Evolution and treatment of vitamin B12 deficiency as a risk factor for (cognitive and functional) neurodegenerative diseases in institutionalized elderly = Evolución y tratamiento de la deficiencia de vitamina B12 como factor de riesgo de enfermedades neurodegenerativas (cognitivas y funcionales) en las personas mayores institucionalizadas.

Prevalence of vitamin B12 deficiency is very common in elderly people and can reach values as high as 40.5% of the population. It can be the result of the interaction among several factors. Vitamin B12 deficiencies have been associated with neurological, cognitive deterioration, haematological abnormalities and cardiovascular diseases that have an important influence on the health of the elderly and their quality of life. It is necessary to approach the problems arisen from the lack of data relative to them. The main objective of this thesis was to analyse the evolution of vitamin B12 status and related parameters, lipid and haematological profiles and their relationship to health risk factors, and to functional and cognitive status over one year and to determine the effect of an oral supplementation of 500 μg of cyanocobalamin for a short period of 28 days. An additional objective was to analyze the possible effects of medicine intakes on vitamin B status. Three studies were performed: a) a one year longitudinal follow-up with four measure points; b) an intervention study providing an oral liquid supplement of 500 μg of cyanocobalamin for a 28 days period; and c) analysis of the possible effect of medication intake on vitamin B status using the ATC classification of medicines. The participants for these studies were recruited from nursing homes for the elderly in the Region of Madrid. Sixty elders (mean age 84 _ 7y, 19 men and 41 women) were recruited for Study I and 64 elders (mean age 82 _ 7y, 24 men and 40 women) for Study II. For Study III, baseline data from the initially recruited participants of the first two studies were used. An informed consent was obtained from all participants or their mentors. The studies were approved by the Ethical Committee of the University of Granada. Blood samples were obtained at each examination date and were analyzed for serum cobalamin, holoTC, serum and RBC folate and total homocysteine according to laboratory standard procedures. The haematological parameters analyzed were haematocrit, haemoglobin and MCV. For the lipid profile TG, total cholesterol, LDL- and HDLcholesterol were analyzed. Anthropometric measures (BMI, skinfolds [triceps and subscapular], waist girth and waist to hip ratio), functional tests (hand grip, arm and leg strength tests, static balance) and MMSE were obtained or administered by trained personal. The vitamin B12 supplement of Study II was administered with breakfast and the medication intake was taken from the residents’ anamnesis. Data were analyzed by parametric and non-parametric statistics depending on the obtained data. Comparisons were done using the appropriate ANOVAs or non-parametric tests. Pearsons’ partial correlations with the variable “time” as control were used to define the association of the analyzed parameters. XIII The results showed that: A) Over one year, in relationship to vitamin B status, serum cobalamin decreased, serum folate and mean corpuscular volumen increased significantly and total homocysteine concentrations were stable. Regarding blood lipid profile, triglycerides increased and HDL-cholesterol decreased significantly. Regarding selected anthropometric measurements, waist circumference increased significantly. No significant changes were observed for the rest of parameters. B) Prevalence of hyperhomocysteinemia was high in the elderly studied, ranging from 60% to 90 % over the year depending on the cut-off used for the classification. LDL-cholesterol values were high, especially among women, and showed a tendency to increase over the year. Results of the balance test showed a deficiency and a tendency to decrease; this indicates that the population studied is at high risk for falls. Lower extremity muscular function was deficient and showed a tendency to decrease. A highly significant relationship was observed between the skinfold of the triceps and blood lipid profile. C) Low cobalamin concentrations correlated significantly with low MMSE scores in the elderly studied. No correlations were observed between vitamin B12 status and functional parameters. D) Regarding vitamin B12 status, holo-transcobalamin seems to be more sensitive for diagnosis; 5-10% of the elderly had a deficiency using serum cobalamin as a criterion, and 45-52% had a deficiency when using serum holotranscobalamin as a criterion. E) 500 μg of cyanocobalamin administered orally during 28 days significantly improved vitamin B12 status and significantly decreased total homocysteine concentrations in institutionalized elderly. No effect of the intervention was observed on functional and cognitive parameters. F) The relative change (%) of improvement of vitamin B12 status was higher when using serum holo-transcobalamin as a criterion than serum cobalamin. G) Antiaenemic drug intake normalized cobalamin, urologic drugs and corticosteroids serum folate, and psychoanaleptics holo-transcobalamin levels. Drugs treating pulmonary obstruction increased total homocysteine concentration significantly. H) The daily mean drug intake was 5.1. Fiftynine percent of the elderly took medication belonging to 5 or more different ATC groups. The most prevalent were psycholeptic (53%), antiacid (53%) and antithrombotic (47%) drugs.

