The aging brain Flashcards
LO
- 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.
What are the ways in which the brain ages?
- Decrease in brain size and morphology
- Changes in vasculature
Tell me about the changes in brain size and morphology during brain aging?
- 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
What are the techniques for looking at the aging brain?
What does each technique detect?
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
How does the changes in vasculature show an aging brain?
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
What are some techniques to look at vasculature in the aging brain?
- MRI scan can show microbleeds which can be quantified. Volume of potential regions of microbleeds increase in number and volume with age
What is meant by a brain microbleed?
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
What are the consequences of brain microbleeds?
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).
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
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
Could these gross changes explain age-related change in cognition?
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
What are some of the areas of the neuronal circuit that changes with age?
- Axonal changes/ white matter changes
- Dendritic changes
- Synaptic changes
What are some of the axonal changes/ white matter changes that occur with age?
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
What are some dendritic changes that occur with age?
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
What are some synaptic changes that occur with age?
- 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
What techniques are used to study these neuronal circuit changes?
Tell me a few facts about each one
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)
What are the two potential hypotheses to show how aging enhances the risk to proteinpathy?
