APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer's Disease.

BACKGROUND: Variants in APOE and PSEN1 (encoding apolipoprotein E and presenilin 1, respectively) alter the risk of Alzheimer's disease. We previously reported a delay of cognitive impairment in a person with autosomal dominant Alzheimer's disease caused by the PSEN1 E280A variant who also had two copies of the apolipoprotein E3 Christchurch variant (APOE3 Ch). Heterozygosity for the APOE3 Ch variant may influence the age at which the onset of cognitive impairment occurs. We assessed this hypothesis in a population in which the PSEN1 E280A variant is prevalent. METHODS: We analyzed data from 27 participants with one copy of the APOE3 Ch variant among 1077 carriers of the PSEN1 E280A variant in a kindred from Antioquia, Colombia, to estimate the age at the onset of cognitive impairment and dementia in this group as compared with persons without the APOE3 Ch variant. Two participants underwent brain imaging, and autopsy was performed in four participants. RESULTS: Among carriers of PSEN1 E280A who were heterozygous for the APOE3 Ch variant, the median age at the onset of cognitive impairment was 52 years (95% confidence interval [CI], 51 to 58), in contrast to a matched group of PSEN1 E280A carriers without the APOE3 Ch variant, among whom the median age at the onset was 47 years (95% CI, 47 to 49). In two participants with the APOE3 Ch and PSEN1 E280A variants who underwent brain imaging, 18F-fluorodeoxyglucose positron-emission tomographic (PET) imaging showed relatively preserved metabolic activity in areas typically involved in Alzheimer's disease. In one of these participants, who underwent 18F-flortaucipir PET imaging, tau findings were limited as compared with persons with PSEN1 E280A in whom cognitive impairment occurred at the typical age in this kindred. Four studies of autopsy material obtained from persons with the APOE3 Ch and PSEN1 E280A variants showed fewer vascular amyloid pathologic features than were seen in material obtained from persons who had the PSEN1 E280A variant but not the APOE3 Ch variant. CONCLUSIONS: Clinical data supported a delayed onset of cognitive impairment in persons who were heterozygous for the APOE3 Ch variant in a kindred with a high prevalence of autosomal dominant Alzheimer's disease. (Funded by Good Ventures and others.).

Psychological Status of the Participants in Alzheimer's Prevention Initiative Autosomal Dominant Alzheimer's Disease Colombia.

BACKGROUND: The SARS-CoV2 global pandemic impacted participants in the Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease (ADAD) clinical trial, who faced three stressors: 1) fear of developing dementia; 2) concerns about missing treatment; and 3) risk of SARS-CoV2 infection. OBJECTIVE: To describe the frequency of psychological disorders among the participants of the API ADAD Colombia clinical study, treated by a holistic mental health team during the COVID-19 pandemic. The extent of use of mental health team services was explored considering different risk factors, and users and non-users of these services were compared. METHODS: Participants had free and optional access to psychology and psychiatry services, outside of the study protocol. Descriptive statistics was used to analyze the frequency of the mental health difficulties. A multivariable logistic regression model has been used to assess associations with using this program. RESULTS: 66 participants were treated by the Mental Health Team from March 1, 2020, to December 31, 2020. Before and after the start of the pandemic, the most common psychological problems were anxiety (36.4% before, 63.6% after) and depression (34.8% before, 37.9% after). 70% of users assisted by psychology and 81.6% of those assisted by psychiatry felt that the services were useful for them. Female sex, depression, and anxiety before the pandemic were positively associated with being assisted by either psychology or psychiatry, while the association with hyperlipidemia was negative. CONCLUSIONS: A holistic mental health program, carried out in the context of a study, could mitigate psychopathology during pandemics such as COVID-19.

Genetic associations with age at dementia onset in the PSEN1 E280A Colombian kindred.

