Diagnostic Imaging in Parkinson's and Alzheimer's

Question 1

Role of microglia in the amyloid cascade?

Answer 1

[unknown trigger] -> increased amyloid production -> oligomers -> plaques -> activate microglia -> neurotoxicity -> neuronal damage -> neurofibrillary tangles (NFTs)

NB: neuronal death itself catalyses microglial activation (vicious cycle)

Question 2

Effect of clearing amyloid in AD pts?

Answer 2

No effect

Question 3

Microglia relationship w/ amyloid plaque?

Answer 3

MIcroglia surround b-amyloid plaques (clearing it?)

Question 4

Briefly describe the mechanism of PET imaging

Answer 4

PET ligand with radioisotope binds to target

Radiation (positrons) detected by scanner

Radiation detected from tissue and tracer in blood

Arterial line used to take blood sample to subtract radioactivity in blood

Question 5

What does 11C-PIB PET measure?

Answer 5

Amyloid

Question 6

Describe amyloid’s presence in cerebellum

Answer 6

Cerebellum has no amyloid in AD and in control

Therefore we can use it as a reference for 11C-PIB PET (instead of using arterial line)

Question 7

Amyloid’s presence in AD and its progression?

Answer 7

Significant amyloid throught the cortex (90% of AD)

Starts in basal forebrain and then spreads (1st deposition 10-15 yrs before symptoms)

Question 8

Experimental observation of amyloid and glucose metabolism in AD?

Answer 8

Longitudinal study over 20 months:

AD has no change in amyloid over time (but reduced glucose metabolism)

Question 9

Amyloid’s presence in mild cognitive impairment (MCI)?

Answer 9

60% of MCI has high amyloid (50% of amyloid +ve MCI will develop AD within 2 years)

[but if it converts to AD, no change in amyloid after 2 yrs]

Question 10

Amyloid’s presence in Lewy Body Dementia (DLB)?

Answer 10

Amyloid throughout

80% DLB has high amyloid (Amyloid not specific in AD diagnosis)

Question 11

Amyloid’s presence in Parkinson’s Disease Dementia (PDD)?

Answer 11

Amyloid throughout

20% of PDD has high amyloid

Question 12

Amyloid’s presence in cognitively normal people?

Answer 12

By 75 yrs, 20% of cog. normal ppl will have amyloid deposition

Question 13

What does PK11195 measure?

Answer 13

Measures activated microglia (binds to TSPO)

NB: increased microglial activation is associated w/ a decreased MMSE

Question 14

Microglial activation in AD?

Answer 14

Significant microglial activation throughout cortex

[some areas overlap w/ amyloid deposition, some don’t]

Question 15

Microglial activation in MCI?

Answer 15

60% of amyloid +ve MCI have increased microglial activation

30% of amyloid -ve MCI have increased microglial activation (can happen without amyloid)

Question 16

Microglial activation in AD trend over time?

Answer 16

Bimodal peak

1st peak is M2 neuroprotective

2nd peak is M1 damaging

Question 17

Microglial activation in PDD?

Answer 17

Significant increased microglial activation compared to PD

In established disease, microglial activation is associated w/ neuronal damage and decreased glucose metabolism

Question 18

What does FGD PET measure?

Answer 18

Glucose metabolism

Question 19

Glucose metabolism distribution in AD?

Answer 19

Hypometabolism in Medial Temporal Lobe and Temporal-Parietal Cortices

Question 20

Glucose metabolism in AD over time?

Answer 20

As disease progresses, decreased glucose metabolism

Question 21

Relevance of measuring glucose metabolism?

Answer 21

Glucose metabolism is surrogate measure of assessing cognitive function (Tau is best correlated, but limited Tau PET)

Question 22

Glucose metabolism in MCI?

Answer 22

Hypermetabolism (short compensatory phase) precedes hypometabolism

Question 23

Glucose metabolism in PD and PDD?

Answer 23

Decreased glucose metabolism

therefore neural damage occurs throughout cortex even before cognitive symptoms

Question 24

Problems with using imaging for AD and PD?

Answer 24

These techniques aren’t routinely available (because they are expensive_

Also there is no treatment available (so no point knowing the results)

Question 25

Biochemical progression of AD?

Answer 25

1. Aβ in CSF
2. Amyloid seen on PET
3. Tau in CSF
4. MRI changes + glucose seen on PET
5. Cognitive impairment

[all these biochemical changes occur BEFORE symptom onset]

Question 26

Biomarkers in CSF in AD?

Answer 26

Increased tau in CSF

Decreased amyloid in CSF

Question 27

Describe amyloid sequestration theory?

Answer 27

Decreased amyloid in CSF over time as it becomes deposited as plaques in the brain

Question 28

Biomarkers in imaging of AD?

Answer 28

Increased amyloid

Increased Tau (T807 is a Tau PET tracer)

Question 29

Relevance of tau and FDG in imaging for AD?

Answer 29

Tau- marker of disease
FDG- marker of neuronal death

Changes in tau and FDG correlate w/ cognitive function