El fitness como factor determinante en el riesgo de discapacidad, su relación con la composición corporal y el estado cognitivo en población mayor institucionalizada y de vida independiente = Fitness as a determinant factor in the risk of disability, and its relationship to body composition and cognitive status in institutionalized elderly population and independent living

La condición física, o como mejor se la conoce hoy en día el “fitness”, es una variable que está cobrando gran protagonismo, especialmente desde la perspectiva de la salud. La mejora de la calidad de vida que se ha experimentado en los últimos años en las sociedades desarrolladas, conlleva un aumento de la esperanza de vida, lo que hace que cada vez más personas vivan más años. Este rápido crecimiento de la población mayor de 60 años hace que, un grupo poblacional prácticamente olvidado desde el punto de vista de la investigación científica en el campo de la actividad física y del deporte, cobre gran relevancia, con el fin de poder ayudar a alcanzar el dicho “no se trata de aportar años a la vida sino vida a lo años”. La presente memoria de Tesis Doctoral tiene como principal objetivo valorar los niveles de fitness en población mayor española, además de analizar la relación existente entre el fitness, sus condicionantes y otros aspectos de la salud, tales como la composición corporal y el estado cognitivo. Entendemos que para poder establecer futuras políticas de salud pública en relación a la actividad física y el envejecimiento activo es necesario conocer cuáles son los niveles de partida de la población mayor en España y sus condicionantes. El trabajo está basado en los datos del estudio multicéntrico EXERNET (Estudio Multi-céntrico para la Evaluación de los Niveles de Condición Física y su relación con Estilos de Vida Saludables en población mayor española no institucionalizada), así como en los datos de dos estudios, llevados a cabo en población mayor institucionalizada. Se han analizado un total de 3136 mayores de vida independiente, procedentes de 6 comunidades autónomas, y 153 mayores institucionalizados en residencias de la Comunidad de Madrid. Los principales resultados de esta tesis son los siguientes: a) Fueron establecidos los valores de referencia, así como las curvas de percentiles, para cada uno de los test de fitness, de acuerdo a la edad y al sexo, en población mayor española de vida independiente y no institucionalizada. b) Los varones obtuvieron mejores niveles de fitness que las mujeres, excepto en los test de flexibilidad; existe una tendencia a disminuir la condición física en ambos sexos a medida que la edad aumenta. c) Niveles bajos de fitness funcional fueron asociados con un aumento en la percepción de problemas. d) El nivel mínimo de fitness funcional a partir del cual los mayores perciben problemas en sus actividades de la vida diaria (AVD) es similar en ambos sexos. e) Niveles elevados de fitness fueron asociados con un menor riesgo de sufrir obesidad sarcopénica y con una mejor salud percibida en los mayores. f) Las personas mayores con obesidad sarcopénica tienen menor capacidad funcional que las personas mayores sanas. g) Niveles elevados de fuerza fueron asociados con un mejor estado cognitivo siendo el estado cognitivo la variable que más influye en el deterioro de la fuerza, incluso más que el sexo y la edad. ABSTRACT Fitness is a variable that is gaining in prominence, especially from the health perspective. Improvement of life quality that has been experienced in the last few years in developed countries, leads to an expanded life expectancy, increasing the numbers of people living longer. This population consisting of people of over 60 years, an almost forgotten population group from the point of view of scientific research in the field of physical activity and sport, is becoming increasingly important, with the main aim of helping to achieve the saying “do not only add years to life, but also add life to years”. The principal aim of the current thesis was to assess physical fitness levels in Spanish elderly people, of over 65 years, analyzing relationship between physical fitness, its determinants, and other aspects of health such as body composition and cognitive status. In order to establish further public health policies in relation to physical activity and active ageing it is necessary to identify the starting physical fitness levels of the Spanish population and their determinants. The work is based on data from the EXERNET multi-center study ("Multi-center Study for the Evaluation of Fitness levels and their relationship to Healthy Lifestyles in noninstitutionalized Spanish elderly"), and on data from two studies conducted in institutionalized elderly people: a total of 3136 non-institutionalized elderly, from 6 Regions of Spain, and 153 institutionalized elderly in nursing homes of Madrid. The main outcomes of this thesis are: a) sex- and age-specific physical fitness normative values and percentile curves for independent and non-institutionalized Spanish elderly were established. b) Greater physical fitness was present in the elderly men than in women, except for the flexibility test, and a trend toward decreased physical fitness in both sexes as their age increased. c) Lower levels of functional fitness were associated with increased perceived problems. d) The minimum functional fitness level at which older adults perceive problems in their ADLs, is similar for both sexes e) Higher levels of physical fitness were associated with a reduced risk of suffering sarcopenic obesity and better perceived health among the elderly. f) The elderly with sarcopenic obesity have lower physical functioning than healthy counterparts. g) Higher strength values were associated with better cognitive status with cognitive status being the most influencing variable in strength deterioration even more than sex and age.

