Cognitive Stimulation in Older Adults

Ian Robertson
Trinity College Dublin
I
Can you see anything?
Can you see anything?
Can you see anything?
 BRAIN CELLS
THAT FIRE
TOGETHER,
WIRE
TOGETHER
7.45
Metronome beats (60/min)
 TMS: Cortical Motor Output Mapping

1 cm

1 mV
Anterior
20 ms
 Changes in Cortical Motor Output Maps

5 cm

5 cm Cz
Probability (%)
S 20 60 100

Day 1 Day 2 Day 3 Day 4 Day 5

Changes in Cortical Motor Output Maps

Physical Practice

Mental Practice
Economic and Social Inequalities Across the World are Strongly
Determined by Inequities of Brain Function

Economic, neurobiological, and behavioral perspectives

on building Americas future workforce

Eric I. Knudsen et al 2006

Proceedings of the National Academy of Sciences 103, 10155.

These Brain Inequalities are partly due to poor
stimulation of the brain in early life due to the
social, economic and educational inequalities

Brain Structure density of connections between brain

cells is predicted by number of years of education
Jacobs and Scheibel, J Comp Neurol 1993
 and can be partly reversed by early
interventions
 Mean IQ scores as a function of age for intervention and control groups in the Perry
Preschool and Abecedarian Programs

Knudsen E. I. et.al. PNAS 2006;103:10155-10162

2006 by National Academy of Sciences

 Academic, economic, and social outcomes for the Perry Preschool and Abecedarian
Programs

Knudsen E. I. et.al. PNAS 2006;103:10155-10162

2006 by National Academy of Sciences

But this is not just true for
children.
Learning to Juggle Over 3 months increases
grey cortical matter

V5/hMT bilaterally; left inferior

intraparietal sulcus
Draganski B, Gaser C, Busch V, Schuierer
G, Bogdahn U, May A. Neuroplasticity:
Changes in grey matter induced by training.
Nature 2004; 427: 311-312
and mentally and socially engaged
old people succumb less to dementia..

Verghese et al NEJM 2003, 348.

Leisure Activities and the Risk of Dementia in the
Elderly
469 subjects older than 75 years of age who resided in
the community and did not have dementia at base line.
5 year follow up

14

12

10

8
No Dementia
6 Dementia

0
Bennet et al, Lancet Neurology Cognitive Physical
 And Brain Training for Healthy Elderly
Delays Cognitive Decline

Long-term Effects of Cognitive Training on Everyday Functional Outcomes in

Older Adults
Willis et al, Journal of the American Medical Association 2007
 Basak et al (2008) , Psychology and Aging
23.5 hours of Rise of Nations versus control
Playing an Action Video Game Reduces Gender Differences in Spatial Cognition
Jing Feng, Ian Spence, and Jay Pratt (2007)
Medal of Honor

Psychological Science
 These Brain Inequalities Arising from Early and
Continuing Social and Economic Inequalities
Greatly Increase Dementia Levels as these People Age:
Less Education - More Dementia

Gatz et al, Physiology and Behaviour, 2007

These education effects on dementia rates are NOT
caused by genetic or racial factors
(Identical Twin Study, Sweden)

Gatz et al, Physiology and Behaviour, 2007

What can we do?
 Ozlaran et al, Neurology, 2004

* Patients in the CMI group maintained cognitive status at month 6, whereas

patients in the control group had significantly declined at that time.

Cognitive response was higher in the patients with fewer years of

formal education

Olazaran, J. et al. Neurology 2004;63:2348-2353

 MMSE
ADAS-COG

Remote, computer-delivered mental stimulation

Tarraga et al JNNP 2006

24-week, single-blind, randomised pilot study conducted on 46 mildly

impaired patients suspected of having Alzheimers disease receiving stable
treatment with cholinesterase inhibitors (MMSE average 20-22)
 Obstacles
1. Equity of access the Matthew Effect to him that hath shall be
given the economically deprived do not have equal access to the tiny
amount of brain stimulation methods.
2. Bottleneck in Delivery current labour-intensive methods inadequate
to deal with forthcoming pandemic and will only reach privileged few.
3. Inadequate Doses Current methods deliver largely homeopathic-
level doses of brain stimulation
4. Largely Primitive Technologies Current methods not based on
latest neural engineering
5. Not embedded in neuroscience Current methods not embedded
in understanding of neuroscience and so cannot be combined with latest
pharmacological approaches.
6. Not embedded in culture Current methods not culturally flexible
7. No healthcare delivery models
THEORETICALLY-BASED
COGNITIVE TRAINING

So that it can be aligned with pharmaceutical and other types of

intervention.
Vigilant Attention
 Why Vigilant Attention is Important
Attention Gates 9

experience dependent 8
7

plasticity (Rencanzone and Pegs in 2 min

6
5
Impaired
Merzenich) 4
3
Normal

2
Vigilant Attention deficits 1
0

predict motor recovery 2 month 2 year

after RH stroke (Robertson et

al 1997)
40

Vigilant Attention deficits 35

predict everyday problems

Everyday attention failures

30

rated by relatives of TBI 25

20

VA predictes everyday 15

attention failures in normal 10

-2 0 2 4 6 8 10 12 14 16

adults (Bellgrove, Errors of Commission on SART

Robertson et al 2005)
 DBH Noradrenergic Gene
Predicts Vigilant Attention
Performance
Vigilant attention
performance
!

