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ALZHEIMER’S DISEASE!

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Most common degenerative disease of the brain and the most common type of dementia
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Genetic risk factor of AD: E4 allele of the Apolipoprotein E (Apo E) gene
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Onset : < 45 years usually autosomal dominant!
Memory is the early complaint in AD
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Small day-to-day happenings are not remembered
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Little-used words from an earlier period of life also tend to be lost
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Questions are repeated again and again, the patient having
forgotten what was just discussed
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Episodic Memory Impairment!

- Episodic memory is the memory store for personal experiences that occur in a particular
spatial and temporal context, it is depended on the hippocampus
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- Early course: distant episodic memories (e
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memories before disease onset) tend to be !
spared
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Working Memory Impairment!

- Working memory can be divided into 2 systems: One responsible for storage of information,
and another responsible for coordinating information processing and manipulation
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3
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- Hippocampus and Medial temporal lobes (MTL) is responsible
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Procedural Memory!
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Depends on the implicit learning of tasks and actions is preserved in AD
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Every sentence is broken by a pause and search for the wanted word; if the desired word is not
found, a circumlocution is substituted or the sentence is left unfinished
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g
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Apraxia: The inability to execute learned purposeful movements, despite having the desire and the
physical capacity to perform the movements
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Late in the course of the illness, the patient forgets how to use common objects and tools while
retaining the necessary motor power and coordination for these activities
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Decline in visuospatial skills:!
Parietooccipital functions are derange,!
Losing one's way in familiar surroundings or inability to interpret a road map, to distinguish right
from left, or to park or garage a car, and difficulty in setting the table or dressing are all
manifestations of a special failure to orient the schema of one's body with that of surrounding
space!

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Anosognosia or unawareness of the illness!
In conditions like schizophrenia and Alzheimer's disease, frontal lobe difficulty is central to the
neurological processes that underlie the disorders
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Neuropsychiatric Features!
Mood state (depressed, euphoric), vegetative status (eating, sleeping), changes in perosnality, and
alterations in perceptions or thought (hallucinations or delusions), paranoia
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This may appear before the more obvious memory or language defects announce themselves
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He may hide his belongings, even relatively worthless ones, and
go about spying on family members
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g
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It is thought to reflect disruption of the connections within the
frontosubcortical–anterior cingulate circuitry and their connections with other cortical regions
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Risk factors for developing
depression are familial or personal history of depressive disorder, female gender, and younger age!

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Anxiety: In the early stages, anxiety may be a manifestation of the patient’s subjective awareness
of his/her cognitive decline, his or her increased dependency on others, and fear of the disease
and its progression
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Changes in the daily routine and the environment can trigger anxiety in the demented
patient and could easily escalate to agitation and aggression!

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NEUROIMAGING!
At least one unenhanced CT or MRI scan should be performed in patients with cognitive decline to
rule out unexpected structural lesions and also to provide information about potential silent
vascular injury
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- In the dementia stage, global brain atrophy—more striking in the temporoparietal than in the
frontal regions—and ventricular enlargement are also pronounced
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PET using [18F]fluorodeoxyglucose (FDG), a measure of energy utilization in the brain that
predominantly marks synaptic activity, also shows temporoparietal deficits, is more sensitive than
SPECT, and can confirm the diagnosis
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DIAGNOSTIC CRITERIA!
Dubois Criteria!

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NINCDS-ADRDA!

NEUROLOGICAL EXAMINATION!
• Early: Mild abnormalities of tone (gegenhalten
or more commonly, mitgehen) may be present,
parkinsonian symptoms (akinetic rigid type
without tremor)!
• Pathological reflexes: grasp, root, and suck
reflexes!
• Midstage: Weight loss!
• End stage: Mute, incontinent, and bedridden
with flexion deformities of the limbs and

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impaired swallowing
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Ubiquitin levels in CSF are increased in AD, but the levels are similar to those found in other
neurodegenerative disorders
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Tau is hyperphosphorylated and aggregates, resulting in paired helical filaments that make up the neurofibrillary tangles
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PATHOGENESIS!
Histologic techniques assist in this endeavor, including refined methods for silver impregnation that
stain both amyloid and its main constituent (beta-amyloid protein [Aβ]); immunostaining using
antibodies specific to such proteins as ubiquitin, neuronal tau protein, and beta-amyloid protein;
and visualization of β-pleated protein sheets using thioflavine S and Congo red with ultraviolet and
polarized light
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Aβ protein is a small portion of amyloid precursor protein (APP), which normally bound to neuronal
membranes
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Normally: cleaved by α, then cleaved by γ which
produce tiny fragments that are not toxic to neurons
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• Aβ42 causes the formation of aggregated fibrillary
amyloid protein rather than the normal APP
degradation
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Neuropil as the

• Formation of Aβ42 is promoted by the mutations

core substance of

of APP gene or mutations of Presenilin 1 and 2
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PSEN2, a protease homologous to PSEN1 but
encoded by a gene located on chromosome 1,
also appears capable of making the second cut

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inside the membrane
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ApoE plays a role in amyloid removal, while patients with AD has ApoE E4 allele which is less
effective in aiding the removal of β-amyloid from the brain
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Alzheimer brain also shows a loss of monoaminergic neurons and a diminution of noradrenergic,
gabanergic, and serotonergic functions in the affected neocortex
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TREATMENT!
• Acetylcholinesterase Inhibitors (AChEIs): Donepezil, rivastigmine, and galantimine
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• Depression, anxiety, irritability: Selective Serotonin Uptake Inhibitors (SSRIs)!
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Fluoxetine (100-300 mg/d)!

• Antipsychotic: Quetiapine, risperidone, olanzapine!
• Sleep disorder: short acting benzodiazepines: Trazodone!
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5-HT2 Antagonist!

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Single dose at night as a hypnotic in lower doses 150 mg- 300 mg/d!



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