PHYSIOLOGICAL BASIS OF MEMORY,LEARNING AND SPEECH.pptx

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1. PHYSIOLOGICAL BASIS OF MEMORY,LEARNING AND SPEECH PATHOPHYSIOLOGY OF ALZHEIMERS DISEASE LATE SMT. INDIRA GANDHI MEMORIAL MEDICAL COLLEGE, KANKER CHATTISGARH KUNDAN YADAV(49) SONU RAM GAWDE(109) LAKHAN MEENA(52) PIYUSHA MARKAM(81)

2. INTRODUCTION P rocess of learning involves the storage of new information in memory and its retrieval at appropriate time Process of memory involves repeated acquirement of new knowledge (learning) F requent learning of newer facts increases the horizon of memory Thus, learning utilizes memory and memory utilizes learning

3. 1. The common sites of learning and memory in the human brain are the association areas of the cerebral cortex and sub-cortical structures in the temporal lobe, including the hippocampus and amygdala . 2. The association cortical areas imbibe sensory information from the somatosensory cortex, and visual, auditory, and olfactory cortices. They also receive information about emotional feelings from limbic system. 3. These information are integrated with previous experiences of learned skills and are then stored in the memory

4. Definations Learning is defined as acquirement of information or knowledge by experience that results in the alteration of behavior. Memory is defined as retention of learned information and experiences

5. 1.Registration of memory that includes proper perception and attention 2. Integration and retention 3. Recognition and recall 4. Reutilization

6. Types of memory 1.Explicit or declarative memory 2.Implicit or nondeclarative memory

7. Explicit Memory 1. The explicit memory, also known as declarative memory is connected with awareness. 2. It has two forms: memories of events ( episodic memory ), memories of facts ( semantic memory ). 3. The declarative memory is dependent on the hippocampus and other parts of the medial temporal lobes of the brain for its retention

8. Short-term Memory 1. Short-term memory is the memory that lasts for seconds to hours , during which processing in the hippocampus and elsewhere lays down long-term changes in synaptic strength. 2. Working memory is a form of short-term memory that makes information available for a brief period. 3. As a result of repeated training, short-term memory can be transferred into long-term memory, which depends on a process called consolidation . 4. During short-term memory, the memory traces are subject to disruption by trauma and various drugs

9. Long-term Memory 1. Long-term memory is the one that stores information for years together, and sometimes for life. 2. Long-term memory traces are remarkably resistant to disruption. 3. This is broadly divided into explicit and implicit memory. Some forms of implicit memories also involve short-term and long-term memories

10. Implicit Memory 1. The implicit memory is not associated with awareness and is therefore also called as reflexive or nondeclarative memory . 2. It includes skills, habits, priming and conditioned reflexes etc. 3. Explicit memory is initially required to develop implicit memory. For example, a learner of motorcycle riding initially remembers the steps of changing the gear (he changes gears with conscious knowledge) till it becomes a reflexive habit to do so (he changes gear without awareness). Once skill is acquired, the acts become unconscious and automatic.

11. Priming It is the facilitation of recognition of words or objects by prior exposure to them. An example is improved recall of a word when presented with first few letters of it.

12. Procedural Memory Includes skills and habits, which once acquired become unconscious and automatic

13. Nonassociative Learning The organism learns about a single stimulus. Examples are habituation and sensitization .

14. Habituation 1. Habituation is a simple form of learning in which repeated application of a neutral stimulus elicits less and less response. 2 . Habituation implies learning and therefore can be studied for its cellular mechanisms. It can be short term , or it can be prolonged if exposure to the benign stimulus is repeated many times.

15. The response that was first studied was gill withdrawal in Aplysia when the gill is stroked. After a few strokes, the response is not seen. The withdrawal is an aversive response ( eye blink or head movement response to bright light ) , and if the stroke is harmless, the animal gets habituated to it.

16. Sensitization Sensitization is the opposite reaction in which repeated application of stimulus evokes greater and greater response. Sensitization occurs especially when the stimulus to which habituation has developed is coupled with a pleasant or unpleasant stimulus . For example, application of noxious stimulus to gill results in greater withdrawal of gill (an increased responsiveness). Sensitization may occur as a transient response, or if it is reinforced by additional pairings of the noxious stimulus and the initial stimulus, it can exhibit features of short-term or long-term memory.

