Nervous system intrinsic change with aging. Lect. Dr.Nisamanee Charoenchon

Transcription

1 Nervous system intrinsic change with aging Lect. Dr.Nisamanee Charoenchon Edited:

2 Scope In this section the prominent molecular biochemical cellular changes that occur in the aging nervous system, How the changes might result in dysfunction of neural circuits How the changes may predispose to neurodegenerative disorders such as Alzheimer s and Parkinson s diseases

3 Introduction probability of developing a neurodegenerative disorder increases dramatically with advancing age it is likely that at least some of the cellular and molecular changes that occur in the nervous system during normal aging are also fundamental to disease processes

4 Function performance of the nervous system slowed reaction times sensory and motor deficits disturbances of circadian rhythms a decline in cognitive performance

5 the rate of nervous system functional decline varies considerably among individuals, as does the particular regions of the nervous system affected.

6 Environmental factors are tightly related to cellular aging and nervous system decline. Cellular changes associated with aging result in neuron dysfunction and death. Neuron dysfunction leads to agingrelated changes in nervous system function, such as cognitive declines and sensory deficits. protective environmental and genetic factors can delay aging-related declines and protect against neurodegenerative disease. Genetic and environmental factors influence nervous system aging and development of agingrelated neurodegenerative diseases.

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9 Intrinsic Changes in the Nervous System Associated with Aging Sensory Loss Olfaction Hearing Vision Cognitive Decline relating to cognition

10 Sensory Loss

11 Sensory Loss Aging is associated with gradual functional loss in the sensory systems, such as olfaction, hearing and vision, which has profound impacts on daily activities of the elderly. Population studies indicate that more than 60% of people over 80 display olfactory impairment and more than 50% of people over 75 show hearing loss.

12 Epidemiological studies Environmental and genetic factors as risk factors for sensory loss.

13 1. Olfactory impairment Characteristics of age-associated olfactory impairment include 1. defects in thresholds to detect odors 2. recognition and discrimination of odors 3. perception of odor intensity

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15 Chemosensory function (olfaction and gustation) safety and quality of the life of older adults. compromised chemosensory function greater risk for food poisoning and cooking heating gas injuries due to their inability to identify spoiled food or detect the odour warning of a gas leak. Olfactory dysfunction has been identified as an early marker of neurodegenerative disorders Gustatory and olfactory dysfunction in older adults: a national probability study, 2011

16 A study of 80 healthy elderly persons and 80 patients with Alzheimer disease noted a lack of awareness of decreased ability to detect odor (Prevalence of Olfactory Impairment in Older Adults, 2002). Many neurodegenerative diseases including Parkinson's, Alzheimer's, and Huntington's are associated with non-inflammatory neuronal cell loss and they are accompanied in the early stages with olfactory disturbances.

17 Most attempts to explain olfactory dysfunction in common neurodegenerative diseases have focused on neuropathological markers such as Olfaction and neurodegenerative diseases are linked clinically and pathologically Classic neuropathological markers of neurodegenerative diseases amyloid β neurofibrillary tangles α-synuclein

18 The pathology of the olfactory mucosa most cases of hyposmia and anosmia appear to be associated with a decline in the number of functioning mature olfactory sensory neurons (OSNs). Very early siqn of Pakinson s disease เย อเม อกร บกล น (olfactory mucosa) Hyposmia is a reduced ability to smell and to detect odors. Anosmia is the inability to perceive odor or a lack of functioning olfaction the loss of the sense of smell.

19 Olfactory Dysfunction: Common in Later Life and Early Warning of Neurodegenerative Disease, 2013 Classification of olfactory dysfunction Olfactory dysfunction (dysosmia) Quantitative Hyperosmia Oversensitivity Normosmia Hyposmia Anosmia (functional anosmia, specific anosmia) Normal sensitivity Reduced sensitivity Complete anosmia: absolute loss of olfactory function; no sense of smell detectable Functional anosmia: severe limitation of olfactory function; includes complete loss as well as residual odor perception Partial anosmia: greatly reduced sensitivity to a particular odoriferous substance/group of substances compared with the general population, usually not viewed as pathological

20 Qualitative Parosmia Altered perception of odors in the presence of a stimulus Phantosmia Perception of odors in the absence of a stimulus

21 The principal causes of olfactory dysfunction include: Trauma Viral infections Rhinosinusitis or nasal polyposis Neurodegenerative illnesses such as Parkinson disease or Alzheimer dementia

22 2. Age-related hearing loss (ARHL) is associated with increased thresholds to low-frequency sound (e.g khz), but decreased thresholds to the high frequency sound (e.g. 8 khz) Age-related hearing loss most often occurs in both ears, affecting them equally. A common form of ARHL is called presbycusis, in which a patient has difficulty understanding speech due to inability distinguishing high-frequency tones (also spelled presbyacusis, from Greek presbys old + akousis hearing )

23 Pathophysiology Histologic changes associated with aging occur throughout the auditory system from the hair cells of the cochlea to the auditory cortex in the temporal lobe of the brain.

24 The auditory hair cells are located within the spiral organ in the cochlea of the inner ear. Inner Ear The inner ear contains a snail-shaped structure filled with fluid called the cochlea. Sound vibrations create waves in the cochlear fluids. As the waves peak, they cause tiny hair cells (types of receptors that can detect sound) to bend, which converts the vibrations into electrical signals.