INTRODUCTION: Genetic associations with Alzheimer's disease (AD) age at onset (AAO) could reveal genetic variants with therapeutic applications. We present a large Colombian kindred with autosomal dominant AD (ADAD) as a unique opportunity to discover AAO genetic associations. METHODS: A genetic association study was conducted to examine ADAD AAO in 340 individuals with the PSEN1 E280A mutation via TOPMed array imputation. Replication was assessed in two ADAD cohorts, one sporadic early-onset AD study and four late-onset AD studies. RESULTS: 13 variants had p<1×10-7 or p<1×10-5 with replication including three independent loci with candidate associations with clusterin including near CLU. Other suggestive associations were identified in or near HS3ST1, HSPG2, ACE, LRP1B, TSPAN10, and TSPAN14. DISCUSSION: Variants with suggestive associations with AAO were associated with biological processes including clusterin, heparin sulfate, and amyloid processing. The detection of these effects in the presence of a strong mutation for ADAD reinforces their potentially impactful role.

Signatures for viral infection and inflammation in the proximal olfactory system in familial Alzheimer's disease.

Alzheimer's disease (AD) is characterized by deficits in olfaction and olfactory pathology preceding diagnosis of dementia. Here we analyzed differential gene and protein expression in the olfactory bulb (OB) and tract (OT) of familial AD (FAD) individuals carrying the autosomal dominant presenilin 1 E280A mutation. Compared to control, FAD OT had increased immunostaining for ß-amyloid (Aß) and CD68 in high and low myelinated regions, as well as increased immunostaining for Iba1 in the high myelinated region. In FAD samples, RNA sequencing showed: (1) viral infection in the OB; (2) inflammation in the OT that carries information via entorhinal cortex from the OB to hippocampus, a brain region essential for learning and memory; and (3) decreased oligodendrocyte deconvolved transcripts. Interestingly, spatial proteomic analysis confirmed altered myelination in the OT of FAD individuals, implying dysfunction of communication between the OB and hippocampus. These findings raise the possibility that viral infection and associated inflammation and dysregulation of myelination of the olfactory system may disrupt hippocampal function, contributing to acceleration of FAD progression.

Ataxia with Ocular Apraxia Type 1 (AOA1) (APTX, W279* Mutation): Neurological, Neuropsychological, and Molecular Outlining of a Heterogenous Phenotype in Four Colombian Siblings.

Hereditary ataxias are a group of devastating neurological disorders that affect coordination of gait and are often associated with poor coordination of hands, speech, and eye movements. Ataxia with ocular apraxia type 1 (AOA1) (OMIM: 606,350.0006) is characterized by slowly progressive symptoms of childhood-onset and pathogenic mutations in APTX; the only known cause underpinning AOA1. APTX encodes the protein aprataxin, composed of three domains sharing homology with proteins involved in DNA damage, signaling, and repair. We present four siblings from an endogamic family in a rural, isolated town of Colombia with ataxia and ocular apraxia of childhood-onset and confirmed molecular diagnosis of AOA1, homozygous for the W279* p.Trp279Ter mutation. We predicted the mutated APTX with AlphaFold to demonstrate the effects of this stop-gain mutation that deletes three beta helices encoded by amino acid 270 to 339 rescinding the C2H2-type zinc fingers (Znf) (C2H2 Znf) DNA-binding, the DNA-repair domain, and the whole 3D structure of APTX. All siblings exhibited different ages of onset (4, 6, 8, and 11 years old) and heterogeneous patterns of dysarthria (ranging from absence to mild-moderate dysarthria). Neuropsychological evaluation showed no neurocognitive impairment in three siblings, but one sibling showed temporospatial disorientation, semantic and phonologic fluency impairment, episodic memory affection, constructional apraxia, moderate anomia, low executive function, and symptoms of depression. To our knowledge, this report represents the most extensive series of siblings affected with AOA1 in Latin America, and the genetic analysis completed adds important knowledge to outline this family's disease and general complex phenotype of hereditary ataxias.

A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects.