17. Associative Learning The organism learns about the relation of one stimulus with other. The classical example is conditioned response

18. Conditioned Reflexes Reflex response to a stimulus that hardly elicited any response in the past, but presently the response to the stimulus is acquired by pairing the stimulus with another stimulus that normally produces the response, is called a conditioned response

19. Types of Conditioned Reflexes There are two types of conditioned responses: classical conditioning and operant conditioning . Conditioned reflexes have two components that are associated with emotional responses and motor responses. E motional responses are regulated by amygdala M otor responses are controlled by cerebellum .

20. Classical Conditioning 1. In classic conditioning, in the beginning, there is a stimulus that normally elicits a specific innate response (the response which is already present without training). The stimulus is called unconditioned stimulus (UCS). 2. Later, an arbitrary stimulus that normally does not produce any response, on application does produce a significant response when paired with the UCS. The stimulus is called conditioned stimulus (CS).

21. 3. Example of classic conditioning is Ian Pavlov’s experiment on salivation in dog . First , Pavlov produced salivation in dog by placing a piece of meat in its mouth. Then , he rung a bell just before placing meat in dog’s mouth, and repeated the procedure a number of times till the animal was made to salivate with bell-ringing , Finally without even placing meat in the mouth.

22. 4. In this experiment, salivation in dog by placing meat in the mouth is the UCS and bell ringing is the CS . Salivation in response to CS (sound of the bell) occurred by pairing it sufficient number of times with UCS (placing meat in the mouth). 5. Finally, CS produced the response even in the absence of UCS, which was initially evoked only by UCS

23. Operant Conditioning In this type of conditioning, animal is trained to carry out a task for either to receive a reward or to avoid a punishment. The UCS may be a pleasant or unpleasant event. The CS is applied as a signal in the form of light or sound that alerts the animal to perform. BF Skinner had extensively studied this type of conditioning. The animal, usually a rat is kept in the Skin n er box, in which provision is made in such a way that pressing a bar results in delivery of food pallet, or prevention of an electric shock

24. Initially, the response occurs by chance. However, later response occurs with greater probability as reward follows the response (animal learns that food is obtained by pressing the bar or the shock is prevented). Thus, the reinforcement may be a positive reinforcement (by pressing bar animal gets food), or a negative reinforcement (by pressing bar animal prevents electric shock).

25. Conditioned motor response results in avoidance of electric shock. Therefore, this is also called conditioned avoidance reflexor aversion conditioning . Another example of negative reinforcement (conditioned avoidance reflex) if food aversion conditioning, in which animal severely develops aversion to a particular food, if the taste of food (UCS) is coupled with injection of a chemical that develops physical illness (CS)

26. Inhibition of Conditioned Reflex Conditioned reflexes can be inhibited in two ways: internal and external inhibitions: Internal inhibition- If the CS is presented indefinitely without UCS, the response decreases and eventually stops. External inhibition - Conditioned reflex response can also be abolished if animal is disturbed externally just after the application of CS.

27. Reinforcement of Conditioned Reflex I f CS is paired repeatedly with UCS from time to time, conditioned reflex becomes permanent (reinforcement of conditioned reflex) Conditioned reflex can also be strongly formed by associating UCS with a pleasant or unpleasant affect. Accordingly, there are two types of reinforcements: Positive and negative reinforcement. If the UCS is associated with a pleasant affect, positive reinforcement occurs and if associated with an unpleasant affect negative reinforcement occurs

28. Mechanism of learning and memory Cellular (molecular ) Neural B iochemical mechanisms

29. Molecular Mechanisms Learning and memory are initiated and established by several neurochemical changes like increased synaptic connection neurotransmitter secretion formation of intracellular second messenger gene activation protein synthesis

30. Habituation 1. Habituation occurs due to decreased neurotransmitter release from the presynaptic sensory ending in response to repeated application of a particular stimulus. Serotonin secretion decreases from the modulator neuron. 2. The stimuli gradually inactivate calcium channel resulting in decreased calcium content at the presynaptic terminal that in turn inhibit neurotransmitter release

31. Sensitization Sensitization occurs due to prolongation of action potential in the sensory endings that results in increase in intracellular calcium , which in turn increases neurotransmitter release .

32. Serotonin activates cyclic AMP in the sensory neuron terminal . Cyclic AMP phosphorylates one set of K+ channels closes the K+ channels slowing of repolarization and prolongation of action potential voltage dependent calcium influx into the sensory terminal increases release of transmitter by exocytosis .

