alzheimer's dementia

Question 1

what is AD?

Answer 1

progressive degenerative disease of the brain accounting for majority of dementia in UK

Question 2

what are risk factors for AD?

Answer 2

increasing age

family history of Alzheimer’s disease

5% of cases are inherited as an autosomal dominant trait
- mutations in the amyloid precursor protein (chromosome 21), presenilin 1 (chromosome 14) and presenilin 2 (chromosome 1) genes are thought to cause the inherited form

apoprotein E allele E4 - encodes a cholesterol transport protein

Caucasian ethnicity

Down’s syndrome

Question 3

what are macroscopic pathological changes seen in AD?

Answer 3

widespread cerebral atrophy, particularly involving the cortex and hippocampus

Question 4

what are microscopic pathological changes seen in AD?

Answer 4

cortical plaques due to deposition of type A-Beta-amyloid protein and intraneuronal neurofibrillary tangles caused by abnormal aggregation of the tau protein

hyperphosphorylation of the tau protein has been linked to AD

Question 5

what are biochemical pathological changes seen in AD?

Answer 5

deficit of acetylcholine from damage to an ascending forebrain projection

Question 6

what is pathophysiology of AD?

Answer 6

paired helical filaments are partly made from a protein called tau

tau is a protein that interacts with tubulin to stabilize microtubules and promote tubulin assembly into microtubules

in AD are tau proteins are excessively phosphorylated, impairing its function

Question 7

what is non-pharmacological management of AD?

Answer 7

group cognitive stimulation therapy for mild-mod dementia

group reminiscence therapy + cognitive rehabilitation

Question 8

what is pharmacological management of AD?

Answer 8

mild to mod AD: acetylcholinesterase inhibitors- donepezil, galantamine, rivastigmine

2nd line: memantine- NMDA receptor antagonist

Question 9

when is memantine used for AD?

Answer 9

moderate AD who are intolerant or CI to acetylcholinesterase inhibitors

add-on drug to acetylcholinesterase inhibitors for mod-severe AD

monotherapy in severe AD

Question 10

how do you manage non-cognitive symptoms of AD?

Answer 10

does not recommend antidepressants for mild-mod depression in AD

antipsychotics if pts at risk of harming themselves/others or agitated/hallucinations/delusions cause severe distress

Question 11

what are CI to using donepezil?

Answer 11

relative CI if bradycardia/sick sinus syndrome

Question 12

what are adverse effects of donepezil?

Answer 12

insomnia