Cognitive impairment as an invisible symptom in multiple sclerosis

Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2021, Universidade de Lisboa, Faculdade de Farmácia.A Esclerose Múltipla é uma doença imunitária desmielinizante do sistema nervoso central que leva a sintomas clínicos muito generalizados, os quais incluem principalmente a incapacidade física entre os jovens adultos. No entanto, os doentes com EM podem experimentar outros sintomas que não são, aparentemente, visíveis ou óbvios para aqueles que os rodeiam, tais como o défice cognitivo, que é um dos sintomas mais comuns e incapacitantes da EM, ocorrendo em cerca de 40-70% dos doentes com EM. Assim, o que parece estar mais comprometido neste são a lentidão no processamento de informação, a diminuição da memória episódica, dificuldades na função executiva, alterações na fluência verbal, e reduções na análise visuoespacial. Devido à heterogeneidade da EM, não existe uma única característica patognomónica ou teste de diagnóstico que possa diagnosticar a EM com precisão, pelo que o diagnóstico se baseia na integração de vários resultados clínicos, imagiológicos e laboratoriais. Quanto à avaliação das funções cognitivas, existem várias versões escritas e orais, e mais recentemente digitais, de baterias neuropsicológicas. Neste sentido, devido à sua fiabilidade, validade e sensibilidade, o Symbol Digit Modalities Test é o teste mais frequentemente utilizado para monitorizar as taxas de recidivas cognitivas. Nos últimos anos, os desenvolvimentos notáveis das novas sequências de ressonância magnética permitiram definir correlações estruturais e funcionais de défices cognitivos, que parecem estar associados à neurodegeneração, atrofia cerebral e rutura funcional da rede. Embora as terapias modificadoras da doença tenham sido eficazes na redução das taxas de recidiva na EM, tais tratamentos, assim como o tratamento sintomático, são ineficazes para o tratamento do défice cognitivo na EM. Neste sentido, são necessárias abordagens alternativas de tratamento para atenuar estes sintomas. Assim, a reabilitação cognitiva e a prática de exercício físico são potenciais candidatos ao tratamento do défice cognitivo relacionado com a EM, embora estes ainda sejam considerados como sendo pobremente geridos em doentes com EM. Para concluir, uma investigação futura centrada no défice cognitivo é necessária e crucial para adquirir novas informações e, assim, melhorar a qualidade de vida dos doentes com EM, bem como a dos seus cuidadores.Multiple Sclerosis is an immune-mediated demyelinating disease of the central nervous system that leads to widespread clinical symptoms, including mainly physical disability among young adults. However, MS patients can experience symptoms that are not, apparently, visible or obvious, to those around them, such as cognitive impairment that is one of the most common and disabling symptoms of MS, occurring in about 40-70% of MS patients. Thus, what appears to be impaired are slowness in information processing, decreased episodic memory, difficulties in executive function, changes in verbal fluency, and reductions in visuospatial analysis. Owing to the heterogeneity of MS, there is no single pathognomonic feature or diagnostic test that can accurately diagnose MS, so the diagnosis is based on the integration of various clinical, imaging and laboratory findings. As for the assessment of cognitive functions, there are several written and oral, and more recently digital, versions of neuropsychological batteries. In this sense, due to its reliability, validity and sensitivity, the Symbol Digit Modalities Test is the most frequently used test to monitor cognitive relapse rates. In recent years, outstanding developments of new Magnetic Resonance Imaging sequences have allowed structural and functional correlates of cognitive impairments to be defined, which appear to be associated with neurodegeneration, brain atrophy and functional network disruption. Although Disease-modifying Therapies have been effective in reducing relapse rates in MS, such treatments, just like symptomatic treatment, are ineffective for the treatment of cognitive impairment in MS. In this sense, alternative treatment approaches for mitigating these symptoms are needed. Hence, cognitive rehabilitation and exercise training are potential candidates for the treatment of MS-related cognitive impairment, though these are still considered to be poorly managed in MS patients. To conclude, future research focusing on cognitive impairment is necessary and crucial to acquire new information and thus improve the quality of life of MS patients as well as their caregivers

Comparing multiple criteria for species identification in two recently diverged seabirds