BACKGROUND: The Colombian population, as well as those in other Latin American regions, arose from a recent tri-continental admixture among Native Americans, Spanish invaders, and enslaved Africans, all of whom passed through a population bottleneck due to widespread infectious diseases that left small isolated local settlements. As a result, the current population reflects multiple founder effects derived from diverse ancestries. METHODS: We characterized the role of admixture and founder effects on the origination of the mutational landscape that led to neurodegenerative disorders under these historical circumstances. Genomes from 900 Colombian individuals with Alzheimer's disease (AD) [n = 376], frontotemporal lobar degeneration-motor neuron disease continuum (FTLD-MND) [n = 197], early-onset dementia not otherwise specified (EOD) [n = 73], and healthy participants [n = 254] were analyzed. We examined their global and local ancestry proportions and screened this cohort for deleterious variants in disease-causing and risk-conferring genes. RESULTS: We identified 21 pathogenic variants in AD-FTLD related genes, and PSEN1 harbored the majority (11 pathogenic variants). Variants were identified from all three continental ancestries. TREM2 heterozygous and homozygous variants were the most common among AD risk genes (102 carriers), a point of interest because the disease risk conferred by these variants differed according to ancestry. Several gene variants that have a known association with MND in European populations had FTLD phenotypes on a Native American haplotype. Consistent with founder effects, identity by descent among carriers of the same variant was frequent. CONCLUSIONS: Colombian demography with multiple mini-bottlenecks probably enhanced the detection of founder events and left a proportionally higher frequency of rare variants derived from the ancestral populations. These findings demonstrate the role of genomically defined ancestry in phenotypic disease expression, a phenotypic range of different rare mutations in the same gene, and further emphasize the importance of inclusiveness in genetic studies.

Substance Use-Related Cognitive Decline in Families with Autosomal Dominant Alzheimer's Disease: A Cohort Study.

BACKGROUND: Cigarette smoking is a known risk factor for Alzheimer's disease (AD). However, the association between neurodegeneration and other substances has not been fully determined. It is of vital importance to evaluate this relationship in populations at high risk of dementia. Since substance use possibly modifies the progression rate of cognitive decline, we studied this association in a unique and well-phenotyped cohort from the University of Antioquia: carriers of the PSEN1-E280A genetic variant. OBJECTIVE: To determine the association between substance use and cognitive decline in carriers of the PSEN1-E280A genetic variant. METHODS: A retrospective cohort study was conducted with 94 carriers and 69 noncarriers recruited between January 2019 and April 2020. A psychiatrist interviewed the participants using the Consumption of Alcohol, Cigarettes and other Substances questionnaire. The participants were also submitted to cognitive evaluation. The relationship between cognitive decline and substance use was explored through a mixed effects regression model. RESULTS: There was an association between cigarettes and better performance on tasks related to perceptual organization, verbal fluency, and memory in carriers. Alcohol had a positive or negative effect on memory according to the type of alcoholic beverage. Results on marijuana use were no conclusive. Coffee was associated with progressive improvements in executive function and verbal fluency. CONCLUSION: Cigarette and alcohol were associated with an improvement of some cognitive assessments, possibly by a survival bias. In addition, coffee was related to improvements in executive function and language; therefore, its short-term neuroprotective potential should be studied.

Quality of life in early-onset Alzheimer's disease due to a PSEN1-E280A mutation.

PURPOSE: The present study aims to explore the association between the quality of life (QoL) score and the clinical and sociodemographic variables in patients with the PSEN1-E280A mutation. We also seek to evaluate the differences between the QoL reported by the patients (P-QoL) and the scores reported by the caregivers (C-QoL). METHODS: An analysis of 75 patients with the PSEN1-E280A mutation with mild cognitive impairment and dementia was performed. We used the Quality of Life in Alzheimer Disease (QoL-AD) survey to evaluate QoL as an outcome and evaluated its association with sociodemographic, lifestyle, clinical, and past medical history variables. RESULTS: The largest difference in the median of the QoL-AD score was in those who needed help to eat, those with moderate or severe dementia, those classified as frail or pre-frail, those with moderate social risk, and those with depression. Also, C-QoL was lower than the P-QoL, and the QoL-AD of individuals with severe dementia was lower than for milder forms of the disease. Not needing help to eat, not having a stressful situation in the past 3 months, and the years of education were positively correlated with QoL-AD in the linear model. CONCLUSION: As studies in similar populations with AD, factors with more impact on QoL are those related to loss of functionality and independence. These factors are also associated with variables related to the current literature with the burden of the disease for the caregivers.

