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1. Relate how Alzheimer’s Disease was first recognized and how it came to be recognized as a common disease.

· 1907: First recognized in 46 yo F “Auguste D.”, sub-acute onset of pathological jealousy, dysnomia, short term memory deficits

· 1964: community survey, recognize AD as a fairly common disease of the elderly, “senile” dementia


2. Understand the general symptoms, pathology and disease mechanisms for Alzheimer’s Disease.

Sx’s

  • Memory loss
  • Language disturbances
  • Visuospatial deficits
  • “dysecutive”: impaired judgment, motivation, insight
  • neuropsychiatric: depression, anxiety, sleep disturbance, psychosis


Pathology

  • brain atrophy
  • neuritic plaques
  • altered metabolism of APP
  • deposition of beta amyloid
  • Neurofibrillary Tangles
  • Cytoskeletal pathology (girders and trusses)
  • Altered metabolism of tau protein
  • Neuronal death in specific brain regions
  • Specifice neurotransmitter deficits (esp. Ach, serotonin, norepinephrine, glutamate)


Disease Mechanisms

  • Metabolism of Amyloid Precursor Protein (APP) to form beta-amyloid
  • APP cut by alpha secretase
  • APP cut by beta secretase, then gamma secretase forming beta-amyloid
  • Beta amyloid (the fragment) increases in concentration, forms dimmers, then trimers, then oligomers (polymers), then aggregates into plaques
  • Tau (Microtubule Associated Protein MAP2): axonal dissolution and dysfunction in AD
  • Neurofrillary Tangles
  • Found inside neurons
  • The paired helical filaments are the microtubule associated protein tau in an abnormally phosphorylated state
  • Associated with neuronal death
  • Good correlation with cognitive impairment



3. List some risk factors for Alzheimer’s Disease: Genetic and Environmental.

Genetic

  • Causative mutations: APP, Presenilin 1 (PS1), Presenilin 2 (PS2)
  • Risk alleles: APOE4 (apolipoprotein E)
  • premorbid intelligence


Environmental

  • Education (“protective”)
  • Cognitive activities/premorbid intelligence
  • Physical Activities
  • Social networks/engagement in games/activities


4. Describe how Alzheimer’s Disease is currently diagnosed and treated.

  • Clinical examination
  • History
  • Time and type of onset
  • Physical
  • Laterality on neuro exam
  • Extrapyramidal sx’s
  • Cognitive screening test (MMSE) with deficits in two or more areas of cognition
  • Progressive worsening of memory and other cognitive functions
  • No disturbances of consciousness
  • Absence of systemic disorders or other brain diseases that could account for the deficits and progression
  • Neuroimaging: atrophy (first in medial temporal lobe), energy metabolism declines in posterior temporal/parietal regions, amyloid plaque distributions


Treatment

  • Symptomatic improvement (cognitive and behavioral)
  • Non-specific therapies (antioxidants, anti-inflammatory agents)
  • Anti-amyloid therapy
  • Anti-tau phosphorylation/ neurofibrillary tangle strategies


5. Discuss how Alzheimer’s can possibly be prevented or its progression postponed/slowed. Prevention

  • Maintain ideal body weight
  • Reduce intake of foods high in fat and cholesterol


6. Have a general understanding of how current research advances may translate into future therapeutic strategies for Alzheimer’s Disease.


· Clinical trials include ginkgo, beta-carotene, folic acid, Vit E, etc.

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