Alzheimer’s Disease
Jun 01, 2015
Alzheimer’s 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 Down’s 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
Pick’s Disease
Diffuse Lewy Body Disease
Parkinson’s 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)???
Parkinson’s 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
Parkinson’s 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