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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/118843
Nuevos instrumentos subjetivos y objetivos para evaluar la fase preclínica de la enfermedad de Alzheimer
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[spa] En la última década, frente al fracaso de los tratamientos farmacológicos para detener el proceso patológico de la enfermedad de Alzheimer, la fase preclínica se ha convertido en un importante foco de investigación, puesto que se ha postulado que la intervención temprana puede ofrecer la mejor oportunidad de éxito terapéutico. En este contexto, el enfoque de la investigación se ha ampliado desde las fases clínicas de la enfermedad hacía fases preclínicas, donde pueden aparecer tanto una percepción subjetiva de declive como posibles disfunciones cognitivas o motoras sutiles detectables por nuevos test computarizados más sensibles que las pruebas neuropsicológicas clásicas. En la presente tesis, que incluye 4 trabajos científicos, hemos desarrollado nuevos instrumentos para evaluar tanto el rendimiento subjetivo como el objetivo en la fase preclínica. En el grupo preclínico, el declive cognitivo subjetivo referido por el informador, evaluado a través del nuevo cuestionario, fue mayor que en el grupo control. Además, en comparación con el grupo control, el grupo preclínico mostró un peor rendimiento en las pruebas experimentales de coordinación visuomotora y control motor. Por último, el rendimiento en estas medidas experimentales se encontró asociado con los niveles de β-amiloide (el primer biomarcador afectado en el continuum de la enfermedad de Alzheimer) en la muestra de individuos cognitivamente sanos. Los resultados de la presente tesis sugieren que nuevas herramientas de evaluación del deterioro cognitivo subjetivo y de funciones cognitivo-motoras específicas (y quizás más cercanas y más sensibles a los precoces cambios neuronales que ocurren en la enfermedad de Alzheimer), como la velocidad y la variabilidad intra-individual, pueden ofrecer información adicional única en la identificación de individuos que presentan un substrato patológico de la enfermedad de Alzheimer, sin exhibir por ello síntomas clínicos.
[eng] In the last decade, against the failure of pharmacological treatments to stop the pathological process of Alzheimer's disease, the preclinical phase has become an important focus of research, since it has been postulated that early intervention may offer the best opportunity for therapeutic success. In this context, the research approach has expanded from the clinical phases of the disease to preclinical stages, where both subjective perception of decline and possible subtle cognitive or motor dysfunctions can be detected by new computerized tests, which may be more sensitive than classic neuropsychological measures. In the present thesis, which includes 4 scientific papers, we have developed new instruments to evaluate both subjective and objective performance in the preclinical phase. In the preclinical group, the subjective cognitive decline reported by the informant, evaluated through the new questionnaire, was greater than in the control group. In addition, compared to the control group, the preclinical group showed worse performance in the experimental tests of visuomotor coordination and motor control. Finally, performance in these experimental measures was found to be associated with the levels of β-amyloid (the first biomarker affected in the continuum of Alzheimer's disease) in the sample of cognitively healthy individuals. The results of the present thesis suggest that new tools for evaluating subjective cognitive impairment and specific cognitive-motor functions (and perhaps closer and more sensitive to the early neural changes that occur in Alzheimer's disease), such as speed and intra-individual variability, may offer unique additional information in the identification of individuals presenting a pathological substrate for Alzheimer's disease, without thereby exhibiting clinical symptoms.
[eng] In the last decade, against the failure of pharmacological treatments to stop the pathological process of Alzheimer's disease, the preclinical phase has become an important focus of research, since it has been postulated that early intervention may offer the best opportunity for therapeutic success. In this context, the research approach has expanded from the clinical phases of the disease to preclinical stages, where both subjective perception of decline and possible subtle cognitive or motor dysfunctions can be detected by new computerized tests, which may be more sensitive than classic neuropsychological measures. In the present thesis, which includes 4 scientific papers, we have developed new instruments to evaluate both subjective and objective performance in the preclinical phase. In the preclinical group, the subjective cognitive decline reported by the informant, evaluated through the new questionnaire, was greater than in the control group. In addition, compared to the control group, the preclinical group showed worse performance in the experimental tests of visuomotor coordination and motor control. Finally, performance in these experimental measures was found to be associated with the levels of β-amyloid (the first biomarker affected in the continuum of Alzheimer's disease) in the sample of cognitively healthy individuals. The results of the present thesis suggest that new tools for evaluating subjective cognitive impairment and specific cognitive-motor functions (and perhaps closer and more sensitive to the early neural changes that occur in Alzheimer's disease), such as speed and intra-individual variability, may offer unique additional information in the identification of individuals presenting a pathological substrate for Alzheimer's disease, without thereby exhibiting clinical symptoms.
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MOLLICA, Maria Antonella. Nuevos instrumentos subjetivos y objetivos para evaluar la fase preclínica de la enfermedad de Alzheimer. [consulted: 8 of August of 2026]. Available at: https://hdl.handle.net/2445/118843