DEGENERATIVE DISEASES Flashcards
Most of the degenerative diseases, as are characterized by the selective involvement of anatomically and physiologically related systems of neurons. Thus, these degenerative diseases had in the past been
called_______
SYStem atrophies .
MOST IMPT mechanism that lead to neuronal degeneration
APOPTOSIS
the rate of cerebral atrophy, specifically
of the ____________, is accelerated in the early stages of Alzheimer
disease, and
hippocampus and medial parts of the temporal
lobes
The survival of patients with Alzheimer disease
is reduced to______ the expected rate, mainly because of
respiratory and cardiovascular causes and inanition, but
also for other reasons that are not entirely clear
half
The failial occurrence of Alzheimer disease has been
well established.
In less than ________ of such cases there
is a dominant inheritance pattern with a high degree of
penetrance and appearance of disease at a younger age
1 percent
Major sx of AD
The gradual development of forgetfulness is the major
symptom.
remote memories are preserved and recent ones lost
(the Ribot law of memory),
presence of cognitive difficulties in one or all spheres that are not severe enough to interfere with daily life
MCI
5 early symptoms of AD
1. amnesia 2 dysnomia 3. Visuospatial disorientation 4. Paranoia and personality changes 5. Executive dysfunction
The early stages of Alzheimer disease are
usually dominated by a disproportionate failure of
______
episodic (autobiographical) memory
AD definition according to NINCDS and ARDA
(1) dementia defined by clinical examination, the \_\_\_\_\_\_\_ (see Table 21-6), the \_\_\_\_\_\_ or similar mental status examination;
(2) patient older than age ___
(3) deficits in 2 or more
areas of cognition and progressive worsening of memory
and other cognitive functions, such as language, perception,
and motor skills (praxis);
(4) absence of disturbed
consciousness; and
(5) exclusion of other brain diseases
Mini-Mental Scale, Blessed
Dementia Scale,
40 years;
Using NINCDS and ARDA,
the correct diagnosis is achieved in more than ____
percent of patients,
85
________, the most prominent finding
visible on MRI (mainly coronal images), is diagnostic in the proper clinical circumstances.
atrophy of the hippocampus
Microscopically, there is widespread loss of nerve
cells. Early in the disease this is most pronounced in
____________
Layer II of the entorhinal cortex.
Pathology:
______ (more than proliferation) is in evidence as a
compensatory or reparative process, most prominent in
layers III and V.
Astrocytic hypertrophy
3 microscopic changes give this disease
its distinctive character
- Alzheimer neurofibrillary changes or
“tangles” - neuritic plaques
- Granulovacuolar degeneration
Alzheimer neurofibrillary changes or
“tangles” are composed of a
hyperphosphorylated form of the microtubular protein,_____and appear as pairs of helical filaments when studied
ultrastructurally.
tau
Amyloid is also scattered throughout the cerebral
cortex in a nascent “diffuse” form, without organization or core formation and then is appreciated mainly by
immunohistochemical methods, as well as deposition
in the walls of small blood vessels near the plaques, so called
__________
congophilic angiopathy.
This last change is least important
in diagnosis but there is uncertainty regarding its nature;
it had been thought to be simply a reactive process but
recent studies suggest it reflects a defect in phagocytosis of degraded proteins
Granulovacuolar degeneration
favored sites of neuronal loss
CAl and CA2 zones
(of Lorente de N6) and the entorhinal cortex, subiculum,
and amygdala.
_____ percent of their Alzheimer patients showed
the pathologic (and clinical) changes of Parkinson disease,
a much higher incidence than can be attributed
to chance
25
Electrophoretically, tau moves with the /32-globulins and
is thought to function as a _______, that is it binds iron
and delivers it to the cell
transferrin
The AB protein is a small portion of a larger entity,
the _____
amyloid precursor protein (APP),
During normal cellular
metabolism, APP is cleaved by either _______. The
products of this reaction are then cleaved by the __________ isoform of the enzyme
alpha and beta secretase
gamma secretase
cleavage by ______results in
a 40-amino-acid product, AB40, and a longer 42-aminoacid form.
