Alzheimer s disease and the frontotemporal dementias: an integrated clinical neuroscience approach
Award Number
G9724461Programme
Research GrantStatus / Stage
CompletedDates
1 August 1998 -1 November 2008
Duration (calculated)
10 years 03 monthsFunder(s)
MRC (UKRI)Funding Amount
£2,137,086.00Funder/Grant study page
MRCContracted Centre
University of CambridgePrincipal Investigator
John R HodgesWHO Catergories
Understanding risk factorsUnderstanding Underlying Disease
Disease Type
Alzheimer's Disease (AD)Frontotemporal Demential (FTD)
CPEC Review Info
| Reference ID | 623 |
|---|---|
| Researcher | Reside Team |
| Published | 29/06/2023 |
Data
| Award Number | G9724461 |
|---|---|
| Status / Stage | Completed |
| Start Date | 19980801 |
| End Date | 20081101 |
| Duration (calculated) | 10 years 03 months |
| Funder/Grant study page | MRC |
| Contracted Centre | University of Cambridge |
| Funding Amount | £2,137,086.00 |
Abstract
This programme takes an integrated multidisciplinary approach to two important causes of dementia: Alzheimer?s disease (AD) and the frontotemporal dementias (FTD). It is based upon the following general principles: (1) applying theoretically-based models of cognition to the analysis of the dementias, (2) combining cross-sectional and longitudinal evaluation of cohorts of patients, (3) applying a common battery of tests to study a number of dementing illnesses, notably the early stages of AD, FTD and dementia with Lewy bodies, (4) developing clinically applicable diagnostic instruments based upon insights gained in the theoretical studies, (5) using converging methods of assessment, particularly clinical and radiological (both structural MRI and functional FDG-PET), (6) developing novel methods of image analysis with aid diagnosis and/or understanding of these disorder, (7) obtaining pathological confirmation of diagnosis to refine criteria (especially for FTD) and (8) relating in vivo clinical (neuropsychological and imaging) and quantitative neuropathological findings to gain insight into brain structure-function relationships.
The overarching aims of the programme are: (1) to improve the early diagnosis and differentiation of the primary degenerative dementias, particularly early stage AD and the FTD syndromes; (2) to understand the cognitive and behavioural changes which occur in the early stages of these disorders within the framework of contemporary cognitive models; and (3) to define the neuroanatomical and neuropathological bases of these disorders.
The new programme will capitalize on established strengths but also expand in scope by bringing together a team of researchers, each with specialised expertise, whose joint contributions will ensure progress in this area.
Plain English Summary
Dementia presents a huge burden on society, the health services (current cost #1 billion per annum) and the families of sufferers. This programme focuses on two major causes of dementia: Alzheimer’s disease (AD) and frontotemporal causes (FTD). AD is the commonest cause of dementia at all ages, yet despite major advances in understanding the neurobiology of the disease, we still know relatively little about its early course. With the advent of disease modifying drug treatments it is vitally important to improve the early detection of AD, particularly when patients present with memory complaints but do not yet meet criteria for dementia (so- called Mild Cognitive Impairment or MCI). We build upon the findings from our recent cognitive and brain imaging studies to refine the definition of this predementia stage of AD and to identify MCI subjects at high risk of conversion to AD. Another major goal is to understand more fully the biological basis of the cognitive deficits that occur at this early stage of AD using convergent neuropsychological, structural and functional imaging approaches.
Although rarer than AD, FTD is an important cause of early-onset dementia. As with AD, there have been major breakthroughs in understanding FTD with the discovery of mutations in the gene encoding for the brain protein tau in some familial cases. Unlike AD, however, there is considerable heterogeneity in the pathology of FTD with a number of distinct subtypes and in the clinical manifestations. The relationship between the pathological and clinical subtypes of FTD is unclear. Many patients with FTD present with changes in personality and behaviour which are difficult to detect and to quantify. We have already made considerable headway in developing tests which are more sensitive to the behavioural changes of FTD and have begun to define which regions of the brain are involved in vivo using structural (MRI) and functional (PET) brain imaging techniques. We plan to build upon these studies to develop more widely applicable tests for the accurate detection of FTD. Central to our approach is the longitudinal study of cohorts of patients with suspected FTD with subsequent post mortem confirmation of the pathological diagnosis so that existent diagnostic criteria can be validated and refined.