33. 5. The short-term prolongation of sensitization is due to a calcium-mediated change in adenylyl cyclase that leads to a greater production of cAMP . 6. The long-term potentiation also involves protein synthesis and growth of the presynaptic and postsynaptic neurons and their connections

34. Conditioned Reflexes 1. In classical conditioning, pairing of UCS with CS causes biochemical changes in target neurons. The basic mechanism involved is the prolongation of action potential that causes presynaptic facilitation. 2. For the classic conditioned reflex to develop, it is important that the UCS should come soon after the CS to cause a temporal association. 3. The UCS acts on neurons that are activated by CS. UCS increases calcium in the presynaptic terminal. The long-term increase in presynaptic calcium alters adenylyl cyclase activity . 4. Thus, when CS activates the presynaptic neuron, adenylyl cyclase is activated to a greater extent that forms more and more cAMP . Increased cAMP causes phosphorylation of a set of K+ channels and closes the channel. This slows the repolarization and prolongs the action potential

35. Post-tetanic Potentiation 1. This is the production of enhanced postsynaptic potentials in response to stimulations. This enhancement lasts upto 60 seconds and occurs after a brief (tetanizing) train of stimuli in the presynaptic neuron. 2. The tetanizing stimulation causes Ca ++ to accumulate in the presynaptic neuron to such a degree that the intracellular binding sites that keep cytoplasmic Ca ++ low are overwhelmed.

36. Learning and Long-term Potentiation 1. Repeated stimulation of presynaptic neurons results in change in excitability of postsynaptic neurons by altering the rate of discharge, new protein synthesis and neurotransmitter release. These changes are found to be associated with learning. 2. Long-term potentiation (LTP) is an important process for establishment of learning and memory. 3.Unlike post tetanic potentiation, it is initiated by an increase in intracellular Ca ++ in the postsynaptic rather than the presynaptic neuron. Increased excitability and change in intracellular protein formation by repeated synaptic stimulation are known mechanisms of LTP.

37. 4 . In LTP, the initial step is the phosphorylation of a number of proteins that are stimulated by formation of receptor-mediated second messengers. Phosphorylation of proteins activates various intracellular enzymes and alters neuronal excitability. In the later stage of LTP, the synaptic connections between neurons increase. 5. LTP occurs in the hippocampus in mammals. This is a process of potentiation of impulse transmission in neuronal pathways in hippocampus that lasts for days to weeks when they are stimulated at a high frequency. The potentiation is mediated by calcium influx

38. Hippocampal LTP Hippocampal LTP is of two types: the mossy fiber LTP and Schaffer collateral LTP 1. The mossy fiber LTP is NMDA independent. It is mediated by presynaptic mechanisms that involve cAMP and Ih , a hyperpolarization-activated cation channel. 2. The Schaffer collateral LTP is initiated by increased intracellular calcium in the postsynaptic neuron and depends on NMDA receptors. Increased calcium level makes glutamate receptors accessible to glutamate molecules.

39. Long-term Depression Though long-Term Depression (LTD) was first described in the hippocampus , it was subsequently demonstrated in all the fibers as for LTP LTD is just the opposite of LTP. It is mainly characterized by a decrease in synaptic strength. It is demonstrated by slower stimulation of presynaptic neurons and there is smaller rise in intracellular Ca ++ compare to that as occurs in LTP. In cerebellum, LTD requires phosphorylation of the GluR2 subunit of AMPA (α–Amino-3-hydroxy-5-Methylisooxazole-4-Propionic acid) receptors, which may be involved in motor learning.

40. Neural Mechanisms Brain Regions Involved Prefrontal cortex, Inferotemporal cortex and H ippocampus.

41. Prefrontal Cortex 1. Removal of the frontal lobes in monkeys resulted in delayed response to different memory tasks. It was suggested that spatial short-term memory resides in the frontal lobes. 2. It was further investigated by ablation studies that spatial short-term memory is the function of dorsolateral frontal cortex. 3. Thalamic fibers concerned with memory project to prefrontal cortex and from there to the basal forebrain. From basal forebrain, fibers project to amygdala, hippocampus and neocortex . These fibers are mainly cholinergic fibers

