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Alzheimer's y Parkinson dis..ppt

Date post: 01-Jun-2015
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Alzheimer’s Disease
Transcript
  • 1. Alzheimers Disease

2. 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

3. 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

4. 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

5. Etiology and Pathogenesis

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

6. Genetics

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

7. 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

8. 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

9. 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

10. 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%

11. 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

12. Neurologic Examination

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

13. Neurologic Examination

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

14. 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

15. 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

16. Differential Diagnosis

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

17. Neuropathology

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

18. Treatment

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

19. Parkinsons Disease 20. Background

  • James Parkinson in 1817
  • Involuntary tremulous motion, with lessenedmuscularpower, 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, thesenses and intellect uninjured
  • No reference to rigidityor to slowness of movement

21. 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

22. Clinical Picture

  • Resting tremor (pill rolling)
  • Rigidity
  • Poverty and slowness of voluntary movement
  • Expressionless face
  • Festinating gait
  • Stooped posture
  • Infrequency of blinking
  • Dementia

23. Differential Diagnosis

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

24. Pathology

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

25. 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

26. Treatment

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

27. Treatment

  • Thalamotomy
  • Pallidotomy
  • Grafts
  • Striatum
  • Substantia nigra

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