NEUROBIOLOGY OF AGING
Aim: knowledge of, and insight into the biological processes that underlie aging of the brain and
peripheral nervous system. And the consequences of brain aging for the behavioral functions mediated
by the central nervous system.
Rule of thumb: the older you get, the more the brain has to work to do certain things
LECTURE 1. VAN DER ZEE. INTRODUCTION IN BRAIN AGING; LEARNING &
MEMORY
What is brain ageing? It is not possible to determine when someone belongs to the elderly as aging
goes so 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.
Healthy aging is important to understand the underlying mechanism, and to reduce morbidity
Mortality: death rate
Morbidity: disease rate
Comorbidity: the presence of one or more additional conditions co-occurring with a primary
condition
The age structure in the Netherlands and the gray wave; in 2040 >25% of the population is 65 or older
(now ca.15%). The life expectancy at birth is increasing, it is predicted to be increasing.
The role of the brain and cognition in aging: the older brain has not yet been given its own place in
science and society.
What is normal aging, and what is
pathological aging? Normal aging and
pathological aging viewed as continuum
without a clear turning point.
We all want, when we get older, to keep the cognitive
performance OK. We have a target area, some people
in older life seem to escape from the aging brain, this
has to do with healthy lifestyle and genetics.
Henny van Andel-Schipper died at the age of 115 years
due to a stomach cancer. Scientist hoped to show that
,her brain has not traces of Alzheimer’s or Parkinson. This
could establish for the first time that these are real diseases
and therefore no signs of aging. 60% of the elderly do not
develop Alzheimer’s or Parkinson.
Parkinson’s disease: Lewy bodies: deposition of the protein
alpha-synuclein. There needs to be a loss of > 60% of
dopaminergic cells to be leading to a physical problem.
Alzheimer’s disease: senile plaques and
neurofibrary tangles. Amyloid imaging
à many amyloid. Massive shrinkage in
the brain; pattern of the Braak stages.
The Snowdon Nun Study: healthy nuns despite plaque presence à If you talk to pathologists, there
are also people diagnosed with Alzheimer’s without the average numbers of plaques and tangles.
In the older brain the total amount of brain activity is reduced. This is not only in humans but also in
other mammals. The decrease in brain activity is in the conscious and unconscious. The greater part of
the brain is the unconscious. There are some calculations made; there are 11 million pieces of
information at any one time. The brain can only process 40 pieces of information at any one time.
There is a brain region tightly connected to personal identity. This is called the cingulate gyrus. This
area exists of several subregions. In females the region is somewhat larger. It is part of the limic system.
During aging, between the age of 20 and 80 years, the area reduces in volume with about 5,5%.
Anatomical features of brain aging:
With normal aging the ventricles
become larger, the white and grey
matter decrease. (5% of the grey matter
gets lost between 60 and 90 years). At
AD the ventricles are already enlarged
at the age of 60. There is more loss of
white matter, and at the age of 60 there
is already many loss of grey matter.
At the age of 60 and 90 there is more
variation in the data, this is because there is less data available, which leads to a greater variation
because you have less sample.
,The default network is a
network of brain regions
that are active when an
individual is not focused
on the outside world
while the brain is awake.
Other names are default
mode network, default
stat network and taks-
negative network. For older people it is harder to stay in the alert state, it takes
for them more energy to activate again. Therefore it is hareder to switch between
those two states.
There are a number of brain areas (dorso-lateral PFC, hippocampus, cerebellum)
that change as first and strongest with aging: do they have an intrinsic “problem”?
It fits a little bit toe the last in, first out principle. This can be used as a rule of
thumb, but is not always accurate in detail. The brain areas lasts developed contain the vulnerable
areas, forming the aging hotspots.
The ascending systems (input to the hotspots) also decrease during aging. The rate of aging:
noradrenalin = dopamine > acetylcholine > serotonin > noradrenaline & dopamine: this starts at young
adult; ca. 10% loss per 10 year.
