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Year 2 Medicine > Dementia: Neuropathology & Clinical Aspects > Flashcards

Dementia: Neuropathology & Clinical Aspects Flashcards

(36 cards)

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1
Q

Dementia disorders (4)

A
  • Alzheimer’s disease
  • Dementia with Lewy bodies
  • Frontotemporal dementia
  • Vascular dementia
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2
Q

Neuropathology of Dementia

  • Microscopically
    • Intra neuronal inclusion bodies
    • Extra neuronal changes (p…)
  • Macroscopically
    • Generalised brain …
    • Region specific … depending on dementia disorder
    • Enlarged …
A
  • Microscopically
    • Intra neuronal inclusion bodies
    • Extra neuronal changes (plaques)
  • Macroscopically
    • Generalised brain atrophy
    • Region specific atrophy depending on dementia disorder
    • Enlarged ventricles
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3
Q

Neuropathology of Dementia (2)

  • … of proteins
  • Abnormal …
  • Neuroinflammatory environment
    • Damaged neurons, cell …
  • Protein involved:
    • Amyloid, t…, s…
A
  • Misfolding of proteins
  • Abnormal accumulation
  • Neuroinflammatory environment
    • Damaged neurons, cell death
  • Protein involved:
    • Amyloid, tau, synuclein
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4
Q

Tau abnormalities

  • … disease
  • … dementia
A
  • Alzheimer’s disease
  • Frontotemporal dementia
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5
Q

Tau:

  • Normal …
  • Highly …
  • Mostly found in …
  • Mainly present in …
  • Function: modulate stability of axonal microtubules, transport
  • 6 isoforms -> 352-441 amino acid length (don’t need to know exactly)
  • Disease -> … forms
    • Leading to paired helical filaments (PHF)
    • Neurofibrillary tangles (NFTs)
    • PHFs -> NFTs -> Neurodegeneration
  • Phosphorylation of tau is regulated by activated kinases
  • … of tau can result in self-assembly of tangles of paired helical filaments (PHF)
A
  • Normal protein
  • Highly soluble
  • Mostly found in brain
  • Mainly present in axons
  • Function: modulate stability of axonal microtubules, transport
  • 6 isoforms -> 352-441 amino acid length (don’t need to know exactly)
  • Disease -> hyperphosphorylated forms
    • Leading to paired helical filaments (PHF)
    • Neurofibrillary tangles (NFTs)
    • PHFs -> NFTs -> Neurodegeneration
  • Phosphorylation of tau is regulated by activated kinases
  • Hyperphosphorylation of tau can result in self-assembly of tangles of paired helical filaments (PHF)
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6
Q

Tau:

  • Normal protein
  • Highly soluble
  • Mostly found in brain
  • Mainly present in axons
  • Function: modulate stability of axonal microtubules, transport
  • 6 isoforms -> 352-441 amino acid length (don’t need to know exactly)
  • Disease -> hyperphosphorylated forms
    • Leading to … helical filaments (PHF)
    • … tangles (NFTs)
    • PHFs -> NFTs -> …
  • Phosphorylation of tau is regulated by activated …
  • Hyperphosphorylation of tau can result in self-assembly of tangles of paired helical filaments (PHF)
A
  • Normal protein
  • Highly soluble
  • Mostly found in brain
  • Mainly present in axons
  • Function: modulate stability of axonal microtubules, transport
  • 6 isoforms -> 352-441 amino acid length (don’t need to know exactly)
  • Disease -> hyperphosphorylated forms
    • Leading to paired helical filaments (PHF)
    • Neurofibrillary tangles (NFTs)
    • PHFs -> NFTs -> Neurodegeneration
  • Phosphorylation of tau is regulated by activated kinases
  • Hyperphosphorylation of tau can result in self-assembly of tangles of paired helical filaments (PHF)
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7
Q

How can hyperphosphorylation of tau cause neurodegeneration?

A

results in self-assembly of tangles of paired helical fillaments - leading to neurofibrillary tangles - leading to neurodegeneration

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8
Q

What are Neurofibrillary tangles (NFTs)?

