11/12- Aging and the CNS, PNS, and ANS Flashcards
What are CNS changes that occur with aging?
- Loss of brain mass
- Loss of neurons
- Reduced synaptic density
- Presence of neurofibrillary tangles
- Presence of neuritic plaques
- Loss of “intellectual function”
CT scan:
- Wider sulci
- Gyri are narrower
- Overall darker
- Larger ventricles (hydrocephalus ex vacuo)
What are the ratios of cerebral volume to cranial volume during normal aging?
- Young: non-brain: 7%
- Older: non-brain: 17%
Which neurons are preferentially lost with aging, small or large? What is the location of the greatest lost?
Large
- The number of neurons decreases as does the brain mass
- Large neurons are lost preferentially and the distribution is not random but focused in the cortex
- There is relatively little loss in the brainstem
T/F: Neuron losses with age are regionally heterogeneous
True
- Most in post-central area
What else is there in addition to decreases synaptic density and dendritic arbor?
There is fractional anisotropy
T/F: Aging alters the number of neural progenitor cells in the old (rat hippocampus)?
False; not altered
- Recover after lesion is impaired in old rat brain, however
Describe changes that occur contributing to old brains recovering less well from insults
- If the recovery is slower, but the number of precursors is not reduced, then the problem must be in the ability to access and mobilize the precursors
- This could be due to inadequate neurotrophin production
- The role of precursor differentiation in learning is under scrutiny. Early evidence shows you learn some things with new cells (in the gray matter) and old learn with new connection soft existing cells (white matter)
How do neurotrpohins change with age?
- NGF (nerve growth factor) and IGF-1 both produced locally
- They are keys to happy and healthy neurons and repopulation from progenitors
- Local decreases in both neurotrophins in old rats
- Data suggestive but less conclusive in older healthy people
How do neurotransmitters change with age?
- Decreases in Dopamine
- Contributes to gambling behavior in elderly
- Regional decreases in ACh
- Only minor decreases in Nucleus Basalis of Meynert with age
- It depends where you look
- Very different from Alzheimer’s Disease
- Decreases in Serotonin
- Prone to depression
- Decreases in NE
Age related changes in enzymes/NTs are specific not global. Describe how
Ex) Choline acetyl transferase doesn’t change in putamen, accumbens, or substantia nigra, but does decrease in caudate and pallidum (20-50 yo)
T/F: Dopamine receptors decrease with age in the striatum
True
- It takes greater DA stimulus to give same level of pleasure
(In addition to gambling), the reward-role of Dopamine is also important for what function?
- Decrease is due to what
Learning
- D2 receptor
- Dopamine transporter
- D2 and D3 receptors
- All correlate with cognitive function in models
Describe how old brains tolerate psychological stress
They do so poorly
- Young rat brains tolerate psychological stress better than old
- Middle aged brains tolerate stress fairly well
- Neurons of stressed old rat show decreased arbor and decreased complexity
- Stress modeled by giving corticosteroids
How was it found that old brains work harder to accomplish the same task?
PET scan shows old people without cognitive compromise use bilateral brain to do memory task
How does performance change with age?
Decreases (reaction time increases)
How does intellectual function change with age?
It declines (found in cross-sectional studies)
- Cohort longitudinal study found little fall in function within each cohort
T/F: Cognitive decline occurs in both men and women
True
T/F: There is high heterogeneity in intellectual changes
True
- Test scores showed high heterogeneity in change over 60 yrs
- Most are stable, some decline, less gain (but practices can change this)
- Also, decliners do NOT show IRREVERSIBLE losses in function
What may improve performance in older people?
Transcutaneous direct current stimulation
How does recall change in older people?
May involve different mechanisms
- Left anterior insula is activated on fMRI in older people when they say “tip of tongue” and leads to enhanced* recall
Old brain = vulnerable brain so old brain + systemic illness is BAD. Describe.
- The stress of a systemic illness may make the marginal older person confused
- That confusion, delirium, is associated with increased mortality
- It is also a marker for brain reserve limitation
What is the definition of delirium?
- Reduced ability to maintain and shift attention
- Disorganized thinking
- At least 2 of the following:
- Reduced consciousness
- Perceptual disturbances
- Sleep-wake cycle disturbances
- Psychomotor activity increased/decreased
- Disorientation to time, place or person
- Memory or learning impairment
- Features that develop over hours or days and fluctuate during the day
- Impaired long or short term memory
- 1 or more of the following are sufficient to interfere with work, normal social activities, or relationships with others, and do not occur exclusively during the course of delirium:
- Impaired abstract thinking or judgment
- Other higher cortical function
- aphasia, apraxia, agnosia
- visual spatial difficulties
- Personality change
- Not normal aging
Plaques and tangles occur in Alzheimer’s disease. How does this compare to normal changes in aging?
- Some plaques and tangles with aging, but not nearly to the same extent as AD
- Normal aging neuritic plaques are limited to the hippocampus and tangles are only present in small numbers
- In SDAT, plaques are in cortex and hippocampus, and tangles occur in almost all neocortex
What make up the tangles?
Paired helical fibers
How does the spinal cord change with age?
- Not as well studied as brain
- Unclear if there are changes in cervical cord
- 30-50% decrease in anterior horn cells in lumbrosacral spinal cord
- 30% loss of myelinated fibers in posterior root ganglia
- Similar losses in lateral white columns
What are implications of age-changes in CNS and peripheral NS on physical exam?
- Diminished/absent Achilles tendon reflex
- Decreased vibratory sense in both feet
- Limited upward gaze beyond horizontal
- Impaired rapid alternating movements
- Sluggish pupillary reflexes
- Diminished light touch
- Most old people cannot stand on one leg and cannot draw 2D representations of 3D objects
What are age changes in the sympathetic NS?
- Decreased baroreceptor responsiveness (confounded by decreased elasticity of vessels??)
- Decreased heart rate response to B-agonists
- Decreased cardiac NE stores
- Decreased inotropic response to B-agonists
- Decreased venodilator response to B-agonists
- Decreased arterial dilation to B-agonists
- Decreased NE clearance
- Increased plasma NE at rest
- Increased NE turnover
- Increased max exercise plasma NE levels
There is elevated __ in the old while _____
There is elevated NE in the old while standing
With deep breaths, how does sinus rhythm respond in elderly?
There is loss of sinus arrhythmia with age
What contributes to more falls in old people?
- Many pre-disposing factor sin the elderly (only a few sparing factors)
- In many elders any additional CV burden will lead to orthostatic hypotension and a fall
- This is especially true the morning after older people have taken all their BP medicines and eaten breakfast
Typical nursing home patients fall ___x per year. Why?
Typical nursing home patients fall 1.6x per year
- Increasing sway especially without visual input
- Slowed reaction time
- Slower light dark accommodation
- Decrease proprioceptive input
- Loss of cerebellar neurons
- Weakness of ankle and knee musculature
- Higher frequency of premonitory falls
- Orthostatic hypotension common
- 50% of falls are “accidental”