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27 Histologic changes in the cochleae of human ears with presbycusis The histologic changes are correlated approximately with symptoms and auditory test results. Sensory presbycusis This refers to epithelial atrophy with loss of sensory hair cells and supporting cells in the organ of Corti. Neural presbycusis This refers to atrophy of nerve cells in the cochlea and central neural pathways.

28 Metabolic (ie, strial) presbycusis This condition results from atrophy of the stria vascularis. The stria vascularis normally maintains the chemical and bioelectric balance and metabolic health of the cochlea. Mechanical (ie, cochlear conductive) presbycusis This condition results from thickening and secondary stiffening of the basilar membrane of the cochlea.

29 For hearing loss, noise is an obvious environmental risk factor, such as long-term exposure to noise. Noise-induced hearing loss is caused by long-term exposure to sounds that are either too loud or last too long. This kind of noise exposure can damage the sensory hair cells in your ear that allow you to hear. By the time you notice hearing loss, many hair cells have been destroyed and cannot be repaired. The average person is born with about 16,000 hair cells. Up to 30% to 50% of hair cells can be damaged or destroyed before changes in your hearing can be measured by a hearing test.

30 The pictures below show electron micrographs of healthy hair cells (left) and hair cells after exposure to excessive noise (right).

31 Calcium ions (Ca 2+ ) play numerous and fundamental roles in the inner ear. Calcium signaling in the cochlea Molecular mechanisms and physiopathological implications, 2012 aspects of sound transduction that are influenced by Ca 2+ mechanotransduction function and neurotransmitter release at the hair cell synapse Ca 2+ signaling in the network of non-sensory cells in the developing cochlea

32 Quantitative trait loci (QTL) mapping studies in human and mice have identified several genes and modifiers potentially involved in age-related hearing loss (ARHL). (=presbycusis) One possible candidate involved in ARHL is ATP2B2, a plasma membrane ATPase type 2-Ca2 + transporter pump, located in the hair cells of the cochlea, suggesting a critical role for Ca2+ signaling in age-related changes of the auditory system A unique role of ATP2B2 in hearing was indicated by the high levels of its expression in cochlear outer hair cells, it played an important role in intracellular calcium homeostasis. PON2 and ATP2B2 gene polymorphisms with noise-induced hearing loss, 2016

33 3. Vision Maculopathy is damage to the macula, the part of the eye which provides us with our central vision. Age-related macular degeneration (AMD) is the most common cause of visual loss in adults in the developed world. AMD affects the macula, which is the most sensitive part of the retina.

34 Macular Degeneration is caused by the deterioration of the central portion of the retina, the inside back layer of the eye that records the images we see and sends them via the optic nerve from the eye to the brain

35 Age-Related Macular Degeneration progressive sight loss. It is characterised changes in pigmentation in the Retinal Pigment Epithelium, the appearance of drusen on the retina of the eye and choroidal neovascularization.

36 Drusen are yellow deposits under the retina. Drusen are made up of lipids, a fatty protein. Drusen likely do not cause age-related macular degeneration (AMD). But having drusen increases a person's risk of developing AMD.

37 Choroidal neovascularization growth of new blood vessels that originate from the choroid through a break in the Bruch membrane into the sub retinal pigment epithelium (sub-rpe) or subretinal space.

38 Age-related Macular Degeneration The image on the left shows bleeding at the macula due to wet AMD. The image on the right shows yellow deposits called drusen in dry AMD.

39 Wet AMD occurs when abnormal blood vessels behind the retina start to grow under the macula. These new blood vessels tend to be very fragile and often leak blood and fluid. With wet AMD, loss of central vision can occur quickly. Dry AMD light-sensitive cells in the macula slowly break down, gradually blurring central vision in the affected eye. As dry AMD gets worse, you may see a blurred spot in the center of your vision. Over time, as less of the macula functions, central vision is gradually lost in the affected eye. Patients with dry AMD are at higher risk of getting wet AMD.

40 Risk Factors for AMD AMD affects mainly people aged older than 60 years. The major risk factors for developing AMD are: age, family history of AMD, and, smoking.

41 Cognitive Decline

42 Cognitive function gradually declines with increasing age although the impairment varies among individuals with different ages of onset As a part of cognitive function, memory is a complex process involving the peripheral and central nervous systems.

43 A memory process Information is received by the sensory system, transmitted to the central nervous system, and processed and stored in the brain to form memory

44 Despite its complexity, memory can be classified into several different types based on the difference in information acquisition, retention and recall. Not all types of memory are equally affected by aging. It appears that aging primarily affects memory for recent events while having little effect long on short term memory

45 Age-related memory impairment (AMI) Structural studies indicate that the age-related memory impairment (AMI) appears not to result from gross morphological change since general brain structures and neuron numbers remain relatively unchanged during aging Stages Simple Mild Dementia (diseasse stage) Dementia: is a term used to describe a series of conditions that can affect a person s ability to think, remember, understand, make judgments, communicate, and interact socially

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47 Alterations of Ca 2+ homeostasis in AMI AMI can be attributed to agerelated alterations of Ca 2+ homeostasis, cyclic AMP (camp) level synapse number in the neurons One group of neurons implicated in AMI is central cholinergic neurons primarily located in the pontine reticular formation and basal forebrain

48 Dysfunction of brain cholinergic neurons in AMI A number of rodent studies have demonstrated age-related changes of calcium buffering systems and Ca 2+ signaling, which may cause dysfunction of brain cholinergic neurons A cholinergic neuron is a nerve cell which mainly uses the neurotransmitter acetylcholine (ACh) to send its messages.

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