Auditory attention in the amnesia of Alzheimer's disease; and the response to a central cholinesterase inhibitor
Lead Research Organisation:
Imperial College London
Department Name: Dept of Medicine
Abstract
Alzheimer‘s disease (AD), the most common form of dementia, is typically associated with poor memory for recent information and events. However, early in its course the disease affects other mental processes, and these contribute to the difficulties with memory. Thus, for example, remembering what one has been told when there are additional conversations in the background requires the ability to pay attention to one speaker and not be distracted by the others. Attention depends on a specialised right brain system, one whose function may be improved by the current drugs licensed to modify the symptoms of AD. My study plans to use imaging techniques to study the effects of AD on the functional and anatomical integrity of the attention system, and compare these results with those from age-matched normal subjects. I will then study the effects of a drug used to treat AD on the imaging measures, and relate these to any changes in psychological tests of memory and attention. Importantly, my study will separate natural variability in imaging measures from those due to the influence of the drug. This study will further our understanding of the effects of AD on higher brain functions and their treatment.
Technical Summary
Aims and Objectives
My study will investigate whether impairment of the cortical system for attention contributes to poor verbal memory encoding and retrieval in Alzheimer‘s disease (AD).
Incorporated into the design is the investigation of the modulatory effect of galantamine, a central cholinesterase inhibitor (CChI), on attention.
Background
Explicit episodic memory encoding and recall are dependent on attention. AD is associated with impaired episodic memory, but attention and its executive control are impaired early in the course of the disease. The motivation for my study is based on the notion that episodic memory impairment in AD is in part the consequence of reduced attention; and that the benefit of CChIs in AD may be attributed in part to modulation of attention.
Design
I will determine the functional and anatomical integrity of the right fronto-parietal cortical components of attention in patients with mild AD, using magnetic resonance imaging (MRI) techniques. The imaging data will be correlated with behavioural measures of attention, memory and executive function.
Methodology
The study will comprise 50 patients and 25 age-matched normal subjects. The control subjects will be scanned once and the patients will be scanned twice, before and six weeks after they have been randomised to treatment or no treatment with galantamine. Inclusion criteria will include:
A clinical diagnosis of AD.
MMSE <28 and >20 and ACE-R <85.
Functional MR images will be obtained using standard echo-planar imaging sequences. The study design will investigate verbal memory encoding and retrieval with differing demands on selective and sustained attention. Anatomical imaging will consist of acquiring data suitable for DTI analysis. Image analysis will be performed with FSL and SPM software packages. Behavioural data will be acquired using CANTAB Alzheimer.
Scientific and Medical Opportunities
Major advances are being made in the application of symptom- and disease-modifying agents in AD. The ability to visualise, in vivo, the effects of these agents on brain networks, and the future potential to use the same techniques to study the reorganisation that may follow the initiation of disease-modifying drugs, is an important area of clinical neuroscience research. My study is designed to establish imaging biomarkers to investigate the interaction between attention and memory in AD, and its potential restoration with a licensed symptom-modifying agent. This research can, in future, be extended into an investigation of disease-modifying agents, and potential ‘cognitive restoration‘ after their use.
My study will investigate whether impairment of the cortical system for attention contributes to poor verbal memory encoding and retrieval in Alzheimer‘s disease (AD).
Incorporated into the design is the investigation of the modulatory effect of galantamine, a central cholinesterase inhibitor (CChI), on attention.
Background
Explicit episodic memory encoding and recall are dependent on attention. AD is associated with impaired episodic memory, but attention and its executive control are impaired early in the course of the disease. The motivation for my study is based on the notion that episodic memory impairment in AD is in part the consequence of reduced attention; and that the benefit of CChIs in AD may be attributed in part to modulation of attention.
Design
I will determine the functional and anatomical integrity of the right fronto-parietal cortical components of attention in patients with mild AD, using magnetic resonance imaging (MRI) techniques. The imaging data will be correlated with behavioural measures of attention, memory and executive function.
Methodology
The study will comprise 50 patients and 25 age-matched normal subjects. The control subjects will be scanned once and the patients will be scanned twice, before and six weeks after they have been randomised to treatment or no treatment with galantamine. Inclusion criteria will include:
A clinical diagnosis of AD.
MMSE <28 and >20 and ACE-R <85.
Functional MR images will be obtained using standard echo-planar imaging sequences. The study design will investigate verbal memory encoding and retrieval with differing demands on selective and sustained attention. Anatomical imaging will consist of acquiring data suitable for DTI analysis. Image analysis will be performed with FSL and SPM software packages. Behavioural data will be acquired using CANTAB Alzheimer.
Scientific and Medical Opportunities
Major advances are being made in the application of symptom- and disease-modifying agents in AD. The ability to visualise, in vivo, the effects of these agents on brain networks, and the future potential to use the same techniques to study the reorganisation that may follow the initiation of disease-modifying drugs, is an important area of clinical neuroscience research. My study is designed to establish imaging biomarkers to investigate the interaction between attention and memory in AD, and its potential restoration with a licensed symptom-modifying agent. This research can, in future, be extended into an investigation of disease-modifying agents, and potential ‘cognitive restoration‘ after their use.