(SART) in health
"

normals
#

predicted by $

DBH gene %

doseage &

'

#"# #"! !"!

(Greene, Gill $%&'()*+,-.)

and Robertson,
Right Dorsolateral Prefrontal and Right Parietal Regions
strongly linked to sustained attention

Activations associated
with fixed SART (Manly,
Robertson et al 2003)

Paus et al (1997)
Continuous performance
task right fronto-parietal
regions principally
involved.
 Self-alert training

OConnell et al Neuropsychologia, in press

 Self-alert training

OConnell et al Neuropsychologia, 2008

 Memory
Nyberg et al, 2003
a) Brain regions showing
increased activity during loci
acquisition relative to baseline:
lateral and medial parietal
cortex and the right dorsal
frontal cortex (32, 6, 58).
(b) Regions where brain
activity increased as a function
of loci acquisition (late > early).
Significant learning-related
changes near left
hippocampus
(c) Rate of acquisition of the
loci structure as a function of
group.
 Nyberg et al PNAS
Method of loci
improved memory for
list of words in young
and some old
Nyberg et al
(a) Brain regions showing
increased activity during loci
use relative to pretest - left
occipito-parietal cortex and left
dorsal frontal cortex (-38, 6,
48).
(b) Group differences in the
comparison of loci use with
pretest. The young but not the
unimproved old, activated the
left occipito-parietal cortex.
(c) Age differences in the
comparison of loci use with
pretest. The young but not the
old subjects activated the left
dorsal frontal cortex (-16, 28,
58).
 Kirchhoff BA, Buckner RL. Functional-
Anatomic Correlates of Individual
Differences in Memory. Neuron 2006; 51:
263-274.
 Participants' verbal
elaboration and
visual inspection
strategy scores
were positively
correlated with
their memory
performance.
J. Logan, A. Sanders, A. Snyder, J. Morris, R. Buckner Under-Recruitment
and Nonselective Recruitment: Dissociable Neural Mechanisms
Associated with Aging. Neuron, Volume 33, Issue 5, Pages 827-840

Figure 5. Individuals' Regional Brain Activity during Intentional Encoding Was Correlated with
Their Subsequent Memory Performance
Participants' brain activity during intentional encoding in the left BA 45/47 a priori region of interest
associated with use of the verbal elaboration strategy was significantly correlated with their
subsequent memory performance.
Logan et al, Neuron
left BA 45/47
previously associated
with verbal
elaboration encoding
strategy
brain activity during
intentional encoding
significantly
correlated with their
subsequent memory
performance.
Working memory
 Fig. 1. Schematic drawing of the WM task performed during scanning. Each cue (filled circle) was presented for 900 ms,
with 500 ms between cues. The subjects were asked to remember the location, as well as the order in which the cues were
presented. After presentation of the last cue a 1000 ms delay ensued, followed by the presentation of the probe for
2000 ms and a 1000 ms inter-trial interval. The probe was a unfilled circle with a number (15) in the middle of it. The
subjects should judge whether the probe was in the same location as any of the five cues, and if so, whether the number
within the probe corresponded to the serial position of that cue. Only if both location and order matched the subject
pressed their index finger to indicate yes, otherwise they pressed the middle finger to indicate no.

Changes in cortical activity after training of working memory

a single-subject analysis
Helena Westerberga and Torkel Klingberg Physiology & Behavior
Volume 92, Issues 1-2, September 2007, Pages 186-192
 Nature Neuroscience 7, 75 - 79 (2003)
Increased prefrontal and parietal activity after training of
working memory Olesen, Helena Westerberg & Torkel Klingberg

Regions where brain activity correlated with increased

working memory capacity (Experiment 2;
Improving fluid intelligence with
training
on working memory

Jaeggi et all
PNAS 2008
Changes in Cortical Dopamine D1
Receptor Binding Associated with
Cognitive Training

McNab et al 2009 Science.

Working memory depends on dopamine.

Training of working memory, which

improves working memory capacity, is
associated with changes in the density of
cortical dopamine D1 receptors.

Fourteen hours of training over 5 weeks

was associated with changes in both
prefrontal and parietal D1 binding potential.

This plasticity of the dopamine D1 receptor

system demonstrates a reciprocal interplay
between mental activity and brain
biochemistry in vivo.