Mental Disorders in Young Adults from Families with the Presenilin-1 Gene Mutation E280A in the Preclinical Stage of Alzheimer's Disease.

BACKGROUND: There are forms of Alzheimer's disease (AD) that have an autosomal dominant inheritance pattern; one of them is caused by the E280A mutation in the gene that codes for Presenilin-1 (PSEN1). Studying families of people with this mutation allows the evaluation of characteristics of the subjects before cognitive decline begins. OBJECTIVE: To determine whether having the mutation E280A in PSEN1 increases the risk of presenting mental disorders in adults under 30 years old who are in the preclinical stage of AD and may be eligible for primary prevention studies of AD. METHODS: A psychiatric evaluation was made to 120 people belonging to families with a history of early onset AD. Of these, 62 carried the E280A mutation in PSEN1. The occurrence of mental disorders between carriers and non-carriers of the mutation was compared. RESULTS: No statistically significant differences were found in the frequency of any mental disorder between the group of carriers and non-carriers of the mutation (Hazard Ratio: 0.80, 95% CI 0.49 to 1.31); nor were differences observed when evaluating specific disorders. CONCLUSION: The E280A mutation does not increase the risk of mental disorders before the age of 30 in the relatives of people affected by familial AD. Studies with larger sample sizes are required to assess the risk of low incidence mental disorders.

WITHDRAWN: Mental Disorders in Young Adults from Families with the Presenilin-1 Gene Mutation E280A in the Preclinical Stage of Alzheimer's Disease.

Ahead of Print article withdrawn by publisher.

Genetic origin of a large family with a novel PSEN1 mutation (Ile416Thr).

INTRODUCTION: A small percentage of Alzheimer's disease (AD) cases are caused by genetic mutations with autosomal dominant inheritance. We report a family with a novel variant in PSEN1. METHODS: We performed clinical and genetic evaluation of 93 related individuals from a Colombian admixed population. 31 individuals had whole-genome sequencing. RESULTS: Genetic analysis revealed a missense variant in PSEN1 (NM_000021.3: c.1247T>C p.Ile416Thr), which originated on an African haplotype and segregated with AD logarithm of the odds score of 6. Their clinical phenotype is similar to sporadic AD except for earlier age at onset: the mean age at onset for mild cognitive impairment was 47.6 years (standard deviation 5.83) and for dementia 51.6 years (standard deviation 5.03). DISCUSSION: Ile416Thr is a novel pathogenic variant that causes AD in the sixth decade of life. The history of the region that included slave importation and admixtures within a confined geographic locale represents a "mini-population bottleneck" and subsequent emergence of a rare dominant mutation.

Clusters de casos de suicidio espacio-temporal en la comunidad de Antequera (España) / Space-time suicide clustering in the community of Antequera (Spain)

Introducción. En España, cada año consuman suicidio alrededor de 3.500 personas. El principal objetivo del presente estudio fue examinar si eran evidentes agrupaciones (clusters) espacio-temporales de suicidio en la región de Antequera (Málaga, España). Métodos. Muestra y procedimiento. Entre el 1 de enero de 2004 y el 31 de diciembre de 2008, se identificaron todos los casos de suicidio consumado (fuente: Servicio de Patología Forense del Instituto de Medicina Legal, Málaga, España). Geolocalización. Usamos Google Earth para calcular las coordenadas del domicilio de todos los casos de suicidio. Análisis estadístico. Usamos el programa SaTScan® espacio-temporal y la función K de Ripley para examinar la presencia de agrupaciones (clusters) espacio-temporales de los casos de suicidio. Acto seguido, utilizamos la prueba de la X2 de Pearson para determinar la presencia de diferencias estadísticamente significativas entre los casos de suicidio identificados dentro y fuera de las agrupaciones de suicidio. Resultados. En los análisis del presente estudio efectuado en el municipio de Antequera, de un total de 120 individuos que cometieron suicidio se incluyeron 96 (80%). Se identificaron pruebas estadísticamente significativas para 7 agrupaciones espacio-temporales de suicidio dentro de los límites críticos de 0-2,5 km de distancia y durante la primera y segunda semana después del caso de suicidio (p < 0,05 en ambos casos). Entre los casos de suicidio dentro de agrupaciones (n = 17), no hubo ningún individuo en el que se hubiera establecido un diagnóstico de trastorno psicótico actual, mientras que, entre los casos de suicidio fuera de las agrupaciones espacio-temporales, en el 20%, se había establecido dicho diagnóstico (X2 = 4,13; gl = 1; p < 0,05). Conclusiones. En la región circundante de Antequera están presentes agrupaciones (clusters) espacio-temporales de los casos de suicidio. Entre pacientes con un diagnóstico de trastorno psicótico actual hubo menos probabilidades de una influencia por los factores que determinan las agrupaciones espacio-temporales de los casos de suicidio consumado (AU)

