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: | Ivan koychev |
| Institution: | University of Oxford |
| Department: | Psychiatry |
| Country: | |
| Proposed Analysis: | Diabetes is a major risk factor for the development of cognitive impairment and dementia. Interventional studies targeting diabetes control therefore provide a potential route to disease modification, especially in cognitively normal individuals. Cross-sectional data exist linking insulin resistance (IR) to tau but not amyloid abnormality in insulin resistant individuals, particularly those at genetic risk for Alzheimer’s disease (AD), i.e. APOE4 carriership. In addition, IR has been linked to worse cognitive outcomes and faster cortical atrophy. However, limited data have so far been available to assess longitudinal changes in the molecular biomarkers of AD (tau and amyloid) in cognitively normal insulin resistant individuals, and, to test the interaction effect of IR and APOE4 in predicting such changes. Establishing this dynamic would be critical in informing the design and sample size of any study seeking to demonstrate AD modification of diabetes agents in pre-dementia diabetic individuals. We propose to examine the longitudinal change in three biomarkers relevant to the ATN framework (amyloid in CSF and PET; tau in CSF and PET; hippocampal atrophy on MRI) as well as cognition with respect to the interaction between IR (calculated using the Homeostatic Model Assessment for Insulin Resistance using plasma glucose and insulin) and APOE4 carriership, in a cognitively unimpaired sample. We hypothesise that the combination of IR and APOE4 carriership will lead to significantly higher annual increases in CSF tau, p-Tau and whole brain tau PET SUVR relative to the groups comprised of APOE4-only, IR-only or no risk factor individuals. We hypothesise that there will be no such IR-APOE4 synergistic effect in terms of amyloid change. We also expect that the APOE4+IR group will have significantly worse cognition and higher atrophy rates compared to the other exposure groups. In an exploratory part of the analysis we will test whether IR and APOE4 carriership interact to disrupt resting connectivity (functional MRI), and if so, whether or not the effect is mediated by ATN biomarkers. The main analysis will use linear mixed effects models for examining the AD biomarker trajectories over time (i.e. time in years will be modelled as the repeated measure). Age, sex, education, plasma glucose, insulin, and APOE4 will be included in the models, as well as two-way interaction terms among these factors. The results of the study will provide critical information for trials exploring disease modification through action on insulin resistance, by informing stratification strategy and the choice of outcome measures. |
| Additional Investigators | |
| Investigator's Name: | Catherine Calvin |
| Proposed Analysis: | Diabetes is a major risk factor for the development of cognitive impairment and dementia. Interventional studies targeting diabetes control therefore provide a potential route to disease modification, especially in cognitively normal individuals. Cross-sectional data exist linking insulin resistance (IR) to tau but not amyloid abnormality in insulin resistant individuals, particularly those at genetic risk for Alzheimer’s disease (AD), i.e. APOE4 carriership. In addition, IR has been linked to worse cognitive outcomes and faster cortical atrophy. However, limited data have so far been available to assess longitudinal changes in the molecular biomarkers of AD (tau and amyloid) in cognitively normal insulin resistant individuals, and, to test the interaction effect of IR and APOE4 in predicting such changes. Establishing this dynamic would be critical in informing the design and sample size of any study seeking to demonstrate AD modification of diabetes agents in pre-dementia diabetic individuals. We propose to examine the longitudinal change in three biomarkers relevant to the ATN framework (amyloid in CSF and PET; tau in CSF and PET; hippocampal atrophy on MRI) as well as cognition with respect to the interaction between IR (calculated using the Homeostatic Model Assessment for Insulin Resistance using plasma glucose and insulin) and APOE4 carriership, in a cognitively unimpaired sample. We hypothesise that the combination of IR and APOE4 carriership will lead to significantly higher annual increases in CSF tau, p-Tau and whole brain tau PET SUVR relative to the groups comprised of APOE4-only, IR-only or no risk factor individuals. We hypothesise that there will be no such IR-APOE4 synergistic effect in terms of amyloid change. We also expect that the APOE4+IR group will have significantly worse cognition and higher atrophy rates compared to the other exposure groups. In an exploratory part of the analysis we will test whether IR and APOE4 carriership interact to disrupt resting connectivity (functional MRI), and if so, whether or not the effect is mediated by ATN biomarkers. The main analysis will use linear mixed effects models for examining the AD biomarker trajectories over time (i.e. time in years will be modelled as the repeated measure). Age, sex, education, plasma glucose, insulin, and APOE4 will be included in the models, as well as two-way interaction terms among these factors. The results of the study will provide critical information for trials exploring disease modification through action on insulin resistance, by informing stratification strategy and the choice of outcome measures. |