Correct species identification is a crucial issue in systematics with key implications for prioritising conservation effort. However, it can be particularly challenging in recently diverged species due to their strong similarity and relatedness. In such cases, species identification requires multiple and integrative approaches. In this study we used multiple criteria, namely plumage colouration, biometric measurements, geometric morphometrics, stable isotopes analysis (SIA) and genetics (mtDNA), to identify the species of 107 bycatch birds from two closely related seabird species, the Balearic (Puffinus mauretanicus) and Yelkouan (P. yelkouan) shearwaters. Biometric measurements, stable isotopes and genetic data produced two stable clusters of bycatch birds matching the two study species, as indicated by reference birds of known origin. Geometric morphometrics was excluded as a species identification criterion since the two clusters were not stable. The combination of plumage colouration, linear biometrics, stable isotope and genetic criteria was crucial to infer the species of 103 of the bycatch specimens. In the present study, particularly SIA emerged as a powerful criterion for species identification, but temporal stability of the isotopic values is critical for this purpose. Indeed, we found some variability in stable isotope values over the years within each species, but species differences explained most of the variance in the isotopic data. Yet this result pinpoints the importance of examining sources of variability in the isotopic data in a case-by-case basis prior to the cross-application of the SIA approach to other species. Our findings illustrate how the integration of several methodological approaches can help to correctly identify individuals from recently diverged species, as each criterion measures different biological phenomena and species divergence is not expressed simultaneously in all biological traits

Using marine isoscapes to infer movements of oceanic migrants: the case of Bulwer's petrel (Bulweria bulwerii) in the Atlantic Ocean

Studying the movements of oceanic migrants has been elusive until the advent of several tracking devices, such as the light-level geolocators. Stable isotope analysis (SIA) offers a complementary approach to infer areas used year-round, but its suitability in oceanic environments remains almost unexplored. To evaluate SIA as a tool for inferring movements of oceanic migrants, we sampled an oceanic seabird, the Bulwer's petrel, Bulweria bulwerii, in four breeding colonies spread along its Atlantic distribution. We first studied the species moulting pattern from 29 corpses collected in the colonies. Secondly, based on this moult knowledge, we selected three feathers from tracked birds to infer their breeding and non-breeding grounds using SIA: the 1st primary (P1), the 8th secondary (S8) and the 6th rectrix (R6) feathers. Birds migrated to two main non-breeding areas, the Central or the South Atlantic Ocean. P1 showed similar isotopic values among petrels from different breeding colonies, suggesting this feather is replaced early in the non-breeding period in a common area used by most birds, the Central Atlantic. S8 and R6 feathers correctly assigned 92% and 81%, respectively, of the birds to their non-breeding areas, suggesting they were replaced late in season, when birds were settled in their main non-breeding grounds. Our results showed that the isotopic baseline levels of the Central and South Atlantic are propagated through the food web until reaching top predators, suggesting these ratios can be used to infer the movement of long-distance migrants among oceanic water masses

Population size, breeding biology and on-land threats of Cape Verde petrel (Pterodroma feae) in Fogo Island, Cape Verde

Cape Verde petrel (Pterodroma feae) is currently considered near threatened, but little is known about its population size, breeding biology and on land threats, jeopardizing its management and conservation. To improve this situation, we captured, marked and recaptured (CMR) birds using mist-nets over 10 years; measured and sexed them; monitored up to 14 burrows, deployed GPS devices on breeders and analyzed activity data of geolocators retrieved from breeders in Fogo (Cape Verde). We set cat traps over the colony and investigated their domestic/feral origin by marking domestic cats from a nearby village with transponders, by deploying GPS devices on domestic cats and by performing stable isotope analyses of fur of the trapped and domestic cats. The population of Fogo was estimated to be 293 birds, including immatures (95% CI: 233-254, CMR modelling). Based on geolocator activity data and nest monitoring we determined the breeding phenology of this species and we found biometric differences between sexes. While monitoring breeding performance, we verified a still ongoing cat predation and human harvesting. Overall, data gathered from trapped cats without transponder, cats GPS trips and the distinct isotopic values between domestic and trapped cats suggest cats visiting the colony are of feral origin. GPS tracks from breeders showed birds left and returned to the colony using the sector NE of the islands, where high level of public lights should be avoided specially during the fledging period. Main threats for the Cape Verde petrel in the remaining breeding islands are currently unknown but likely to be similar to Fogo, calling for an urgent assessment of population trends and the control of main threats in all Cape Verde Islands and uplisting its conservation status

Will climate change affect the survival of tropical and subtropical species? Predictions based on Bulwer's petrel populations in the NE Atlantic Ocean