Introduction. Approximately 3,500 people commit suicide every year in Spain. The main aim of this study is to explore if a spatial and temporal clustering of suicide exists in the region of Antequera (Málaga, España). Methods. Sample and procedure: All suicides from January 1, 2004 to December 31, 2008 were identified using data from the Forensic Pathology Department of the Institute of Legal Medicine, Málaga (España). Geolocalisation. Google Earth was used to calculate the coordinates for each suicide decedent's address. Statistical analysis. A spatiotemporal permutation scan statistic and the Ripley's K function were used to explore spatiotemporal clustering. Pearson's chi-squared was used to determine whether there were differences between suicides inside and outside the spatiotemporal clusters. Results. A total of 120 individuals committed suicide within the region of Antequera, of which 96 (80%) were included in our analyses. Statistically significant evidence for 7 spatiotemporal suicide clusters emerged within critical limits for the 0-2.5 km distance and for the first and second semanas (P < .05 in both cases) after suicide. There was not a single subject diagnosed with a current psychotic disorder, among suicides within clusters, whereas outside clusters, 20% had this diagnosis (X2 = 4.13; df = 1; P < .05). Conclusions. There are spatiotemporal suicide clusters in the area surrounding Antequera. Patients diagnosed with current psychotic disorder are less likely to be influenced by the factors explaining suicide clustering (AU)

[Space-time suicide clustering in the community of Antequera (Spain)]. / Clusters de casos de suicidio espacio-temporal en la comunidad de Antequera (España).

INTRODUCTION: Approximately 3,500 people commit suicide every year in Spain. The main aim of this study is to explore if a spatial and temporal clustering of suicide exists in the region of Antequera (Málaga, España). METHODS: Sample and procedure: All suicides from January 1, 2004 to December 31, 2008 were identified using data from the Forensic Pathology Department of the Institute of Legal Medicine, Málaga (España). Geolocalisation. Google Earth was used to calculate the coordinates for each suicide decedent's address. Statistical analysis. A spatiotemporal permutation scan statistic and the Ripley's K function were used to explore spatiotemporal clustering. Pearson's chi-squared was used to determine whether there were differences between suicides inside and outside the spatiotemporal clusters. RESULTS: A total of 120 individuals committed suicide within the region of Antequera, of which 96 (80%) were included in our analyses. Statistically significant evidence for 7 spatiotemporal suicide clusters emerged within critical limits for the 0-2.5 km distance and for the first and second semanas (P<.05 in both cases) after suicide. There was not a single subject diagnosed with a current psychotic disorder, among suicides within clusters, whereas outside clusters, 20% had this diagnosis (X2=4.13; df=1; P<.05). CONCLUSIONS: There are spatiotemporal suicide clusters in the area surrounding Antequera. Patients diagnosed with current psychotic disorder are less likely to be influenced by the factors explaining suicide clustering.

The Alzheimer's prevention initiative composite cognitive test score: sample size estimates for the evaluation of preclinical Alzheimer's disease treatments in presenilin 1 E280A mutation carriers.

