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)

RealNonreal 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 Scenes mean % correct Considered low risk Considered high risk Taylor et al (in preparation) Face Scene % Correct MCI AD Chance

Oddity judgement Lee et al (2006) 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 MCI Nestor et al (2003) Scene Memory Taylor et al (2007) Scene Oddity Lee 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)