Three general features that wher
shown in brain imaging studies. Those
are:
• PFC overactivation (notably the
dorsolateral prefrontal cortex):
At low cognitive load larger PFC
activation is seen in the elderly.
• Posterior à anterior shift: there is more activity in the anterior parts of the older brain. Two
cognitive tasks that each differ in difficulty (M and P). The less active the occipital acitivty is
the more activity there is in the prefrontal cortex
• Loss of lateralization: both hemispheres are very active, compared to only one side that is
active in only one side of the brain.
, LECTURE 2. VAN DER ZEE. LEARNING AND MEMORY; BRAIN TRAINING
Most common memory complains (later in life):
• Forgetting names
• Cannot find the right words
• Forgetting where you put your belongings
• Cannot reproduce text or conversations
• Forgetting planned actions
• Forgetting appointments
• Forget who said something, or where it
was read (source error)
If you look at memory systems, you have short-
term and long-term memory. The long term can be
divided in the declarative (explicit, about the facts)
and non-declarative (implicit).
What is going on during ageing? Do all cognitive
functions deteriorate with ageing? It is given that most of the cognitive functions do deteriorate when
we get old, this is especially due to the speed of information processing is going down. On the other
hand, the level of general knowledge is increasing.
If you look at the difference between implicit and explicit memory, you see that the in general the
older people outperform the younger people if it is a more implicit task. But when it is more explicit
the younger people perform better.
If we look at memory stages; direct memory
(seconds), working memory (seconds-hour), long-
term memory (hours-days-months), permanent long
term memory (months-lifelong). Those memory
stages can overlap, so you have parallel memory
stages. So if you want to study for example the
working memory, also the long term memory is
developing
If you look at the associated brain areas, the prefrontal cortex is mainly linked to the short term
memory, the long term memory uses the neocortex, striatum and cerebellum. Also the hippocampus
is used, but by both the short and long term. The hippocampus starts forming memories, and it is used
for the transformation of short to long term memory. The amygdala is the emotional component of
memory, it can act on the short and long term memory.
Aim: knowledge of, and insight into the biological processes that underlie aging of the brain and
peripheral nervous system. And the consequences of brain aging for the behavioral functions mediated
by the central nervous system.
Rule of thumb: the older you get, the more the brain has to work to do certain things
LECTURE 1. VAN DER ZEE. INTRODUCTION IN BRAIN AGING; LEARNING &
MEMORY
What is brain ageing? It is not possible to determine when someone belongs to the elderly as aging
goes so 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.
Healthy aging is important to understand the underlying mechanism, and to reduce morbidity
Mortality: death rate
Morbidity: disease rate
Comorbidity: the presence of one or more additional conditions co-occurring with a primary
condition
The age structure in the Netherlands and the gray wave; in 2040 >25% of the population is 65 or older
(now ca.15%). The life expectancy at birth is increasing, it is predicted to be increasing.
The role of the brain and cognition in aging: the older brain has not yet been given its own place in
science and society.
What is normal aging, and what is
pathological aging? Normal aging and
pathological aging viewed as continuum
without a clear turning point.
We all want, when we get older, to keep the cognitive
performance OK. We have a target area, some people
in older life seem to escape from the aging brain, this
has to do with healthy lifestyle and genetics.
Henny van Andel-Schipper died at the age of 115 years
due to a stomach cancer. Scientist hoped to show that
,her brain has not traces of Alzheimer’s or Parkinson. This
could establish for the first time that these are real diseases
and therefore no signs of aging. 60% of the elderly do not
develop Alzheimer’s or Parkinson.
Parkinson’s disease: Lewy bodies: deposition of the protein
alpha-synuclein. There needs to be a loss of > 60% of
dopaminergic cells to be leading to a physical problem.
Alzheimer’s disease: senile plaques and
neurofibrary tangles. Amyloid imaging
à many amyloid. Massive shrinkage in
the brain; pattern of the Braak stages.
