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Lecture 8 and Lecture 9

Why did the level of AD rise over time?

Medical and technological advances have led to a fairly longer life expectancy rate, so that led to a great rise in the level of Alzheimer's disease

What are the two types of amnesia?

Anterograde and Retrograde Amnesia

Define anterograde amnesia

the ability to recall events that occurred before the incident

Define retrograde amnesia

the ability to recall events that occurred after the incident

Define aphasia

the ability to speak is compromised

- Caused by damage to the portions of the brain that are responsible for language

- Primary signs include speech problems, trouble understanding speech, and difficulty with reading and writing

Define anomic aphasia (aka anomia):

a type of aphasia characterized by problems recalling words or names

Define apraxia

inability to perform motor tasks even though
• The command is understood
• Patient is willing to perform the task
• Muscles work properly
• The task may have already been learned

Define acquired apraxia

develops in a person who was previously able to perform the tasks or abilities

Define apraxia of speech

speech sounds and words distorted, repeated, or left out. Difficulty to out words in the correct order. Struggling for the right word, etc.

Orofacial apraxia

cannot carry out movements of the face

Ideational apraxia

cannot carry out learned complex tasks in proper order, such as putting on socks before putting on shoes

What is agnosia?

- Inability to recognize objects or persons

- Difficulty recognizing geometric features, or may be able to perceive geometric features but cannot recognize the object or face

-May affect one sensory modality such as vision or hearing: a person may have difficulty in recognizing an object as a cup or identifying a sound as a cough

- Can result from strokes, dementia, developmental disorders, or other neurological conditions - typically results from damage to brain in the occipital cortex or parietal cortex

Brain imaging: Positron Emission Tomography

- PET scans are an important part in the diagnosis of cerebral illness
- The images are obtained by tracing the blood flow with water labeled with 15O or by glucose metabolism with labeled deoxyglucose which has a hydrogen atom replaced by a 18F atom.
- A brain with Alzheimer's Disease has much less tissue than a normal brian

What are the main pathological features of AD?

• Neuronal loss - synaptic loss - connection between neurons fades and the neurons die off

• Depletion of neurotransmitters

• Trying to get rid of: Senile plaques (extracellular lesions)

• Trying to get rid of: a bundle of filaments - Neurofibrillary tangles (intracellular lesions)

• Activation of immune cells

• Amyloid plaque is the senile plaque and the neurofibrillary tangles are also senile plaques - both are bad

• Plaques are specific of AD! If you see plaques in this density, you see AD!

Ideomotor Apraxia

Can not performed a learned task. for example, if given a screw driver, may try to write with it.

Limb-kinetic apraxia

difficulty making precise movements with an arm or leg

Where in the brain does AD start and where does it spread to?

AD starts in the medial-temporal lobe and then spreads to the limbic system and then goes to the cortical regions of the brain

Explain the process of AD taking over the brain

- Pittsburg Compound B binds to the plaques (called something else, ask what) in the brain of the patient

- This maker is believed to bind the amyloid plaques that are ubiquitous in patients with AD

- The cholinergic neurons project to different areas of the cortex - part of the chemical imbalance that is present in AD

The most common treatment for AD attempt to influence the _____ system

cholinergic system

acetylcholinesterase inhibitors (tacrine, donezepil, etc) - also modulator of NMDA recptors (glutamatergic system)

What are the risk factors?

Genetic and Environmental

Genetic: Apo E Polymorphism

Environmental: diet, physical and intellectual activity, education
- vascular disease, diabetes, head trauma, etc.
* studies have shown that Mediterranean diets prevent the onset of AD

look at the picture with the scissors (enzymes) cutting the beta-amyloid

- schematic diagram of the amyloid precursor protein and its cleavage to give Beta amyloid

- the genetic factors pointing toward amyloid Beta is the best hypothesis we have toward AD (I think...)

picture of the (DNA?) strand - the blue and red mean mutations
picture of the evolution of plaques

• this peptide has the ability to self-propagate
• the monomers turn into oligomers which turn into alpha beta fibrils which turn into EM of fibrillar alpha beta
• accumulating AB in the plaques is not good - harms the cells

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