There are many active research projects accessing and applying shared ADNI data. Use the search above to find specific research focuses on the active ADNI investigations. This information is requested annually as a requirement for data access.
| Principal Investigator | |
| Principal Investigator's Name: | Juliana N Souza-Talarico |
| Institution: | The University of Iowa |
| Department: | College of Nursing |
| Country: | |
| Proposed Analysis: | The overall objective of this proposal is to identify allostatic states that predict the pathological changes that feature the AD preclinical stage. Our central hypothesis is that combinations of neuroendocrine, immunological, and metabolic allostatic states at mid-life predict Aβ deposition, hippocampus atrophy, and cognitive decline in late life. Sustained cortisol levels, proinflammatory cytokines, and glucose, which are the primary stress mediators, induce neuroinflammation, which triggers Aβ accumulation, brain atrophy, and consequently, cognitive decline. In line with that, our previous studies demonstrated that cortisol levels and allostatic load biomarkers are associated with low cognitive performance in mid-life individuals and older adults with mild cognitive impairment (MCI) and AD. Interestingly, preliminary cross-sectional findings also demonstrated that cortisol levels were associated with Aβ deposition in MCI patients. Using ADNI dataset (Clinical, Genetic, MRI, PET and Biomarkers) of Cognitively Normal (CN) individuals and those with Significant Memory Concern (SMC) from 55 to 64 years, we propose demonstrating that sustained allostatic states at mid-life contribute to Aβ deposition, hippocampal volume decrease, and cognitive performance decline. To attain the overall objective, the following specific aims will be pursued: Specific aim #1: determine the allostatic states (hypo or hyper) that predict Aβ deposition, hippocampus volume decrease, and memory decline from middle-age to aging. For that, we propose to use the ADNI dataset (Bioespecimen measures, APOE genotyping, cortisol CSF, PET-PIB for Aβ deposition, structural MRI for hippocampal volume and cognitive assessment) at baseline, Month 12, 24, 36, and 48. An allostatic load index (ALI) that combines Hb1, glucose, cholesterol, pro, and anti-inflammatory cytokines and DHEA will be used to determine the allostatic states. ALI slopes across months will be tested as a predictor of Aβ deposition, hippocampus volume decrease, cognitive decline, and conversion from normal or SMC to MCI at Month 48. Upon completing this project, we expect that we will have demonstrated that allostatic load states represent one of the pathways through incubated effects of chronic stress leads to the same set of brain changes that feature the preclinical stage of AD. We also expect to identify sociodemographic factors that moderates the consequences of stress on cognitive functioning from mid-life to aging. This accomplishment would set the basis for screening vulnerable individuals and test effective interventions to delay or transform deleterious cognitive trajectories into promisor aging. |
| Additional Investigators | |
| Investigator's Name: | Yelena Perkhounkova |
| Proposed Analysis: | The overall objective of this proposal is to identify allostatic states that predict the pathological changes that feature the AD preclinical stage. Our central hypothesis is that combinations of neuroendocrine, immunological, and metabolic allostatic states at mid-life predict Aβ deposition, hippocampus atrophy, and cognitive decline in late life. Sustained cortisol levels, proinflammatory cytokines, and glucose, which are the primary stress mediators, induce neuroinflammation, which triggers Aβ accumulation, brain atrophy, and consequently, cognitive decline. In line with that, our previous studies demonstrated that cortisol levels and allostatic load biomarkers are associated with low cognitive performance in mid-life individuals and older adults with mild cognitive impairment (MCI) and AD. Interestingly, preliminary cross-sectional findings also demonstrated that cortisol levels were associated with Aβ deposition in MCI patients. Using ADNI dataset (Clinical, Genetic, MRI, PET and Biomarkers) of Cognitively Normal (CN) individuals and those with Significant Memory Concern (SMC) from 55 to 64 years, we propose demonstrating that sustained allostatic states at mid-life contribute to Aβ deposition, hippocampal volume decrease, and cognitive performance decline. To attain the overall objective, the following specific aims will be pursued: Specific aim #1: determine the allostatic states (hypo or hyper) that predict Aβ deposition, hippocampus volume decrease, and memory decline from middle-age to aging. For that, we propose to use the ADNI dataset (Bioespecimen measures, APOE genotyping, cortisol CSF, PET-PIB for Aβ deposition, structural MRI for hippocampal volume and cognitive assessment) at baseline, Month 12, 24, 36, and 48. An allostatic load index (ALI) that combines Hb1, glucose, cholesterol, pro, and anti-inflammatory cytokines and DHEA will be used to determine the allostatic states. ALI slopes across months will be tested as a predictor of Aβ deposition, hippocampus volume decrease, cognitive decline, and conversion from normal or SMC to MCI at Month 48. Upon completing this project, we expect that we will have demonstrated that allostatic load states represent one of the pathways through incubated effects of chronic stress leads to the same set of brain changes that feature the preclinical stage of AD. We also expect to identify sociodemographic factors that moderates the consequences of stress on cognitive functioning from mid-life to aging. This accomplishment would set the basis for screening vulnerable individuals and test effective interventions to delay or transform deleterious cognitive trajectories into promisor aging. |