42. Inferotemporal Cortex 1. Lesion of this part of the cortex interferes with visual discrimination, whereas tactile, auditory or olfactory cues remain unaffected. 2. The integrity of pre-frontal and inferotemporal cortices is required for performance of tasks that are relatively difficult. Thus it appears that neural substrates for learning are task specific

43. Hippocampus 1. Hippocampus is an important component of the Papez circuit, which is extensively connected with, hypothalamus, thalamus, amygdala and septum. 2. The combined lesions of the hippocampus and the amygdala produce significant amnesia than the individual lesions. 3. The neural basis of learning involves the substrates of reward. The hippocampus and medial forebrain bundle are important structures of the reward system. 4. Prefrontal cortex, the seat of working memory is connected with hippocampus and parahippocampal portion of medial temporal lobe .

44. 5. Bilateral destruction of ventral hippocampus in humans causes striking deficit in short-term memory. They have intact working memory and remote memory. They are capable of learning new tasks and retaining pre-lesion remote memories. However, they can not form new long-term memory 6. Hippocampal connections with mammillary body (hypothalamus), amygdala and thalamus are also involved in memory.

45. 7. Lesion of mammillary body or thalamus causes impairment of recent memory. Hippocampal connection with amygdala is concerned with emotions related to memory. R ecently it has been observed in humans that activity in left parahippocampal cortex and left frontal lobe increases when they recall words and activity in right parahippocampal cortex and right frontal lobe increases when they recall pictures. New neurons are formed in hippocampus in response to learning and memory

46. Neural Mechanisms of Declarative Memory Declarative Memory 1. Declarative memory refers to the memory of events and facts and the ability to knowingly access them. 2. Declarative memory is integrated in medial portion of the temporal lobe. 3. Patients, who have undergone bilateral medial temporal lobectomy, for example for the treatment of intractable temporal lobe epilepsy) lose their declarative memories or become incapable in forming new declarative memory, but retain procedural memory.

47. Procedural Memory 1. Procedural memory refers to the ability to learn and remember new skills and procedures. 2. Procedural memory is integrated in different parts of the brain, depending on type of tasks learned and remembered. 3. Learning and remembering new motor skills and habits require the striatum, motor cortex, and cerebellum. 4. Remembering emotional components associated with tasks and skills require the amygdala. Learning the conditioned reflexes requires the cerebellum and cortex. The medial temporal lobe is not involved in procedural memory

48. Neural Mechanisms of Short-Term and Long-term Memory Short-term Short term memory 1. Learned experiences that are newly and recently acquired can be easily recalled using short-term memory. For example, before an individual dials a telephone number, first he sees the number and repeats that mentally till the number is dialed, and then he forgets the number quickly once he starts talking on phone. This is a form of working memory. However, if the number is repeatedly used or is an important number, the number is stored in the memory for a longer duration.

49. 2. Thus, the permanent storage of information is based on its importance or its repeated use or on whether it is associated with an important or emotional event. 3. For memory to become more permanent, processing occurs in subcortical areas that mainly involve hippocampus.

50. Working Memory 1. Working memory makes the information available for a brief period. 2. The center for working memory is the prefrontal cortex. 3. Working memory has two components: verbal component that retains the verbal memory and visuospatial component that retains the visual and spatial aspects of the objects (spatial short-term memory)

51. Long-term Memory The short-term memory is converted to long-term memory mainly by three ways: i. By repeating the process of learning frequently. ii. By adding more that one sensory modality to the process of learning, for example writing and at the same time also hearing a newly acquired acknowledge. iii. By associating the process of a particular learning with a meaningful emotional event.

52. C onsolidation The process of permanent storage of memory is called consolidation: 1. Hippocampus plays an important role in consolidating memory, which is reinforced by an emotional state that is associated with the learning or the experience. 2. The medial temporal lobe is important for long-term declarative memory formation, especially the hippocampal and parahippocampal cortices. However, the hippocampus is not required for subsequent retrieval of long-term memory.

53. 3. Long-term memories are stored in various parts of the neocortex . Various components of long-term memory reside in concerned cortical regions. For example, visual and auditory parts of memories are located in visual and auditory cortex respectively. Therefore, once long-term memories are established, they can readily be recalled by association with similar events (visual, auditory, olfactory or somatosensory) later in life.

