Impaired Thalamic Connectivity Pattern in Alzheimer

1
Impaired Thalamic Connectivity Pattern in
Alzheimers 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

• Alzheimers disease (AD)
• Irreversible, no effective therapy till now
• Heavy economic 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
NC (n26) MCI (n26) AD (n30) p-value
Gender (M/F) 16/10 13/13 10/20 0.104
Age (year) 69.26.6 73.98.1 72.48.5 0.09
MMSE 28.91.0 26.81.9 19.74.1 lt0.001
AVLT-Immediate Recall 5.91.1 4.81.2 2.71.7 lt0.001
AVLT-Delay Recall 5.82.0 3.12.0 0.81.3 lt0.001
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 of an altered FC 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
• MCIa transitional stage between NC AD
• FC a potential useful noninvasive probe for the
  earlier diagnosis of MCI AD

24
Future Works

• Combining fMRI with PIB-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 !