Publicação
The value of Potentially Toxic Elements as a risk factor for cognitive decline and dementia
| Resumo: | Element homeostasis is essential for normal brain functioning. Both dysregulation of essential elements and exposure to non-essential elements can induce oxidative stress, impair synaptic plasticity and transmission, promote protein misfolding, dysregulate autophagy, cause neuroinflammation, and ultimately lead to neurodegeneration. These effects are particularly detrimental to the aging brain, affecting its structure and function. Given the critical link between brain health and cognitive performance, studying the relationship between Potentially Toxic Elements (PTE) and cognition is crucial to understand how different elements can benefit or compromise individuals who are susceptible to cognitive decline, mild cognitive impairment, and dementia. In our systematic review we observed that, despite the volume of research on this topic, conclusion on how PTE influence the cognitive performance of adults and older adults remain weak. The aim of this thesis was to elucidate these relationships.With a methodology based on the crossing of neuropsychological and elemental profiling, we explored the associations between PTE and the cognition of adults and older adults in three original studies in which we assessed multiple cognitive domains, determined several PTE in various biomarkers, and evaluated different vulnerable groups. In the first study, we used a cross-sectional design to examine community adults and older adults. We measured thirty PTE in nail, hair, and urine samples and assessed global cognition, attention, memory, working memory, executive functioning, language, and dementia staging. The second study involved adults and older adults residing in specific geographical areas and assumed a longitudinal design. Over a 5-year follow-up period, we investigated the effects of baseline levels of nail and hair PTE on future cognitive performances. The third study focused on exploring the relationships between different PTE body levels and the cognitive function of AD patients. In this retrospective clinical investigation, we determined the contents of twenty-one PTE in hair, urine, serum, and whole blood, and analyzed their associations with impairment severity in global cognition, attention, memory, working memory, executive functioning, language, and visuoconstruction. Taken together, our studies demonstrate that poor cognitive outcomes are linked to several non-essential elements, particularly Al, As, Cd, Hg, Sr and Pb, as well as some essential elements, namely as Cu, Mn and Zn. The negative effects of Al, Cu, and Zn can persist for years after biomonitoring. In contrast, favorable cognitive outcomes are associated with certain essential elements, with Se playing a particularly protective role that can be observed in the long term.These findings are crucial for understanding the role of PTE in the cognition of adults and older adults and can have practical implications for the development of public health policies, environmental safety, occupational safety, clinical interventions, and research. |
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| Autores principais: | Gerardo, Bianca Salguinho |
| Assunto: | Neuropsychological Assessment Potentially Toxic Elements Aging Cognitive Impairment Avaliação Neuropsicológica Elementos Potencialmente Tóxicos Envelhecimento Défice Cognitivo - - |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade de Coimbra |
| Idioma: | inglês |
| Origem: | Estudo Geral - Universidade de Coimbra |
| Resumo: | Element homeostasis is essential for normal brain functioning. Both dysregulation of essential elements and exposure to non-essential elements can induce oxidative stress, impair synaptic plasticity and transmission, promote protein misfolding, dysregulate autophagy, cause neuroinflammation, and ultimately lead to neurodegeneration. These effects are particularly detrimental to the aging brain, affecting its structure and function. Given the critical link between brain health and cognitive performance, studying the relationship between Potentially Toxic Elements (PTE) and cognition is crucial to understand how different elements can benefit or compromise individuals who are susceptible to cognitive decline, mild cognitive impairment, and dementia. In our systematic review we observed that, despite the volume of research on this topic, conclusion on how PTE influence the cognitive performance of adults and older adults remain weak. The aim of this thesis was to elucidate these relationships.With a methodology based on the crossing of neuropsychological and elemental profiling, we explored the associations between PTE and the cognition of adults and older adults in three original studies in which we assessed multiple cognitive domains, determined several PTE in various biomarkers, and evaluated different vulnerable groups. In the first study, we used a cross-sectional design to examine community adults and older adults. We measured thirty PTE in nail, hair, and urine samples and assessed global cognition, attention, memory, working memory, executive functioning, language, and dementia staging. The second study involved adults and older adults residing in specific geographical areas and assumed a longitudinal design. Over a 5-year follow-up period, we investigated the effects of baseline levels of nail and hair PTE on future cognitive performances. The third study focused on exploring the relationships between different PTE body levels and the cognitive function of AD patients. In this retrospective clinical investigation, we determined the contents of twenty-one PTE in hair, urine, serum, and whole blood, and analyzed their associations with impairment severity in global cognition, attention, memory, working memory, executive functioning, language, and visuoconstruction. Taken together, our studies demonstrate that poor cognitive outcomes are linked to several non-essential elements, particularly Al, As, Cd, Hg, Sr and Pb, as well as some essential elements, namely as Cu, Mn and Zn. The negative effects of Al, Cu, and Zn can persist for years after biomonitoring. In contrast, favorable cognitive outcomes are associated with certain essential elements, with Se playing a particularly protective role that can be observed in the long term.These findings are crucial for understanding the role of PTE in the cognition of adults and older adults and can have practical implications for the development of public health policies, environmental safety, occupational safety, clinical interventions, and research. |
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