Lecture 9- Memory and Disease Flashcards
What is the most common form of dementia?
Alzheimer’s disease
What is dementia?
Dementia is the term used when a person experiences a gradual loss
of brain function due to physical changes in the structure of their
brain.
Symptoms:
- Loss of memory
- impaired reasoning
- reduced language skills
- loss of daily living skills.
What are the mild symptoms of Alzheimer’s Disease?
- Confusion and memory loss
- Disorientation; getting lost in familiar surroundings
- Problems with routine tasks
- Changes in personality and judgment
What are the moderate symptoms of Alzheimer’s?
- Difficulty with activities of daily living, such as feeding and bathing
- Anxiety, suspiciousness, agitation
- Sleep disturbances
- Wandering, pacing
- Difficulty recognizing family and friends
What are the severe symptoms of Alzheimer’s?
- Loss of speech
- Loss of appetite; weight loss
- Loss of bladder and bowel control
- Total dependence on caregiver
How long in years does it take in Alzheimer’s disease to get from diagnosis to severe symptoms?
6-7 years
What test is commonly used in the diagnosis of Alzheimer’s disease?
- Phonemic and Semantic Verbal Fluency (SVF)
- Patients are asked to generate as many words as they can either starting with a certain letter of the alphabet (phonemic fluency) or belonging to a certain semantic category e.g. animals (semantic fluency).
- Measure the number of correct words spoken by the patient in one minute
In Pakhomov et al (2016) what longitudinal changes were found in SVF tests?
- All cognitively were normal (CN) at start -Assessed at ~15 month intervals and retrospectively reassigned to group
- AD group performance went down a lot, those with minor cognitive impairment had slight decline, control line was relatively flat
What is the primary risk factor for Alzheimer’s disease?
- Age: The likelihood of developing the condition doubles every five years after you reach 65 years of age
- Creates a upwards curve
In what population is Alzheimer’s prevalence meant to keep increasing?
65 plus. 15-39 and 40-64 age groups only increase slightly.
What is the current prevalence rate of Alzheimer’s at age 85?
20%
What are the brain changes observed in Alzheimer’s?
- Shrinkage of tissue/ cortex, especially the hippocampus (consistent with memory issues), temporal lobe is also often shrunk
- Enlargement of ventricles
What are the two main neuronal defects found in Alzheimer’s disease?
- Amyloid plaques: clusters sitting outside neurons/ cells
- Neurofibrillary tangles: Inside neurons, causing degradation
What causes the loss of the cholinergic projection neurons in the basal forebrain?
- This is a brain change associated with Alzheimer’s disease
- These neurons sit in the basal forebrain and project out to other cortex areas communicating via the neurotransmitter acetylcholine. In Alzheimer’s the release of acetylcholine is reduced meaning these is not as much communication across synapses.
How is mild to moderate Alzheimer’s disease sometimes treated in relation to the neurotransmitter acetylcholine?
-Under normal conditions acetylcholine carries a message across the synapse, and then is broken down by a cholinesterase.
-Therefore, an effective treatment for Alzheimer’s can be to use
Cholinesterase inhibitors (AChE-Is) such as Donepezil (Aricept), Rivastigmine (Exelon) and Reminyl (Galantamine).
-These drugs block cholinesterase, giving the acetylcholine extra time to transmit messages.
-Effective in prolonging functioning the early stages of the disease but by no means is a complete solution.
What is beta amyloid? What change to beta amyloid occurs in Alzheimer’s disease?
-Amyloid Precursor Protein (APP) is a protein that appears to
have an important role in synaptic plasticity.
-Beta Amyloid (Aβ) is produced when APP (precursor protein) is cut into segments (cleaved) by secretases.
-In AD, Beta Amyloid is overproduced. It forms fibrillar plaques on the outside surface of cells. Plaques are distributed throughout the cortex.
Where does APP span before it is cleaved into beta amyloid protein?
The cell membrane
What enzymes cleaves APP into beta amyloid?
- First Alpha Secretase cuts APP at the level of the cell membrane
- Beta Secretase and Gamma Secretase then come along and cut allowing the toxic Beta-Amyloid fragment to be produced.
Why do beta-amyloid fragments from clumps or plaques?
Because they are sticky
Does amyloid plaque location map well to Alzheimer’s symptoms? Have
Amyloid Plaque location doesn’t map well onto symptoms: Occur across the cortex not just in areas associated with memory i.e. the temporal lobe also some people have lots of plaques but cognitively are fine
Have Clinical trials of drugs that target Beta Amyloid been successful? What is now the focus?
- No, have been disappointing so far.
- The drugs may be successful at clearing plaques but this has no effect in eleviating Alzheimer’s symptoms.
- Recent focus is on targeting Beta Amyloid Oligomers
Is the oligomer evidence legitimate?
- Possibility that some of the oligomer evidence is fraudulent
- The bands in the research looked identical like they had just been copy and pasted when they should have represented two separate proteins.
- Millions of dollars spent following up on this work but it is fake= real consequences for real people
What changes in the protein TAU are associated with Alzheimer’s?
- Microtubules stabilized by molecule called tau
- In Alzheimer’s tau loses ability and microtubules start to break down forming tangles inside the cell
- Neuron falls apart due to no structural support
Do the locations of neurofibrillary tangles map well to the symptoms of Alzheimer’s?
Yes. As Alzheimer’s progresses NFTs appear initially in the
transentorhinal (perirhinal) cortex and then in neighbouring regions.
NFT progression parallels cognitive deficits. This progression is labelled in terms of Brak stages after the scientist who discovered the link.
