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Flashcards in Symposium 4: Dementia Deck (83):
1

What is dementia?

A syndrome due to disease of the brain usually of a chronic or progressive nature, in which there is disturbance of multiple higher cortical functions, including memory, thinking, orientation, comprehension, calculation, learning capacity, language and judgement.

2

What are the different types of dementia?

- Alzheimer’s disease
- Vascular dementia
- Frontotemporal dementias
- Lewy body dementia
- Progressive supranuclear palsy
- Huntington’s disease
- Prion disease

3

What factors need to be considered in the medical management of dementia?

- Memory disorder
- Manage vascular risk factors
- “Agitation” and aggression
- “Wandering”
- Depression
- Psychosis
- Sleep disturbance
- Incontinence
- Physical co-morbidities - delirium
- Institutional care
- Legal capacity

4

How frequent is incapacity?

40% of acutely ill medical in-patients
25% severely cognitively impaired/unconscious
(in general hospital)

5

What kind if impairments does degenerative disease of the frontal lobe produce?

Impaired judgement, abstract reasoning, strategic planning, emotional restraint, control of appetite and continence.

6

What kind if impairments does degenerative disease of the temporal lobe produce?

Disease of the hippocampus, amygdala and limbic system leads to disorders of memory and hallucinations.

Disease of the temporal neocortex is associated with receptive aphasia and automatisms.

7

What kind if impairments does degenerative disease of the occipital lobe produce?

Failure of visual sensory systems.

8

What kind if impairments does degenerative disease of the parietal lobe produce?

Impairment of visuospatial skills and integration of sensory inputs leading to sensory agnosias and apraxias.

9

What "treatable" conditions may present as dementia?

- Depression
- Iatrogenic (anticholinergics, sedatives, narcotics, H2 blockers, multiple meds)
- Hypothyroidism
- B12 deficiency
- Neurosyphilis
- Normal pressure hydrocephalus
- Subdural hematoma
- Encephalitis

10

Which dementias are classed as neurodegenerative?

- Alzheimer’s Dementia
- Lewy Body Dementias
- Frontotemporal Dementias
- Huntington’s Disease + many others

11

Hold many people in the UK have dementia?

700,000

12

What percentage of over 65s have dementia?

5%

13

What percentage of over 80s have dementia?

20%

14

What are the typical features of anterior (frontal premotor cortex) dementia?

- Behaviour changes
- Loss of inhibition
- Antisocial behaviour
- Facile and irresponsible

15

What are the possible causes of anterior dementia?

- Normal pressure hydrocephalus
- Hydrocephalus
- Huntingtons chorea
- Metabolic disease

16

What are the typical features of posterior (parietal and temporal) dementia?

Disturbance of cognitive function (memory and language) without marked changes in behaviour.

17

What is the cause of posterior dementia?

Alzheimer's disease

18

What are the features of subcortical dementia?

- Apathetic
- Forgetful and slow
- Poor ability to use knowledge
- Associated with other neurological signs and movement disorders

19

What are the possible causes of subcortical dementia?

Parkinson's disease
AIDS dementia complex

20

What are the features of cortical dementia?

- Dysphasia
- Agnosia
- Apraxia

21

What is an example of cortical dementia?

Alzeheimer's disease

22

What are the major divisions in the traditional classification of neurodegenerative diseases?

- Dementias
- Movement disorders

23

Which disorders fall under the 'dementias' group?

Alzheimer’s Disease

Frontotemporal Dementia:
- Behavioural/frontal variant
- Non-fluent progressive aphasia
- Semantic Dementia

Dementia with Lewy bodies

24

Which disorders fall under the 'movement disorders' group?

Parkinson’s Disease

Parkinson Plus Syndromes:
- Progressive Supranuclear Palsy
- Multiple System Atrophy
- Corticobasal Degeneration

Huntington’s Disease

Motor Neuron Disease

25

What is the current molecular genetic classification of neurodegenerative diseases?

Tauopathies
- FTD and FTDP - 17*
- PSP*
- Corticobasal Degeneration*
- Alzheimer’s Disease

Ubiquinopathies
- MND and MND/Dementia*
- Semantic Dementia*

Synucleinopathies
- Parkinson’s Disease
- Dementia with Lewy Bodies
- MSA


26

What triad of clinical features is seen in normal pressure hydrocephalus?

- Dementia
- Gait disturbance
- Urinary incontinence

- Occuring in conjunction with hydrocephalus and normal CSF pressure (possibly, intermittently raised a better term).

27

What are the two types of normal pressure hydrocephalus?

