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Complete Summary: Lectures and Modules
Complete summary of all lectures and modules given in the course Neurobiology of Ageing . Passed the course with a 9
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IntroductionJellyfish: can be considered to be immortal, because it can renew parts of its nerve network.
The nerve net of jellyfish can rejuvenate.
Antarctic sponges: 1550 years of age, even individuals found that are older.
Mammals: The Bowhead whale is 211 years old – this is known because spearheads were
found in the whales that were over 200 years old.
Arctica Icelandica: Ming: reaches almost 400 years. To determine the age, they had to
open the shell = death of Ming
Mollusk: more like a cluster of neurons; it is the starting point of the brain. This is of interest
because it tells us that neurons by itself can live that long. It is not possible to rejuvenate the
brain, but neurons can live very long despite the fact that they use much energy, action
potentials etc.
Oldest human being: we can reach the age of 120 years.
Neurons are either healthy, sick or dead and they can lay next to each other. There is no such
a thing as a healthy and a sick part of the brain: sick and healthy neurons lay next to each
other.
Dichotomy: healthy ageing and pathological ageing in the same brain region
Older people have a higher fold change – the lower the fold change, the more successful the
ageing. Large variation.
Functional consequences of brain-ageing in the fields of:
- Cognition > temporal lobe
- Motor skills > frontal lobe
If you want to age cognitively very well, this cannot go without good motor skills. There is a
clear connection between cognition and motor skills. These two functions are strongly
interconnected > develop jointly the brain + age jointly.
A decline in cognition therefore will also mean a decline in motor performance.
There is a correlation between children that never redo a school year and do much sports/are
sports talents
Daily physical activities and high quality physical education in the age of 5-10 years ensures a
lot of aspects to healthy ageing: - Fitter children and less overweight
- Better motoric skills, more participation in sports
- Positive effects on executive functions, memory and behaviour
- Better performance in maths and language skills
For performing a movement not only brain areas primary involved in the implementation of
the movement, but also those involved in the goal/consequence of the movement.
Ageing means the ageing brain has to work harder and harder to keep up – this is comparable
to a concussion. After mild damage, more brain activity is needed to reach the same
(cognitive) outcome. Old individuals that are able to activate their brain very hard, are the
ones that age successfully.
Lecture 1. Introduction brain ageing: learning and memory
General vision about ageing: it is not possible to determine when someone belongs to the
elderly as ageing goes slowly, and these changes per individual differ greatly. The boundary is
often drawn based on biological age and not on the basis of physical fitness and resilience.
Mortality: Death rate. The number of deaths per 1000 inhabitants over a period of time
Morbidity: Disease rate. Ratio of the number of sufferers of a particular disease to the entire
community within a given time period.
Comorbidity: Presence of one or more additional conditions co-occurring with a primary
condition, e.g. Alzheimer’s.
,“Grey wave”: in 2040, more than 25% of
the population will be 65 or older in the
Netherlands. Life expectancy of people is
increasing.
The older brain has not yet been given its
own status > know about the adult brain
and dementia, but what about the older,
vital brain. Normal ageing and pathological
ageing are viewed as a continuum without
a clear turning point. In reality: you can
have a steady brain condition and nothing
is changing much, but than suddenly it
drops and you can have a temporary dip
(due to illness, or an accident). You can
recover from that: so it is not a gradual process, but it goes with ups and downs and a lot
of periods of stable conditions.
Dips can be caused by massive increase in neuroinflammation; an event that is really
damaging your brain. Can recover entirely or partly from this – overall, the brain reduces
permanently.
If you get older, if we look at cognition, than we would like to keep this “OK”. Whatever
function is talked about, everything is wanted to still work reasonably well.
Target area – cognitive performance is OK – still good enough to handle the society and do
not need much help.
Special ones – old people that are sharp minded.
Society is still struggling with the difference between ageing and neurodegenerative diseases.
Henny van Andel-Schipper: died at the age of 115 years old. Scientists analysed her brain
post-mortem. She was still very sharp, although she was 115. She hardly had any features
from Alzheimer’s or Parkinson’s disease in her brain. This could establish for the first time that
these diseases are real diseases, and no signs of ageing.
Alzheimer’s and Parkinson’s disease are clear examples of pathology.
Parkinson’s disease > +- 60% loss of dopaminergic cells > physical problems
With a loss of less than 60% no signs of the condition can be seen; the brain can still
compensate
Within a dopaminergic cell sits a brown granule filled with dopamine > Parkinson’s has a
structure within the granule that should not be there > Lewy body: deposits of the protein
alpha synuclein
Alzheimer’s disease: Amyloid plaques (B-amyloid which is cut in the wrong way – not
functional) and neurofibrillary tangles (TAU proteins)
Massive shrinkage in the brain – Pattern of the Braak stages – 60-70% of AD patients do have
this – others do not fit very well in the model
Snowdon nun study: healthy nuns despite plaque presence – only plaques does not make
Alzheimer’s. There are also people diagnosed with AD without above average numbers of
plaques and tangles. In biology, always exceptions.
Hendrikje van Andel: Brain was in Braak Stage ll: however, she had no signs of dementia
Total amount of brain activity has reduced in the older brain.
