Are spatial tasks useful for the early diagnosis of Alzheimer’s disease

Talk Overview

A bit about my research interests in the field of dementia

Current research on use of spatial measures for diagnosis of dementia

Ideas for extending this research over the next few years

Frontotemporal Dementia

Semantic dementia (progressive fluent aphasia)

Anomia, impaired comprehension & loss of semantic knowledge, progresses to mutism

Frontal variant FTD

Changes in personality and social behaviour (lack of emphathy, increased risk-taking, poor social understanding)

Semantic dementia

Organisation of semantic memory and its relationship to language, perception and episodic memory (study breakdown of conceptual knowledge)

Visual and verbal memory in semantic dementia, and implications for relearning of names and associated conceptual knowledge (Graham et al., 2001; 2002; Dewar et al., in press)

Colour knowledge in semantic dementia (Rogers et al., 2007)

Letter-by-letter reading in semantic dementia (Cumming et al., 2006)

Real Nonreal

NR > R

R > NR

Colour knowledge

Theoretical model

Alzheimer’s disease

Profiles of memory impairment in Alzheimer’s disease, and how to map cognitive impairments onto early brain changes; development of sensitive measures for early diagnosis

Impairment in episodic memory (Simons et al., 2000; Scahill et al., 2005)

Spatial memory and discrimination (Lee et al., 2006; 2007)

Multidimensional measures for early diagnosis (Dudas et al., 2005; Clague et al., 2005) - tests of people naming, position identification and recognition memory

Recognition Memory

0.25

0.40

0.55

0.70

0.85

1.00

Scenes

mean % correct

Considered low risk

Considered high risk

Taylor et al (in preparation)

40

50

60

70

80

90

100

Face Scene

% C

orr

ect

MCIAD

Chance

Oddity judgement

Lee et al (2006)

0.25

0.40

0.55

0.70

0.85

1.00

Faces Scenes

mean % correct

Semantic dementia

Alzheimer’s disease

Controls

Oddity judgement

Current Research (Study 1)

Testing the sensitivity of spatial tests of memory and discrimination in early diagnosis of Alzheimer’s disease (being able to tell apart worried well from at high risk)

In collaboration with Tony Bayer (Geriatric Medicine)

Involves identifying cases at an early stage of disease (MMSE 28-30)

Testing performance of these individuals on a standard neuropsychological battery, and then an experimental battery of spatial tasks

Longitudinal follow-up of individuals to determine the usefulness of the tests in the clinic

Current Research (Study 2)

Attempting to link the cognitive impairments seen early on in Alzheimer’s disease with early structural and functional brain changes using fMRI

Tony Bayer (Geriatric Medicine) and Derek Jones (CUBRIC)

Subset of the cases from Study 1 in two fMRI studies

Oddity judgement with a recognition memory component (faces, objects and scenes)

Semantic knowledge of famous people (sensitive early in AD, Thompson et al., 2002)

Obtain high quality structural data (diffusion tensor imaging - allows modeling of the integrity of white matter tracts) and measure BOLD signal in key brain regions implicated early in Alzheimer’s disease

Why is this interesting…??

Posterior cingulate involvement in MCI

Nestor et al (2003);Pengas et al (2008)

Parallels across imaging

FDG-PET in MCINestor et al (2003)

Scene MemoryTaylor et al (2007)

Scene OddityLee et al (2008)

Future plans

Neuroimaging and behavioural studies of the same tasks in individuals identifiable high risk of Alzheimer’s disease (ApoE, family history etc.), and in other types of dementia (semantic dementia)

Link this work to other potential biomarkers of early dementia (convergence and divergence) - genetic predispositions, proteins.

Better understanding variability in the normal aged population on these tasks: to gain a better feel for what is pathological or not.

Explore potential links between animal studies of AD and the clinical work (both neurosychology/neuroimaging); there is a real opportunity to test key new proposals about the genesis of pathology in AD in humans (posterior cingulate) in animals, with similar types of tasks

AD vs FvFTD

A. Graham, Hodges & K. Graham (unpublished data)