OBJECTIVE: To identify a cognitive composite that is sensitive to tracking preclinical Alzheimer's disease decline to be used as a primary end point in treatment trials. METHOD: We capitalized on longitudinal data collected from 1995 to 2010 from cognitively unimpaired presenilin 1 (PSEN1) E280A mutation carriers from the world's largest known early-onset autosomal dominant Alzheimer's disease kindred to identify a composite cognitive test with the greatest statistical power to track preclinical Alzheimer's disease decline and estimate the number of carriers age 30 years and older needed to detect a treatment effect in the Alzheimer's Prevention Initiative's (API) preclinical Alzheimer's disease treatment trial. The mean-to-standard-deviation ratios (MSDRs) of change over time were calculated in a search for the optimal combination of 1 to 7 cognitive tests/subtests drawn from the neuropsychological test battery in cognitively unimpaired mutation carriers during a 2- and 5-year follow-up period (n = 78 and 57), using data from noncarriers (n = 31 and 56) during the same time period to correct for aging and practice effects. Combinations that performed well were then evaluated for robustness across follow-up years, occurrence of selected items within top-performing combinations, and representation of relevant cognitive domains. RESULTS: The optimal test combination included Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Recall, CERAD Boston Naming Test (high frequency items), Mini-Mental State Examination (MMSE) Orientation to Time, CERAD Constructional Praxis, and Raven's Progressive Matrices (Set A), with an MSDR of 1.62. This composite is more sensitive than using either the CERAD Word List Recall (MSDR = 0.38) or the entire CERAD-Col battery (MSDR = 0.76). A sample size of 75 cognitively normal PSEN1 E280A mutation carriers aged 30 years and older per treatment arm allows for a detectable treatment effect of 29% in a 60-month trial (80% power, P = .05). CONCLUSIONS: We have identified a composite cognitive test score representing multiple cognitive domains that, compared to the most sensitive single test item, has improved power to track preclinical Alzheimer's disease decline in autosomal dominant Alzheimer's disease mutation carriers and to evaluate preclinical Alzheimer's disease treatments. This API composite cognitive test score will be used as the primary end point in the first API trial in cognitively unimpaired autosomal dominant Alzheimer's disease carriers within 15 years of their estimated age at clinical onset. We have independently confirmed our findings in a separate cohort of cognitively healthy older adults who progressed to the clinical stages of late-onset Alzheimer's disease, described in a separate report, and continue to refine the composite in independent cohorts and compared with other analytic approaches.

Origin of the PSEN1 E280A mutation causing early-onset Alzheimer's disease.

BACKGROUND: A mutation in presenilin 1 (E280A) causes early-onset Alzheimer's disease. Understanding the origin of this mutation will inform medical genetics. METHODS: We sequenced the genomes of 102 individuals from Antioquia, Colombia. We applied identity-by-descent analysis to identify regions of common ancestry. We estimated the age of the E280A mutation and the local ancestry of the haplotype harboring this mutation. RESULTS: All affected individuals share a minimal haplotype of 1.8 Mb containing E280A. We estimate a time to most recent common ancestor of E280A of 10 (95% credible interval, 7.2-12.6) generations. We date the de novo mutation event to 15 (95% credible interval, 11-25) generations ago. We infer a western European geographic origin of the shared haplotype. CONCLUSIONS: The age and geographic origin of E280A are consistent with a single founder dating from the time of the Spanish Conquistadors who began colonizing Colombia during the early 16th century.

