57 - Neurodegenerative Diseases

Question 1

Dementia - Practical Definition

Answer 1

Decline in cognitive functioning
From a previously elevated baseline
Impairs activities of daily living

Question 2

Diagnostic tools for detecting dementia

Answer 2

MMSE
Exam
History
Family Member Accounts

Question 3

Mild Cognitive Impairment

Answer 3

Subjective complaint
Activities of daily living not affected
10% annually progress to dementia (Alzheimer’s)

Question 4

Causes of Dementia

Answer 4

Primary Neurodegenerative Disorders
Vascular Dementias
Inflammatory Dementias
Infectious Dementias
Neoplastic Dementias
Physical Dementias
Metabolic Dementias

Question 5

Alzheimer Disease

Answer 5

Most common cause of

Most cases sporadic

Question 6

Alzheimer Disease - Strongest risk factor

Answer 6

Age

Question 7

Alzheimer Disease - Signs

Answer 7

Memory impairment (Earliest)
Language impairment also common early in presentation (semantic)
Motor and sensory symptoms absent or present late in disease course

Question 8

Alzheimer Disease - Definite Diagnosis

Answer 8

Neuropathology

Question 9

Alzheimer - Gross Path

Answer 9

Thinning of gyri
Widening of sulci
Occipital sparing (until the very end)

Question 10

Alzheimer Disease - Hippocampus

Answer 10

Loss of neurons and damage earliest in the disease

Question 11

Alzheimer Disease - Histology

Answer 11

Neuritic Plaques = Beta Amyloid Plaques (Hippocampus)
Dense core = more demented

See plaques in normal aging, though!!! Plaques don’t correlate

Question 12

Beta Amyloid Formation

Answer 12

APP
Step 1 - Cleaved by α-secretatse (good) or β-secretase (bad)
Step 2 - Cleaved by γ-secretase

Good pathway - no plaque
Bad pathway - plaque

Question 13

Alzheimer Disease - Deposits that correlate more

Answer 13

Tau - Neurofibrillary Tangles (INSIDE the neuron)

Tau normally stabilizes microtubules
Begins in transentorhinal cortex and hippocampus
Progresses to other areas of temporal cortex, amygdala, limbic areas
Spreads to neocortex in frontal, parietal areas
Finally reaches primary motor cortex and primary visual cortex

Question 14

Ghost tangles

Answer 14

Tombstones! Neuron dies but deposit remains

Question 15

Genes involved in AD

Answer 15

Genetic changes all related to β-amyloid!!

APP - Chromosome 21
Presenilin 1 & 2 (part of γ-secretase complex)
Trisomy 21
ApoE ε4 - Lipoprotein produced in liver & brain, transports β-amyloid, involved in sporadic cases

ApoE ε2 seems to be PROTECTIVE though. Weirdsies.

Question 16

Which happens earlier? β-amyloid or Tau?

Answer 16

β-amyloid

Question 17

Alzheimer Disease - Therapy

Answer 17

Cholinesterase Inhibitors:

Donepezil
Rivastigmine
Galantamine

NMDA partial antagonists:

Memantine

Question 18

Alzheimer Disease - Future Therapies

Answer 18

Clear β-amyloid from brain
Inhibit β-amyloid oligimerization
Remove phospho-tau or prevent tau phosphorylation
Rescuing synaptic dysfunction

Question 19

Parkinson Disease - Locations

Answer 19

Dorsal nucleus of vagus
Locus Coeruleus
Pars compacta of Substantia Nigra
Hypothalamus
Substantia Innominata -> Mesolimbic Cortex

Question 20

Parkinsonism - Criteria

Answer 20

Bradykinesia
Tremor (resting)
Rigidity
Postural Instability

Question 21

Parkinson’s Disease

Answer 21

Most common cause of Parkinsonism
Mean age of onset - 61
Mean duration - 13 years

Neuronal loss with Lewy Bodies (α-synuclein)

Question 22

Parkinson’s Disease - Symptoms

Answer 22

Parkinsonism
Autonomic dysfunction
Cognitive Disturbances
Dysphagia

Question 23

Lewy Bodies

Answer 23

Round
Cytoplasmic
8 - 30 μm
α-synuclein
Ubiquitin
5% asymptomatic

Concentric look, lightens neuromelanin

Question 24

Diffuse Lewy Body Disease - Clinical

Answer 24

Similar symptoms to AD
Fluctuations in cognitive ability
Visual hallucinations
Neuropsychiatric symptoms (anxiety, depression)
Parkinsonism

Oft comorbid with AD