Aging Nervous System

Neurotrophic Factors Necessary for Maintenance of Neurons

• Neurotrophin functiono Play role in development of

NSo Interact with receptor cells to

prolong life of neurono Play role in suppressing

apoptosis (death of cell nuclei – programmed cell death)

• Nerve growth factor • Brain-derived

neurotrophic factor (BDNF)

• Neurotrophin 3 (NT3)• Neurotrophin 4/5

(NT4,5)

Free Radicals and Oxidative Stress

• Free radicals can cause oxidative stress in brain injury and disease and trigger apoptosis

• Oxidative stress is a secondary complication of many progressive NS disorders– Alzheimer’s Disease– Parkinson’s Disease– Amyotrophic Lateral Sclerosis (ALS)

• Enhanced antioxidant status associated with reduced risk of some NS diseases

Anatomic NS Changes with Age

• By 8th decade, mean loss of 15% of velocity in myelinated fibers

• Blood supply decreases by 10-15%

• Selective atrophy of brain tissue including glial cells and blood vesselso Nerve cell shrinkage may be

more significant to function than actual nerve cell loss

Morphological Changes with Aging

• Serotonin reduced• Reduced memory• Sleep pattern effects• Thermoregulation

– MAO (monoamine oxidase) increased with age – may contribute to depression

• Decreased # of some receptors

• Decreased concentration of enzymes involved in synthesis of neurotransmitters– Decreased synthesis of some

neurotransmitters– May decrease control of:

• Visceral function• Emotions• Attention

Senile Plaques• Direct relationship between

number of senile plaques and:o severity of the clinical impairment o decreased neurotransmission of

acetylcholine

• Because acetylcholine is associated with memory loss, it is believed that the senile plaques are a major cause of short term memory loss in Alzheimer’s disease.

• Neuritic (senile) plaques found outside of neurons with degenerating axons, dendrites, astrocytes– extracellular deposits of amyloid

(starchlike protein-carbohydrate complex) in the gray matter of the brain

– Occur most often in cortex and hippocampus=declarative memory

– Associated with Alzheimer’s and dementia

– proportion of people with plaques:• Age 60 years (10%) • Age 80 years (60%)

Edwardson et al.

Neurofibrillary Tangles (NFT)

• pathological accumulation of paired helical filaments composed of abnormally formed tau protein

• found chiefly in the cytoplasm of nerve cells of the brain and especially the cerebral cortex and hippocampus

• Found in higher concentration in older adults

• occurs in Alzheimer's disease and other forms of dementia

PNS Changes• Somatosensory

systemo Decreased # of

unmyelinated and myelinated fibers

o Blood vessels become atherosclerotic loss of blood supply to nerve fibers• Major contributor to

increased prevalence of peripheral neuropathies in older adults

• Vestibular systemo Hair cell receptors decline

beginning at age 30o Vestibular receptor

ganglion cells decrease by age 55-60

o Myelinated fiber loss in vestibular system is 40%

o May lead to c/o dizziness

PNS Changes• Motor system

o Loss of motor units remaining motor units become larger which can reduce ability to fine tune motor coordination

o Signs of re-innervation (space between nodes in myelin was reduced leads to reduced NCV)

• Autonomic NSo Sympathetic control of

dermal vasculature is reduced• Results in reduced

wound repair efficiency• In aging animal

models, TENS improved vascular response through increasing activity of sympathetic nerves

PNS Changes• Wallerian degeneration is delayed• Regeneration takes longer because secretion of

trophic factors is slower than in younger adults• Density of regenerated neurons is reduced• Less collateral sprouting• In PNS, loss of αMN occurs with age.

o Remaining αMN will innervate the stranded muscle cellso Results in larger motor units, which can effectively reduce motor

coordination for finely tuned movements

Balance Changes with Aging

• Functional balance changeso With eyes closed single limb stance,

balance decreases begin at age 40o More co-contraction of muscles

during balance responses with aging

o In some elders, see proximal muscle activation before distal with minor perturbations on solid floor

• Decreased NCVs for sensory and motor nerves

• Apparent decrease in ability to integrate senses involved in determining postural responses

Choy, Brauer, Nitz, JAGS, 2003

Loss of Functional Reserve

• Normally, a significant loss of neural tissue can occur before functional change occurs

• In older adults, there are less redundant neurons to take over the function so functional changes occur more readily