Dementia Flashcards
Define dementia.
Dementia is an acquired global impairment of intellect, memory and personality without impairment of consciousness.
List the major causes of dementia.
Causes of dementia include:
1 - Alzheimer’s disease.
2 - Dementia with Lewy bodies.
3 - Vascular disease.
4 - Frontotemporal dementia.
5 - Creutzfeldt–Jakob disease.
List the cognitive deficits in Alzheimer’s disease.
Cognitive deficits in Al\heimer’s disease include:
1 - Long and short term memory loss.
2 - Poor decision making / judgement.
3 - Language deficits.
4 - Deficits of praxis.
5 - Impaired visuospatial processing.
However, the following are relatively spared:
1 - Procedural memory.
2 - Some aspects of language.
3 - Sensation, with the exception of smell.
How does the morphology of the brain change in Alzheimer’s disease?
- In alzheimer’s disease, there is shrinkage of the medial temporal lobe.
- As a result, the ventricles enlarge to fill the space.
- There is atrophy in other areas, but the medial temporal lobe is affected the worst.
List 2 histopathological findings in Alzheimer’s disease.
Histopathological findings in Alzheimer’s disease include:
1 - Amyloid-beta plaques.
2 - Tau neurofibrillary tangles.
What is homocysteine?
How does it relate to Alzheimer’s?
- Homocysteine is an indicator of altered folate metabolism due to vitamin B12 and B9 deficiency.
- High homocysteine is associated with Alzheimer’s.
- Therefore, vitamin B12 and B9 supplements can help prevent Alzheimer’s.
- See A* card 18 in neurobiology of ageing deck for more info on homocysteine.
From which protein is amyloid-beta formed?
How is it formed?
- Amyloid-beta is formed from amyloid precursor protein (APP).
- Normally, APP is cleaved to form a soluble protein, which has a role in neuroprotection and neuroplasticity.
- Amyloid-beta, which is normally a part of the soluble APP protein, is formed by abnormal cleavage of APP by secretase enzymes, which occurs due to mutations to the APP gene.
What causes the abnormal outgrowths in Alzheimer’s disease?
- Microglia invade amyloid plaques and become activated.
- The activated microglia release cytokines and growth factors such as fibroblast growth factor.
- The cytokines and growth factors result in excess tissue growth (resulting in outgrowths).
List 6 ways of reducing risk of Alzheimer’s disease.
Alzheimer’s disease risk can be reduced by:
1 - Physical activity.
2 - Memory aids.
3 - Healthy nutrition.
4 - Lowering blood pressure.
5 - Folic acid B vitamin supplements.
6 - Oestrogen replacement following menopause.
- If left later than 5 years following menopause, the menopause-induced reorganisation of oestrogen receptors in the brain leads to such changes that oestrogen supplementation becomes harmful.
On which chromosome is the APP gene found?
The APP gene is found on chromosome 21.
What are the main functions of tau?
The main functions of tau include:
1 - Stabilising microtubules.
2 - Promoting tubulin assembly into microtubules.
How is tau altered in Alzheimer’s disease?
- Tau is not mutated in Alzheimer’s disease.
- However, changes in posttranslational modification of tau cause it to become heavily phosphorylated.
- This is due to overactive kinases and hypoactive phosphatases.
- This causes tau proteins to form aggregates with each other rather than assisting in microtubule assembly / stabilisation.
What is the problem with the tau hypothesis for drug development?
The problem with the tau hypothesis for drug development is that the possible targets it offers (kinases and phosphatases) are too ubiquitous and promiscuous to be targeted therapeutically.
What is the inflammatory hypothesis of Alzheimer’s disease?
What triggered research into this hypothesis?
When in Alzheimer’s disease are these processes seen?
- The inflammatory hypothesis of Alzheimer’s disease is that proinflammatory agents:
1 - Cause neuronal death directly through the inflammatory response.
2 - Potentiate APP cleavage, forming amyloid beta.
- This forms a self-perpetuating cycle, as amyloid-beta stimulates microglia to release more proinflammatory agents.
- The inflammatory hypothesis of Alzheimer’s disease was triggered by the finding that rheumatoid arthritis patients who are treated with NSAIDs for long periods of time are significantly less likely to develop Alzheimer’s disease.
- These processes are only seen in the late stages of dementia, indicating that it is not a trigger for the disease.
What is the problem with the inflammatory hypothesis for treating Alzheimer’s disease?
The problem with the inflammatory hypothesis for treating Alzheimer’s disease is that NSAIDs cause:
1 - Gastric bleeding.
2 - Renal failure.
- This is due to the decrease in prostaglandin production, which has a protective effect against ulcers and is required for renal blood flow autoregulation.
- Since NSAIDs would need to be used chronically to treat Alzheimer’s, they would be unsuitable.