- NPH with a preceding cause (SAH, meningitis, trauma, radiation-induced).
- NPH with no known preceding cause – idiopathic (50%).

28

What is the microscopic appearance of brain tissue in transmissible spongiform encephalopathies (TSEs)?

the affected brain tissue looks like a
sponge

29

What is seen on the EEG of a person with a TSE?

Triphasic waves, on repeat testing.

30

What sort of MRI changes might be seen in sporadic CJD?

Non-specific changes in basal ganglia

31

What highly specific sign of variant CJD is see on MRI?

Pulvinar sign - characteristic abnormality seen in the posterior thalamic region.

32

What are the microscopic features of tauopathy seen in corticobasal degeneration?

- Electron microscopy shows phospho-tau filaments within the neuron
- Also cytoplasmic tangles, neuropil threads etc.

33

What are the clinical features of VGKC Ab.LE (limbic encephalitis).

- Subacute memory loss
- Psychiatric/behavioural disturbance
- Seizures, usually partial
- Hyponatraemia common
- 60 % show MTL high signal on MRI
- Most cases serum and CSF antibodies to LGI1 subunit of the K channel, others CASPR2

34

What is the epidemiology of VGKC Ab. LE?

Median age 65 years, 2:1 male:female

35

What is commonly associated with VGKC Ab. LE?

Thymoma/SCLC and other tumour may be present but are not commonly associated (more so if CASPR2 ab.)

36

What is the prognosis for VGKC Ab. LE?

If no tumour prognosis very good with immuno-modulation

37

What is the overall economic impact of dementia?

£26.3 billion = an average annual cost of £32,250 per person

38

What are the various causes of dementia?

- Alzheimer’s disease
- Vascular dementia
- Frontotemporal dementias
- Lewy body dementia
- Progressive supranuclear palsy
- Huntington’s disease
- Prion disease

39

What are the issues for the medical management of dementia?

- Memory disorder
- Manage vascular risk factors
- “Agitation” and aggression
- “Wandering”
- Depression
- Psychosis
- Sleep disturbance
- Incontinence
- Physical co-morbidities delirium
- Institutional care
- Legal capacity

40

What percentage of acutely ill medical patients lack capacity?

40%

41

What is the frontal lobe broadly responsible for?

Executive functions: motor planning, strategic thinking.

42

What is the frontal (&parietal) lobe responsible for?

Perception and integration of sensory (&motor) stimuli anf encoding knowledge.

43

What is the hippocampus responsible for?

Memory

44

What is the limbic system responsible for?

Arousal, emotion, motivation, attention and memory.

45

What is cognition?

The sum of brain functions which allows us to integrate in the environment.

46

What intellectual skills are included in cognition?

- Learning and Memory
- Language
- visuospatial skills
- Emotion
- Personality

47

Which type of dementia can show temporal, frontal and parietal degeneration?

Alzheimer's

48

What type of dementia shows multifocal degeneration?

Corticobasal degeneration (CBD)

49

What type of dementia shows impairment of cognition and movement?

Dementia with Lewy bodies

50

What role does trisomy 21 play in Alzheimer's?

- increased APP
- onset 20y

51

What role does presenilin 1 on chromosome 14 play in Alzheimer's?

- altered β-amyloid
- onset 40-45y

52

What role does presenilin 2 on chromosome 1 play in Alzheimer's?

- altered β-amyloid
- onset 45-50y

53

What role does a single mutation on chromosome 21 play in Alzheimer's?

- increased APP
- altered sAPP
- altered β-amyloid
- onset 50-60y

54

What role does the Apo-E mutation on chromosome 19 play in Alzheimer's?

- increased stability of β-amyloid deposits

55

What proteins are involved in dementia?

- β-amyloid
- Tau
- α-synclein
- Ubiquitin

56

What are amyloid proteins?

- Insoluble fibrous proteins aggregates sharing specific structural traits.

- They arise from at least from 18 inappropriately folded versions of proteins and polypeptides present naturally in the body.

57

How are amyloid proteins involved in pathogenesis?

These misfolded structures alter their proper configuration such that they erroneously interact with one another or other cell components forming insoluble fibrils.

58

What are tau proteins?

- A group of proteins that stabilize microtubules in neurons.

- There are six isoforms.

59

How are tau proteins involved in pathogenesis?

When Tau proteins are defective the microtubules become instable and dysfunctioning.

60

Stimulation of which receptors modulates APP processing?

- cholinergic (ACh)
- serotinergic (5HT)

61

Which protein traffics APP to the endosomal vesicle and what is generated?

