1. 1/44 Early Detection Of Alzheimer’s Disease Based on Cortical Thickness Measurements Master’s Thesis Defence Morten Simoni Spjuth Flemming H Gravesen 27. June – 2006

2. 2/44 Discussion Pros Automatic Not biased by prior landmarks Observer independent Cons Difficult to evaluate Restricted to thickness analysis No prior knowledge Very few miss-registered (sulci  gyri) Similar results as the literature

3. 3/44 Group Models of Cortical Thickness - Thickness distribution for each point -A statistical representation of cortices -Spatial information retained -Enables group comparisons

4. 4/44 Average Representation of Cortical Thickness in Young and Healthy Subjects sulci: 2.44mm (std: 0.13) gyri: 3.12mm (std: 0.20) Von Economo (1929) Left

5. 5/44 Average Representation of Cortical Thickness in mild AD AD:

6. 6/44 Average Representation of Cortical Thickness in mild AD AD: Young and healthy:

7. 7/44 Group Differences Mild AD vs. Healthy age-matched Can the thickness differences be related to AD? Comparison to other studies: - Braak & Braak (1991) - O’Brien (2001) - Lerch et.al. (2004) - Thompson et.al. (2003) Lateral viewMedial view

8. 8/44 Feature reduction - Principal component analysis Feature selection - Separability measure Normalization - Mean thickness removed - Age-matched (atrophy in ageing) Classification of mild AD

9. 9/44 Results MMSE-score of AD patients: 23.3 (std: 2.6) Segmentation parameters Two additional young and healthy subjects Flemming

10. 10/44 Investigation of atrophy using PCA

11. 11/44 Perspectives Investigation of AD-progression: - Longitudinal study - Understanding of the disease - Linear/stepwise progression - Mapping treatment effects Other diseases causing cerebral atrophy: - Frontotemporal dementia - Huntington etc. Clinical use - Complementary to psychological testing

12. 12/44 Conclusion -Possible to detect AD at an early stage -Statistical model of cortical thickness -Developed method for inter subject comparison -Registration favouring thickness comparisons -Quantitative measure -Observer independent tool -In vivo -Investigation of cortical thickness differences