Alzheimer disease made simple

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Alzheimer’s disease:
Clinical Review
By
Dr. Tarek A. Gouda
Professor of neurology
Licensed consultant neurologist ,KSA(2009)

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Overview
-Definition
-CliniCal piCture anD Diagnosis
-pathology
-Differential Diagnosis
-treatment

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INTRODUCTION
- Progressive deterioration in cognitive ability in the
absence of other known neurologic or medical
problems.
-It is the most common type of dementia (50-70% of
cases of dementia)
-Alzheimer’s disease is progressive and irreversible.

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History

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1- Cognitive dysfunction.
e.g. memory loss.
2-Non-cognitive symptoms:
- psychiatric symptoms(depression)
- behavioral changes(agitation)
3- Impaired activities of daily living.
What is Alzheimer’s disease..

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What is Alzheimer’s disease..
-Alzheimer’s disease is not a part of normal
aging.
-Memory loss is universal and is the first
symptom in the majority of cases, The
gradual onset of memory loss means that it
may misattributed to normal ageing and is
often recognized only in retrospect as the
onset of Alzheimer's disease.

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DSM-IV criteria for dementia
A1-memory impairment.
A2-At least one of the following:
- Aphasia
- Apraxia
- Agnosia
- Disturbance in executive functioning
B-The cognitive deficits in A1 and A2 each cause significant
impairment in social or occupational functioning and represent
a significant decline from a previous level of functioning
C-The cognitive deficits do not occur exclusively during the course
of delirium.

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Diagnosis
Postmortem examination, psychologic testing, and brain
imaging help establish three levels of diagnostic certainty:
- “Definite” Alzheimer disease is reserved for autopsy-confirmed
disease.
-“Probable” Alzheimer disease is the highest level of clinical
diagnosis if there is no associated illness.
-“Possible” refers to those who meet clinical criteria for dementia
but have another illness that may contribute, such as
hypothyroidism or cerebrovascular disease.
-Except for the mental state, the
neurologic examination is usually

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Mild cognitive impairment
-Individual has subjective symptoms (predominantly
of memory loss) and measurable cognitive deficits
but without notable impairment in activities of
daily living.
-Are up to 15 times more likely to develop dementia
at follow-up, suggesting it may be a precursor to
Alzheimer's disease.
-No treatment approved by FDA for mild cognitive
impairment

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Pathology of Alzheimer’s disease

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Pathology of Alzheimer’s disease

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Pathology of Alzheimer’s disease

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Pathology of Alzheimer’s disease

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Pathology of Alzheimer’s disease

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TAU HYPOTHESIS

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FREE RADICLE HYPOTHESIS

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Pathology of Alzheimer’s disease

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Pathology of Alzheimer’s disease
-Amyloid-β is a proteolytic byproduct of the transmembrane protein
(APP)
-In Alzheimer disease, amyloid is deposited around meningeal and
cerebral vessels and in gray matter.
-Although neurofibrillary tangles are not specific to Alzheimer
disease, they occur first in the hippocampus; later,
neurofibrillary tangles may be seen throughout the cerebral
cortex.

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Stages of Alzheimer’s disease
Mild Alzheimer’s disease :
Forgetfulness, short term memory loss, impaired activities
of daily livings.
Moderate Alzheimer’s disease :
Progression of cognitive deficits, further impaired activities
of daily living ,emergence of behavioral and psychological
symptoms of dementia
Severe Alzheimer’s disease :
Agitation ,altered sleep patterns ,assistance required in
dressing ,feeding ,bathing ,established behavioral and
psychological symptoms of dementia
Very severe Alzheimer’s disease :
Bed bound ,incontinent ,no speech ,basic psychomotor skills
lost.

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Alzheimer’s disease and seizures
-An estimated 10-20% patient with AD develop
unprovoked seizures with higher rates in familial and
early onset cases.
-The relationship of epileptic activity to AD is of great
clinical importance. It has been suggested that seizure
activity is related to pathogenesis of AD.