- PS1 traffics
- Aβ1-42 is generated

62

What happens to Aβ1-42 when it is secreted?

It forms multimeric aggregates - these can active microglia and can participate in exitotoxic reactions with neurons.

63

What is the role in fibrillar Aβ1-42 in neuropathology?

Initiates senile plaque formation, which involves dystrophic neurites, recruitment of activated microglia, interactions with ApoE and the deposition of Aβ amyloid as plaque.

64

What does plaque formation result in?

Degeneration of susceptible neurons and tangle formation by an unknown mechanism. Activated microglia act in a positive feedback loop to enhance Aβ1-42 generation from neurons, and plaque formation.

65

What is the role of α-Synuclein?

Aggregates to form insoluble fibrils in pathological conditions characterized by Lewy bodies, such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy.

66

What is ubiquitin?

A small regulatory protein that has been found in almost all cells (ubiquitously) of eukaryotic organisms. It directs proteins to compartments in the cell, including the proteasome which destroy and recycle proteins. It can be attached to proteins and label them for destruction.

67

What other forms of pathogenesis may be involved in dementia?

- Oxidative stress: free radicals
- Excitotoxicity: glutamine stimulation
- Induction of programmed cell death (apoptosis)
- Cytokines: inflammatory response?
- Genetic factors: single gene mutations, multiple genes
- Aging: age-related decline in the efficiency of some metabolic pathways (e.g RNA synthesis)
- Accumulation of abnormal proteins

68

Which type of dementia is the accumulation of α-Synuclein involved in ?

Dementia with Lewy bodies

69

Which type of dementia is the accumulation of polyglutamine involved in?

Huntington's disease

70

What type of dementia is the accumulation of ubiquitin involved in?

Pick's disease/FTD

71

What are the clinical features of disease of the frontal lobe disease?

Impairments in:
- judgement
- abstract reasoning
- strategic planning
- emotional restraint
- control of appetite
- continence

72

What are the clinical features of disease of the medial temporal lobe, hippocampus, amygdala and limbic system?

- Disorders of memory
- Hallucination

73

What are the clinical features of diseases of the temporal neocortex?

- receptive dysphasia
- automatisms

74

What are the clinical features of disease of the occipital lobe?

Failure of visual sensory systems

75

What are the clinical features of disease of the parietal lobe?

Impairments in:
- visuospatial skills
- integration of sensory input
- leading to sensory agnosias and apraxias

76

What sort of pathological finding might be seen in someone with dementia?

- Low brain weight
- Atrophy in central gyri
-Atrophy in white matter - thin white matter
- Ventricular dilatation
- Atrophy in brainstem and cerebellum
- Pale substantia nigra and locus cereleus
- Microvacuolation in cerebral neocortex
- Attenuation in white matter
- Wide perivascular spaces in white matter
- Accumulation of abnormal proteins

77

What are the typical neuropathological findings in AD?

Macroscopic
- Brain weight: 900 –1200 (Normal: 1200 – 1400)
- Atrophy of gyri and widening of sulci: frontal, temporal, parietal, and hippocampus
- Ventricular dilatation

Microscopic
- Neuronal loss
- neurofibrillary tangles and neuropil threads

78

What are the typical neuropathological findings in dementia with Lewy bodies?

Macroscopically:
- Pale substantia nigra and locus cereleus
- Atrophy in amygdala, cingulate gyrus, temporal, parietal and frontal lobes

Microscopically:
- Neuronal loss from the substantia nigra and locus cereleus
- Accumulation of α – Synuclein +ve bodies in the neurons of the substantia nigra, amygdala and later in the cerebral cortex

79

What is the aetiology of multi-infarct dementia?

Atherosclerosis

80

What is Binswanger's disease?

Also known as subcortical leukoencephalopathy, is a form of small vessel vascular dementia caused by damage to the white brain matter.

81

What are Pick's bodies?

Build up of ubiquitin

82

Aside from Pick's cells, what other histopathological abnormality is seen in Pick's disease?

Balloon cells

83

What are the major neuropathological dementia diagnoses?

- Alzheimer’s Disease (AD)
- Frontotemporal lobar degeneration (FTLD)
- Dementia with Parkinsonism:
-- Idiopathic Parkinson Disease (IPD)
-- Dementia with Lewy Body (DLB)
- Corticobasal degeneration (CBD)
- Progressive Supranuclear Palsy (PSP)
- Vascular Dementia (VaD)
- Normal Pressure Hydrocephalus (NPH)
- Creutzfeldt-Jakob Disease (CJD)