3-10 Learning, Memory, Amnesia & Brain Function (Part 3)

Front 1

Objective

Identify the cause and symptoms of Korsakoff's syndrome.

Back 1

Korsakoff’s syndrome is brain damage caused by prolonged thiamine deficiency. Severe thiamine deficiency occurs mostly in chronic alcoholics who go for weeks at a time on a diet of nothing but alcoholic beverages, which contain carbohydrates but no vitamins. The brain needs thiamine to metabolize glucose, its primary fuel. Prolonged thiamine deficiency leads to a loss or shrinkage of neurons throughout the brain, especially in the mamillary bodies (part of the hypothalamus) and in the dorsomedial thalamus (a nucleus that sends axons to the prefrontal cortex). Therefore, the symptoms of Korsakoff’s syndrome are similar to those of people with damage to the prefrontal cortex, including apathy, confusion, and both retrograde and anterograde amnesia. A distinctive symptom of Korsakoff’s syndrome is confabulation, in which the patient takes a guess to fill in the gaps in his/her memory.

Front 2

Objective

Give an example of memory confabulation in Korsakoff's patients.

Back 2

Korsakoff’s patients do not confabulate on all questions, but only on those for which they would expect to know the answer. For example, to a nonsense question like “Who is Princess Lolita?” they reply, “I don’t know.” They confabulate mainly on questions about themselves, their families, and other familiar topics. Usually, the confabulated answer was true in the past but not now, such as, “I went dancing last night,” or “I need to go home and take care of my children.” Most of the confabulated answers are more pleasant than the currently true answers. That tendency may reflect the patient’s attempt to maintain pleasant emotions or merely the fact that for a patient in a hospital, life in the past was, on the whole, more pleasant than the present.

Front 3

Objective

Describe the symptoms of Alzheimer's disease.

Back 3

Patients with Alzheimer’s disease tend to have better procedural than declarative memory, while showing deficits in both explicit and implicit memory. The disease gradually progresses to serious memory loss, confusion, depression, restlessness, hallucinations, delusions, sleeplessness, and loss of appetite. It occasionally strikes people younger than age 40, but becomes more common with age, affecting almost 5% of people between the ages of 65-74 and almost 50% of people over 85.

Front 4

Objective

Cite evidence for and against the claim that Alzheimer's is a genetic disease.

Back 4

The first major clue to the cause of AD was the fact that people with Down syndrome (a type of mental retardation) almost invariably get AD if they survive into middle age. People with Down syndrome have three copies of chromosome 21 rather than the usual two. That fact led investigators to examine chromosome 21, where they found a gene linked to many cases of early-onset AD. Later researchers found genes on other chromosomes that are associated with larger percentages of early-onset AD.

However, more than 99% of cases have a late onset, after age 60. Researchers identified genes that increase the risk of late-onset AD, but these genes account for only a small percentage of cases. About half of all patients have no known relatives with the disease. Further evidence that genes do not explain late-onset AD comes from cross-cultural studies. The Yoruba people of Nigeria have a much lower incidence of AD than do Americans, despite having similar frequencies of the genes linked to AD. A likely hypothesis is that the Yorubas’ low-calories, low-fat, low-sodium diet decreases their vulnerability.

Front 5

Objective

Discuss the role of amyloid and tau proteins in Alzheimer’s disease.

Back 5

The genes controlling early-onset AD lead to accumulation of a protein called amyloid. Brain cells contain amyloid precursor protein, which is broken to form a smaller protein. In most people, it is cleaved into a protein consisting of 40 amino acids, called amyloid beta protein 40. Presumably, this protein serves some useful function. In people with AD, amyloid precursor protein is cleaved mostly to a longer protein with 42 amino acids, amyloid beta protein 42, which accumulates, clumps, and damages the membranes of axons and dendrites. Amyloid deposits produce widespread atrophy of the cerebral cortex, hippocampus, and other areas.

In addition to this protein, AD patients also accumulate an abnormal form of the tau protein that is part of the intracellular support structure of neurons. Amyloid produces plaques, structures formed from degenerating axons and dendrites. Plaques accumulate in the spaces between neurons. Tau produces tangles, structures formed from degenerating structures within neuronal cell bodies.

Researchers have debated the relative roles of amyloid and tau proteins in the onset of AD. Although the research continues, most of the evidence favors beta amyloid as the primary cause. Injections of beta amyloid disrupt learning and memory in rats, whereas tau by itself does not produce significant symptoms. Nevertheless, tau is part of the problem, as treatments that suppress tau decrease the memory impairments of mice with a condition resembling AD.

Front 6

Objective

List four possible ways to treat or prevent Alzheimer's disease.

Back 6

A common treatment is to use drugs that stimulate acetylcholine receptors or prolong acetylcholine release. An area of major damage is the basal forebrain, which arouses brain activity via axons containing acetylcholine. Enhanced acetylcholine activity increases some aspects of memory even in healthy people.

Another drug, still in the experimental stage, stimulates cannabinoid receptors. Such a drug limits overstimulation by glutamate. Researchers have demonstrated benefits of this drug for rats with a condition resembling AD.

Another approach is to block beta amyloid production with antioxidants, such as those found in dark fruits and vegetables. A particularly promising possibility is curcumin, a component of yellow food dye and of turmeric, a spice used in Indian curries. Research with aged mice found that curcumin reduced amyloid levels and plaques.

Research with mice also suggests the possibility of immunizing against AD. One genetic strain of mice overproduces beta amyloid and develops symptoms resembling AD. Researchers injected small amounts of beta amyloid into young mice, causing their immune system to produce antibodies that protected against the brain deterioration and learning deficits that the mice would have developed otherwise. Later research found they could also induce people with AD to produce antibodies against the amyloid protein.

Front 7

Korsakoff's syndrome

Back 7

Brain damage caused by prolonged thiamine deficiency

Front 8

priming

Back 8

One type of implicit memory; phenomenon that seeing or hearing words temporarily increases one’s probability of using them

Front 9

confabulation

Back 9

Symptom of Korsakoff’s syndrome; making up an answer to a question and then accepting the invented info as if it were a memory

Front 10

Alzheimer’s disease

Back 10

Progressive disease, most common in old age, characterized by a severe impairment of memory and attention; caused partly by the deposition of amyloid-B protein in the brain

Front 11

amyloid beta protein

Back 11

Protein that accumulates, clumps with other AB molecules, and damages the membranes of axons and dendrites

Front 12

tau

Back 12

Protein that is part of the intracellular support structure of neurons

Front 13

plaques

Back 13

Structures formed from degenerating axons and dendrites

Front 14

tangles

Back 14

Structures formed from degenerating structures within neuronal cell bodies