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Alzheimer’s disease and
depression
For a person to be diagnosed with depression in Alzheimer's, he or
she must have either :(DSM 4 Criteria)
-depressed mood .
OR -decreased pleasure in usual activities, along with two or more
of the following symptoms for two weeks or longer:
-Social isolation or withdrawal
-Disruption in appetite that is not related to another medical
condition
-Disruption in sleep
-Agitation or slowed behavior
-Irritability
-Fatigue or loss of energy

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Alzheimer’s disease and depression
-Feelings of worthlessness or hopelessness, or inappropriate or
excessive guilt
-Recurrent thoughts of death, suicide plans or a suicide attempt
-Medication to treat depression in Alzheimer's :
Selective Serotonin Reuptake Inhibitors (SSRIs) are often used
for people with Alzheimer's and depression because they have
a lower risk than other antidepressants of causing interactions
with other medications.

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Lewy body dementia
In developed countries ,Lewy body dementia(LBD) is the
second commonest cause of dementia after
Alzheimer's disease.
Main features include:
1-Development of dementia with features overlapping
with those of Alzheimer's disease
2-Development of features of Parkinson's disease
3-Fluctuation in severity of condition on a day-to-day
basis
4-Early development of visual hallucinations

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Lewy body dementia
Patients with DLB are often abnormally sensitive to
neuroleptic therapy, developing parkinsonism even if
they have not shown such signs before drug
administration.

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Vascular dementia
-Historically, considered the second most common cause of
dementia, accounting for about 20 percent of cases.
- Stepwise deterioration.
-Focal neurological signs consistent with stroke may be present.
-Pure” vascular dementia may be relatively unusual; vascular
changes may more commonly coexist with Alzheimer's
plaques.
- Most of the drugs used to treat cognitive symptoms of
Alzheimer’s disease have also been shown to help individuals
with vascular dementia.

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Normal pressure hydrocephalus
Triad of dementia, gait apraxia and urinary incontinence
Normal pressure hydrocephalus must be differentiated from patients whose
ventricular enlargement is due to brain atrophy e.g. Alzheimer’s disease

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CT brain in Alzheimer’s disease

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Chronic subdural hematomas

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Frontotemporal dementia(FTD)
-FTD is the fourth most common dementia (after Alzheimer
disease, vascular dementia, and dementia with Lewy bodies),
- Personality change occurs before any form of memory loss,
unlike Alzheimer's, where memory loss typically presents first.
-40% of cases of FTD are familial, but only 10% follow a clear
autosomal dominant pattern.

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Frontotemporal dementia(FTD

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Causes of death
-Appetite decreases , patients lose the ability to
swallow, leading to poor nutrition and a high risk
of aspiration pneumonia.
-Aspiration, where a person's food goes "down the
wrong tube" when they swallow it, greatly increases
the risk of pneumonia developing because they're not
able to fully cough and clear the food out of their
esophagus and then it settles into their lungs.

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Cholinesterase inhibitors
.Rivastigmine 6-12 mg
.Galantamine 8-24 mg
Rationale: Acetylcholine is reduced in the cerebral
cortex and hippocampus due to a selective loss of
cholinergic neurons.
Glutamate antagonist
“Memantine 10-20 mg”
Pharmacotherapy

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Memantine – new perspectives in dementia
treatment
 Memantine represents the first and only drug in a new class –
NMDA receptor antagonists – for the treatment of Dementia
 Memantine blocks pathological activation of NMDA receptors
by excessively high synaptic levels of glutamate while
preserving physiological activation required in learning and
memory formation
 Memantine is indicated for the treatment of moderate and
severe Dementia – the first treatment approved for this
indication
Memantine SmPC; Danysz et al 2000

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 Both cholinesterase inhibitors and memantine
produce modest but identifiable improvements
in activities of daily living.
 Patients and their care givers often report the
improvements in activities of daily living
Pharmacology

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Although antipsychotic drugs consistently
reduce agitated behavior, concerns have
been expressed recently over the safety
of both the older antipschotics (such as
haloperidol) and the new generation of
antipsychotics (such as risperidone,
olanzapine, and quetiapine). It increase
risk of stroke and mortality.
WARNING

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Thank you