Brain Plasticity in Aging - The MacArthur Foundation Research

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Education and Cognitive
Functioning
Lars Nyberg
Umeå University
Sweden
Research on Aging at UmU
• Cross-faculty environment ”Aging and Living Conditions” (ALC)
• One of 10 national ”Linnaeus” centra funded by the Swedish Research Council
• Three main themes:
Ageing population
•Fertility
•Mortality
•Migration
•Biological
ageing
Participation
Interdisciplinary research
Linnaeus database
Conceptual
development
Successful ageing
•Health
•Cognition
•Economy
•Network
•Care
•Work
•Leisure
•Social
relations
•Society
•Image of
ageing
The Linnaeus Database
Statistics Sweden
register data
Inpatient and
death cause data
VIP
Västerbotten
county
Betula
Umeå
Geographical
extension
Sweden
Sweden
Västerbotten
county
Umeå
Number of
individuals
Total national
population
Total national
population
110 000
4200
Time coverage
1960 – 1990
1990 - 2005
1980s - 2006
1987, 19..
1988, 19..
Time resolution
5 year (60 -90)
Annual (90-05)
Continuous
Spatial
resolution
100 meter squares
Kind of
information
Socio-economic
Income
Family (links)
Work
Residence etc.
Hospital care
Death
Death cause
5 year
Health indicators
Life style
Living conditions
Socio-economic
Cognitive
function
Health
Socioeconomic
The Betula Study:
A prospective study of aging, memory & health
Sample
Wave 1
(1988-90)
Wave 2
(1993-95)
Wave 3
(1998-00)
Wave 4
(2003-05)
1
N=1000
35-80 yrs
N=862 (86%)
40-85 yrs
N=730 (85%)
45-90 yrs
609 (83%)
50-95 yrs
2
N=1000
35-80 yrs
N=684 (86%)
50-85 yrs
3
N=1000
40-85 yrs
N=829 (83%)
45-90 yrs
4
698 (84%)
50-95 yrs
N=600
35-90 yrs
Total of > 4200 participants
S5: 563
35-95 yrs
Two sessions
1. Health examination
- current & past health
- demographics
- subjective measures
- social variables
- critical life events
- personality
- genetics (APOE, COMT)
2. Cognitive testing
Cross-sectional analyses
N = 1959
• Episodic: significant decline already at age 45
• Semantic memory: significant decline after 55
Rönnlund et al (2005) Psych & Aging
Longitudinal analyses
Practice-adjusted data*
• Episodic: significant decline at age 80
• Semantic : significant decline at age 85
• Episodic: significant decline at age 65
• Semantic : significant decline at age 80
*P= D-A
Difference (D) = S1T2 – S2T2 = Attrition (A) + Practice (P)
A = S1T1 (returnees) – S1T1 (whole group);
Comparing longitudinal and
cross-sectional data
Cross-sectional data ≠ Practice-adjusted longitudinal data
Influence of cohort differences in education on cross-sectional data?
Education
Self-reported # years of formal education
Education-adjusted crosssectional data
Identical pattern as practice-adjusted longitudinal data
(significant decline in episodic memory 60-65 yrs)
Intermediate summary
Cohort differences in education account for
disparity between cross-sectional and
longitudinal trajectories across the adult
age span
-- control removes early onset of episodic
decline (35-60)
Substantial portion of the age-related
variance remained after controlling for
education in the 5 oldest cohorts
Variability in cognitive aging
Most studies consider group-averaged cognitive changes
-- less focus on distribution of individual scores =>
=> Some elderly with a high level of functioning are ”hidden”
Inspired by Rowe and Kahn (1987) we used Q-mode factor
analysis to identify usual and successful aging on basis of
longitudinal change in performance across cognitive and
non-cognitive variables (Habib, Nyberg & Nilsson, 2007).
