Diseases of Cognition

Question 1

Alzheimer’s Disease

Answer 1

-a progressive neurodegenerative disease characterized by dementia, a state
of confusion accompanied by loss of short and long term memory
-Alzheimer’s disease mainly affects the elderly: ~1% by age 65 and ~11-14% by age 85

Question 2

The early stages of Alzheimer’s disease are marked by

Answer 2

-transient confusion, loss of short-term memory, visuospatial deficits, errors in judgement, restlessness, lethargy, and depression.

Question 3

In advanced stages, Alzheimer’s patients exhibit

Answer 3

• severe cognitive decline
• loss of long-term memories
• loss of speech
• loss of bodily functions (e.g. incontinence, difficulty eating, inability to care for oneself) that ultimately result in death ~8-10 years after symptom onset

Question 4

the principle anatomical features of Alzheimer’s are

Answer 4

plaques, tangles, neuronal degeneration, and

synapse loss.

Question 5

Senile plaques

Answer 5

are dense spherical deposits of protein and cellular material (neuronal and glial) in the extracellular space.

Question 6

Neurofibrillary tangles

Answer 6

are tangled helical filaments of damaged cytoskeletal proteins proliferating intracellularly.

Question 7

which anatomical feature more highly correlates with dementia severity?

Answer 7

tangle density is highly correlated with dementia severity

Question 8

Plaque contains ____

Answer 8

ß-amyloid

Question 9

Beta-amyloid

Answer 9

a peptide fragment of ß-amyloid precursor
protein (ß-APP)
-Insoluble clumps of fibrillar ß-amyloid ultimately
damage cellular processes (42 AA long)

Question 10

Enzymes (alpha-, Beta-, and gamma-secretases) normally cleave APP into a _ amino acid-long
soluble and non-toxic fragment.

Answer 10

40

Question 11

Enzymes (alpha-, Beta-, and gamma-secretases)
normally cleave APP into a 40 amino acid-long
soluble and non-toxic fragment. The slightly
longer and “sticky” __ amino acid fragment is
insoluble and toxic; it accumulates in brain,
blood vessels and meninges

Answer 11

-42

Question 12

The chief component of tangles is a protein

called ___

Answer 12

tau

Question 13

Tau

Answer 13

-the chief component of tangles (intracellular)
-Tau normally functions to bind
and stabilize microtubules.

Question 14

In Alzheimer’s disease, chemically altered tau
twists into paired helical filaments.
___ fall apart, and ___ causes cell death.

Answer 14

• Microtubules

- loss of the cell’s transport system

Question 15

where are plaques and tangles found early on in Alzheimer’s disease?

Answer 15

they are found most commonly in layer II of the entorhinal cortex, which gives rise to the perforant
pathway.
-Pyramidal neurons in the CA1 and subiculum also become affected

Question 16

How is short term memory loss explained in Alzheimer’s ?

Answer 16

-the hippocampus’s major inputs and outputs are interrupted essentially isolating the hippocampus

Question 17

Plaque and tangle density is greatest in the ___ and ___

Answer 17

-temporal lobe and association cortices

Question 18

Describe the synapse loss experienced in Alzheimer’s Disease

Answer 18

• exaggerated compared to normal aging
• greatest in the hippocampus and association cortices
• least in primary sensory and motor areas
• causes widening of sulci and shrinking of gyri

Question 19

what is the the primary cause of cognitive impairment and loss of long term memory

Answer 19

-reductions of synapse

Question 20

what observations provide evidence for the genetic underlying of Alzheimer’s?

Answer 20

• given that some cases are familial

- most Down’s syndrome patients (trisomy 21) develop features of the illness after age 35

Question 21

Mutations in what 3 genes are associated with familial cases of Alzheimer’s?

Answer 21

APP, presenilin 1, presenilin 2

-Autosomal dominant inheritance of any one of these mutations is sufficient to cause early-onset Alzheimer’s disease

Question 22

Risk of late-onset Alzheimer’s is increased with inheritance of the _______ allele on chromosome __, whereas the ApoE epsilon 2 may be protective against Alzheimer’s.

Answer 22

• apolipoprotein E epsilon4 (ApoE epsilon4)

- 19

Question 23

ApoE

Answer 23

-is a lipoprotein that carries cholesterol and other lipids in the blood. It can bind to ß-
amyloid and render it insoluble.

Question 24

when is schizophrenia commonly diagnosed?

Answer 24

-typically occurs in late adolescence or early adulthood when psychotic symptoms first present. Schizophrenia often persists for life.

