1
BRAIN AGEING
As a person gets older, changes occur in all parts of the body, including the brain. Certain parts
of the brain shrink, especially those important to learning and other complex mental activities
The effects of ageing on the brain and cognition are widespread and have multiple aetiologies.
Ageing has its effects on the molecules, cells, vasculature, gross morphology, and cognition. As
we age our brains shrink in volume, particularly in the frontal cortex. As our vasculature ages
and our blood pressure rises the possibility of stroke and ischaemia increases and our white
matter develops lesions. Memory decline also occurs with ageing and brain activation becomes
more bilateral for memory tasks. This may be an attempt to compensate and recruit additional
networks or because specific areas are no longer easily accessed. Genetics, neurotransmitters,
hormones, and experience all have a part to play in brain ageing. But, it is not all negative,
higher levels of education or occupational attainment may act as a protective factor. Also
protective are a healthy diet, low to moderate alcohol intake, and regular exercise. Biological
ageing is not tied absolutely to chronological ageing and it may be possible to slow biological
ageing and even reduce the possibility of suffering from age related diseases such as dementia.
Physical changes
It has been widely found that the volume of the brain and/or its weight declines with age at a
rate of around 5% per decade after age 401 with the actual rate of decline possibly increasing
with age particularly over age 70.2 The manner in which this occurs is less clear. The shrinking
of the grey matter is frequently reported to stem from neuronal cell death3,4,5 but whether this
is solely responsible or even the primary finding is not entirely clear.6 It has been suggested that
a decline in neuronal volume rather than number contributes to the changes in an ageing brain
and that it may be related to sex with different areas most affected in men and women.7
1
, 2
Additionly, there may be changes in dentritic arbour, spines, and synapses. Dendritic sprouting
may occur thus maintaining a similar number of synapses5 and compensating for any cell
death.4 Conversely a decrease in dendritic synapses or loss of synaptic plasticity has also been
described.8 Functional organisational change may occur and compensate in a similar way to
that found in patients after recovery from moderate traumatic brain injury.9 However research in
the latter area suffers from small numbers of cases. The role of white matter in the ageing brain
also needs to be considered.3 White matter may decline with age, the myelin sheath
deteriorating after around the age of 40 even in normal ageing and it has been suggested that
the late myelinating regions of the frontal lobes are most affected by white matter lesions
(WML)10,11,12) although not all studies support this view.13 Leukoariosis/WML increase with
age and may indicate subclinical ischaemia. They will be discussed in more detail below.
Brain changes do not occur to the same extent in all brain regions.6 That these brain changes
are not uniform is supported by a longitudinal study, using two MRI scans separated by around
one or two years,2 and by a review of cross sectional studies. The latter included only those
studies that compared younger (aged less than 30) and older (greater than 60) groups to
compare wider age ranges and in contrast with much of the other work in this area. The review
looked at volume and found that the prefrontal cortex was the most affected. The striatum came
second with the analysis including over seven studies. The temporal lobe, cerebellar vermis,
cerebellar hemispheres, and hippocampus also reduced volume with between 8 and 18 studies
and the prefrontal white matter also showed a reduction (five studies). The occipital cortex was
the least affected (five studies).3 The finding that the prefrontal cortex is most affected and the
occipital least, fits well with the cognitive changes seen in ageing, although some studies also
suggest that ageing has the greatest effect in the hippocampus.4,8 Men and women may also
differ with frontal and temporal lobes most affected in men compared with the hippocampus and
parietal lobes in women.7,14 Finally the rate of reduction in brain volume may increase with age
particularly over 70 although numbers studied are very small.2 Because of the individual
differences seen in brain development and ageing15 mapping structure to function and change
because of ageing is a complex task,16 however there are studies that show links between
volume and neuropsychological function. A study looking at cortical volume and white matter
hyperintensity volume in 140 people aged 50 to 81 years pre‐screened for dementia and
depression, found an association between increasing age, a reduction in prefrontal cortical
volume, increased subcortical white matter lesions, and an increase in perseverative behaviour
(decreased executive function).17
Cognitive change
The most widely seen cognitive change associated with ageing is that of memory. Memory
function can be broadly divided into four sections, episodic memory, semantic memory,
procedural memory, and working memory.18 The first two of these are most important with
regard to ageing. Episodic memory is defined as “a form of memory in which information is
stored with ‘mental tags', about where, when and how the information was picked up”.19 An
example of an episodic memory would be a memory of your first day at school, the important
meeting you attended last week, or the lesson where you learnt that Paris is the capital of
France. Episodic memory performance is thought to decline from middle age onwards. This is
particularly true for recall in normal ageing and less so for recognition.20 It is also a
characteristic of the memory loss seen in Alzheimer's disease (AD).18
Semantic memory is defined as “memory for meanings”, for example, knowing that Paris is the
2
BRAIN AGEING
As a person gets older, changes occur in all parts of the body, including the brain. Certain parts
of the brain shrink, especially those important to learning and other complex mental activities
The effects of ageing on the brain and cognition are widespread and have multiple aetiologies.
