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Molecular Ecological Insights into Neotropical Bird–Tick Interactions
In the tropics, ticks parasitize many classes of vertebrate hosts. However, because many tropical tick species are only identifiable in the adult stage, and these adults usually parasitize mammals, most attention on the ecology of tick-host interactions has focused on mammalian hosts. In contrast, immature Neotropical ticks are often found on wild birds, yet difficulties in identifying immatures hinder studies of birds’ role in tropical tick ecology and tick-borne disease transmission. In Panama, we found immature ticks on 227 out of 3,498 individually–sampled birds representing 93 host species (24% of the bird species sampled, and 13% of the Panamanian land bird fauna). Tick parasitism rates did not vary with rainfall or temperature, but did vary significantly with several host ecological traits. Likewise, Neotropical–Nearctic migratory birds were significantly less likely to be infested than resident species. Using a molecular library developed from morphologically–identified adult ticks specifically for this study, we identified eleven tick species parasitizing birds, indicating that a substantial portion of the Panamanian avian species pool is parasitized by a diversity of tick species. Tick species that most commonly parasitized birds had the widest diversity of avian hosts, suggesting that immature tick species are opportunistic bird parasites. Although certain avian ecological traits are positively associated with parasitism, we found no evidence that individual tick species show specificity to particular avian host ecological traits. Finally, our data suggest that the four principal vectors of Rocky Mountain Spotted Fever in the Neotropics rarely, if ever, parasitize Panamanian birds. However, other tick species that harbor newly–discovered rickettsial parasites of unknown pathogenicity are frequently found on these birds. Given our discovery of broad interaction between Panamanian tick and avian biodiversity, future work on tick ecology and the dynamics of emerging tropical tick-borne pathogens should explicitly consider wild bird as hosts.In the tropics, ticks parasitize many classes of vertebrate hosts. However, because many tropical tick species are only identifiable in the adult stage, and these adults usually parasitize mammals, most attention on the ecology of tick-host interactions has focused on mammalian hosts. In contrast, immature Neotropical ticks are often found on wild birds, yet difficulties in identifying immatures hinder studies of birds’ role in tropical tick ecology and tick-borne disease transmission. In Panama, we found immature ticks on 227 out of 3,498 individually–sampled birds representing 93 host species (24% of the bird species sampled, and 13% of the Panamanian land bird fauna). Tick parasitism rates did not vary with rainfall or temperature, but did vary significantly with several host ecological traits. Likewise, Neotropical–Nearctic migratory birds were significantly less likely to be infested than resident species. Using a molecular library developed from morphologically–identified adult ticks specifically for this study, we identified eleven tick species parasitizing birds, indicating that a substantial portion of the Panamanian avian species pool is parasitized by a diversity of tick species. Tick species that most commonly parasitized birds had the widest diversity of avian hosts, suggesting that immature tick species are opportunistic bird parasites. Although certain avian ecological traits are positively associated with parasitism, we found no evidence that individual tick species show specificity to particular avian host ecological traits. Finally, our data suggest that the four principal vectors of Rocky Mountain Spotted Fever in the Neotropics rarely, if ever, parasitize Panamanian birds. However, other tick species that harbor newly–discovered rickettsial parasites of unknown pathogenicity are frequently found on these birds. Given our discovery of broad interaction between Panamanian tick and avian biodiversity, future work on tick ecology and the dynamics of emerging tropical tick-borne pathogens should explicitly consider wild bird as hosts
A Multicomponent Animal Virus Isolated from Mosquitoes