Cambios emocionales y alteraciones en la Inmunoglobulina A (IgA) tras el tratamiento psicológico en mujeres víctimas de violencia doméstica / Emotional changes and Inmunoglobulin A (IgA) after psychological treatment in women victims of domestic violence

El objetivo de este estudio ha sido determinar, en mujeres víctimas de maltrato, los beneficios de un tratamiento psicológico y evaluar su impacto en la salud psicológica y en el sistema inmune. Las participantes fueron 60 mujeres usuarias del Área de Igualdad del Ayuntamiento de Málaga. Se constituyeron 2 grupos en función de si acudieron o no a la terapia psicológica. Se evaluaron antes y después del tratamiento las variables psicológicas Autoestima, Depresión y Ansiedad, así como el nivel de Inmunoglobulina A en saliva. Los resultados muestran diferencias en las mujeres que recibieron el tratamiento antes y después de éste en todas las variables, mejorando en todos los indicadores. Estas diferencias no se observan en las mujeres que no acudieron a las sesiones de terapia, y en alguna variable, como depresión e Inmunoglobulina A, incluso existe un empeoramiento. Entre ambos grupos existen diferencias en todas las variables después del tratamiento, así, las mujeres que lo recibieron muestran menos indicadores de alteración psicológica y mayor nivel de Inmunoglobulina A; en el pretratamiento en cambio, estas diferencias no se encontraron. Se hace patente la importancia del tratamiento psicológico en esta población, tanto para su salud psicológica como física (AU)

The aim of this study was to determine the benefits of a psychological treatment in women victims of mistreatments in psychological health and in the immune system. The participants in this study were 60 women users of the Equality Area of the City Council of Malaga. We set two groups of women up in relation of whether the women attended or not to the given therapy. Psychological variables (self-esteem, depression and anxiety) and levels of Inmunoglobulin A were evaluated before and after the treatment. The results showed differences between all the variables before and after the treatment, with better valuation after the treatment. These differences were not shown in women that did not assist to the therapeutic sessions, and even, the values of depression and immunoglobulin A levels were worse. We found also differences in the values of these variables when the two groups were compared. Women that received the treatment showed fewer indicators of psychological alterations and higher levels of immunoglobulin A than the women that did not assist to the sessions; in the pre-treatment these differences were not shown. This study enhances the significance of the psychological treatment for psychological and physic health in women victims of abuses (AU)

Exploratory data from complete genomes of familial alzheimer disease age-at-onset outliers.

Identifying genes that modify the age at onset (AAO) of Alzheimer disease and targeting them pharmacologically represent a potential treatment strategy. In this exploratory study, we sequenced the complete genomes of six individuals with familial Alzheimer disease due to the autosomal dominant mutation p.Glu280Ala in PSEN1 (MIM# 104311; NM_000021.3:c.839A>C). The disease and its AAO are highly heritable, motivating our search for genetic variants that modulate AAO. The median AAO of dementia in carriers of the mutant allele is 49 years. Extreme phenotypic outliers for AAO in this genetically isolated population with limited environmental variance are likely to harbor onset modifying genetic variants. A narrow distribution of AAO in this kindred suggests large effect sizes of genetic determinants of AAO in these outliers. Identity by descent (IBD) analysis and a combination of bioinformatics filters have suggested several candidate variants for AAO modifiers. Future work and replication studies on these variants may provide mechanistic insights into the etiopathology of Alzheimer disease.

Hacia el enunciado de dilemas éticos sobre la enfermedad de Alzheimer precoz, en Antioquia, Colombia / Towards the enunciation of ethical dilemmas regarding early onset Alzheimer's disease in Antioquia, Colombia

Hemos tratado de presentar, principalmente, aspectos legales y morales que tienen que ver con la enfermedad de Alzheimer de inicio precoz, con énfasis en la situación epidemiológica de Antioquia, Colombia. Más allá de la discusión moderna sobre los aspectos moleculares, queremos enfocarnos en las condiciones objetivas de nuestros pacientes y sus familias incluídas sus condiciones socioeconómicas. Esperamos que, ojalá más temprano que tarde, nuestras reflexiones sean de importancia práctica y, eventualmente, que sean también de utilidad para otros grupos humanos en condiciones similares.

This paper discusses moral and legal aspects regarding early onset Alzheimer's Disease (EOAD) focusing on the epidemiological situation in Antioquia, Colombia. Beyond modern discussions on molecular aspects of genetic diseases we want to try to look at the objective situation of our patients, their families and their socioeconomic environments. It is our hope that as soon as possible our thoughts could be of practical help. Eventually, some of these reflections may be applicable to other human groups under similar conditions