Diagnostic Imaging in Parkinson's and Alzheimer's Flashcards Preview

NMH: Module 2 > Diagnostic Imaging in Parkinson's and Alzheimer's > Flashcards

Flashcards in Diagnostic Imaging in Parkinson's and Alzheimer's Deck (29)
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Role of microglia in the amyloid cascade?

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

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


Effect of clearing amyloid in AD pts?

No effect


Microglia relationship w/ amyloid plaque?

MIcroglia surround b-amyloid plaques (clearing it?)


Briefly describe the mechanism of PET imaging

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


What does 11C-PIB PET measure?



Describe amyloid's presence in cerebellum

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)


Amyloid's presence in AD and its progression?

Significant amyloid throught the cortex (90% of AD)

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


Experimental observation of amyloid and glucose metabolism in AD?

Longitudinal study over 20 months:

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


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

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]


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

Amyloid throughout

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


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

Amyloid throughout

20% of PDD has high amyloid


Amyloid's presence in cognitively normal people?

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


What does PK11195 measure?

Measures activated microglia (binds to TSPO)

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


Microglial activation in AD?

Significant microglial activation throughout cortex

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


Microglial activation in MCI?

60% of amyloid +ve MCI have increased microglial activation

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


Microglial activation in AD trend over time?

Bimodal peak

1st peak is M2 neuroprotective

2nd peak is M1 damaging


Microglial activation in PDD?

Significant increased microglial activation compared to PD

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


What does FGD PET measure?

Glucose metabolism


Glucose metabolism distribution in AD?

Hypometabolism in Medial Temporal Lobe and Temporal-Parietal Cortices


Glucose metabolism in AD over time?

As disease progresses, decreased glucose metabolism


Relevance of measuring glucose metabolism?

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


Glucose metabolism in MCI?

Hypermetabolism (short compensatory phase) precedes hypometabolism


Glucose metabolism in PD and PDD?

Decreased glucose metabolism

(therefore neural damage occurs throughout cortex even before cognitive symptoms)


Problems with using imaging for AD and PD?

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

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


Biochemical progression of AD?

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]


Biomarkers in CSF in AD?

Increased tau in CSF

Decreased amyloid in CSF


Describe amyloid sequestration theory?

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


Biomarkers in imaging of AD?

Increased amyloid

Increased Tau (T807 is a Tau PET tracer)


Relevance of tau and FDG in imaging for AD?

Tau- marker of disease
FDG- marker of neuronal death

Changes in tau and FDG correlate w/ cognitive function