RNA viruses exhibit a variety of genome organization strategies, including multicomponent genomes in which each segment is packaged separately. Although multicomponent genomes are common among viruses infecting plants and fungi, their prevalence among those infecting animals remains unclear. We characterize a multicomponent RNA virus isolated from mosquitoes, designated Guaico Culex virus (GCXV). GCXV belongs to a diverse clade of segmented viruses (Jingmenvirus) related to the prototypically unsegmented Flaviviridae. The GCXV genome comprises five segments, each of which appears to be separately packaged. The smallest segment is not required for replication, and its presence is variable in natural infections. We also describe a variant of Jingmen tick virus, another Jingmenvirus, sequenced from a Ugandan red colobus monkey, thus expanding the host range of this segmented and likely multicomponent virus group. Collectively, this study provides evidence for the existence of multicomponent animal viruses and their potential relevance for animal and human health.RNA viruses exhibit a variety of genome organization strategies, including multicomponent genomes in which each segment is packaged separately. Although multicomponent genomes are common among viruses infecting plants and fungi, their prevalence among those infecting animals remains unclear. We characterize a multicomponent RNA virus isolated from mosquitoes, designated Guaico Culex virus (GCXV). GCXV belongs to a diverse clade of segmented viruses (Jingmenvirus) related to the prototypically unsegmented Flaviviridae. The GCXV genome comprises five segments, each of which appears to be separately packaged. The smallest segment is not required for replication, and its presence is variable in natural infections. We also describe a variant of Jingmen tick virus, another Jingmenvirus, sequenced from a Ugandan red colobus monkey, thus expanding the host range of this segmented and likely multicomponent virus group. Collectively, this study provides evidence for the existence of multicomponent animal viruses and their potential relevance for animal and human health
Blood Stage Plasmodium falciparum Exhibits Biological Responses to Direct Current Electric Fields
The development of resistance to insecticides by the vector of malaria and the increasingly faster appearance of resistance to antimalarial drugs by the parasite can dangerously hamper efforts to control and eradicate the disease. Alternative ways to treat this disease are urgently needed. Here we evaluate the in vitro effect of direct current (DC) capacitive coupling electrical stimulation on the biology and viability of Plasmodium falciparum. We designed a system that exposes infected erythrocytes to different capacitively coupled electric fields in order to evaluate their effect on P. falciparum. The effect on growth of the parasite, replication of DNA, mitochondrial membrane potential and level of reactive oxygen species after exposure to electric fields demonstrate that the parasite is biologically able to respond to stimuli from DC electric fields involving calcium signaling pathwaysThe development of resistance to insecticides by the vector of malaria and the increasingly faster appearance of resistance to antimalarial drugs by the parasite can dangerously hamper efforts to control and eradicate the disease. Alternative ways to treat this disease are urgently needed. Here we evaluate the in vitro effect of direct current (DC) capacitive coupling electrical stimulation on the biology and viability of Plasmodium falciparum. We designed a system that exposes infected erythrocytes to different capacitively coupled electric fields in order to evaluate their effect on P. falciparum. The effect on growth of the parasite, replication of DNA, mitochondrial membrane potential and level of reactive oxygen species after exposure to electric fields demonstrate that the parasite is biologically able to respond to stimuli from DC electric fields involving calcium signaling pathway
Marine cyanobacteria-derived serotonin receptor 2C active fraction induces psychoactive behavioral effects in mice
Context—Marine cyanobacteria offer a robust resource for natural products drug discovery due to the secondary metabolites they produce.
Objective—To identify novel cyanobacterial compounds that exhibit CNS psychoactive effects.
Materials and methods—Cyanobacteria were collected from Las Perlas Archipelago, Panama and subjected to dichloromethane/methanol extraction and fractionation by column chromatography before being screened for affinity against a panel of CNS targets. A 50:50 ethyl acetate:methanol fraction of one cyanobacterial extract (2064H) was subjected to HPLC and the major peak was isolated (2064H3). At a dose of 20 μg per animal, 2064H and 2064H3 were tested in mice using behavioral assays that included the forced swim, open field, and formalin tests.Context—Marine cyanobacteria offer a robust resource for natural products drug discovery due to the secondary metabolites they produce.
Objective—To identify novel cyanobacterial compounds that exhibit CNS psychoactive effects.
