Title: Impaired Thalamic Connectivity Pattern in Alzheimer
1Impaired Thalamic Connectivity Pattern in
Alzheimers Disease and Mild Cognitive Impairment
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
2Earlier 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
3Resting-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?
4Structure of Thalamus
5Pathway of Thalamus
6Thalamus 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
7Whether the pattern of functional connectivity
follows the disease or disease severity?
8Subjects 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
9Design of The Study
- Data preprocessing
- statistical parametric
- mapping software (SPM8)
- Definition of the thalamus
- WFU_PickAtlas tool
10Results
11Functional Connectivity Map of Thalamus
12Altered FC of Thalamus in AD
13How about the MCI?
14Strength of FC in NC, MCI and AD
?
?
?
?
?
15Correlation between FC and MMSE
16Correlation between FC and AVLT Immediate Recall
17Correlation between FC and AVLT Delayed Recall
18Discussion
19Disrupted 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
20FC 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
21Increased 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?
22MCI 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
23Conclusion
- 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
24Future Works
- Combining fMRI with PIB-PET and genotype
- Pre-clinical stage
- FC of the thalamus
- subdivision defined
- by functional parcellation
- in AD and MCI
25Acknowledgements
- 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
26Thanks for your attention !