Climate change has repeatedly been shown to impact the demography and survival of marine top predators. However, most evidence comes from single populations of widely distributed species, limited mainly to polar and subpolar environments. Here, we aimed to evaluate the influence of environmental conditions on the survival of a tropical and migratory seabird over the course of its annual cycle. We used capture-mark-recapture data from three populations of Bulwer's petrel (Bulweria bulwerii) spread across the NE Atlantic Ocean, from the Azores, Canary, and Cabo Verde Islands (including temperate to tropical zones). We also inferred how the survival of this seabird might be affected under different climatic scenarios, defined by the Intergovernmental Panel on Climate Change. Among the environmental variables whose effect we evaluated (North Atlantic Oscillation index, Southern Oscillation Index, Sea Surface Temperature [SST] and wind speed), SST estimated for the breeding area and season was the variable with the greatest influence on adult survival. Negative effects of SST increase emerged across the three populations, most likely through indirect trophic web interactions. Unfortunately, our study also shows that the survival of Bulwer's petrel will be profoundly affected by the different scenarios of climate change, even with the most optimistic trajectory involving the lowest greenhouse gas emission. Furthermore, for the first time, our study predicts stronger impacts of climate change on tropical populations than on subtropical and temperate ones. This result highlights the devastating effect that climate change may also have on tropical areas, and the importance of considering multi-population approaches when evaluating its impacts which may differ across species distributions

Leapfrog migration and habitat preferences of a small oceanic seabird, Bulwer's petrel (Bulweria bulwerii)

Aim Our current understanding of migratory strategies and the reasons for their high variability along the phylogenetic tree remains relatively poor. Most of the hypotheses relating to migration have been formulated for terrestrial taxa; classically, oceanic migrations were considered as merely dispersive because of the scarcity of observations in the open ocean. We describe for the first time, the migration strategy of a small seabird, the Bulwer's petrel (Bulweria bulwerii), and provide new insights into the ecology and evolution of long-distance marine migrations. Location Subtropical and tropical Atlantic Ocean. Methods Using cutting-edge geolocators, we examined the year-round distribution and at-sea activity patterns of adult Bulwer's petrels sampled at five localities throughout the species' breeding range in the Atlantic, within the Azores, Salvages, Canary and Cape Verde archipelagos. We assessed the migratory connectivity of the species and its habitat use at population and metapopulation scales. Results Our results provide the first evidence of an oriented leapfrog migration in oceanic seabirds. Ecological niche models based on breeding-season data effectively predicted that subtropical waters of the South Atlantic would be the preferred habitat for the northern populations of Bulwer's petrels during the non-breeding season. Habitat modelling also highlighted similarities in distributions between the breeding and non-breeding periods for the southern populations. Data on at-sea activity patterns suggested that birds from the northern and southern populations behave differently during the breeding season, as well as in the northern and southern non-breeding ranges during the non-breeding period. Main conclusions These results indicate that specific habitat preferences, presumably related to differences in prey availability, explain the observed distributions and hence the pattern of leapfrog migration described for Bulwer's petrel. Our study demonstrates the utility of integrating diverse tracking data from multiple populations across international boundaries, and habitat modelling, for identifying important areas common to many marine species in the vast oceanic environments

Year-round individual specialization in the feeding ecology of a long-lived seabird

Many generalist species are composed of individuals varying in the size of their realized niches within a population. To understand the underlying causes and implications of this phenomenon, repeated samplings on the same individuals subjected to different environmental conditions are needed. Here, we studied individual specialization of feeding strategies in breeding and non-breeding grounds of Cory's shearwaters (Calonectris borealis) for 2-8 years, and its relationship with fitness. Individuals were relatively flexible in non-breeding destinations, but specialized in diet, habitat use and daily activity across years. Daily activity was also consistent throughout the year for the same individual, suggesting that it is driven by individual constraints, whereas individual diet and habitat use changed between breeding and non-breeding grounds, indicating that these specializations may be learned at each area. Moreover, individuals that were intermediate specialized in their diet tended to show higher breeding success than those with weakly and highly specialized diets, suggesting stabilizing selection. Overall, this study suggests that the development of individual specialization is more flexible than previously thought, i.e. it emerges under specific environmental conditions and can develop differently when environmental conditions vary. However, once established, individual specialization may compromise the ability of individuals to cope with environmental stochasticity

Leapfrog migration and habitat preferences of a small oceanic seabird, Bulwer's petrel (Bulweria bulwerii)