Materials and methods—Cyanobacteria were collected from Las Perlas Archipelago, Panama and subjected to dichloromethane/methanol extraction and fractionation by column chromatography before being screened for affinity against a panel of CNS targets. A 50:50 ethyl acetate:methanol fraction of one cyanobacterial extract (2064H) was subjected to HPLC and the major peak was isolated (2064H3). At a dose of 20 μg per animal, 2064H and 2064H3 were tested in mice using behavioral assays that included the forced swim, open field, and formalin tests
Influencias del paisaje, climatología y manejo agrícola sobre la biodiversidad asociada a viña: efectos sobre servicios ecosistémicos y sostenibilidad frente a cambio global (Proyecto BA C O)
Dentro de un contexto dominado por el cambio rápido y frecuente, es básico analizar sus efectos sobre la biodiversidad y los servicios ecosistémicos que ésta provee. El cultivo de la viña es uno de los sistemas agrícolas más antiguos de la región Mediterránea, con una interacción muy estrecha entre el manejo humano y el ambiente natural circundante. El proyecto BA C O pretende, desde un enfoque multidisciplinar, evaluar el papel del clima, paisaje y manejo sobre la biodiversidad y los servicios ecosistémicos asociados a viñedos. Se proponen los siguientes objetivos: i) caracterizar el paisaje, ambiente, clima y tipo de manejo de las principales explotaciones de vid; ii) evaluar la influencia del paisaje, ambiente y manejo en la biodiversidad de los viñedos y iii) estimar los servicios ecosistémicos que esta diversidad aporta. Se usarán tres escalas espaciales de resolución: a) Regional, considerando todos los viñedos y sistemas de manejo (convencional/ ecológico; variedades de uva) presentes en Andalucía; b) F inca, situadas en un gradiente altitudinal (proxi de Tª) y de paisaje, en las que se realizarán medidas de biodiversidad, servicios ecosistémicos, productividad, funcionalidad y sostenibilidad del viñedo frente a cambio global y c) Cepa, en las que se tomarán muestras de suelo, sarmientos, hojas, raíces, estado fisiológico, afectación por plagas, productividad y calidad. Los resultados esperamos que sirvan para: 1) mejorar predicciones y tomas de decisiones de gestión; 2) generar documentos de transferencia identificando las prácticas de manejo y uso agrícola más sostenibles que optimicen la conservación de los recursos naturales y los beneficios socioeconómicos y 3) el desarrollo de herramientas que permitan predecir efectos futuros derivados de cambio climático y de usos de suelo, así como su interacción y sus efectos sobre la biodiversidad, servicios ecosistémicos asociados y su capacidad de resiliencia.Dentro de un contexto dominado por el cambio rápido y frecuente, es básico analizar sus efectos sobre la biodiversidad y los servicios ecosistémicos que ésta provee. El cultivo de la viña es uno de los sistemas agrícolas más antiguos de la región Mediterránea, con una interacción muy estrecha entre el manejo humano y el ambiente natural circundante. El proyecto BA C O pretende, desde un enfoque multidisciplinar, evaluar el papel del clima, paisaje y manejo sobre la biodiversidad y los servicios ecosistémicos asociados a viñedos. Se proponen los siguientes objetivos: i) caracterizar el paisaje, ambiente, clima y tipo de manejo de las principales explotaciones de vid; ii) evaluar la influencia del paisaje, ambiente y manejo en la biodiversidad de los viñedos y iii) estimar los servicios ecosistémicos que esta diversidad aporta. Se usarán tres escalas espaciales de resolución: a) Regional, considerando todos los viñedos y sistemas de manejo (convencional/ ecológico; variedades de uva) presentes en Andalucía; b) F inca, situadas en un gradiente altitudinal (proxi de Tª) y de paisaje, en las que se realizarán medidas de biodiversidad, servicios ecosistémicos, productividad, funcionalidad y sostenibilidad del viñedo frente a cambio global y c) Cepa, en las que se tomarán muestras de suelo, sarmientos, hojas, raíces, estado fisiológico, afectación por plagas, productividad y calidad. Los resultados esperamos que sirvan para: 1) mejorar predicciones y tomas de decisiones de gestión; 2) generar documentos de transferencia identificando las prácticas de manejo y uso agrícola más sostenibles que optimicen la conservación de los recursos naturales y los beneficios socioeconómicos y 3) el desarrollo de herramientas que permitan predecir efectos futuros derivados de cambio climático y de usos de suelo, así como su interacción y sus efectos sobre la biodiversidad, servicios ecosistémicos asociados y su capacidad de resiliencia
Host specificity in a diverse Neotropical tick community: an assessment using quantitative network analysis and host phylogeny
Background: Host specificity is a fundamental determinant of tick population and pathogen transmission dynamics, and therefore has important implications for human health. Tick host specificity is expected to be particularly high in the tropics, where communities of ticks, hosts and pathogens are most diverse. Yet the degree to which tropical tick species are host-specific remains poorly understood. Combining new field data with published records, we assessed the specificity of tick-host associations in Panama, a diverse Neotropical region.