A

Neurofibrillary tangles (NFTs) are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer’s disease.

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9
Q

Neurofibrillary tangles (NFTs) are aggregates of … tau protein that are most commonly known as a primary biomarker of … disease.

A

Neurofibrillary tangles (NFTs) are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer’s disease.

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10
Q

Neurofibrillary tangles (NFTs)

  • Described by alois Alzheimer
  • Seen in neurons after staining
    • Hamatoxylin
    • Eosin
    • Bielschowsky
    • Bodian
    • Congo red
  • Most commonly found in temporal lobe structures
    • …
    • …
  • Consist of … 10 nanometer diameter filaments twisted around each other in a helical manner (… helical filaments HF)
A
  • Described by alois Alzheimer
  • Seen in neurons after staining
    • Hamatoxylin
    • Eosin
    • Bielschowsky
    • Bodian
    • Congo red
  • Most commonly found in temporal lobe structures
    • Hippocampus
    • Amygdala
  • Consist of paired 10 nanometer diameter filaments twisted around each other in a helical manner (paired helical filaments HF)
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11
Q

Amyloid

  • Amyloid precursor protein (APP) is a transmembrane glycoprotein
  • Broken down and eliminated in … brain
  • APP is split by enzymes B-secretase then y-secretase (Gamma)
  • B-amyloid is a peptide of 39-43 amino acids
  • Most common forms are AB40 and AB42
  • … is more common of the two, but … is the more fibrillogenic and is associated with disease states
  • Fragments accumulate to form P…
  • Build up of B-amyloid … cause neuronal damage
  • Amyloid pathology - occurs outside neurons
A
  • Amyloid precursor protein (APP) is a transmembrane glycoprotein
  • Broken down and eliminated in normal brain
  • APP is split by enzymes B-secretase then y-secretase (Gamma)
  • B-amyloid is a peptide of 39-43 amino acids
  • Most common forms are AB40 and AB42
  • AB40 is more common of the two, but AB42 is the more fibrillogenic and is associated with disease states
  • Fragments accumulate to form plaques
  • Build up of B-amyloid plaques cause neuronal damage
  • Amyloid pathology - occurs outside neurons
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12
Q

Amyloid

  • Amyloid precursor protein (APP) is a transmembrane glycoprotein
  • Broken down and eliminated in normal brain
  • APP is split by enzymes B-secretase then y-secretase (Gamma)
  • B-amyloid is a peptide of 39-43 amino acids
  • Most common forms are AB40 and AB42
  • AB40 is more common of the two, but AB42 is the more fibrillogenic and is associated with disease states
  • Fragments accumulate to form plaques
  • Build up of B-amyloid plaques cause neuronal damage
  • Amyloid pathology - occurs outside neurons
A
  • Amyloid precursor protein (APP) is a transmembrane glycoprotein
  • Broken down and eliminated in normal brain
  • APP is split by enzymes B-secretase then y-secretase (Gamma)
  • B-amyloid is a peptide of 39-43 amino acids
  • Most common forms are AB40 and AB42
  • AB40 is more common of the two, but AB42 is the more fibrillogenic and is associated with disease states
  • Fragments accumulate to form plaques
  • Build up of B-amyloid plaques cause neuronal damage
  • Amyloid pathology - occurs outside neurons
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13
Q

Amyloid - … is more common of the two, but … is the more fibrillogenic and is associated with disease states

A

Amyloid - AB40 is more common of the two, but AB42 is the more fibrillogenic and is associated with disease states

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14
Q

Frontotemporal dementia:

  • … pathology
  • Pick’s disease
  • Pick bodies -rounded, microscopic structures found within neurons, aggregates of tau
  • Hirano bodies
  • Neurons swell, taking on a “ballooned” appearance. Hence called balloon cells
  • Plaques and tangles are not found in Pick’s disease
  • FTD is present in … and … temporal lobes
A
  • Tau pathology
  • Pick’s disease
  • Pick bodies -rounded, microscopic structures found within neurons, aggregates of tau
  • Hirano bodies
  • Neurons swell, taking on a “ballooned” appearance. Hence called balloon cells
  • Plaques and tangles are not found in Pick’s disease
  • FTD is present in frontal and anterior temporal lobes
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15
Q

