Impaired Thalamic Connectivity Pattern in Alzheimer’s Disease and Mild Cognitive Impairment

1. Impaired Thalamic Connectivity Pattern in Alzheimer’s Disease and Mild Cognitive Impairment Bo Zhou Department of Neurology, Institute of Geriatrics and Gerontology, Chinese PLA General Hospital, Beijing, China LIAMA Center for Computational Medicine, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China

2. Earlier Diagnosis of AD Alzheimer’s disease (AD） • Irreversible, no effective therapy till now • Heavyeconomic and social costs Mild cognitive impairment ( MCI ) • A transitional stage between normal cognition and AD ? • A prospective phase for effective intervention ? • Calling for earlier diagnosis and intervention

3. Resting-state fMRI: A Promising Tool • Keeping awake and closing eyes, not moving • No task, may suitable for clinical research of dementia • Functional connectivity（FC）based on Region of Interest • synchronized neural activity among brain regions • AD/MCI: decreased FC among hippocampus, medial frontal cortex, posterior cingulate cortex ——Default Mode Network (DMN)? • Other subcortical structure? eg. Thalamus?

4. Structure of Thalamus

5. Pathway of Thalamus

6. Thalamus in AD/MCI • An important signaling “relay” station • Processes and pass on information • Thalamo-cortical network:a critical loop for cognition-disrupted in AD & MCI by EEG /DTI • Resting-state FC of thalamus in AD/MCI: rare Disrupted Thalamo-DMN connection in MCI • No comparative study in AD/MCI on thalamus by rs-fMRI

7. Whether the pattern of functional connectivity follows the disease or disease severity?

8. Subjects and Clinical Data

9. Design of The Study Data preprocessing statistical parametric mapping software (SPM8) Definition of the thalamus WFU_PickAtlas tool

10. Results

11. Functional Connectivity Map of Thalamus

12. Altered FC of Thalamus in AD

13. How about the MCI?

14. Strength of FC in NC, MCI and AD ● ● ● ● ●

15. Correlation between FC and MMSE

16. Correlation between FC and AVLT Immediate Recall

17. Correlation between FC and AVLT Delayed Recall

18. Discussion

19. Disrupted Thalamo-DMN in AD • Post cingulate cortex, medial prefrontal cortex, hippocampus –default mode network–processing episodic memory -crucial for human cognitive function • Default mode network is susceptible to a-beta deposition-disrupted in AD & MCI

20. FC and Cognition of AD/MCI • Correlation of FC and clinical variables indicates that cognitive ability is significantly correlated with the FC index between thalamus and these regions • Disrupted thalamo-default mode network FC patterns may underlie the impaired cognitive ability of AD and MCI

21. Increased FC: Compensation? • ITG: visual working memory • MTG: semantic knowledge and verbal short-term memory • INS: social, affective and higher-order mental processes, working memory • Cerebellum: posterior lobe-working memory Increased FC: compensatory reallocation for episodic memory? Thalamus: enhanced modulation?

22. MCI: A Transitional Stage between NC and AD • FC strength of MCI: median of AD and NC • An explicit trend ofan alteredFC pattern that corresponds to disease progression • Provided new functional evidence that MCI is a transitional stage between the NC and early AD

23. Conclusion • FC between the thalamo-default mode network and the thalamo-cortical connectivity is significantly impaired in AD • FC index was significantly correlated with the clinical variables in MCI & AD • MCI：a transitional stage between NC & AD • FC: a potential useful noninvasive probe for the earlier diagnosis of MCI & AD

24. Future Works • Combining fMRI withPIB-PET and genotype • Pre-clinical stage • FC of the thalamus subdivision defined by functional parcellation in AD and MCI

25. Acknowledgements • Dr. Yong Liu • Prof. Xi Zhang • Prof. Luning Wang • Prof. Tianzi Jiang • Dr. Hengge Xie • Dr. Wei Wang • Cognitive Disorder Diagnosis Work Group of Chinese PLA General Hospital • NSFC 60831004, 30970770 • 973program, 2011CBA00408

26. Thanks for your attention !