Methods: The resulting dataset includes 5,298 adult ticks belonging to 41 species of eight genera that were directly collected from 68 vertebrate host species of 17 orders. We considered three important aspects of tick host specificity: (i) the relative ecological importance of each host species (structural specificity); (ii) relatedness among host species (phylogenetic specificity); and (iii) spatial scale-dependence of tick-host relationships (geographical specificity). Applying quantitative network analyses and phylogenetic tools with null model comparisons, we assessed the structural and phylogenetic specificity across three spatial scales, ranging from central Panama to countrywide. Further, we tested whether species-rich tick genera parasitized a wider variety of hosts than species-poor genera, as expected when ticks specialize on different host species.
Results: Most tick species showed high structural and/or phylogenetic specificity in the adult stage. However, after correcting for sampling effort, we found little support for geographical specificity. Across the three scales, adult ticks tended to be specific to a limited number of host species that were phylogenetically closely related. These host species in turn, were parasitized by tick species from distinct genera, suggesting switching among distantly related hosts is common at evolutionary timescales. Further, there was a strong positive relationship between the taxonomic richness of the tick genera and that of their hosts, consistent with distinct tick species being relatively specific to different host species.
Conclusions: Our results indicate that in the adult stage, most ticks in the diverse Neotropical community studied are host specialists. This contrasts with earlier assessments, but agrees with findings from other host-parasite systems. High host specificity in adult ticks implies high susceptibility to local tick-host co-extirpation, limited ability to colonize new habitats and limited potential for interspecific pathogen transmission.Background: Host specificity is a fundamental determinant of tick population and pathogen transmission dynamics, and therefore has important implications for human health. Tick host specificity is expected to be particularly high in the tropics, where communities of ticks, hosts and pathogens are most diverse. Yet the degree to which tropical tick species are host-specific remains poorly understood. Combining new field data with published records, we assessed the specificity of tick-host associations in Panama, a diverse Neotropical region.
Methods: The resulting dataset includes 5,298 adult ticks belonging to 41 species of eight genera that were directly collected from 68 vertebrate host species of 17 orders. We considered three important aspects of tick host specificity: (i) the relative ecological importance of each host species (structural specificity); (ii) relatedness among host species (phylogenetic specificity); and (iii) spatial scale-dependence of tick-host relationships (geographical specificity). Applying quantitative network analyses and phylogenetic tools with null model comparisons, we assessed the structural and phylogenetic specificity across three spatial scales, ranging from central Panama to countrywide. Further, we tested whether species-rich tick genera parasitized a wider variety of hosts than species-poor genera, as expected when ticks specialize on different host species.
Results: Most tick species showed high structural and/or phylogenetic specificity in the adult stage. However, after correcting for sampling effort, we found little support for geographical specificity. Across the three scales, adult ticks tended to be specific to a limited number of host species that were phylogenetically closely related. These host species in turn, were parasitized by tick species from distinct genera, suggesting switching among distantly related hosts is common at evolutionary timescales. Further, there was a strong positive relationship between the taxonomic richness of the tick genera and that of their hosts, consistent with distinct tick species being relatively specific to different host species.