Ageing has its effects on the molecules, cells, vasculature, gross morphology, and cognition. As
we age our brains shrink in volume, particularly in the frontal cortex. As our vasculature ages
and our blood pressure rises the possibility of stroke and ischaemia increases and our white
matter develops lesions. Memory decline also occurs with ageing and brain activation becomes
more bilateral for memory tasks. This may be an attempt to compensate and recruit additional
networks or because specific areas are no longer easily accessed. Genetics, neurotransmitters,
hormones, and experience all have a part to play in brain ageing. But, it is not all negative,
higher levels of education or occupational attainment may act as a protective factor. Also
protective are a healthy diet, low to moderate alcohol intake, and regular exercise. Biological
ageing is not tied absolutely to chronological ageing and it may be possible to slow biological
ageing and even reduce the possibility of suffering from age related diseases such as dementia.
Physical changes
It has been widely found that the volume of the brain and/or its weight declines with age at a
rate of around 5% per decade after age 401 with the actual rate of decline possibly increasing
with age particularly over age 70.2 The manner in which this occurs is less clear. The shrinking
of the grey matter is frequently reported to stem from neuronal cell death3,4,5 but whether this
is solely responsible or even the primary finding is not entirely clear.6 It has been suggested that
a decline in neuronal volume rather than number contributes to the changes in an ageing brain
and that it may be related to sex with different areas most affected in men and women.7
1
, 2
Additionly, there may be changes in dentritic arbour, spines, and synapses. Dendritic sprouting
may occur thus maintaining a similar number of synapses5 and compensating for any cell
death.4 Conversely a decrease in dendritic synapses or loss of synaptic plasticity has also been
described.8 Functional organisational change may occur and compensate in a similar way to
that found in patients after recovery from moderate traumatic brain injury.9 However research in
the latter area suffers from small numbers of cases. The role of white matter in the ageing brain
also needs to be considered.3 White matter may decline with age, the myelin sheath
deteriorating after around the age of 40 even in normal ageing and it has been suggested that
the late myelinating regions of the frontal lobes are most affected by white matter lesions
(WML)10,11,12) although not all studies support this view.13 Leukoariosis/WML increase with
age and may indicate subclinical ischaemia. They will be discussed in more detail below.
Brain changes do not occur to the same extent in all brain regions.6 That these brain changes
are not uniform is supported by a longitudinal study, using two MRI scans separated by around
one or two years,2 and by a review of cross sectional studies. The latter included only those
studies that compared younger (aged less than 30) and older (greater than 60) groups to
compare wider age ranges and in contrast with much of the other work in this area. The review
looked at volume and found that the prefrontal cortex was the most affected. The striatum came
second with the analysis including over seven studies. The temporal lobe, cerebellar vermis,
cerebellar hemispheres, and hippocampus also reduced volume with between 8 and 18 studies
and the prefrontal white matter also showed a reduction (five studies). The occipital cortex was
the least affected (five studies).3 The finding that the prefrontal cortex is most affected and the
occipital least, fits well with the cognitive changes seen in ageing, although some studies also
suggest that ageing has the greatest effect in the hippocampus.4,8 Men and women may also
differ with frontal and temporal lobes most affected in men compared with the hippocampus and
parietal lobes in women.7,14 Finally the rate of reduction in brain volume may increase with age
particularly over 70 although numbers studied are very small.2 Because of the individual
differences seen in brain development and ageing15 mapping structure to function and change
because of ageing is a complex task,16 however there are studies that show links between
volume and neuropsychological function. A study looking at cortical volume and white matter
hyperintensity volume in 140 people aged 50 to 81 years pre‐screened for dementia and
depression, found an association between increasing age, a reduction in prefrontal cortical
volume, increased subcortical white matter lesions, and an increase in perseverative behaviour
(decreased executive function).17
Cognitive change
The most widely seen cognitive change associated with ageing is that of memory. Memory
function can be broadly divided into four sections, episodic memory, semantic memory,
procedural memory, and working memory.18 The first two of these are most important with
regard to ageing. Episodic memory is defined as “a form of memory in which information is
stored with ‘mental tags', about where, when and how the information was picked up”.19 An
example of an episodic memory would be a memory of your first day at school, the important
meeting you attended last week, or the lesson where you learnt that Paris is the capital of
France. Episodic memory performance is thought to decline from middle age onwards. This is
particularly true for recall in normal ageing and less so for recognition.20 It is also a
characteristic of the memory loss seen in Alzheimer's disease (AD).18
Semantic memory is defined as “memory for meanings”, for example, knowing that Paris is the
2