Question 25

describe schizophrenia

Answer 25

-It is a cognitive disorder characterized by loss of contact with reality.
-There are many manifestations of schizophrenia,
and it is not clear that it represents a single disease. -There are three major symptom classes

Question 26

Positive symptoms of schizophrenia

Answer 26

-represent the experience of sensations or ideas that are normally absent; these
occur primarily during acute psychotic episodes
-hallucinations (abnormal perceptions, especially auditory)
• delusions (abnormal beliefs)
• thought disorder (incomprehensible thought patterns)
• movement disorders (agitation or catatonia)

Question 27

Negative symptoms of schizophrenia

Answer 27

-flattened affect
• anhedonia
• alogia
• avolition

Question 28

anhedonia

Answer 28

inability to feel pleasure.

Question 29

alogia

Answer 29

is the inability to speak because of mental defect, mental confusion, or aphasia

Question 30

avolition

Answer 30

means a severe lack of initiative or motivation. A psychological term used to describe the lack of interest or will to become engaged in goal-oriented behavior, avolition is found in schizophrenia

Question 31

Cognitive symptoms in schizophrenia include deficits in

Answer 31

-executive functioning
• attention
• working memory

Question 32

stats review

Answer 32

If a data distribution is approximately normal then about 68 percent of the data values are within one standard deviation of the mean (mathematically, μ ± σ, where μ is the arithmetic mean), about 95 percent are within two standard deviations (μ ± 2σ), and about 99.7 percent lie within three standard deviations

Question 33

Dopamine Hypothesis of Schizophrenia

Answer 33

Early on, schizophrenia was thought to result
from excessive dopamine transmission
in limbic pathways.
• Psychosis can be induced by drugs that
increase dopamine transmission (e.g.
chronic amphetamine, excessive LDOPA).

• Drugs that block dopamine transmission
(e.g. antipsychotic dopamine receptor
antagonists) can be used to treat
schizophrenia.
• There is a strong correlation between the
clinicallyeffective dose of antipsychotics
and their affinity for the dopamine D2 receptor subtype.

Question 34

The dopamine hypothesis needs to be refined:

Answer 34

• Excessive dopamine transmission in subcortical regions may underlie positive symptoms, whereas reduced dopamine transmission in the prefrontal cortex may underlie negative and cognitive symptoms.
• PET studies show that excessive dopamine transmission is restricted to the head of the caudate
nucleus (i.e. the associative loop of the basal ganglia).
• There are a number of unresolved issues surrounding the dopamine hypothesis.
% Dopamine receptor antagonists block dopamine receptors acutely, but for unknown
reasons, their antipsychotic effects take several weeks to manifest.
–Dopamine receptor blockers are better at treating positive than negative or cognitive
symptoms.
– It is not known what causes excessive subcortical dopamine transmission in the disease

Question 35

Patients with _____

exhibit characteristics that resemble the negative and cognitive symptoms of schizophrenia.

Answer 35

-frontal lobe damage (stroke, tumors, psychosurgery)

Question 36

Name the two major divisions of the prefrontal cortex

Answer 36

• dorsolateral cortex

- orbitofrontal cortex

Question 37

The dorsolateral convexity is heavily connected with

Answer 37

posterior parietal and superior and inferior temporal multimodal association areas.

Question 38

Orbitofrontal regions have prominent interconnections with

Answer 38

limbic structures:

amygdala, hypothalamus, and hippocampus

Question 39

The PFC organizes ____

Answer 39

-behavior across time in order to plan for the future

Question 40

what types of information does the PFC hold at a time

Answer 40

-interoceptive and exteroceptive sensory signals
• memories of the consequences of various actions
• appropriate responses (motor or cognitive)

Question 41

What brain structure mediates working memory?

Answer 41

the prefrontal cortex

Question 42

The orbitofrontal division of the PFC is also thought

to be responsible for ____ through projections to structures like_____.

Answer 42

-inhibiting inappropriate
behaviors
-the amygdala

Question 43

what is the clinical evidence for cortical deficits in schizophrenia?

Answer 43

-Functional imaging studies indicate that the normal increase in cerebral blood flow to the PFC during working memory tasks is markedly reduced in people with schizophrenia
-MRI images suggest ~10% reduction in cortical volume and
widening of the sulci, especially in the frontal and temporal
lobes.
-Reduced cortical thickness is associated with enlargement of the lateral ventricles

Question 44

why is schizophrenia not a neurodegenerative disorder?

Answer 44

-Postmortem studies show that schizophrenia is not associated with gliosis, and therefore is not a neurodegenerative disorder.

Question 45

Gliosis

Answer 45

-is a nonspecific reactive change of glial cells in response to damage to the central nervous system (CNS). In most cases, gliosis involves the proliferation or hypertrophy of several different types of glial cells, including astrocytes, microglia, and oligodendrocytes.

Question 46

Postmortem studies of schizophrenia patients reveal ____but rather _____

Answer 46

-no change in cell number in the PFC
BUT
-a loss of neuropil

Question 47

neuropil:

Answer 47

• pyramidal dendrites and spines
• axon terminals
• synapses