--usual vs successful: based on performance levels at two test
sessions and change in levels across sessions
Sample composition
Middle age = 50-65 at T1; 55-70 at T2
Measures
Results
55 / 663 successful (8.3%)
25 / 403 successful (6.2%)
Variables defining usual vs.successful aging
Longitudinal analysis
51 of the 55 successful elderly at T1 were re-tested at T2
Of these 51, 18 (35%) were again classified as successful
352 of the 608 usual elderly at T1 were re-tested at T2
Of these 352, 345 (98%) were again classified as usual
-- 7 (2%) were classified as successful (”positive reversal”)
Predictors of success over time:
Successful-Successful (N=18) vs Successful-Usual (N=33)
• no difference on cognitive measures
• one difference on non-cognitive measures; education
(12.1 vs 9.6 years)
Neural correlates of success over time
(Persson et al., 2006, Cerebral Cortex)
Participants from the Betula Study
(selected from population of 1000 ss at T1)
’Memory’ defined by 3 episodic tests
Stable & Decline groups well matched (N=20/20):
• Age: 68.2 / 68.2
• MMSE: 28.25 / 28.35
• Female/male: 13/7 / 13/7
• Education: 10.1 / 10.7
2002-03: MRI/fMRI-session
fMRI – categorization task (abs/conc)
- left PFC activity for young adults (Wagner et al. 2000, Cer Cortex)
• Hippocampus volume
• Diffusion Tensor Imaging (DTI)
Group differences: brain structure
Hippocampal volume
Anterior white matter integrity
Functional changes
Categorization vs Rest
Overall analysis (N=40) revealed bilateral frontal activity
Both groups showed
typical left PFC activity
Atypical right frontal activity driven by declining elderly
-- compensatory response?
Fostering positive reversals:
Cognitive training
”Spontaneous” positive reversals rare (2%) => directed training
Several recent demonstrations that training can improve
performance on various executive tasks (e.g. working memory)
- transfer / generalization of learning more difficult to show
Present study: updating training
(Dahlin et al., 2008, Science;
Dahlin et al., 2009, Psychology & Aging)
Training of updating
FMRI I
LM
n-back
Stroop
L
WEEK 1
WEEK 2
WEEK 3
WEEK 4
WEEK 5
Time
FMRI II
LM
n-back
Stroop
3
V
M
1
4
Always memorize last 4 items
Variable list length — 5-15 items
Also ”keep track” task
Graded training (3 levels; all at level 3 at week 5)
Younger (15) and older adults in training group
Control group did fMRI I & II
Extensive transfer battery outside scanning
18-month maintenance test session
Behavioral findings: criterion task
Substantial training effect
in both groups
Significant long-term maintenance
Transfer
Speed
Working memory Episodic memory Semantic memory Reasoning
-letter fluence (FAS) -Raven’s
-digit symbol -computation span -recall of nouns
-digit span (F/B)
-paired associates -category fluency
-n-back (1/2/3)
Limited transfer effects
-no significant transfer for elderly group
-significant transfer to 3-back working memory of numbers for young
(transfer effect maintained after 18 months)
FMRI findings: young adults
Pre-training
-- fronto-parietal activity for all 3 tasks
-- striatal activity for LM & 3-back
Training-related changes
--no common fronto-parietal changes
--overlapping increase in striatum for LM & 3-back
(No significant training-related fMRI changes on Stroop)
FMRI findings: older adults
• Pronounced fronto-parietal activity during LM prior to training
• No significant striatal activation during LM prior to training
• Training-related striatal increase for LM (cf., younger adults)
• No training-related increase for 3-back
Variability within older group – those who showed transfer displayed striatal activation
Summary
• Substantial and durable training effects in
both groups
– Weak transfer effects
• More narrow view on process-region
overlap
– No support that a task-general fronto-parietal
system mediates transfer
– Support that transfer rests on shared process
(updating) and related striatal brain system
Concluding points
• Education – substantial influence on
”cognitive profile” across the adult life span
– Strong impact on slope for younger cohorts
• Education also explains some of the
heterogeneity among older adults
• Neural changes additional factor
– Hippocampus & striatum; ant. WM changes
• Functional compensation?
• Next step: Imaging at Betula T5
– Brain x education interactions?
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