Conclusions: Our results indicate that in the adult stage, most ticks in the diverse Neotropical community studied are host specialists. This contrasts with earlier assessments, but agrees with findings from other host-parasite systems. High host specificity in adult ticks implies high susceptibility to local tick-host co-extirpation, limited ability to colonize new habitats and limited potential for interspecific pathogen transmission
Global, regional, national, and selected subnational levels of stillbirths, neonatal, infant, and under-5 mortality, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015
Established in 2000, Millennium Development Goal 4 (MDG4) catalysed extraordinary political, fi nancial, and social commitments to reduce under-5 mortality by two-thirds between 1990 and 2015. At the country level, the pace of progress in improving child survival has varied markedly, highlighting a crucial need to further examine potential drivers of accelerated or slowed decreases in child mortality. The Global Burden of Disease 2015 Study (GBD 2015) provides an analytical framework to comprehensively assess these trends for under-5 mortality, age-specifi c and cause-specifi c mortality among children under 5 years, and stillbirths by geography over time.Established in 2000, Millennium Development Goal 4 (MDG4) catalysed extraordinary political, fi nancial, and social commitments to reduce under-5 mortality by two-thirds between 1990 and 2015. At the country level, the pace of progress in improving child survival has varied markedly, highlighting a crucial need to further examine potential drivers of accelerated or slowed decreases in child mortality. The Global Burden of Disease 2015 Study (GBD 2015) provides an analytical framework to comprehensively assess these trends for under-5 mortality, age-specifi c and cause-specifi c mortality among children under 5 years, and stillbirths by geography over time
Enzootic Arbovirus Surveillance in Forest Habitat and Phylogenetic Characterization of Novel Isolates of Gamboa Virus in Panama
Landscape changes occurring in Panama, a country whose geographic location and climate have historically supported arbovirus transmission, prompted the hypothesis that arbovirus prevalence increases with degradation of tropical forest habitats. Investigations at four variably degraded sites revealed a diverse array of potential mosquito vectors, several of which are known vectors of arbovirus pathogens. Overall, 675 pools consisting of 25,787 mosquitoes and representing 29 species from nine genera (collected at ground and canopy height across all habitats) were screened for cytopathic viruses on Vero cells. We detected four isolates of Gamboa virus (family: Bunyaviridae; genus: Orthobunyavirus) from pools of Aedeomyia squamipennis captured at canopy level in November 2012. Phylogenetic characterization of complete genome sequences shows the new isolates to be closely related to each other with strong evidence of reassortment among the M segment of Panamanian Gamboa isolates and several other viruses of this group. At the site yielding viruses, Soberanía National Park in central Panama, 18 mosquito species were identified, and the predominant taxa included A. squamipennis, Coquillettidia nigricans, and Mansonia titillans.Landscape changes occurring in Panama, a country whose geographic location and climate have historically supported arbovirus transmission, prompted the hypothesis that arbovirus prevalence increases with degradation of tropical forest habitats. Investigations at four variably degraded sites revealed a diverse array of potential mosquito vectors, several of which are known vectors of arbovirus pathogens. Overall, 675 pools consisting of 25,787 mosquitoes and representing 29 species from nine genera (collected at ground and canopy height across all habitats) were screened for cytopathic viruses on Vero cells. We detected four isolates of Gamboa virus (family: Bunyaviridae; genus: Orthobunyavirus) from pools of Aedeomyia squamipennis captured at canopy level in November 2012. Phylogenetic characterization of complete genome sequences shows the new isolates to be closely related to each other with strong evidence of reassortment among the M segment of Panamanian Gamboa isolates and several other viruses of this group. At the site yielding viruses, Soberanía National Park in central Panama, 18 mosquito species were identified, and the predominant taxa included A. squamipennis, Coquillettidia nigricans, and Mansonia titillans
Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015
Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defi ned criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specifi c DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI).Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defi ned criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specifi c DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI)
Deterioro cognitivo leve y enfermedad de Alzheimer: Revisión de conceptos
La enfermedad de Alzheimer (EA) es una enfermedad neurológica degenerativa que afecta a más de 46 millones de personas alrededor del mundo. Representa el tipo de demencia más común en los adultos mayores y cursa con una alteración grave en la memoria y en la funcionalidad de la persona. La EA impacta al individuo, a su familia y/o cuidador y a la sociedad, generando grandes cargas para los sistemas sanitarios, sociales y económicos. La detección temprana de la EA se ha vuelto el foco de estudio en el área del envejecimiento en los últimos años. Diagnosticar la EA en etapas prodrómicas, cuando hay cambios cerebrales subyacentes a EA pero aún no se ha desarrollado la demencia pudiera incidir en mejorías en la intervención y en retrasar la aparición de los síntomas demenciales. Por ende es crucial estudiar el deterioro cognitivo leve (DCL), fase que precede a EA. Delimitar sus manifesta-ciones, criterios diagnósticos y su relación con EA es fundamental para identificar a aquellos sujetos que tienen mayor riesgo de progresar a EA. El estudio de las alteraciones cognitivas y biomarcadores de DCL y EA es la base para realizar diagnósticos diferenciales oportunos. La evaluación neuropsico-lógica es fundamental para determinar perfiles cognitivos y evaluar la progresión de la enfermedad. Una memoria episódica deficiente es la primera manifestación en DCL amnésico. Si la persona pro-gresa a EA, este déficit se vuelve más severo inhabilitando la recuperación de la información. Otras funciones como la atención, el lenguaje, las capacidades visuoespaciales, razonamiento, y la flexibilidad mental pueden también estar afectadas en DCL, deteriorándose progresivamente en EA hasta dete-riorar severamente la autonomía de la persona. El estudio de los biomarcadores en líquido cefalorra-quídeo (LCR), estudios con neuroimagen y biomarcadores en sangre ha permitido establecer los pro-cesos patológicos subyacentes en DCL y EA y junto con la evaluación neuropsicológica constituyen el enfoque más eficaz para el diagnóstico precoz.La enfermedad de Alzheimer (EA) es una enfermedad neurológica degenerativa que afecta a más de 46 millones de personas alrededor del mundo. Representa el tipo de demencia más común en los adultos mayores y cursa con una alteración grave en la memoria y en la funcionalidad de la persona. La EA impacta al individuo, a su familia y/o cuidador y a la sociedad, generando grandes cargas para los sistemas sanitarios, sociales y económicos. La detección temprana de la EA se ha vuelto el foco de estudio en el área del envejecimiento en los últimos años. Diagnosticar la EA en etapas prodrómicas, cuando hay cambios cerebrales subyacentes a EA pero aún no se ha desarrollado la demencia pudiera incidir en mejorías en la intervención y en retrasar la aparición de los síntomas demenciales. Por ende es crucial estudiar el deterioro cognitivo leve (DCL), fase que precede a EA. Delimitar sus manifesta-ciones, criterios diagnósticos y su relación con EA es fundamental para identificar a aquellos sujetos que tienen mayor riesgo de progresar a EA. El estudio de las alteraciones cognitivas y biomarcadores de DCL y EA es la base para realizar diagnósticos diferenciales oportunos. La evaluación neuropsico-lógica es fundamental para determinar perfiles cognitivos y evaluar la progresión de la enfermedad. Una memoria episódica deficiente es la primera manifestación en DCL amnésico. Si la persona pro-gresa a EA, este déficit se vuelve más severo inhabilitando la recuperación de la información. Otras funciones como la atención, el lenguaje, las capacidades visuoespaciales, razonamiento, y la flexibilidad mental pueden también estar afectadas en DCL, deteriorándose progresivamente en EA hasta dete-riorar severamente la autonomía de la persona. El estudio de los biomarcadores en líquido cefalorra-quídeo (LCR), estudios con neuroimagen y biomarcadores en sangre ha permitido establecer los pro-cesos patológicos subyacentes en DCL y EA y junto con la evaluación neuropsicológica constituyen el enfoque más eficaz para el diagnóstico precoz