The aging brain Flashcards

1
Q

LO

A
  • Be familiar with the changes that occur in normal aging brain.
  • Changes occur at gross anatomical and molecular levels
  • Recognise how some of these may predispose to neurodegenerative disease.
  • Understand how this knowledge may be used to prevent neurodegenerative disease.
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2
Q

What are the ways in which the brain ages?

A
  • Decrease in brain size and morphology
  • Changes in vasculature
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3
Q

Tell me about the changes in brain size and morphology during brain aging?

A
  • Sulci and gyri have more gaps which suggests cell death in the aging brain
  • Ventricles enlarged in elderly brain. They are wider which suggests death and cells of tissues which is why the gaps occur
  • Cortical thickness declines with increasing age
  • Ventricle area also declines with increasing age
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4
Q

What are the techniques for looking at the aging brain?

What does each technique detect?

A

Voxel-based morphometry (VBM), this is a technique using MRI that allow to look at the focal differences in brain anatomy. It tell why there is a reduction in brain matter and the areas of where the cell death is occurring

Whole brain tractography picks up white matter changes. It assess the large-scale connections in the brain

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5
Q

How does the changes in vasculature show an aging brain?

A

Including age-related reduction in cerebral blood flow a cerebral perfusion dysfunction including increased cerebral microbleeds

The brain and its vasculature has a high requirement for blood supply in order to function correctly.

Such a high demands by neurons for oxygen and glucose due to energy dependent processes in synapse such as reuptake, endocytosis, exocytosis, and energy dependent processes in the axon like vesicle transport. Presence of Na+-K+ ATPase also requires energy

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6
Q

What are some techniques to look at vasculature in the aging brain?

A
  • MRI scan can show microbleeds which can be quantified. Volume of potential regions of microbleeds increase in number and volume with age
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7
Q

What is meant by a brain microbleed?

A

These are defined as small, circulat hypointents changes in T2-sequences (these are one of the basic pulse sequences on MRI) of brain MRI, well demarcated (separate) from the surrounding tissue

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8
Q

What are the consequences of brain microbleeds?

A

Consequence of microbleeds: vascular dementia due to cell death and alteration in blood supply to the brain (occurs over long period of time, sometimes have proteins deposited), increase chance of acute conditions like strokes (reduced blood supply).

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9
Q

Whats the main functions of the following brain areas and what happens if there is an impairment in the brains circuitry in these locations?

  • Temporal cortex
  • Occipital love
A

Function of temporal cortex and effect if circuitry is affected: working memory before being stored in memory banks in parietal cortex. Short time memory loss in conditions like Alzheimer’s because it effects temporal cortex

Circuit breaking in occipital lobe is involved in visual processing and this impairment leads to phenotype of

Where the change or impairment in the circuity occurs is what leads to the clinical phenotype

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10
Q

Could these gross changes explain age-related change in cognition?

A

Age-related changes in memory and other cognitive functions are a part of aging

… age-related decline in sensory/ motor function?

However that is speculation and maybe for locomotion the sensory motor system could be affected by either muscular-skeletal system or circuitry decline could be all age-related decline

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11
Q

What are some of the areas of the neuronal circuit that changes with age?

A
  • Axonal changes/ white matter changes
  • Dendritic changes
  • Synaptic changes
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12
Q

What are some of the axonal changes/ white matter changes that occur with age?

A

Age related decline in microtubule integrity can be looked at with electron microscopy.

Axonal transport, transport vital materials like NT, if these are declining every 5 years then there could be a substantial decline in say 20 years

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13
Q

What are some dendritic changes that occur with age?

A

Reduction in synaptic nobs with age: increase surface area where input can be received and allows this input from more areas. These decline with age and therefore a reduction in ability of circuit to receive input as SA has been reduced

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14
Q

What are some synaptic changes that occur with age?

A
  • Age-related reduction in pre-synaptic markers: overall a reduction in synaptic transmission
  • The markers include e.g., SNAP-25 and synaptophysin, these markers show decrease in density
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15
Q

What techniques are used to study these neuronal circuit changes?

Tell me a few facts about each one

A

Magnetic Resonance Imaging (MRI) especially structural MRI (in vivo, non-invasive, longitudinal)

Gross anatomy/histology (scarcity of tissue; PM delay (PM interval varies between each individual), co-morbidities)

Animal models (manipulation possible; no PM delay, pure aging, longitudinal, behavioural corelations possible)

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16
Q

What are the molecular changes in an aging brain?

A

Cytoskeletal changes- discussed above

Changes in disease associated proteins

  • Age related reduction in protein amounts such as TAU (protein found in axon) and actin could be due to reduction in gene expression

Changes in disease associated pathways

17
Q

How do the changes in clearance and they cytoskeleton make an individual more predisposed to disease?

A

Changes in clearance?

  • Evidence of reduced autophagy/ UPS in AD brain compared to age-matched control

Changes in cytoskeleton?

  • Cytoskeletal breakdown more pronounced in AD

Increased risk of stroke and vascular disease?

18
Q

What is the flaw in correlating aging studies to disease?

What can be done about this?

A

Mistaken belief that dementia is a continuum of normal aging

(Same proteins same pathways implicated but role is NOT physiological but pathological )

Need to study normal brain aging in NORMAL non-diseased animals and humans

(Studying AD va age-matched control is not enough)

19
Q

What are the two potential hypotheses to show how aging enhances the risk to proteinpathy?

A
20
Q

How can one intervene to improve brain aging?

A

Improve CVS function

  • Improve diet (antioxidants will protect against age-related insults)

Enhance synaptic function/plasticity

  • Brain games

Intake of agents that stimulate neurofortification- autophagy stimulators

Autophagy is the bodies way of cleaning out damaged cells in order to regenerate newer, healthier cells

21
Q

summary

A
  • Know that aging brains undergo shrinkage due to neuronal loss, changes in vasculature and white matter changes
  • Know that aging circuits undergo changes in cytoskeletal morphology, dendritic spine loss and synapse loss
  • Age-related changes in autophagy and UPS are also evident
  • Some of these may pre-dispose to age-related neurodegenerative disease.
  • Understand how measures to promote healthy aging may protect against these conditions.