____ is critical to the neuronal toxicity of amyloid.
B and then Gamma
ratio of AB42 to AB40
the gene
coding for APP is located on _____
chromosome 21
TDP-43, the product of inadequate functioning of the
progranulin gene, is also deposited in neurons and may
play a substantial role in the ______
severity of expression of
Alzheimer disease
marked reduction in ________ in the hippocampus and neocortex of patients with Alzheimer disease
choline acetyltransferase (ChAT) and acetylcholine
Other kindreds with familial Alzheimer
disease have been linked to rare dorrtinant mutations of the presenilin genes on ____
chromosome 14
Of the
several isoforms of Apo E, the presence of _____ (and itscorresponding allele e4 on chromosome 19) is associated
with a tripling of the risk of developing sporadic Alzheimer disease
The e4 allele also modifies the _____ of some of the familial forms of the disease
E4
age of onset
In sporadic Alzheimer disease, the TREM2
polymorphism that is implicated in Alzheimer disease putatively causes inadequate _______
phagocytic clearance of
amyloid
Newer PET ligand
agents that bind to amyloid, such as the _________
and tau-ligands are more sensitive in identifying
and observing the course of Alzheimer disease
“Pittsburgh compound”
this drug has been approved for use in
late-stage Alzheimer disease and in conjunction with cholinergic drugs.
Memantine
the symptoms of dementia and parkinsonism
are related to neurofibrillary changes in the cerebral cortex
and substantia nigra, respectively; senile plaques and
Lewy bodies are unusual findings
Guamanian
Parkinson-dementia complex,
The finding of neurofibrillary tangles (and to a lesser extent of plaques) in boxers_____ is another interesting ramification
of the Alzheimer disease process in that trauma appears
to be able to elicit one of the core features of the disease
(“punch-drunk” syndrome, or demen tia p ugilistica)
Pathologic changes in lobar atrophty
Pick inclusion bodies,
neurofibrillary
tangles,
other inclusions, or with no characteristic
changes except for neuronal loss.
variants of FTD
behavioral variant and a language variant (semantic dementia, progressive nonfluent aphasia, and a logopenic variant,)
A form of motor neuron disease is also linked
to frontotemporal dementia in a small number of cases.
This is particularly the case in the Guamanian (now called western Pacific) variety and in the heredofamilial
frontotemporal atrophy linked to a mutation on chromosome
1 7.
Focal disturbances,
particularly aphasia and apraxia, occur early and prominently in certain patients with lobar degenerations,
indicating a lesion in the left frontal or temporal lobes
Primary Progressive Aphasias (PPA)
_______ is characterized by
early difficulty naming items, people, and words, followed
by verbal perseveration, but fluency is retained.
semantic dementia,
________,
that shares most aspects of nonfluent aphasia but in
which the meaning of words is retained.
logopen ic aphasia
The fundamental
feature is the progressive loss of the ability to
understand and use visual information.
The result is
progressive and ultimately severe visuospatial difficulty
with a relative preservation of memory.
Posterior Cortical Atrophy
The disease is defined by the diffuse involvement of
cortical neurons with Lewy-body inclusions and by an
absence or inconspicuous number of neurofibrillary
tangles and amyloid plaques
LBD
_____, main components of the Lewy body
ubiquitin
and synuclein
parkinsonian
features, dementia, and a tendency to episodic delirium,
especially nocturnally, and rapid eye movement (REM)
sleep behavior disorde
LBD
Diagnostic criteria have been offered by a working group,
requiring 2 of 3 of the following:
a parkinsonian syndrome
(usually symmetric),
fluctuations in behavior and cognition,
and recurrent hallucinations (McKeith et
Some patients with LBD also have orthostatic
hypotension corresponding to cell loss and Lewy bodies in the ______
intermediolateral cell column of the spinal cord or
in the sympathetic ganglia,
LBD
At least one randomized trial has described benefit
_________, in
reducing delusions, hallucinations, and anxiety in pts with LBD
from the anticholinesterase inhibitor, rivastigrnine
dominant
inheritance, choreoathetosis, and dementia,
HD
in HD
The usual age of onset is in the_______decades, but 3 to 5 percent begin before the fifteenth year
and some even in childhood, where it takes on special
form.
fourth and fifth
Huntington gene and localized to the short arm of _____
excessively long repeat
of the trinucleotide ____ within the Huntington gene
chromosome 4
CAG
Individuals
with 35 to 39 triplets may eventually manifest the disease
but it tends to be late in onset and mild in degree, or limited
to _____
“senile chorea”
Gross atrophy bilaterally o f the_________ is the characteristic abnormality,
usually accompanied by a moderate degree of gyral
atrophy in the frontal and temporal regions
head o f the caudate
nucleus and putamen
the _________ratio is
increased, which corroborates the clinical diagnosis in the
moderately advanced case.
bicaudate-to-cranial
The striatal degeneration in HD begins in the medial part ofthe caudate nucleus and spreads, tending to spare the
nucleus accumbens
The presence of more
_______ at the Huntington locus essentially
confirms the disease and gives some indication of the
expected time of onset;
than 39 CAG repeats
