Mental health, brain resilience and vulnerability in people at risk for Alzheimer's disease
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Document Version
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M. Arenaza-Urquijo, Eider
Tutor
Navarro, Arcadi
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455 p.
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Citation
Palpatzis, E. Mental health, brain resilience and vulnerability in people at risk for Alzheimer's disease. Universitat Pompeu Fabra; 2025. handle: http://hdl.handle.net/10803/695450
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Doctoral program
Universitat Pompeu Fabra. Doctorat en Biomedicina
Abstract
La enfermedad de Alzheimer (EA) comienza con una fase preclínica donde emergen cambios fisiopatológicos sin síntomas clínicos. Comprender cómo los factores de salud mental se asocian con la vulnerabilidad y resiliencia a la EA es esencial para desarrollar intervenciones efectivas. Esta tesis identifica factores que influyen en las etapas más tempranas cuando las intervenciones pueden ser más efectivas. Los resultados demuestran que eventos estresantes se asocian con la EA, con asociaciones dependientes del tipo de estresor, sexo/género, educación e historia psiquiátrica. Los hallazgos sugieren que síntomas psiquiátricos pueden ser tanto manifestaciones tempranas como contribuyentes a la patología de EA, y que pensamientos intrusivos constituyen una vía psicológica con base neurobiológica en regiones de procesamiento emocional. Las estrategias de afrontamiento adaptativas pueden conferir resiliencia cognitiva. Esta tesis proporciona la primera evidencia que asocia eventos estresantes, síntomas de Trastorno de Estrés Postraumático y estilos de afrontamiento con patología temprana de EA y deterioro cognitivo. Estos hallazgos apoyan intervenciones de salud mental como objetivos terapéuticos para retrasar la enfermedad—especialmente manejo del estrés, tratamiento de síntomas neuropsiquiátricos y mejora de estrategias adaptativas—abriendo nuevas direcciones para investigación sobre este creciente desafío de salud pública.
Alzheimer's disease (AD) begins with a prolonged preclinical phase during which pathophysiological changes emerge without clinical symptoms. Understanding how mental health factors associate with vulnerability and resilience to AD during this phase is essential for developing effective interventions. This thesis aims to identify factors that may influence the earliest stages of AD when interventions may be most effective. Results demonstrate that stressful life events associate with AD-related outcomes, with distinct associations contingent on type and timing of stressors, sex/gender, education and psychiatric history. Further, findings suggest that psychiatric symptoms may represent both early manifestations of and contributors to advancing AD pathology. Further, the findings suggest that intrusive thoughts may be a distinct psychological pathway in preclinical AD, having a neurobiological basis in emotion-processing brain regions. Additionally, adaptive coping strategies may confer cognitive resilience against AD pathology. Altogether, this thesis contributes to the growing body of evidence linking psychiatric factors to AD and, importantly, provide the first evidence associating stressful life events, PTSD symptoms and coping styles with early AD pathology and cognitive decline. These findings support mental health interventions as potential therapeutic targets to delay disease trajectories—particularly stress-management, treatment of neuropsychiatric symptoms, and enhancement of adaptive coping strategies in at-risk populations—thereby opening new directions for future research addressing the growing public health challenge of AD.
Alzheimer's disease (AD) begins with a prolonged preclinical phase during which pathophysiological changes emerge without clinical symptoms. Understanding how mental health factors associate with vulnerability and resilience to AD during this phase is essential for developing effective interventions. This thesis aims to identify factors that may influence the earliest stages of AD when interventions may be most effective. Results demonstrate that stressful life events associate with AD-related outcomes, with distinct associations contingent on type and timing of stressors, sex/gender, education and psychiatric history. Further, findings suggest that psychiatric symptoms may represent both early manifestations of and contributors to advancing AD pathology. Further, the findings suggest that intrusive thoughts may be a distinct psychological pathway in preclinical AD, having a neurobiological basis in emotion-processing brain regions. Additionally, adaptive coping strategies may confer cognitive resilience against AD pathology. Altogether, this thesis contributes to the growing body of evidence linking psychiatric factors to AD and, importantly, provide the first evidence associating stressful life events, PTSD symptoms and coping styles with early AD pathology and cognitive decline. These findings support mental health interventions as potential therapeutic targets to delay disease trajectories—particularly stress-management, treatment of neuropsychiatric symptoms, and enhancement of adaptive coping strategies in at-risk populations—thereby opening new directions for future research addressing the growing public health challenge of AD.
Keywords
Malaltia d'Alzheimer, Alzheimer's disease, Enfermedad de Alzheimer, Salut mental, Mental health, Salud mental, Resiliència, Resilience, Resiliencia
Subjects
616.8 - Neurology. Neuropathology. Nervous system
Publisher
Universitat Pompeu Fabra
