1. Neuroimaging Markers of Cognitive Reserve and Brain Aging
Lihong Wang
Department of Psychiatry
09/05/2018

2. Overview Neural Compensatory Activation & Cognitive Reserve
Semi-quantitative Measure of Neural Compensation
Physical Exercise & Neural Compensatory Activation
Future Directions

3. Cognitive Aging
Park et al, Psychol Aging, 2002; Dialogues Clin Neurosci. 2013

4. Structural Changes across Life Span
Sowell et al, Nat Neurosci, 2003

5. Over-Activation in Older Adults
HAROLD (hemispheric asymmetry reduction in older adults) model – Cabeza, 2002

6. Compensatory or Deficiency
Rossi, et al, J Neurosci,2005
Cabeza, NeuroImage, 2002

7. Task demands Brain Activation Compensation Successful Compensation
Failure
Brain Activation
Older
Younger

8. (Compensation-Related Utilization of Neural Circuits)
The CRUNCH model
(Compensation-Related Utilization of Neural Circuits)
Mattay, et al. Neurosci Lett 2006

9. Reserve Capaticy Cognitive Reserve Brain Function Reserve
Brain Reserve
Brain Structures
Stern Y, Neuropsychologia. 2009; Lancet Neurol. 2012

11. Quantitative Measure of Cognitive Reserve -Decomposing Episodic Memory Variance
 Residual Variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes)
x1: education, sex
x2: gray matter volume, hippocampus volume, WMH
Reed B.R., et al, 2010
High Residual Reserve ∞ higher reading ability, lower likelihood of MCI, lower odds of dementia conversion independent of age, and less decline in language abilities over 3 years
Zahodne, et al, J Int Neuropsychol Soc, 2014

12. Network-based Neural Compensation Model
Compensatory Networks
Aging/Neurodegeneration

13. Participants: healthy older adults > 60 yrs N=26
Neuropsych test
MMSE
HVLT-R
Immediate and Delayed Story Recall
WAIS-III Digital symbol
Trail Making Test
Stoop test
Mood State
POM
Gait Speed
6MWT

14. Cognitively Challenging Task
Involved whole brain – attentional working memory
Ji et al. Front. Aging Neurosci., 2018 

15. Task Activations Encoding Retrieval
Involved whole brain – attentional working memory

16. Correlations to the hemodynamic response the task design
Neural Networks – Independent Component Analysis (ICA)
Spatial ICA
15 components
26 subjects
Correlations to the hemodynamic response the task design
Networks’ time courses showing significant correlations to task design (p<0.001) were counted as task-related networks
Number of activated networks of each subject
Activation rate of each network
ICA – count the network

17. Validation of Threshold

18. Compensatory Capacity
Why we want to control the core networks volume
Compensatory capacity was defined as the number of activated networks in the challenging task controlled with core networks’ volume.

19. Compensatory Capacity & Cognitive Reserve
x1: education, sex
x2: gray matter volume, hippocampus volume
Reed B.R., et al, 2010
1.5
Good Performance
Poor Performance
25-50% 1
50-75%
More
Network
0.5
Cognitive Reserve
Only one for quantitative to cognitive reserve
Fewer
Network
-0.5 -1
Fewer
Network
More
Network

20. Working Memory 6 MWT Compensatory capacity Compensatory capacity 21 1713 9 5 -3 -2 -1 1 2
r16= 0.528, p=0.035
700
300
500
100 -2 2
6 MWT
r16= 0.660, p=0.015
Compensatory capacity
Only one for quantitative to cognitive reserve

21. The Effect of Physical Exercise on Neural Compensation

22. Participants: healthy older adults > 60 yrs N=25
Dance training
First T1/fmri scan
Second T1/fmri scan
Output measures
Cognition
Gait speed
Mood state
Week0
Week6
Ji et al. Int J. Geriatric Psychiatry, 2018

23. Memory function

24. Physical Exercise Increases Gait Speed, Memory, and Cognitive Reserve in Older Adults
Motor Cortices
Cerebellum
Memory function
Gait Speed
X-box
Pre-exercise
Post-exercise
0.35
0.65
0.76
0.94
Activated ratio of motor cortices
Activated ratio of cerebellum
J Int Geriatric Psychiatry, 2018 13 12 11 10 9 8 7 6 5
Pre-exercise
Post-exercise
Logical Memory
Individual subject
Average

25. Summary
We proposed a new data-driven measure for neural compensatory capacity using a highly cognitive-demanding task and a brain network-based approach.
We demonstrated that our neural compensatory capacity measure is correlated with cognitive function as well as gait speed.
We also demonstrated that physical exercise may improve cognitive function through increasing neural compensatory capacity in older adults.

26. Motor System with Cognition & Aging

27. Ji et al. Front Aging Neurosci. 2017

28. Exercise Improved Executive Function and Memory

29. Structural MRI Results

30. Resting-State ALFF
ALFF change in Striatum / Caudate/Insula

31. Resting-State ReHo ReHo change in PCC / Precuneus
ReHo change in Caudate/Thalamus

32. Functional Connectivity

33. Functional Connectivity

34. Correlation with Cognitive Improvement

35. Index of Aging
44-73 years

36. Index of Aging Predicted Age Random Forest Analysis Actual Age (years)
The correlation of predicted age based on these imaging data and actual age was 0.92 in the training set, and was 0.72 in the test set.
Unpublished data

37. Index of Aging

38. Future Directions
Validate our neural compensatory capacity measure in MCI, AD, and late-life depression
Refine index of aging- combines Random Forest imputation and LASSO
Clarifying the relationship between sensorimotor network with cognitive function

39. Resource of Attention Bias (RAB)
RAB= FC (RAI-RDLPFC) + FC (RAI-PCC)
RAB (Post-Pre Math)
RAB (ATD – Control)

40. Stress level_ 24months RAB RAB r40=0.41, p=0.007 r34=0.35, p=0.039
Unpublished data

41. Acknowledgement Tsinghua University UCHC ONRC/IOL Lanxin Ji
David Steffens
Godfrey Pearlson
Xue Zhang
Kevin Manning
Keith Hawkins
Hua Guo
NSFC
1R01MH A1

42. Thank you for your attention!!!