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: | Kathy Liu |
| Institution: | University College London |
| Department: | Division of Psychiatry |
| Country: | |
| Proposed Analysis: | The locus coeruleus (LC), the main source of noradrenaline (NA) in the human brain, plays an important role in cognitive processes including attention, decision-making and memory. It is one of the earliest brain structures to show neurodegenerative change in Alzheimer's disease (AD), and thus may underlie some of the earliest changes in cognition and behaviour in patients with AD. For example, there is strong evidence that central NA system dysfunction may underlie agitation in AD, and the intensity of the LC neuromelanin signal (measured using MRI) has been associated with cognitive performance in healthy older adults and may have the potential to serve as a biomarker for pre-symptomatic stages of AD. Neuromelanin inside LC neurons allows the structure to be visualised using T1-weighted and magnetisation transfer (MT) weighted MRI. Consistent with post-mortem findings on the pattern of LC neuron loss, my systematic review of MRI studies identified reliable reports of lower LC signal intensity in patients with AD compared to age-matched controls. Further, analysis of MRI data from over 600 healthy adults using the Cam-CAN dataset revealed age-related decline in rostral LC signal intensity from the age of 60 years. Analysis of the ADNI database can potentially build on this work, as previous in vivo MRI studies have used relatively small sample sizes, and none have associated LC structure with cognitive/behavioural function. This study aims to answer the following questions: 1. Can the LC be visualized on the structural MRI scans in AD patients and its signal intensity measured, to create a neural measure of NA function? 2. Is there a relationship between putative NA-dependent cognitive and/or behavioural measures and neural measures of LC integrity in AD patients? (Specific cognitive measures include emotional memory, attention, inhibitory control, and specific behavioural measures include anxiety/agitation). 3. What is the longitudinal relationship between anxiety and agitation in AD? Agitation in AD has been viewed as an expression of anxiety, and both are hypothesized to involve the NA system, but the overlap and association between them is unclear. Key hypotheses: 1. LC signal intensity will be lower in AD patients than healthy controls. 2. Within the AD group, lower LC signal intensity will be associated with agitation and cognitive deficits on tasks putatively dependent on the NA system. 3. In AD patients, higher anxiety scores at baseline will be associated with greater severity and/or odds of developing agitation. Changes in agitation scores will be highly correlated with changes in anxiety scores. Planned methodology and statistical tests: Structural MRI images will be inspected to identify the LC. If the LC can be observed, an LC template will be created from T1-weighted files using ANTs (Advanced Normalisation Tools) to identify the LC at the group and individual level. Signal intensity of LC will be extracted to measure LC integrity for each individual. Using Lavaan in R, the relationship between LC signal intensity, behavioural and cognitive measures will be assessed in AD patients using regression analyses and structural equation modelling. The longitudinal relationship between agitation and anxiety in AD will be analysed using multilevel regression analyses. |
| Additional Investigators |
