Aging Nervous System

1. Aging Nervous System

2. Neurotrophic Factors Necessary for Maintenance of Neurons • Nerve growth factor • Brain-derived neurotrophic factor (BDNF) • Neurotrophin 3 (NT3) • Neurotrophin 4/5 (NT4,5) • Neurotrophin function • Play role in development of NS • Interact with receptor cells to prolong life of neuron • Play role in suppressing apoptosis (death of cell nuclei – programmed cell death)

3. 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

4. Anatomic NS Changes with Age • Selective atrophy of brain tissue including glial cells and blood vessels • Nerve cell shrinkage may be more significant to function than actual nerve cell loss • By 8th decade, mean loss of 15% of velocity in myelinated fibers • Blood supply decreases by 10-15%

5. Morphological Changes with Aging • 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 • Serotonin reduced • Reduced memory • Sleep pattern effects • Thermoregulation • MAO (monoamine oxidase) increased with age – may contribute to depression

6. Senile Plaques • 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%) • Direct relationship between number of senile plaques and: • severity of the clinical impairment • 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. Edwardson et al.

7. 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

8. PNS Changes • Vestibular system • Hair cell receptors decline beginning at age 30 • Vestibular receptor ganglion cells decrease by age 55-60 • Myelinated fiber loss in vestibular system is 40% • May lead to c/o dizziness • Somatosensory system • Decreased # of unmyelinated and myelinated fibers • Blood vessels become atherosclerotic  loss of blood supply to nerve fibers • Major contributor to increased prevalence of peripheral neuropathies in older adults

9. PNS Changes • Autonomic NS • 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 • Motor system • Loss of motor units remaining motor units become larger which can reduce ability to fine tune motor coordination • Signs of re-innervation (space between nodes in myelin was reduced  leads to reduced NCV)

10. 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. • Remaining αMN will innervate the stranded muscle cells • Results in larger motor units, which can effectively reduce motor coordination for finely tuned movements

11. Balance Changes with Aging • Decreased NCVs for sensory and motor nerves • Apparent decrease in ability to integrate senses involved in determining postural responses • Functional balance changes • With eyes closed single limb stance, balance decreases begin at age 40 • More co-contraction of muscles during balance responses with aging • In some elders, see proximal muscle activation before distal with minor perturbations on solid floor Choy, Brauer, Nitz, JAGS, 2003

12. 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