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NEUR3005 > WK9 - Common Features of Neurodegen. Disease > Flashcards

WK9 - Common Features of Neurodegen. Disease Flashcards

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1
Q

What is a neurodegenerative disease?

A

Disease characterized by progressive loss of neurons in brain and/or spinal cord

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2
Q

What are some of the “dementia-type” of neurodegenerative disease?

A
  1. AD
  2. FTD
  3. Lewy body Dementia
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3
Q

What are some general chacracteristics of “dementia-type” diseases?

A
  1. Memory loss
  2. Disorientation
  3. Changes in personality
  4. Lapses in judgement
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4
Q

What are some of the “movement-type” of neurodegenerative disease?

A
  1. PD
  2. MND
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5
Q

What are some general chacracteristics of “movement-type” diseases?

A
  1. Walking/balancing difficulties
  2. Involuntary movements eg. tremors
  3. Swallowing/breathing difficulties
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6
Q

How are neurodegen. diseases viewed in healthcare?

A

We see clinical symptoms but the disease pathogenesis is often not seen (neuron loss seen in autopsy)

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7
Q

Diagnosis of AD

A

Ave. diagnosis in mid-60s
* 15/1000
* Median survival ~8-10y
* Ave. diagnostic delay ~1.5y (Self-delay or Dr take too long to do tests)

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8
Q

Typical symptoms of AD

A
  1. Memory loss
  2. Confusion of time/place
  3. Poor judgement
  4. Mood changes
  5. Difficulty completing familiar tasks
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9
Q

Neuropathology in AD

A

Macro - loss of vol. in cortex, hippocampus, medial-temporal lobes
Micro - a-beta plaques + Tau neurofibrillary tangles

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10
Q

Diagnosis of MND

A

~40% diagnosed < 65y
* 8.7/100k
* More common in men
* Median survival ~2-3y
* Ave. diagnostic delay ~1-1.5y

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11
Q

Typical symptoms of MND

A
  1. Muscle weakness
  2. Slurred speech
  3. Swallowing difficultues
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12
Q

Neuropathology of MND

A

Micro - selective loss of MN in motor cortex, hypoglossal N. and anterior horn of spinal cord
* accumulation of TDP43

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13
Q

Why is the macroscopic neuropathology not as relevant for MND?

A

Atrophy is not clear because MN only make up 10% of N in layer 5

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14
Q

Staged anatomical progression of TDP-43 pathology

A

Progress to Frontal and Temporal regions
* some say spread determine cognitive deficit
* 20% w/ MND > diagnosed w/ FTD

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15
Q

Diagnosis of PD

A

Ave. diagnosis ~60y
* 4/1000
* Median survival ~6-22y
* Ave. diagnostic delay ~1 year

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16
Q

Typical symptoms of PD

A
  1. Tremor
  2. Rigidity
  3. Bradykinesia (slowed movement)
  4. Postural instability
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17
Q

Neuropathology of PD

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A

Macro - substania nigra less pigmented
Micro - loss of dopamine-producing neurons, surviving dopamine Ns have accumulation of alpha-synuclein

18
Q

What is a Lewy body?

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A

Round and compacted inclusion of alpha synuclein

19
Q

Diagnosis of bvFTD

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A

Predominantly < 65y
* 2.7-4.4/100k
* Median survival ~8-10y
* Ave. diagnostic delay 5-6y

20
Q

Typical symptoms of bvFTD

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A
  1. Changes in personality/behaviour
  2. Disinhibition
  3. Lack of insight
  4. Changes in eating behaviour
21
Q

Neuropathology of bvFTD

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A

Macro - noticeable shrinkage
Micro - accumulation of TDP43 (~60%) accumulation of Tau (~40%)

22
Q

How is the accumulation of Tau different in bvFTD?

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A

3R (Pick body rounded inclusions in N) or 4R (aggregates around glial cells) isoforms
* AD is a mix of these isoforms

23
Q

Spreading and staging of bvFTD pathology

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A

Beyond Frontal and Temporal > Motor Cx., cerebellum
* 20-25% also have MND

24
Q

Pick’s Disease

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A

40% of bvFTD have Pick’s
* compact 3R Tau
* moves to brainstem, motor cx. and cerebellum in severe cases

25
Outline how sporadic each neurodegeneratiev disease is:
1. **AD** - **95**% 2. **MND** - **95**% 3. **PD** - ***85-90***% 4. **bvFTD** ***60-80***%
26
***Language*** variants of FTD
1. **Semantic** PPA - forget ***meaning*** of words 2. **Non-fluent** PPA - struggle to get ***words out*** 3. **Logopenic** PPA - word ***finding*** difficulty, sentence ***repetition*** deficits
27
What does PPA stand for?
**P**rimary **P**rogressive **A**phasia
28
***Movement*** variants of FTD
*Less* common 1. **Corticobasal** syndrome - ***alien limb*** phenomenon 2. **Progressive** **Supranuclear** Palsy - ***eye movement*** difficulties
29
What are the shared symptoms of movement variants of FTD?
1. **Rigidity** 2. ***Brady***kinesia 3. **Balance** & **coordination** problems
30
What is common across all the degenerative diseases?
1. Diagnostic ***delay*** 2. ***Overlapping*** **clinical** features 3. ***Protein***opathies 4. Predominantly ***sporadic***
31
Neuroimaging Tools
1. ***Structural*** - eg. **MRI, CT** (***visualisation*** of structure) 2. ***Functional*** - eg. **PET, TMS** (*indirect* measure of ***brain activity***)
32
MRI
Can identify brain regions with ***volume loss*** * **Not** a *direct* measure of **pathology** * *Less* helpful for **MND**
33
PET-FDG
1. **FDG** taken up by *neurons* 2. PET images ***emission*** of **positrons** 3. Cerebral **metabolic** rate of ***glucose*** > ***indirect*** measure of neuronal **function**
34
What is FDG?
Fluorodeoxyglucose (FDG) – glucose ***analog*** (**radioactive** atom *applied* to glucose)
35
Are there pathology-specific ligands for PET?
1. **Amyloid**-PET – ***not*** definitive alone 2. **Tau**-PET – *newer*, not widely available yet. More ***definitive*** though 3. **Syn**-PET: In ***development*** 4. **TDP**-PET: **N/A**
36
Advantages and Disadvantages of MRI
**A** - *High* **spatial** res., *no* **radiation**, ***widely*** available **D** - *cannot* distinguish **pathology type**, *structural* changes appear ***later***
37
Advantages and Disadvantages of PET
**A** - assess ***metabolic*** activity and ***pathological*** markers, **changes** in activity/patho may appear ***before*** *structural* **D** - *Low* **spatial** res., ***radiation***, ***spenny***
38
What are some biofluid biomarkers?
1. **Blood** 2. **CSF**
39
Advantages and Disadvantages of Blood
**A** - ***less-invasive***, *easy* to **collect**, ***affordable***, *easier* to ***scale*** for **screening** **D** - *only* **peripheral** (filtered through **BBB**), requires high **sensitive** tech
40
Advantages and Disadvantages of CSF
**A** - ***closer*** to brain **pathology** **D** - **Invasive** (LP), ***spenny***, *less* suitable for **screening**, requires **expertise**

NEUR3005 (19 decks)

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