The Snowdon Nun Study: healthy nuns despite plaque presence à If you talk to pathologists, there
are also people diagnosed with Alzheimer’s without the average numbers of plaques and tangles.
In the older brain the total amount of brain activity is reduced. This is not only in humans but also in
other mammals. The decrease in brain activity is in the conscious and unconscious. The greater part of
the brain is the unconscious. There are some calculations made; there are 11 million pieces of
information at any one time. The brain can only process 40 pieces of information at any one time.
There is a brain region tightly connected to personal identity. This is called the cingulate gyrus. This
area exists of several subregions. In females the region is somewhat larger. It is part of the limic system.
During aging, between the age of 20 and 80 years, the area reduces in volume with about 5,5%.
Anatomical features of brain aging:
With normal aging the ventricles
become larger, the white and grey
matter decrease. (5% of the grey matter
gets lost between 60 and 90 years). At
AD the ventricles are already enlarged
at the age of 60. There is more loss of
white matter, and at the age of 60 there
is already many loss of grey matter.
At the age of 60 and 90 there is more
variation in the data, this is because there is less data available, which leads to a greater variation
because you have less sample.
,The default network is a
network of brain regions
that are active when an
individual is not focused
on the outside world
while the brain is awake.
Other names are default
mode network, default
stat network and taks-
negative network. For older people it is harder to stay in the alert state, it takes
for them more energy to activate again. Therefore it is hareder to switch between
those two states.
There are a number of brain areas (dorso-lateral PFC, hippocampus, cerebellum)
that change as first and strongest with aging: do they have an intrinsic “problem”?
It fits a little bit toe the last in, first out principle. This can be used as a rule of
thumb, but is not always accurate in detail. The brain areas lasts developed contain the vulnerable
areas, forming the aging hotspots.
The ascending systems (input to the hotspots) also decrease during aging. The rate of aging:
noradrenalin = dopamine > acetylcholine > serotonin > noradrenaline & dopamine: this starts at young
adult; ca. 10% loss per 10 year.
Three general features that wher
shown in brain imaging studies. Those
are:
• PFC overactivation (notably the
dorsolateral prefrontal cortex):
At low cognitive load larger PFC
activation is seen in the elderly.
• Posterior à anterior shift: there is more activity in the anterior parts of the older brain. Two
cognitive tasks that each differ in difficulty (M and P). The less active the occipital acitivty is
the more activity there is in the prefrontal cortex
• Loss of lateralization: both hemispheres are very active, compared to only one side that is
active in only one side of the brain.
, LECTURE 2. VAN DER ZEE. LEARNING AND MEMORY; BRAIN TRAINING
Most common memory complains (later in life):
• Forgetting names
• Cannot find the right words
• Forgetting where you put your belongings
• Cannot reproduce text or conversations
• Forgetting planned actions
• Forgetting appointments
• Forget who said something, or where it
was read (source error)
If you look at memory systems, you have short-
term and long-term memory. The long term can be
divided in the declarative (explicit, about the facts)
and non-declarative (implicit).
What is going on during ageing? Do all cognitive
functions deteriorate with ageing? It is given that most of the cognitive functions do deteriorate when
we get old, this is especially due to the speed of information processing is going down. On the other
hand, the level of general knowledge is increasing.
If you look at the difference between implicit and explicit memory, you see that the in general the
older people outperform the younger people if it is a more implicit task. But when it is more explicit
the younger people perform better.
If we look at memory stages; direct memory
(seconds), working memory (seconds-hour), long-
term memory (hours-days-months), permanent long
term memory (months-lifelong). Those memory
stages can overlap, so you have parallel memory
stages. So if you want to study for example the
working memory, also the long term memory is
developing
If you look at the associated brain areas, the prefrontal cortex is mainly linked to the short term
memory, the long term memory uses the neocortex, striatum and cerebellum. Also the hippocampus
is used, but by both the short and long term. The hippocampus starts forming memories, and it is used
for the transformation of short to long term memory. The amygdala is the emotional component of
memory, it can act on the short and long term memory.