Synuclein abnormalities

  • … disease
  • Dementia with … bodies
  • … aggregates of alpha-synuclein protein
A
  • Parkinson’s disease
  • Dementia with Lewy bodies
  • Fibrillary aggregates of alpha-synuclein protein
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16
Q

Frontotemporal dementia = present in … and … temporal lobes

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A

Frontotemporal dementia = present in frontal and anterior temporal lobes

17
Q

Dementia with Lewy bodies

  • S..
    • Small, Presynaptic neuronal proteins comprised of alpha, beta, gamma-synucleins of which only alpha-synuclein aggregates
    • Found in neurons and … cells
    • Function is lipid vesicle binding, inhibition of phospholipase D2 and protein kinase C, dopamine uptake and as a chaperone have been ascribed to alpha-synuclein
    • Proteins of 140 amino acids, that is expressed predominantly in neurons
    • Predominantly expressed in neocortex, hippocampus, substantia nigra and cerebellum
    • Can … to form intracytoplasmic inclusions in neurons (Lewy bodies)
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A
  • Synuclein
    • Small, Presynaptic neuronal proteins comprised of alpha, beta, gamma-synucleins of which only alpha-synuclein aggregates
    • Found in neurons and glial cells
    • Function is lipid vesicle binding, inhibition of phospholipase D2 and protein kinase C, dopamine uptake and as a chaperone have been ascribed to alpha-synuclein
    • Proteins of 140 amino acids, that is expressed predominantly in neurons
    • Predominantly expressed in neocortex, hippocampus, substantia nigra and cerebellum
    • Can aggregate to form intracytoplasmic inclusions in neurons (Lewy bodies)
18
Q

Dementia with Lewy bodies

  • Lewy body dementia (LBD) is a disease associated with abnormal deposits of a protein called alpha-… in the brain
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A
  • Lewy body dementia (LBD) is a disease associated with abnormal deposits of a protein called alpha-synuclein in the brain
19
Q

Lewy bodies

  • Spherical, intranuclear, cytoplasmic eosinophilic inclusions
  • Abnormally truncated and phosphorylated neurophilament proteins
  • Contain: alpha-…, ubiquitin, associated enzymes
Study These Flashcards
A
  • Spherical, intranuclear, cytoplasmic eosinophilic inclusions
  • Abnormally truncated and phosphorylated neurophilament proteins
  • Contain: alpha-synuclein, ubiquitin, associated enzymes
20
Q

Vascular dementia

  • Can result from … or … brain damage
  • The three most common mechanisms causing disease:
    • Single, strategically placed …
    • Multiple cortical …
    • Subcortical small-vessel disease
  • Clinical deficits are determined by the size, location, and type of … damage
  • Because of the variety of pathogenic mechanisms involved in vascular dementia, clinical manifestations can be heterogeneous
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A
  • Can result from ischaemic or haemorrhagic brain damage
  • The three most common mechanisms causing disease:
    • Single, strategically placed infarcts
    • Multiple cortical infarcts
    • Subcortical small-vessel disease
  • Clinical deficits are determined by the size, location, and type of cerebral damage
  • Because of the variety of pathogenic mechanisms involved in vascular dementia, clinical manifestations can be heterogeneous
21
Q

