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| Author(s): |
Gabriela Cabett Cipolli
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2025-05-20 |
| Examining board members: |
Mônica Sanches Yassuda;
Claudia Regina Cavaglieri;
Tiago da Silva Alexandre;
Fabiana de Souza Orlandi;
Renato Gorga Bandeira de Mello
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| Advisor: | Mônica Sanches Yassuda |
| Abstract | |
Introduction: Sarcopenia, frailty, and cognitive impairment are interrelated geriatric syndromes that deserve attention, as they negatively impact the health and functionality of the older population. Both sarcopenia and frailty may be associated with cognitive decline, suggesting a bidirectional relationship between these conditions. However, little is known about the brain microstructural changes associated with frailty in cognitively unimpaired older adults. Objective: This thesis investigated these relationships through three complementary studies, including a longitudinal study, a scoping review, and a cross-sectional study. Methods: In Study 1, a longitudinal study, we analyzed the association between cognitive impairment and sarcopenia in 521 older adults from the Frailty in Brazilian Older Adults (FIBRA) study over nine years. Measures of sarcopenia, cognition, nutritional status, depressive symptoms, comorbidities, and physical activity levels were assessed over time. In Study 2, we conducted a scoping review of the literature, including 17 studies, to synthesize evidence on frailty and functional and/or structural changes in cognitively unimpaired older adults. The search was conducted in nine databases—PubMed, PubMed PMC, BVS/BIREME, EBSCOHOST, Scopus, Web of Science, Embase, and PROQUEST—following the methodology of the Joanna Briggs Institute. In Study 3, a cross-sectional study, we investigated the associations between frailty, gait speed, and handgrip strength on the white matter microstructure using Diffusion Tensor Imaging (DTI) in 51 cognitively unimpaired older adults. Frailty was assessed based on the frailty phenotype, along with an analysis of sociodemographic data, including sex, age, education level, nutritional status, and the presence of hypertension and diabetes. Results: Study 1 indicated that being 80 years or older, being underweight or overweight, and having baseline cognitive impairment were predictors of sarcopenia after nine years. The association was assessed using logistic regression adjusted for sociodemographic and clinical variables, with the application of Inverse Probability Weighting (IPW) to correct for sample losses. Study 2 concluded that frail yet cognitively unimpaired older adults exhibit brain alterations, including reduced volume of cortical and subcortical structures, white matter hyperintensities, and ß-amyloid accumulation. These changes, more frequent in frail individuals, may have neurodegenerative, inflammatory, or cerebrovascular origins. In Study 3, we observed that fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were primarily associated with age, while frailty was specifically associated with FA. Furthermore, both frailty and age were related to alterations in white matter microstructural integrity, particularly within the corpus callosum, with age impacting multiple brain regions. Conclusion: The findings of this thesis reinforce the interconnection between frailty, sarcopenia, and cognition, demonstrating that these conditions are associated with both adverse clinical outcomes and structural brain changes. These results contribute to the advancement of our understanding of the pathophysiology of sarcopenia and frailty, and open new avenues for research integrating muscle function, brain structure, and cognitive impairment in longitudinal or translational models (AU) | |
| FAPESP's process: | 19/24713-2 - Relationship between Sarcopenia and cognition in the old people: data from the fibra study |
| Grantee: | Gabriela Cabett Cipolli |
| Support Opportunities: | Scholarships in Brazil - Doctorate |