Aim Our current understanding of migratory strategies and the reasons for their high variability along the phylogenetic tree remains relatively poor. Most of the hypotheses relating to migration have been formulated for terrestrial taxa; classically, oceanic migrations were considered as merely dispersive because of the scarcity of observations in the open ocean. We describe for the first time, the migration strategy of a small seabird, the Bulwer's petrel (Bulweria bulwerii), and provide new insights into the ecology and evolution of long‐distance marine migrations. Location Subtropical and tropical Atlantic Ocean. Methods Using cutting‐edge geolocators, we examined the year‐round distribution and at‐sea activity patterns of adult Bulwer's petrels sampled at five localities throughout the species' breeding range in the Atlantic, within the Azores, Salvages, Canary and Cape Verde archipelagos. We assessed the migratory connectivity of the species and its habitat use at population and metapopulation scales. Results Our results provide the first evidence of an oriented leapfrog migration in oceanic seabirds. Ecological niche models based on breeding‐season data effectively predicted that subtropical waters of the South Atlantic would be the preferred habitat for the northern populations of Bulwer's petrels during the non‐breeding season. Habitat modelling also highlighted similarities in distributions between the breeding and non‐breeding periods for the southern populations. Data on at‐sea activity patterns suggested that birds from the northern and southern populations behave differently during the breeding season, as well as in the northern and southern non‐breeding ranges during the non‐breeding period. Main conclusions These results indicate that specific habitat preferences, presumably related to differences in prey availability, explain the observed distributions and hence the pattern of leapfrog migration described for Bulwer's petrel. Our study demonstrates the utility of integrating diverse tracking data from multiple populations across international boundaries, and habitat modelling, for identifying important areas common to many marine species in the vast oceanic environments

Sea surface temperature, rather than land mass or geographic distance, may drive genetic differentiation in a species complex of highly dispersive seabirds

Seabirds, particularly Procellariiformes, are highly mobile organisms with a great capacity for long dispersal, though simultaneously showing high philopatry, two conflicting life-history traits that may lead to contrasted patterns of genetic population structure. Landmasses were suggested to explain differentiation patterns observed in seabirds, but philopatry, isolation by distance, segregation between breeding and nonbreeding zones, and oceanographic conditions (sea surface temperatures) may also contribute to differentiation patterns. To our knowledge, no study has simultaneously contrasted the multiple factors contributing to the diversification of seabird species, especially in the gray zone of speciation. We conducted a multilocus phylogeographic study on a widespread seabird species complex, the little shearwater complex, showing highly homogeneous morphology, which led to considerable taxonomic debate. We sequenced three mitochondrial and six nuclear markers on all extant populations from the Atlantic (lherminieri) and Indian Oceans (bailloni), that is, five nominal lineages from 13 populations, along with one population from the eastern Pacific Ocean (representing the dichrous lineage). We found sharp differentiation among populations separated by the African continent with both mitochondrial and nuclear markers, while only mitochondrial markers allowed characterizing the five nominal lineages. No differentiation could be detected within these five lineages, questioning the strong level of philopatry showed by these shearwaters. Finally, we propose that Atlantic populations likely originated from the Indian Ocean. Within the Atlantic, a stepping-stone process accounts for the current distribution. Based on our divergence time estimates, we suggest that the observed pattern of differentiation mostly resulted from historical and current variation in sea surface temperatures

Global spatial ecology of three closely-related gadfly petrels

The conservation status and taxonomy of the three gadfly petrels that breed in Macaronesia is still discussed partly due to the scarce information on their spatial ecology. Using geolocator and capture-mark-recapture data, we examined phenology, natal philopatry and breeding-site fidelity, year-round distribution, habitat usage and at-sea activity of the three closely-related gadfly petrels that breed in Macaronesia: Zino's petrel Pterodroma madeira, Desertas petrel P. deserta and Cape Verde petrel P. feae. All P. feae remained around the breeding area during their non-breeding season, whereas P. madeira and P. deserta dispersed far from their colony, migrating either to the Cape Verde region, further south to equatorial waters in the central Atlantic, or to the Brazil Current. The three taxa displayed a clear allochrony in timing of breeding. Habitat modelling and at-sea activity patterns highlighted similar environmental preferences and foraging behaviours of the three taxa. Finally, no chick or adult was recaptured away from its natal site and survival estimates were relatively high at all study sites, indicating strong philopatry and breeding-site fidelity for the three taxa. The combination of high philopatry, marked breeding asynchrony and substantial spatio-temporal segregation of their year-round distribution suggest very limited gene flow among the three taxa