Impact attribution models to evaluate drought effects: economic impacts, risk analyses and management strategies in Spain and Chile

La sequía es un fenómeno natural que se origina por el descenso de las precipitaciones con respecto a una media, y que resulta en la disponibilidad insuficiente de agua para alguna actividad. La creciente presión que se ha venido ejerciendo sobre los recursos hídricos ha hecho que los impactos de la sequía se hayan visto agravados a la vez que ha desencadenado situaciones de escasez de agua en muchas partes del planeta. Los países con clima mediterráneo son especialmente vulnerables a las sequías, y, su crecimiento económico dependiente del agua da lugar a impactos importantes. Para reducir los impactos de la sequía es necesaria una reducción de la vulnerabilidad a las sequías que viene dada por una gestión más eficiente y por una mejor preparación. Para ello es muy importante disponer de información acerca de los impactos y el alcance de este fenómeno natural. Esta investigación trata de abarcar el tema de los impactos de las sequías, de manera que plantea todos los tipos de impactos que pueden darse y además compara sus efectos en dos países (España y Chile). Para ello se proponen modelos de atribución de impactos que sean capaces de medir las pérdidas económicas causadas por la falta de agua. Los modelos propuestos tienen una base econométrica en la que se incluyen variables clave a la hora de evaluar los impactos como es una variable relacionada con la disponibilidad de agua, y otras de otra naturaleza para distinguir los efectos causados por otras fuentes de variación. Estos modelos se adaptan según la fase del estudio en la que nos encontremos. En primer lugar se miden los impactos directos sobre el regadío y se introduce en el modelo un factor de aleatoriedad para evaluar el riesgo económico de sequía. Esto se hace a dos niveles geográficos (provincial y de Unidad de Demanda Agraria) y además en el último se introduce no solo el riesgo de oferta sino también el riesgo de demanda de agua. La introducción de la perspectiva de riesgo en el modelo da lugar a una herramienta de gestión del riesgo económico que puede ser utilizada para estrategias de planificación. Más adelante una extensión del modelo econométrico se desarrolla para medir los impactos en el sector agrario (impactos directos sobre el regadío y el secano e impactos indirectos sobre la Agro Industria) para ello se adapta el modelo y se calculan elasticidades concatenadas entre la falta de agua y los impactos secundarios. Por último se plantea un modelo econométrico para el caso de estudio en Chile y se evalúa el impacto de las sequías debidas al fenómeno de La Niña. iv Los resultados en general muestran el valor que brinda el conocimiento más preciso acerca de los impactos, ya que en muchas ocasiones se tiende a sobreestimar los daños realmente producidos por la falta de agua. Los impactos indirectos de la sequía confirman su alcance a la vez que son amortiguados a medida que nos acercamos al ámbito macroeconómico. En el caso de Chile, su diferente gestión muestra el papel que juegan el fenómeno de El Niño y La Niña sobre los precios de los principales cultivos del país y sobre el crecimiento del sector. Para reducir las pérdidas y su alcance se deben plantear más medidas de mitigación que centren su esfuerzo en una gestión eficiente del recurso. Además la prevención debe jugar un papel muy importante para reducir los riesgos que pueden sufrirse ante situaciones de escasez. ABSTRACT Drought is a natural phenomenon that originates by the decrease in rainfall in comparison to the average, and that results in water shortages for some activities. The increasing pressure on water resources has augmented the impact of droughts just as water scarcity has become an additional problem in many parts of the planet. Countries with Mediterranean climate are especially vulnerable to drought, and its waterdependent economic growth leads to significant impacts. To reduce the negative impacts it is necessary to deal with drought vulnerability, and to achieve this objective a more efficient management is needed. The availability of information about the impacts and the scope of droughts become highly important. This research attempts to encompass the issue of drought impacts, and therefore it characterizes all impact types that may occur and also compares its effects in two different countries (Spain and Chile). Impact attribution models are proposed in order to measure the economic losses caused by the lack of water. The proposed models are based on econometric approaches and they include key variables for measuring the impacts. Variables related to water availability, crop prices or time trends are included to be able to distinguish the effects caused by any of the possible sources. These models are adapted for each of the parts of the study. First, the direct impacts on irrigation are measured and a source of variability is introduced into the model to assess the economic risk of drought. This is performed at two geographic levels provincial and Agricultural Demand Unit. In the latter, not only the supply risk is considered but also the water demand risk side. The introduction of the risk perspective into the model results in a risk management tool that can be used for planning strategies. Then an extension of the econometric model is developed to measure the impacts on the agricultural sector (direct impacts on irrigated and rainfed productions and indirect impacts on the Agri-food Industry). For this aim the model is adapted and concatenated elasticities between the lack of water and the impacts are estimated. Finally an econometric model is proposed for the Chilean case study to evaluate the impact of droughts, especially caused by El Niño Southern Oscillation. The overall results show the value of knowing better about the precise impacts that often tend to be overestimated. The models allow for measuring accurate impacts due to the lack of water. Indirect impacts of drought confirm their scope while they confirm also its dilution as we approach the macroeconomic variables. In the case of Chile, different management strategies of the country show the role of ENSO phenomena on main crop prices and on economic trends. More mitigation measures focused on efficient resource management are necessary to reduce drought losses. Besides prevention must play an important role to reduce the risks that may be suffered due to shortages.