analyses showed no evidence that these associations were dependent on the volume of hippocampus/amygdala. No relationship was found between phosphorylated‐tau or Aβ42 levels and novelty responses. Discussion Our data show that CSF levels of total tau are associated with anatomically specific reductions in novelty processing, which cannot be fully explained by atrophy.

Late onset Alzheimer's disease is the most common form of dementia for which about 30 susceptibility loci have been reported. The aim of the current study is to identify novel genes associated with Alzheimer's disease using the largest up-to-date reference single nucleotide polymorphism (SNP) panel, the most accurate imputation software and a novel gene-based analysis approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 million genotypes from 17,008 Alzheimer's cases and 37,154 controls. In addition to earlier reported genes, we detected three novel gene-wide significant loci PPARGC1A (p = 2.2 × 10-6), RORA (p = 7.4 × 10-7) and ZNF423 (p = 2.1 × 10-6). PPARGC1A and RORA are involved in circadian rhythm; circadian disturbances are one of the earliest symptoms of Alzheimer's disease. PPARGC1A is additionally linked to energy metabolism and the generation of amyloid beta plaques. RORA is involved in a variety of functions apart from circadian rhythm, such as cholesterol metabolism and inflammation. The ZNF423 gene resides in an Alzheimer's disease-specific protein network and is likely involved with centrosomes and DNA damage repair.

Isolated energy systems in archipelagos are characterized for having a great dependence on fossil sources due to isolation and territorial fragmentation. The island of La Palma is situated on the northwest of the Canary Islands, and its electric system is very small. Sustainability policies planned by local authorities are aimed to increase the share of renewable energies and the reduction of fossil energies. However, intermittence and the concentration of unmanageable renewable energies in few locations may hinder the operation of the system. In order to solve these problems, energy storage plays an essential role. The aim of this paper is to analyse the effects of the introduction of two possible alternatives as a way of energy storage: pumped hydro storage and electric vehicles. For this, we use a simulation model adapted to the features of La Palma, considering different scenarios. Results show that, in the most favourable scenario, the installation of an additional 25 MW from renewables (more than double the current power), supported by 20 MW of pumped hydro storage and a fleet of 3361 electric vehicles, would allow the current share of renewables to increase from 11% (in 2015) to 49%. Furthermore, this would mean a 26% reduction in CO2 emissions, 10% in costs of generated kWh and 19% in energy dependence.

The accumulation of amyloid beta (Aβ) peptide (Amyloid cascade hypothesis), an APP protein cleavage product, is a leading hypothesis in the etiology of Alzheimer's disease (AD). In order to identify additional AD risk genes, we performed targeted sequencing and rare variant burden association study for nine candidate genes involved in the amyloid metabolism in 1886 AD cases and 1700 controls. We identified a significant variant burden association for the gene encoding caspase-8, CASP8 (p = 8.6x10-5). For two CASP8 variants, p.K148R and p.I298V, the association remained significant in a combined sample of 10,820 cases and 8,881 controls. For both variants we performed bioinformatics structural, expression and enzymatic activity studies and obtained evidence for loss of function effects. In addition to their role in amyloid processing, caspase-8 and its downstream effector caspase-3 are involved in synaptic plasticity, learning, memory and control of microglia pro-inflammatory activation and associated neurotoxicity, indicating additional mechanisms that might contribute to AD. As caspase inhibition has been proposed as a mechanism for AD treatment, our finding that AD-associated CASP8 variants reduce caspase function calls for caution and is an impetus for further studies on the role of caspases in AD and other neurodegenerative diseases.