54. Neural Mechanisms of Learning Prefrontal cortex is critical for coordinating the process of learning and memory. 1. The cerebral cortex processes information related to learning and communicates them to the limbic structures . The prefrontal cortex gathers sensory information from the somatosensory, visual and auditory cortices. Prefrontal cortex integrates inputs related to language and mathematical ability in the light of previously acquired learning

55. 2. The prefrontal cortex is considered as the site of working memory . New experiences are processed in the prefrontal cortex. The processed information is then transmitted to the hippocampus. 3. Consolidation of information occurs in hippocampus over several hours into a lasting from. 4.Then , the learned experience is stored in the association cortices, from where it can be retrieved whenever needed

56. Role of Cholinergic Neurons in Memory 1. Acetylcholine is the major transmitter in learning and memory, and other cognitive function. 2. Cholinergic neurons that are present plentily in basal forebrain region project heavily to the hippocampus and different parts of cerebral cortex. The cell bodies of these cholinergic neurons are highly concentrated in basal forebrain nuclei especially in the nucleus basalis of Meynert and the nucleus accumbens .

57. 3. Cholinergic fibers are also main projecting neurons from brainstem reticular formation (mainly from pedunculopontine nucleus) to the thalamus and spinal cord. More than 90% of projections from brainstem to thalamic nuclei are cholinergic. 4. Loss of cortical and subcortical cholinergic neurons, especially in the basal forebrain region is associated with dementia, an impairment of memory, abstract thinking, and judgment

58. Brain Areas for Integration of Various forms of Memory EXPLICIT or DECLARATIVE MEMORY(fact and event):medial temporal lobe Short-term memory : Hippocampus Working memory : Prefrontal cortex Long-term memory : Various parts of neocortex

59. 2. Implicit or nondeclarative memory Priming : Neocortex Procedural memory : Striatum (Skills and habits Associative learning (Classical and operant conditioning) Emotional responses : Amygdala Skeletal musculature : Cerebellum Nonassociative learning : Reflex pathways (Habituation and sensitization

60. Biochemical Basis Changes underlying learning is the repeated transmission of impulses along neural circuits that results in permanent changes in the concerned neurons. One important consequence is the new protein formation in the nerve cells. Increased RNA synthesis in response to learning has been well documented. Recently it has been suggested that activation of specific gene is responsible for learning.

61. Stangeness and Familiarity Stimulation of some parts of the temporal lobes causes change in interpretation of one’s surroundings such as the subject feels strange in a familiar place or familiarity with the new events. Such of strangeness or familiarity helps the normal individual to adjust to different environments. But, inappropriate feeling of familiarity with new events or surroundings is clinically known as the déjà vu phenomenon, (a French word, which means ‘already seen’. This phenomenon may occur in normal individuals. However, this usually occurs as an aura that precedes the onset of temporal lobe epilepsy

62. APPLIED PHYSIOLOGY Amnesia Amnesia means impairment of memory Types Anterograde amnesia Retrograde amnesia

63. Retrograde Amnesia 1. Loss of memory for events that just precede the head injury or the disease is called retrograde amnesia. 2. Usually, the loss occurs only for short-term memory. 3. Retrograde amnesia occurs commonly in head injury in which patient develops concussion

64. Anterograde Amnesia 1. Inability to recall the memory or to form new memories after the event (head injury, mental shock or disease) is called anterograde amnesia. 2. Anterograde amnesia also follows head injury but the duration covered by the amnesia usually shortens with time.

65. Dementia 1.Dementia is a syndrome consisting of several intellectual inabilities. 2. The deficits occur for many cognitive functions including learning and memory. 3. It occurs in many conditions that affect cortical functions. 4. The commonest is the senile dementia. 5. Pathological dementia is commonly seen in neurodegenerative diseases like Alzheimer’s disease. 6. However, drug induced dementia and alcoholic dementias are not uncommon

66. Alzheimer’s Disease Alzheimer’s disease is the common degenerative disease of the brain characterized mainly by premature and progressive dementia. Etiology 1. There is severe loss of cholinergic neurons projecting from basal forebrain to neocortex , amygdala and hippocampus. Especially, fibers projecting from nucleus basalis of Meynert ( substantia innominata ) are severely affected. 2. Cerebral atrophy mainly involves frontal, temporal and parietal lobes. Pronounced neuronal loss occurs in hippocampus, entorhinal cortex, parahippocampalgyri and subiculum .

