Cognition and Dementia - Alzheimer's disease.

What percentage of the government's research budget is spent on alzheimer's research?

What is the annual cost of dementia in the UK?

How is the money spent on dementia distributed? (Highest first)

Which sex is more likely to get dementia?

What are three things are dementia characterised by?

What are the cognitive impairments associated with dementia?1

When was the pathology of alzheimer's disease first recorded? By who?

What percentage of people over the age of 65 have Alzheimer's? Over 85?

What precentage of dementia does alzheimer's account for in the UK?

How many dementia cases are there in the UK?

How many dementia cases are there in under 25s?

What is average length of survival after diagnosis?
What is the range of length of survival?

How do the symptoms in Alzheimers progress?

What are the four ways of diagnosing AD?

What does a PET/Spect fMRI look for?

Which drug is used in a pupil dilation test? Why is the pupil dilation test used?

How are TAU and AB proteins altered?

What are the signs of AD post mortem?

Describe neurofibrillary tangles

Describe senile plaques.

Which are the three areas most affected by AD? (Lobes)

How thick are the protein fibres in plaques?

What are the four hypotheses for AD pathophysiology?

What is the reasoning behind the cholinergic hypothesis?

What is the reasoning behind the glutamatergic hypothesis?

What is the reasoning behind the amyloid hypothesis? (2)

What is the reasoning behind the TAU hypothesis? (2)

Which cholinergic pathway(s) are affected in AD?

Which is one of the first areas in the brain to be affected by AD? Which pathway does this therefore affect?

Which other pathway/peptide is effect?

Where is choline acetylcholinesterase (CAT) lost from in AD?

What else is lost in relation to acetylcholine?

What correlates with the formation of plaques?

Which receptors are affected in the cholinergic hypothesis?

What effect does the knockout of nACHR have on the cognitive ability of mice?

How does the degree of cell loss vary between post mortem and biopsy?

Which other brain regions are effected in AD? Markers for which transmitter and what type of neuron is lost?

What type of AD is genetically linked? Which chromosome is effected which also turns up in which disease? Which other chromosomes are linked?

What are the other 4 potential causes of AD?

What could be the environmental factors that lead to AD?

What are the transmissible agents which could cause AD? How do they spread?

What results from the misprocessing of APP?

What is soluble APP essential for in the cholinergic system?

Why does the cleavage of APP to B-amyloid occur?

What happens to the normal metabolic pathway and what does this result in?

What do Y40 and Y42 correspond to?

Which enzyme cleave APP in normal processing?

Which enzyme is involved in the misprocessing of APP?

What are the two main proteins/genes in a-secretase?

What is the target for y-secretase after
1) a-secretase has cleaved APP?
2) B-secretase has cleaved APP?

What are the five genes/proteins which make up y-secretase?

In familial alzheimer's which proteins/genes in y-secretase are mutated?

What is APP cleaved into by normal processing? Abnormal?

Other than in Y-secretase mutations of what are associated with APP misprocessing?

What two type of AB are produced? Which is more toxic?

What happens after the formation of plaques?

What is the function of Tau usually?

What is responsible for 1) phosphorylation and 2) dephosphorylation of tau?

Why does the detachment of hyperphosphorylated Tau lead to cell death?

What are the three components of neurofibrillary tangles?

What are the five direct events that are involved in the hyperphosphorylation of TAU?

What are the four main indirect effect that lead to Tau hyperphosphorylation?

What happens to normal Tau when it comes into contact with a NFT?

What type of disease is a mutation of chromosome 17 associated with? Which protein does this mutation implicate?

EVIDENCE FOR AB (7)
1) What percentage of alzheimer's is familial/early onset? Where are the mutations found? Which implicates more plaques?

2) What happen to people with Downs Syndrome by the time they reach their 40s? Why?

3) What is APOE4? How is it related to AD?

4) What happened in APP transgenic mice phenotypes?

5) The close proximity of what also implicates AB as being the main cause of AD?

6) What can AB plaques cause in vitro? Why might this not be a valid argument for the AB hypothesis?

7) A positive mutation of what was found to have a protective effect on AD?

What are the main issues with AB and AD? (4)

Which arguments show support for Tau being the most important in AD?

What are the two different pathways which combine Tau and AB pathology?

From which study is AB thought to bring about Tau hyperphosphorylation?

What could be a common upstream driver of AB plaques and Tau hyperphosphorylation?

What are three target pathways?

What happens first: Neuronal death or synaptic loss?

How does tau hyperphosphorylation cause neuronal cell death?

What can be seen in PET scans before full symptoms of AD occur?

What is the main system targeted for treatment of AD?

What are the three potential targets of new treatment for AD?

What are the main effects of acetylcholinesterase inhibitors?

What are the three cholinesterase inhibitors used to treat AD?

What is MEMANTINE used for? Is it effective?

Why are cholinesterase inhibitors only useful for a limited period of time?

When is Memantine used in AD?

How is B-amyloid involved in glu excitotoxicity? (3)

What are some of the future targets for dementia treatment?

XANOMELINE

AF102B

What positive effects might nicotine have on cognitive factors? What doesn't it affect?

How is M1 agonists thought to help treat AD?

What was the aim of vaccination therapies for AD? Why didn't it work?

How are B- and Y-secretase inhibitors meant to help treat AD?

How are statins meant to help help treat alzheimer's?

What is Clionquinol (PBT-2) and how is meant to help treat AD?

Give an example of NSAIDs. How are they meant to treat alzheimers?

What was and what went wrong in the AN-1792 trial?

What is the mechanism of statins that is thought to help with AD, why?

What is solanezumab? How does it work?

What happened in the first human trial?

Why was the first trial wrong?

How have they modified the trial?

What is Bapineuzumab?

What else is being developed as an immune therapy?

Why has B-secretase inhibitors been hindered so far?

What is semagacestat? What did it show in clinical trials?

What else does y-secretase effect? What does blocking y-secretase also cause?

What does notch usually suppress? What effect did semagacestat have?

What is an important target of y-secretase? What is it involved in?

What does tarenflurbil do? Why did it perform badly in phase III trials?

What is tramiprostate? How did it do in clinical trials

How does lithium potentially treat AD?

What is paclitaxel? What was it first used in?

What is TauRX

How does TauRx prevent Tau aggregates?

What is the benefit of TauRX (Rember/methylthioninium chloride)

What have phase II clinical trials of Rember/Methylthioninium chloride shown?