Lameness in dairy cows is a worldwide prevalent disease with a negative impact on animal welfare and herd economy. Oxidative damage and antioxidant system dysfunction are common features of many CNS diseases, including chronic pain. The aim of this study was to evaluate the levels of reactive oxygen species (ROS) and oxidative damage markers in the spinal cord of dairy cows with chronic inflammatory lameness. Locomotion score was performed in order to select cows with chronic lameness. Dorsal horn spinal cord samples were obtained post mortem from lumbar segments (L2−L5), and ROS, malondialdehyde (MDA), and carbonyl groups were measured along with the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant response (TAR). Lame cows had increased levels of ROS, MDA, and carbonyl groups, while no differences were observed between lame and non-lame cows in SOD, GPx, CAT, and TAR activity. We conclude that painful chronic inflammatory lameness in dairy cows is associated with an increase in ROS, MDA, and carbonyl groups. Nonetheless, an association between ROS generation and dysfunction of the antioxidant system, as previously proposed, could not be established.

Pinguecula is a common disease in tropical countries however there are not so many published articles regarding its aetiology, signs , symptoms and management . It seems that Ultraviolet rays play an important role and it is one of the reasons that explain the prevalence in zones near the equator. Pingüeculas behave different in the nasal than in the temporal side playing an important role in the development of pterygium which explains the high incidence of its nasal location. Regarding treatment and management , there are different approaches that will discussed in this mayor review.

Several genes associated with monogenic forms of Parkinson's disease (PD) have been discovered, opening up new avenues for the investigation of presymptomatic stages of PD. Using voxel-based morphometry in 30 asymptomatic mutation carriers (MC) with mutations in four different genes for PD and 100 healthy controls, we identified an increase in gray matter volume (GMV) in the striatum in asymptomatic Parkin, PINK1, ATP13A2 and, to a much lesser extent, in LRRK2 MC. Moreover, an increase in GMV was found in the parieto-temporo-occipital association cortex in asymptomatic Parkin and ATP13A2 MC. The observed striatal GMV increase might be the common structural correlate of compensatory mechanisms due to the latent dopaminergic deficit, reflecting the different, but probably interrelated pathogenic pathways resulting in nigral cell death. Asymptomatic PINK1 and LRRK2 MC also revealed smaller GMV in the hippocampal region, which might play a role in the observed psychiatric disorders.

Mentoring, as an avenue to support and retain new teachers, has received a renewed interest. As Trubowitz suggests, “School systems are finding that beginning teachers who have access to intensive mentoring are less likely to leave teaching” (2004, p. 59). While several factors may cause teachers to leave, alienation has been identified as one of the major forces. According to previous research, teachers experience “a combination of feelings of isolation, normlessness, powerlessness, and meaninglessness” (Benham & O’Brien, 2002, p. 20). Such feelings of isolation are compounded by the current accountability demands and the professional pressure teachers’ experience. Thus, it is imperative to consider alternative strategies aimed at providing the kind of support congruent with beginning teacher’s needs in order to be successful (Breaux & Wong, 2003, p. iii). A goal of such strategies should be the effective socialization of teachers, and providing on-going support for growth, through different approaches including mentoring (Darling-Hammond, 2003; Brennan, Thames, & Roberts, 1999). Although mentoring can be an effective means to enhance teacher efficacy and help beginning teachers (Breaux & Wong, 2003; Delgado, 1999; Yost, 2002), limited research focuses on teachers’ perspectives associated with their own expectations of mentoring, particularly in diverse school settings (Wang & Odell, 2002). Further, researchers suggest, “There has been limited evidence that points to the expectations of new teachers relative to mentoring” (Tillman, 2005, p. 616). Thus, it is essential that teachers’ voices be illuminated to better understand their needs so that school leaders may “consider the benefits of consulting with novice teachers about their expectations in the mentoring arrangement” (Tillman, 2005, p. 626). Much of the current literature on teacher mentoring is based on experiences of mentors (Ganser, 1996; Trubowitz, 2004), and mentoring internship program descriptions (Brennan, Thames, & Roberts, 1999) however, novice teachers’ voices tend to be absent from the discourse. While few studies have focused on teachers’ perceptions (Rowley, 1999; Olebe, Jackson, & Danielson, 1999), additional research is needed so that beginning teachers’ voices contribute to a better understanding of mentoring as a vehicle to reduce isolation, successfully socialize new teachers into the demands of the profession, provide culturally responsive support to novice teachers, and reduce teacher turnover. Such inquiry could also be useful to avoid the common pitfalls that might have a detrimental effect on teachers and students. Therefore, the purpose of this paper is to present the results of a study conducted to examine teachers’ expectations of mentoring.

