1. Learning and Memory Learning deficiencies and Disorders
CHAPTER 12
Learning
and Memory
Learning deficiencies and Disorders

2. Dementia

3. Memory loss and aging For many years researchers believed:
deficits in the elderly caused by a substantial loss of neurons
Loss was especially from the cortex and the hippocampus.
More recent investigations
number of hippocampal neurons not diminished in aged rats
Even rats with memory deficits show little neuronal loss
What neuronal loss occurs from cortical areas was relatively minor.
BUT: certain circuits in the hippocampus do lose synapses and NMDA receptors as animals age.
Probably as a result of these changes, LTP is impaired in aged rats.

4. dementias Dementia Other dementias:
substantial loss of memory and other cognitive abilities
Typically in elderly
50% of those over 80 show some signs of dementia
Other dementias:
Frontal-temporal dementia
Vascular dementias
Dementias from illness such as stroke/heart attack

5. dementias most common cause of dementia is
Alzheimer’s disease
most common cause of dementia is
progressive brain deterioration, impaired memory, loss of other mental abilities.
Earliest and most severe symptom = impaired declarative memory.
Language, visual-spatial functioning, and reasoning are particularly affected
Behavioral problems such as aggressiveness and wandering away from home.

6. dementias Sundowning: Increased confusion and restlessness in patients
Behavioral problems begin to occur in the evening or while the sun is setting.
More frequent during the middle stages of Alzheimer's disease and mixed dementia.
Subsides with the progression of dementia.
20–45% of Alzheimer's patients will experience some sort of sundowning confusion.
Alzheimer’s affects nearly 10% of people over 65 years of age, and nearly half of those over 85.

8. Brain changes in dementia
There are two notable characteristics of the Alzheimer’s brain, though they are not unique to the disease.
Plaques
Neurofibrillary tangles
Plaques = clumps of amyloid
a type of protein
cluster among axon terminals
interfere with neural transmission.
Abnormal accumulations of the protein tau
form inside neurons.
Tangles are associated with the death of brain cells.

9. Figure 12.14 Neural abnormalities in the brain of an Alzheimer’s patient
(a) The round clumps in the photo are plaques. (b) The dark twisted features are neurofibrillary tangles.
Figure Neural abnormalities in the brain of an Alzheimer’s patient
(a) The round clumps in the photo are plaques. (b) The dark twisted features are neurofibrillary tangles.

10. Dementia brain changes
In the Alzheimer’s brain,
Gyri are smaller
Sulci are wider than in the normal brain.
In the diseased brain, many of the lesions are located in the temporal lobe.
Because of their location, they effectively isolate the hippocampus from its inputs and outputs,
This partially explains the early memory loss.
Plaques and tangles in the frontal lobes account for
Additional memory problems
Attention and motor difficulties.

11. Figure 12.15 Alzheimer’s brain (left) and a normal brain
The illustrations show the most obvious differences, the reduced size of gyri and increased size of sulci produced by cell loss in the diseased brain.
Figure Alzheimer’s brain (left) and a normal brain
The illustrations show the most obvious differences, the reduced size of gyri and increased size of sulci produced by cell loss in the diseased brain.

12. Ach and memory Acetylcholine:
Neural systems in various parts of the brain that produce acetylcholine are critical for cognitive functions
including attention and learning.
Acetylcholine-releasing neurons are among the victims of degeneration in Alzheimer’s disease.
The majority of treatment efforts have focused on restoring acetylcholine functioning.
E.g., cognex, aricept, exelon

13. Drugs for dementia
Currently five drugs approved by the FDA for the treatment of Alzheimer’s.
Four of them improve acetylcholine neurotransmission by preventing the breakdown of acetylcholine at the synapses (AchE inhibitors).
Drugs provide only modest relief for both memory and behavioral symptoms in mild cases of Alzheimer’s
Little or no help when degeneration is advanced.

14. Drugs for dementia Generic Brand Approved For Side Effects donepezil
Aricept
All stages
Nausea, vomiting, loss of appetite and increased frequency of bowel movements.
galantamine
Razadyne
Mild to moderate
memantine
Namenda
Moderate to severe
Headache, constipation, confusion and dizziness.
rivastigmine
Exelon
memantine + donepezil
Namzaric
Headache, diarrhea, dizziness, loss of appetite, vomiting, nausea, and bruising.

15. Drugs for dementia Other drug treatment
Psychotropic drugs to control behavioral symptoms, reduce hallucinations
Haldol, serentil, seroquel, respiridone, mellaril
Antiseizure medications to control onset of seizures
Gabapentin (neurotin), dilantin, tegretol
Tranqulizers and antidepressants
Ativan, valium, xanax,
Wellbutrin, lexapro
Side-effects
May make lethargic
May make memory loss greater
May speed up death

16. Newer dementia drug
Memantine: first approved for use in patients with moderate and severe symptoms.
Some neuron loss in Alzheimer’s occurs when dying neurons trigger the release of the excitatory transmitter glutamate.
The excess glutamate overstimulates NMDA receptors and kills neurons, a phenomenon known as excitotoxicity.
Memantine limits the neuron’s sensitivity to glutamate, reducing further cell death.
Studies indicate moderate slowing of deterioration and improvement in symptoms.

17. Korsakoff’s syndrome Korsakoff’s syndrome
Another form of dementia is, brain deterioration
Almost always caused by chronic alcoholism.
Typically affects people in 50’s and 60’s
With heavy binge drinking, onset earlier: 20’s and 30’s

18. Korsakoff’s syndrome
The deterioration results from a deficiency in the vitamin thiamine (B1), which has two causes:
The alcoholic consumes large quantities of calories in the form of alcohol in place of an adequate diet.
The alcohol reduces absorption of thiamine in the stomach.

19. Korsakoff’s syndrome The most pronounced symptom : anterograde amnesia
Retrograde amnesia is also severe.
Impairment is to declarative memory, while nondeclarative memory remains intact.
Several brain changes:
Hippocampus and temporal lobes are unaffected.
Mammillary bodies and the medial part of the thalamus are reduced in size
Structural and functional abnormalities occur in the frontal lobes.
Thiamine therapy can relieve the symptoms if the disorder is not too advanced,
Brain damage itself it irreversible.

20. Korsakoff’s symptoms Confabulation Confabulation :
Some Korsakoff’s patients show a particularly interesting characteristic in their behavior
Many other dementia patients, particularly frontal-temporal lobe also show this
They fabricate stories and facts to make up for those missing from their memories.
Confabulation :
Depends on abnormal activity in the frontal lobes
Confabulating patients usually have lesions there.

21. Korsakoff’s symptoms Confabulating amnesic patients
More trouble than nonconfabulating amnesiacs in suppressing irrelevant information they have learned earlier.
Why? confabulation is due to an inability to distinguish between current reality and earlier memories.
NOT that they are lying, but that they are unable to tell the difference between real memories and their confabulation
No amount of arguing will tell them that they are wrong, because they have a “memory” of it.
It is as real as any other memory

22. Korsakoff’s symptoms

23. Eloquent Description of Dementia
Dementia is like opening a book of someone’s life and randomly ripping individual pages out, one by one, until there is nothing left but the cover.
Simon Weisenthal