Diseases of Cognition Flashcards
Alzheimer’s Disease
-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
The early stages of Alzheimer’s disease are marked by
-transient confusion, loss of short-term memory, visuospatial deficits, errors in judgement, restlessness, lethargy, and depression.
In advanced stages, Alzheimer’s patients exhibit
- 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
the principle anatomical features of Alzheimer’s are
plaques, tangles, neuronal degeneration, and
synapse loss.
Senile plaques
are dense spherical deposits of protein and cellular material (neuronal and glial) in the extracellular space.
Neurofibrillary tangles
are tangled helical filaments of damaged cytoskeletal proteins proliferating intracellularly.
which anatomical feature more highly correlates with dementia severity?
tangle density is highly correlated with dementia severity
Plaque contains ____
ß-amyloid
Beta-amyloid
a peptide fragment of ß-amyloid precursor
protein (ß-APP)
-Insoluble clumps of fibrillar ß-amyloid ultimately
damage cellular processes (42 AA long)
Enzymes (alpha-, Beta-, and gamma-secretases) normally cleave APP into a _ amino acid-long
soluble and non-toxic fragment.
40
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
-42
The chief component of tangles is a protein
called ___
tau
Tau
-the chief component of tangles (intracellular)
-Tau normally functions to bind
and stabilize microtubules.
In Alzheimer’s disease, chemically altered tau
twists into paired helical filaments.
___ fall apart, and ___ causes cell death.
- Microtubules
- loss of the cell’s transport system
where are plaques and tangles found early on in Alzheimer’s disease?
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
How is short term memory loss explained in Alzheimer’s ?
-the hippocampus’s major inputs and outputs are interrupted essentially isolating the hippocampus
Plaque and tangle density is greatest in the ___ and ___
-temporal lobe and association cortices
Describe the synapse loss experienced in Alzheimer’s Disease
- 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
what is the the primary cause of cognitive impairment and loss of long term memory
-reductions of synapse
what observations provide evidence for the genetic underlying of Alzheimer’s?
- given that some cases are familial
- most Down’s syndrome patients (trisomy 21) develop features of the illness after age 35
Mutations in what 3 genes are associated with familial cases of Alzheimer’s?
APP, presenilin 1, presenilin 2
-Autosomal dominant inheritance of any one of these mutations is sufficient to cause early-onset Alzheimer’s disease
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.
- apolipoprotein E epsilon4 (ApoE epsilon4)
- 19
ApoE
-is a lipoprotein that carries cholesterol and other lipids in the blood. It can bind to ß-
amyloid and render it insoluble.
when is schizophrenia commonly diagnosed?
-typically occurs in late adolescence or early adulthood when psychotic symptoms first present. Schizophrenia often persists for life.
describe schizophrenia
-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
Positive symptoms of schizophrenia
-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)
Negative symptoms of schizophrenia
-flattened affect
• anhedonia
• alogia
• avolition
anhedonia
inability to feel pleasure.
alogia
is the inability to speak because of mental defect, mental confusion, or aphasia
avolition
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
Cognitive symptoms in schizophrenia include deficits in
-executive functioning
• attention
• working memory
stats review
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
Dopamine Hypothesis of Schizophrenia
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.
The dopamine hypothesis needs to be refined:
• 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
Patients with _____
exhibit characteristics that resemble the negative and cognitive symptoms of schizophrenia.
-frontal lobe damage (stroke, tumors, psychosurgery)
Name the two major divisions of the prefrontal cortex
- dorsolateral cortex
- orbitofrontal cortex
The dorsolateral convexity is heavily connected with
posterior parietal and superior and inferior temporal multimodal association areas.
Orbitofrontal regions have prominent interconnections with
limbic structures:
amygdala, hypothalamus, and hippocampus
The PFC organizes ____
-behavior across time in order to plan for the future
what types of information does the PFC hold at a time
-interoceptive and exteroceptive sensory signals
• memories of the consequences of various actions
• appropriate responses (motor or cognitive)
What brain structure mediates working memory?
the prefrontal cortex
The orbitofrontal division of the PFC is also thought
to be responsible for ____ through projections to structures like_____.
-inhibiting inappropriate
behaviors
-the amygdala
what is the clinical evidence for cortical deficits in schizophrenia?
-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
why is schizophrenia not a neurodegenerative disorder?
-Postmortem studies show that schizophrenia is not associated with gliosis, and therefore is not a neurodegenerative disorder.
Gliosis
-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.
Postmortem studies of schizophrenia patients reveal ____but rather _____
-no change in cell number in the PFC
BUT
-a loss of neuropil
neuropil:
- pyramidal dendrites and spines
- axon terminals
- synapses
