Aging Nervous System

Neurotrophic Factors Necessary for Maintenance of Neurons Neurotrophin function o Play role in development of NS o Interact with receptor cells to prolong life of neuron o 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 8 th 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 vessels o 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 system o 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 system o Hair cell receptors decline beginning at age 30 o Vestibular receptor ganglion cells decrease by age 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 NS o 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 cells o Results in larger motor units, which can effectively reduce motor coordination for finely tuned movements

Balance Changes with Aging Functional balance changes o With eyes closed single limb stance, balance decreases begin at age 40 o 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