BACKGROUND:Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. PRINCIPAL FINDINGS:In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) which indexed novel susceptibility loci. SIGNIFICANCE:The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

Deviation from multiplicativity of genetic risk factors is biologically plausible and might explain why Genome-wide association studies (GWAS) so far could unravel only a portion of disease heritability. Still, evidence for SNP-SNP epistasis has rarely been reported, suggesting that 2-SNP models are overly simplistic. In this context, it was recently proposed that the genetic architecture of complex diseases could follow limiting pathway models. These models are defined by a critical risk allele load and imply multiple high-dimensional interactions. Here, we present a computationally efficient one-degree-of-freedom "supra-multiplicativity-test" (SMT) for SNP sets of size 2 to 500 that is designed to detect risk alleles whose joint effect is fortified when they occur together in the same individual. Via a simulation study we show that the SMT is powerful in the presence of threshold models, even when only about 30-45% of the model SNPs are available. In addition, we demonstrate that the SMT outperforms standard interaction analysis under recessive models involving just a few SNPs. We apply our test to 10 consensus Alzheimer's disease (AD) susceptibility SNPs that were previously identified by GWAS and obtain evidence for supra-multiplicativity ([Formula: see text]) that is not attributable to either two-way or three-way interaction.

Aortic insufficiency from iatrogenic valve perforation from nonaortic valve operations is rarely reported despite the prevalence of these procedures. Rapid diagnosis of these defects is essential to prevent deterioration of cardiac function. In this paper, we describe a young man who reported to our institution after two open cardiac surgeries with new aortic regurgitation found to be due to an iatrogenic perforation of his noncoronary aortic valve cusp. This defect was not appreciated by previous intraoperative transesophageal echocardiography and was inadequately visualized on follow-up transthoracic and transesophageal echocardiograms. In contrast, cardiac gated computed tomography clearly visualized the defect and its surrounding structures. This case highlights the utility of cardiac gated computed tomography for cases of suspected valvular perforation when echocardiography is not readily available or inadequate imaging is obtained.

Mutations in Parkin are the most common cause of autosomal recessive Parkinson disease (PD). The mitochondrially localized E3 ubiquitin-protein ligase Parkin has been reported to be involved in respiratory chain function and mitochondrial dynamics. More recent publications also described a link between Parkin and mitophagy.In this study, we investigated the impact of Parkin mutations on mitochondrial function and morphology in a human cellular model. Fibroblasts were obtained from three members of an Italian PD family with two mutations in Parkin (homozygous c.1072delT, homozygous delEx7, compound-heterozygous c.1072delT/delEx7), as well as from two relatives without mutations. Furthermore, three unrelated compound-heterozygous patients (delEx3-4/duplEx7-12, delEx4/c.924C>T and delEx1/c.924C>T) and three unrelated age-matched controls were included. Fibroblasts were cultured under basal or paraquat-induced oxidative stress conditions. ATP synthesis rates and cellular levels were detected luminometrically. Activities of complexes I-IV and citrate synthase were measured spectrophotometrically in mitochondrial preparations or cell lysates. The mitochondrial membrane potential was measured with 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide. Oxidative stress levels were investigated with the OxyBlot technique. The mitochondrial network was investigated immunocytochemically and the degree of branching was determined with image processing methods. We observed a decrease in the production and overall concentration of ATP coinciding with increased mitochondrial mass in Parkin-mutant fibroblasts. After an oxidative insult, the membrane potential decreased in patient cells but not in controls. We further determined higher levels of oxidized proteins in the mutants both under basal and stress conditions. The degree of mitochondrial network branching was comparable in mutants and controls under basal conditions and decreased to a similar extent under paraquat-induced stress.Our results indicate that Parkin mutations cause abnormal mitochondrial function and morphology in non-neuronal human cells.

Copyright of Tecnología y Ciencias del Agua is the property of Instituto Mexicano de Tecnologia del Agua (IMTA) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)