Alzheimers Disease

Background
First description in 1907
51 year old woman with a 4 1/2 year course
of progressive dementia
Autopsy: Neurofibrillary tangles, severe
loss of cortical neurons
AD = senile dementia
Molecular approaches

Epidemiology
Age: strong risk factor 47.2% for 85 years
14 million individuals with AD by 2040
Family history of dementia (70)
Head Trauma
Cardiovascular diseases

Etiology and Pathogenesis

Not known : many theories
Pathologic: neuronal degeneration and death in
specific brain areas that leads to gradual decline
in memory and other cognitive functions
Chronic process
Deficiency of growth factors or excess of
excitatory Aas.
Intracellular calcium, free radicals, abnormal
proteins

Etiology and Pathogenesis

Genetic defect
Systemic metabolic defect
Slow or latent virus disorders
Toxins
Combination

Genetics
Proximal region of chromosome 21 locus
(early onset)
Chromosome 19 locus (late onset)
Correlation with Downs syndrome

Neurochemistry
Loss of cholinergic markers
choline acetyltransferase
acetylcholinesterase
acetylcholine synthesis is diminished
Loss in Nucleus basalis of Meynert
Presynaptic adrenergic deficit (neocortex)
Loss of serotonin and peptides

Clinical Features
Dementia: major health problem
Symptom complex: more than 70 entities
Reversible or irreversible
AD: most common in adults
4 million persons in the US
Fourth leading cause of death

Diagnostic Criteria
Dementia: clinical and neuropsychological
testing
Deficits in two or more cognitive functions
Progressive worsening of memory and other
cognitive function, such as abstract thinking ,
judgement, problem solving , language,
perception, and ability to learn new skills

Diagnostic Criteria
No disturbance of consciousness
Onset between ages 40 and 90
Abscence of others systemic or brain
disorders responsible for the memory loss
Diagnostic accuracy 90%

Clinical Picture
Early decline in recent memory
Loss of judgement and abstract thinking
Impaired language and discalculia
Disorientation
Loss of personality
Apathy and lethargy
Behavior problems

Neurologic Examination
Few subtle abnormalities
Cranial nerves:Olfactory identification deficit
Primitive reflexes (grasp, tonic foot,
palmomental)
Language abnormalities ( 100%)
Impaired word finding (anomia)

Neurologic Examination
Apraxia
Myoclonic jerks
Decline in intellectual function
Mean survival time is 8.1 years
Range of survival 1 to 20 years

Diagnostic tests
No definitive diagnostic test for AD
Differential diagnosis
Blood count, Electrolytes, Ca, Phosphorus,
renal, liver and thyroid function, Vit B12
and folic acid levels, drug screen
EEG: Non specific

Diagnostic tests
CT and MRI: Cerebral atrophy and
ventricular enlargement, other lesions
PET: Reduced regional CBF and glucose and
oxygen metabolism in the parietal and
temporal lobes
Neuropsychological testing

Differential Diagnosis
Vascular Dementia
Picks Disease
Diffuse Lewy Body Disease
Parkinsons plus syndromes
Mass lesions
Metabolic causes

Neuropathology
Severe cortical atrophy
NFT formation
Neuron loss
Altered neuritic process
Senile plaques

Treatment
Non specific
Taking care of the patient and to avoid
systemic complications
Rivastigmine (Exelon)???

Parkinsons Disease

Background
James Parkinson in 1817
Involuntary tremulous motion, with
lessened muscular power, in parts not in
action and even when supported; with a
propensity to bend the trunk forward, and
to pass from a walking to a running pace,
the senses and intellect uninjured
No reference to rigidity or to slowness of
movement

Epidemiology
The disease begins between 40 and 70
Predisposing: Trauma, emotional upset,
overwork, exposure to cold
Familial cases (5%)
Half million patients affected
1% population over 50 years is affected in
the US

Clinical Picture

Resting tremor (pill rolling)

Rigidity
Poverty and slowness of voluntary movement
Expressionless face
Festinating gait
Stooped posture
Infrequency of blinking
Dementia

Differential Diagnosis

Parkinsons syndromes
Post-encephalitic (Von Economo)
Toxic
Drug induced
Vascular
Traumatic
Striatonigral degeneration
Progressive supranuclear palsy
Mass lesions

Pathology
Loss of pigmented cells in the susbtantia
nigra (PR)
Lewy bodies (eosinophilic cytoplasmic
inclusions)
Depletion of striatal dopamine

Staging
Hoehn and Yahr scale
I: Unilateral involvement
II: Bilateral involvement, without postural
abnormalities
III: Bilateral with mild postural imbalance,
independent life
IV: Bilateral, instability, dependent
V: Severe

Treatment
L-dopa- Carbidopa
Bromocriptine
Lisuride and pergolide
Amantadine
Deprenyl
Anticholinergic drugs

Treatment
Thalamotomy
Pallidotomy
Grafts
Striatum
Substantia nigra