In the brain, only a small part of the activity is conscious, A way bigger part is unconscious.
The brain activity, both conscious and unconscious, declines in total amount in the older
brain.
The brain can only process 40% in a conscious way, a lot of the information reaching the brain
is processed unconsciously.
,The Cingulate Gyrus: brain region that is connected to personal identity. This area reduces
between the age of 20-80 years, in volume with about 5.5%.
- Several subregions
- Larger in females compared to males
- Is part of the limbic system: the system involved in emotions (As hippocampus,
amygdala, hypothalamus)
Anatomical features of brain ageing
Normal ageing: ventricles become larger,
white and grey matter reduce.
5% of the grey matter (neurons etc.) get
lost between 60 and 90 years of age.
Alzheimer’s disease: ventricles at 60 are
already enlarged, and much more enlarged
compared to normal ageing. Because you
have a lot of tissue, the ventricles are under
pressure and will take over the space that
comes available.
At the age of 60, patients with AD already have a lot of loss of grey matter
Also white matter declines more in AD than in normal ageing.
sMCI: Mild cognitive impairment: MCI is nicely inbetween normal ageing and AD. More
variation can be seen at the age of 60/65 and around 90 > because more brains and more
data available at the ages of 70-80. With less samples, you always have a larger variation.
The default modus: network of brain regions that is active when the individual is not
focussed. Especially active when a person’s not focussed on the outside world, when you are
awake.
Brain activity balances between cognitive performance and rest (default mode) – ageing shifts
more to the default mode than to cognitive performance.
Default mode is a good and potential beneficial thing – for resting the brain
When a person’s alert, other brain regions play a role: visual cortex, prefrontal cortex, motor
areas and hippocampus and the sensory systems.
Older people stay longer in the default mode and it takes more energy and time to switch for
them from the default mode to the cognitive performance.
Ageing hotspots in the brain – first and strongest changes with ageing:
- Hippocampus (dentate gyrus)
- Cerebellum (Purkinje cells)
- Dorsolateral PCF = executive functions: planning, impulse-inhibition, working memory
Brain regions fully
developed are also more sensitive for ageing.
The last in, first out principle: the brain areas that developed latest, contain the
vulnerable areas forming the ageing hotspots.
The ascending systems (input to the hotspots): Acetylcholine, Serotonin, Dopamine,
Noradrenaline. These cell systems are deeper into the brain and they send signals to the
cortex.
Rate of ageing: Noradrenaline = dopamine, but these two age faster than acetylcholine and
these three age faster than the serotonin.
Noradrenaline and dopamine: start at young adult: can lose up to 10% of these systems per
10 years. If these systems deteriorate, this will have dramatic effects throughout the brain.
Three general features of ageing
1. PFC overactivation (dorsolateral)
- At low cognitive load > larger PFC activation is seen in the elderly
- Slightly higher > much larger PFC activation in the elderly
- High cognitive load > much less PFC activation in the elderly
2. Shift from posterior > anterior brain activity
, More activity in the anterior parts and less in the posterior parts of the older brain
Occipital = posterior vs frontal = anterior
3. Loss of lateralization
Typically seen in young: certain tasks can mostly been done by one hemisphere.
In the old brain, the peak activity is lower > also not unilateral anymore =
bilateral
Loss clear lateralization – the brain tries to compensate.
Cognitive ageing: if you age cognitively successful, then especially, only the people that
show these features named above manage to cope with the tasks. In the beginning people
though this was an expression of the old brain not working well anymore, but there are indeed
changes in the brain and this is the way the brain compensates.
However, if the brain gives up, people cannot cope or master the tasks anymore and the
features cannot be seen anymore.
So, successful cognitive ageing = especially those elderly people who have PFC
overactivation, posterior-anterior shift and loss of lateralization.
Lecture 2. Learning and memory: brain training
Declarative memory (explicit)
Episodic or semantic – facts = Medio temporal lobe
Non-declarative memory (implicit)
Procedural = Basal Ganglia
Priming = Neocortex
Conditioning = Skeletal muscles = Cerebellum
= Emotional response = Amygdala
The speed of information processing and memory goes down with age – the general
knowledge goes up with age.
Sometimes compensate with the loss of speed of information processing
Difference between implicit and explicit memory
Implicit knowledge – Higher cognitive performance by elderly. The more explicit the task, the
worse the cognitive performance of the elderly is. Because with the explicit tasks, a speedy
brain is needed and then the young people will
outcompete the older people.
The different memory stages; memory phases
overlap and can go parallel.
Already during working memory sessions, when it
is longer than seconds, than also in parallel already
long term memory processes are starting up and
they overlap. So not boxes in which memory stage
you are, because the stages namely do overlap.
- long term memory
- permanent long-term memory
- STM + working memory does not require
protein synthesis
- LTM needs protein synthesis to strengthen the synapses.
Associated brain areas
Prefrontal cortex: short-term memory
Neocortex, Striatum, Cerebellum: long-term memory
Hippocampus: the starting point of making new memories and the brain region that is highly
engaged in transforming short-term memory to long-term memory.
Amygdala: the emotional component of memory, can influence both short and long term
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