67. Pathology 1. Presence of neurofibrillary “tangles” in the nerve cell cytoplasm is the cytopathologic hallmark of the disease. These tangles are fiber-like strands composed of hyperphosphorylated form of microtubular protein “tau”. They appear like pairs of helical filaments. 2. Other characteristic feature is the appearance of neuritic plaques scattered throughout the cerebral cortex. The plaques contain amyloid protein (amyloid β protein or Aβ protein) as the central core surrounded by degenerating nerve terminals. 3. Granulovacular degeneration of neurons, especially in pyramidal layer of hippocampus.

68. Role of amyloid precursor protein Normally, amyloid precursor protein (APP) is secreted from nerve cells. APP is hydrolyzed by the enzyme γ- secretase to form A β protein. This protein is hydrolyzed at three different sites by α- secretase , β- secretase , and γ- secretase . B y α- secretase , nontoxic peptide products are produced. B y β- secretase and γ- secretase , polypeptides with 40 to 42 amino acids are produced, that are toxic in nature. The most toxic among them is A βσ1-42 .

69. 1. These toxic polypeptides form extracellular aggregates that can bind to AMPA receptors. 2. They also bind to Ca2+ ion channels and increase Ca2+ influx. 3. They also induce inflammatory responses and produce intracellular tangles. 4. Eventually, the affected cells die.

70. 5. Excessive and abnormal hydrolysis of APP results in more production of A β proteins that form neuritic plaques. 6. Neuritic plaques induce inflammatory reactions, tangle formation, oxidative damage and neuronal degeneration (especially cholinergic neurons)

71. Features 1. Usually the patient is above 50 years. 2. Progressive development of forgetfulness is the major symptom. 3. The disease starts with loss of short-term memory and later followed by loss of other cognitive functions. 4. Dysnomia (forgetting words especially names), visuospatial disorientation, and paranoia and other personality changes usually occur.

72. Treatment Cerebral vasodilators , stimulants, and high dose of vitamin B, C, E have beneficial effects. Trials of oral physostigmine , choline, lecithin and cholinergic precursor and agonists have yielded some results

73. SUMMARY

74. TYPES OF MEMORY

75. ASSOCIATIVE LEARNING EXAMPLE-CONDITIONAL REFLEX CLASSICAL CONDITIONING OPERANT CONITIONING NON ASSOCIATIVE LEARNING HABITUATION SENSETIZATION

76. BRAIN REGION INVOLVED IN NEURAL MECHANISM PREFRONTAL CORTEX INFEROTEMPORAL CORTEX HIPPPOCAMPUS

77. APPLIED PHYSIOLOGY RETROGRADE AMNESIA ANTEROGRADE AMNESIA DEMENTIA ALZHEIMERS DISAESE

78. Quiz

79. The mechanism of learning and memory includes all, except : A . Changes in level of neurotransmitter at synapse B . Increasing protein synthesis C . Recruitment by multiplication of neurons D. Spatial reorganization of synapse

80. Answer: C. Recruitment by multiplication of neurons

81. The processing of short-term memory to long-term memory is done (consolidation of long-term memory occurs) in : A. Prefrontal cortex B . Hippocampus C . Neocortex D . Amygdala

82. ANSWER: B. Hippocampus

83. All are true statements regarding memory, except . A . Structural changes occur in synapses during the developmentof long-term memory B. Short-term memory lasts as long as the person continues to think C . The site for storage of long term memory is in temporal lobe D. B ilateral lobes of hippocampal function leads to loss of encode event of the recent pass in long term memory

84. C. The site for storage of long term memory is in temporal lobe

85. Associative learning is A . Associated with consciousness B . Including skills and habits C . Relation of one stimulus to another D . Facilitation of recognition of words

86. C. Relation of one stimulus to another

87. Striatum damage affects primarily A. Procedural memory B . Short-term memory C . Long-term memory D . Explicit memory

88. A. Procedural memory

89. 6. All are true about Alzheimer's disease, except A . Loss of cholinergic neurons in basal forebrain B . Neurofibrillary tangles in the neuron is the hallmark of disease C . Neuritic plaques are due to abnormal hydrolysis of amyloid precursor proteins that lead to more production of Ad proteins D. Dysnomia (forgetting words, especially names) does not occur

90. D. Dysnomia (forgetting words, especially names) does not occur

91. Thank you