Improving Diagnosis And Measurement Of Progression In Dementia: Longitudinal Clinical And MRI Studies
Award Number
G0601846Award Type
FellowshipStatus / Stage
CompletedDates
1 September 2007 -2 January 2013
Duration (calculated)
05 years 04 monthsFunder(s)
MRC (UKRI)Funding Amount
£1,175,334.00Funder/Grant study page
MRC UKRIContracted Centre
University College LondonPrincipal Investigator
Professor FoxPI Contact
uclh.cognitivedisordersclinic@nhs.netPrincipal Investigator
Nick CharlesPI Contact
ayan.shire@nhs.netWHO Catergories
Understanding risk factorsUnderstanding Underlying Disease
Disease Type
Alzheimer's Disease (AD)CPEC Review Info
| Reference ID | 281 |
|---|---|
| Researcher | Reside Team |
| Published | 12/06/2023 |
Data
| Award Number | G0601846 |
|---|---|
| Status / Stage | Completed |
| Start Date | 20070901 |
| End Date | 20130102 |
| Duration (calculated) | 05 years 04 months |
| Funder/Grant study page | MRC UKRI |
| Contracted Centre | University College London |
| Funding Amount | £1,175,334.00 |
Abstract
Measures of cerebral change will be improved by optimising MRI acquisition reproducibility and post-acquisition artefact correction. Optimised protocols and artefact correction will be developed for 3T phased array acquisitions for 3D T2-weighted as well as T1-weighted volumetric studies. Linear and non-linear registration will be used to match imaging studies across modality and over time. Registration-based measures of atrophy rates will be further developed – and different approaches critically compared and the topography of progression will be assessed. The precision of measures will be improved with multiple time point imaging. Registration and quantification techniques will be developed that fully incorporate multiple time point studies, fitting the time series rather than each pair of scans independently. I will determine the minimum scan-interval needed for serial MRI to a) detect and b) distinguish neurodegenerative disorders. I will pursue the potential for reduced sample sizes in trials by reducing within-subject variability in atrophy rate measures and investigating run-in designs. I will further develop registration-based methods for quantifying progression of regional and global atrophy and parenchymal change and for measurement of cortical thickness changes: for these aims I will investigate combined serial 3D T2-weighted and T1-weighted imaging. I will combine and correlate atrophy measures with CSF markers and amyloid imaging (C11-PIB- PET) to determine the topography and assiation between amyloid deposition and neuronal loss. I will also correlate imaging changes with neuropsychometry to understand the temporal and topographical association between neuronal loss, amyloid deposition and cognition. I will apply these techniques to well-characterised clinical cohorts with established disease and also to individuals at risk of familial AD, prion, Huntington‘s and fronto-temporal dementia. These cohorts offer a unique opportunity to study pre-symptomatic disease. Additionally I will study mild cognitive impairment (MCI) and subjects who have amnestic complaints but do have a sufficient memory deficit to fulfil criteria for MCI (which may represent a pre-MCI stage). This programme of research offers clinical as well as scientific opportunities in the dementias but should also have relevance to other disorders where precise and yet easily applicable measurements of cerebral changes are important.
Aims
Achieve earlier and more precise diagnosis in Alzheimer‘s disease (AD) and related disorders, including pre-clinical detection of disease; Improve understanding of the pathophysiological evolution of neurodegenerative diseases and the relationships between imaging and clinical manifestations; Measure disease progression, and assess its correlates and influences; Evaluate symptomatic and potentially disease-modifying therapies.