Vascular dementia

  • Can result from ischaemic or haemorrhagic brain damage
  • The three most common mechanisms causing disease:
    • Single, strategically placed infarcts
    • … cortical infarcts
    • Subcortical …-vessel disease
  • Clinical deficits are determined by the …, …, and … of cerebral damage
  • Because of the variety of pathogenic mechanisms involved in vascular dementia, clinical manifestations can be …
Study These Flashcards
A
  • Can result from ischaemic or haemorrhagic brain damage
  • The three most common mechanisms causing disease:
    • Single, strategically placed infarcts
    • Multiple cortical infarcts
    • Subcortical small-vessel disease
  • Clinical deficits are determined by the size, location, and type of cerebral damage
  • Because of the variety of pathogenic mechanisms involved in vascular dementia, clinical manifestations can be heterogeneous
22
Q

The clinical dementia syndrome

  • Common features among the various dementia disorders
    • Symptomatology
    • Diagnosis
    • Treatment
  • But important differences on each of the above
Study These Flashcards
A
  • Common features among the various dementia disorders
    • Symptomatology
    • Diagnosis
    • Treatment
  • But important differences on each of the above
23
Q

Diagnostic guidelines and principles - dementia - National and international diagnostic guidelines

  • NICE guidelines:
    • … clinics
    • … clinics - old age psychiatrists, geriatricians, neurologists
    • … approach
    • Involve …/…
Study These Flashcards
A
  • NICE guidelines:
    • Memory clinics
    • Specialist clinics - old age psychiatrists, geriatricians, neurologists
    • Multidisciplinary approach
    • Involve carer/spouse
24
Q

Diagnostic steps - DEMENTIA

  • …
  • Examination
  • …/ECG
  • Neuropsychological
  • …/activities of daily living
  • Neuro….
Study These Flashcards
A
  • History
  • Examination
  • Bloods/ECG
  • Neuropsychological
  • Behaviour/activities of daily living
  • Neuroimaging
25
_1.History - DEMENTIA_ * History from patient + carer/spouse (if appropriate) * ..., ... (suddenly, slowly), ... (progressive, step-wise deterioration) * Previous ... and mental health problems * Establish presence of behavioural and psychological symptoms of dementia
* History from patient + carer/spouse (if appropriate) * When, how (suddenly, slowly), course (progressive, step-wise deterioration) * Previous physical and mental health problems * Establish presence of behavioural and psychological symptoms of dementia
26
_2.Examination - DEMENTIA_ * General examination * ... examination * ... state examination
* General examination * Neurological examination * Mental state examination
27
_3.Bloods - DEMENTIA_
* FBC * ESR * U/ES * LFT * TFT * B12/folate * Syphilis serology * ECG
28
_4.Neuropsychological tests - DEMENTIA_ * ... assessment * General assessment of ... state * Help identify defects in specific ... domains
* Cognitive assessment * General assessment of cognitive state * Help identify defects in specific cognitive domains
29
_5.Imaging - DEMENTIA_ * ... scan - tolerated better by patients with dementia * MRI scan - better for ... matter * SPECT scan * ... scan
* CT scan - tolerated better by patients with dementia * MRI scan - better for white matter * SPECT scan * PET scan
30
_Treatment for Alzheimer's Disease_ * 4 symptomatic treatments exist * D..., Rivastigmine, G..., Memantine
* 4 symptomatic treatments exist * **Donepezil, Rivastigmine, Galantamine, Memantine**
31
Donepezil, Rivastigmine, Galantamine, Memantine are symptomatic treatments for what type of dementia?
alzheimer's
32
_Vascular Dementia treatment_ * Identify and treat vascular risk factors (Hyper...n, D..., Hyper..., A..., ... disease) * Anti...
* Identify and treat vascular risk factors (Hypertension, Diabetes, Hyperlipidaemia, AF, Carotid disease) * Anticoagulants
33
_Frontotemporal dementia treatment_
SSRIs
34
SSRIs are given for what type of dementia? (not licensed but some evidence)
frontotemporal dementia
35
Dementia with Lewy bodies - what treatment may be given? (not licensed but used widely)
* **Dementia with Lewy Bodies** * **Donepezil and rivastigmine**
36
_Additional Management strategies for dementia disorders_ * ... approach * Involve ... * ... service input
* Multidisciplinary approach * Involve family * Social service input

Year 2 Medicine (162 decks)

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