Alzheimer's Disease

Front 1

What is Alzheimer's Disease?

Back 1

A chronic neurodegenerative that accounts for most cases of dementia.

Front 2

What causes familial AD?

Back 2

Dominant mutations in genes

Front 3

What are the genes that cause familial AD?

Back 3

• Beta Amyloid Protein (APP)
  
• Presenilin 1 (PSEN1)
  
• Presenilin 2 (PSEN2)
  
• They all function in a common pathway
  

Front 4

What is Beta amyloid precursor protein implicated in?

Back 4

Synapse formation and regulation, neural plasticity and iron export.

Front 5

What is B-Amyloid deposition a pathological feature of?

Back 5

AD and normal ageing

Front 6

Mutations cluster near parts important for what function?

Back 6

Cleavage (cutting up proteins)

Front 7

What is TREM2's role?

Back 7

• Anti-inflammatory
  
• Interferes with the ability to prevent plaque buildup
  

Front 8

What are PSEN1 & 2?

Back 8

Transmembrane proteins and components of gamma secretase.

Front 9

What does Gamma Secretase do?

Back 9

• Cleaves APP and other proteins
  
• GS is a pair of scissors and PSEN1 & 2 are handles.
  

Front 10

What is the amyloid hypothesis?

Back 10

Extracellular amyloid beta deposits (deposits outside the cell) are the main cause of AD.

Front 11

What is the major genetic risk factor in sporadic AD?

Back 11

ApoE4 allele

Front 12

What is the main function of ApoE?

Back 12

• Lipid metabolism
  
• Involved in endocytosis in AD (the transport of molecules into cells)
  

Front 13

How is ApoE4 implicated in sporadic AD?

Back 13

It is not good at amyloid beta breakdown causing a build up of the protein, thus linking to the amyloid hypothesis.

ApoE4 is BAD NEWS.

Front 14

What is the risk of developing AD with ApoE4?

Back 14

1 = 2-3x risk

2 = 12x risk

Also linked to early age onset

Front 15

What are the main symptoms of AD?

Back 15

• Memory problems - forgetting/misplacing items, forgetting friends/family
  
• Confusion - getting lost, wandering
• Psychological - Aggression + irritability, stress, depression, apathy, lashing out
• Language - reduced to simply phrases/words, language coordination loss, reading/writing skills worsen
• Physical - Incontinence, sight loss, poor motor function, muscle mass lose, sundowning

Front 16

What is the main diagnostic problem with AD?

Back 16

Preclinical AD may be mistaken for normal ageing and when symptoms finally become noticeable it becomes clinical AD and too late for treatment.

Front 17

What is the treatment for AD?

Back 17

• Cholinesterase inhibitors - Donepezil, Rivastigmine, Galantamine - for mild to moderate symptoms.
  

• NMDA receptor antagonists - For moderate to severe AD
  

• Antipsychotics - Risperidoe (Off label: Olanzapine, Haloperidol, Quetiapine)
  

Front 18

How do cholinesterase inhibitors work in AD?

Back 18

Prevent acetylcholinesterase breaking down acetylcholine and thus increasing nerve connections.

Front 19

How do NMDA receptor antagonists work in AD?

Back 19

Blocks excess glutamate production which is secreted from damaged cells which cause further damage to more cells.

Front 20

Why are antipsychotics prescribed to AD patients?

Back 20

To deal with aggressive and psychotic symptoms.

Front 21

What supportive measures can be taken for AD patients?

Back 21

• Occupational therapy
  
• Speech therapy
  
• Assistive technology
  
• Home visits
  
• Mobility aids/assistance
  
• CBT
  
• Diaries/Calendars
  

• Adding handrails at home and technology to help live independently
  
• Manage symptoms and prepare
  

Front 22

What are the cortical abnormalities presented in AD?

Back 22

Cortical atrophy - Particularly ventricles and hippocampus