(8/16/10) - Nutrition, Diet and Translational Research in Neuroscience

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.