AD and Neurodegeneration

Question 1

What 5 categories of process can cause dementia?

Answer 1

AD
Stroke
Neurodegenerative conditions (Lewy body disease, PD, Huntington's)
Major organ failure
Other

Question 2

What type of plaques are seen in AD?

Answer 2

Neuritic plaques

Question 3

What else is seen upon staining of brain slides?

Answer 3

Tau neurofibrillary tangles

Question 4

What happens to brain size in AD?

Answer 4

Atrophy of cortex

Frontal and hippocampal especially

Question 5

What are the language deficits seen in AD?

Answer 5

Difficulty finding words
Dysnomia
Verbal paraphasias

Question 6

What are the mental function issues seen in early AD?

Answer 6

Orientation and visuospatial issues
Executive dysfunction (problem solving and mental flexibility)

Question 7

Mental function issues in AD as it progresses?

Answer 7

Agnosia
Apraxia
Aphasia
NO abnormalities on general neuro exam

Question 8

Behavioural and psych symptoms of AD

Answer 8

Psychotic symptoms, disruptive behaviour, depressive symptoms are common

Question 9

3 atypical variants of AD

Answer 9

Frontal lobe syndrome
Posterior lobe syndrome (Balint’s)
Progressive aphasia

Question 10

What is the relation between apolipoprotein E and AD?

Answer 10

Transport protein in 3 forms; the epsilon 4 for increases AD risk 2-3x with 1 copy and 15x with 2

Question 11

What is the amyloid hypothesis of AD?

Answer 11

Cleavage of amyloid precursor protein generates amyloid beta-peptide which forms toxic aggregates

Question 12

What is the tau hypothesis of AD?

Answer 12

Tau is a microtubule associated protein and needed for the neuron cytoskeleton - abnormal hyperphosphorylation causes decreased affinity for microtubules and movement to eh intracellular space, where they form neurofibrillary tangles and neuronal death

Question 13

What is the cholinergic hypothesis of AD?

Answer 13

Neurons with ACh expressed are particularly vulnerable to damage and cognitive defects in AD are similar to anticholinergic effects. We can use some cholinesterase inhibitors to treat because of this

Question 14

4 classes of medication used for AD

Answer 14

Cholinesterase inhibitors (donepezil, rivastigmine)
Memantine (NMDA receptor antagonist)
Antidepressants for depression
Antipsychotics for agitation/psychotic features

Question 15

What are the 3 CSF markers used to diagnose AD?

Answer 15

Amyloid beta low
Total tau high
Phospho-tau high

Question 16

Amyloid-sleep relation?

Answer 16

Amyloid levels associated with awake state.
Fragmented sleep causes increased activity and increased a-beta release which increases AD susceptibility and causes injury to sleep/wake brain regions

Question 17

What is the course of AD?

Answer 17

Progressive lossof function -> vegetative state -> death 8-10yrs post-diagnosis

Question 18

Genetic risk factors for AD

Answer 18

Amyloid precursor protein
Presenilin 1 and 2
Apolipoprotein E

Question 19

What is Braak staging of AD?

Answer 19

Based on predictable spread of tangle pathology

1. Entorhinal complex (Braak 1-2)
2. Entorhinal complex and hippocampus (3-4)
3. Above + association cortex (5-6)