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