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

Alzheimer’s 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

Earlier Diagnosis of AD Earlier Diagnosis of AD

Resting-state fMRI: A Promising Resting-state fMRI: A Promising ToolTool

• 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?

Structure of Thalamus Structure of Thalamus

Pathway of ThalamusPathway of Thalamus

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

Thalamus in AD/MCIThalamus in AD/MCI

Whether the pattern of functional connectivity follows the disease

or disease severity?

Subjects and Clinical DataSubjects and Clinical Data

NC (n=26)MCI (n ＝

26)AD (n ＝

30)p-value

Gender (M/F) 16/10 13/13 10/20 0.104

Age (year) 69.2±6.6 73.9±8.1 72.4±8.5 0.09

MMSE 28.9±1.0 26.8±1.9 19.7±4.1 <0.001

AVLT-Immediate Recall 5.9±1.1 4.8±1.2 2.7±1.7 <0.001

AVLT-Delay Recall 5.8±2.0 3.1±2.0 0.8±1.3 <0.001

Design of The Study Design of The Study

Data preprocessing

statistical parametric

mapping software (SPM8)

Definition of the thalamus

WFU_PickAtlas tool

Results

Functional Connectivity Map of Functional Connectivity Map of ThalamusThalamus

Altered FC of Thalamus in AD Altered FC of Thalamus in AD

How about the MCI?

Strength of FC in NC, MCI and Strength of FC in NC, MCI and ADAD

●●

●

●●

Correlation between FC and Correlation between FC and MMSEMMSE

Correlation between FC and Correlation between FC and AVLT Immediate RecallAVLT Immediate Recall

Correlation between FC and Correlation between FC and AVLT Delayed RecallAVLT Delayed Recall

Discussion

Disrupted Thalamo-DMN in ADDisrupted 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

FC and Cognition of AD/MCIFC 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

Increased FC: Compensation?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?

MCI: A Transitional Stage MCI: A Transitional Stage

between NC and ADbetween 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

ConclusionConclusion

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

Future WorksFuture Works

• Combining fMRI with PIB-PET and genotype

• Pre-clinical stage

• FC of the thalamus

subdivision defined

by functional parcellation

in AD and MCI

AcknowledgementsAcknowledgements

• 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

Thanks for your attention !Thanks for your attention !