Dementia

Question 1

Define: apraxia

Answer 1

Difficulty performing motor tasks

Question 2

Define: spastic paresis

Answer 2

Muscle hypertonia and exaggerated tendon reflexes

Question 3

Which language impairment is associated with Broca’s area?

Answer 3

Expressive aphasia

Question 4

Which language impairment is associated with Wernicke’s area?

Answer 4

Receptive aphasia

Question 5

Which area of the brain is associated with expressive aphasia?

Answer 5

Broca’s area (frontal lobe - near the pre-central gyrus (which controls motor functioning))

Question 6

Which area of the brain is associated with receptive aphasia?

Answer 6

Wernicke’s area (posterior temporal lobe, overlaps with parietal lobe)

Question 7

What are the functions of the frontal lobe?

Answer 7

Judgement
Reasoning
Behaviour
Voluntary movements
Broca's area (expressive language)

Question 8

What are the functions of the parietal lobe?

Answer 8

Spacial orientation
Perception
Initial cortical processing of tactile and proprioception
Wernicke’s area (language comprehension)

Question 9

What are the functions of the temporal lobe?

Answer 9

Emotions
Learning and memory
Auditory
Olfaction
Wernicke's area (language comprehension)

Question 10

What are the functions of the occipital lobe?

Answer 10

Vision

Question 11

What are the principal clinical features of dementia (in order of progression in AD)?

Answer 11

1. Memory loss
2. Impaired thinking
3. Language impairments
4. Deterioration of personal functioning
5. Disturbed personality and behaviour
6. Perceptual abnormalities
7. Motor impairments

Question 12

What is syllogomania?

Answer 12

Compulsive hoarding of rubbish (an example of deterioration in personal functioning associated with dementia. Associated with Diogenes syndrome).

Question 13

What is prosopagnosia?

Answer 13

Inability to recognise faces (perceptual abnormality associated with dementia)

Question 14

What is dementia pugilistica?

Answer 14

Boxer’s dementia - a form of chronic traumatic encephalopathy caused by repeated concussive/sub-concussive blows to the head. Average onset is ~12-16 years after beginning a career in boxing, affects 15-20% of boxers.

Question 15

What is the triad of symptoms associated with Normal Pressure Hydrocephalus?

Answer 15

Gait disturbance/ataxia
Dementia
Urinary incontinence

Question 16

What is the prevalence of Alzheimer’s disease?

Answer 16

1% at 65 years old.
30-40% at 90 years old
(n.b. prevalence doubles every 5y post 65 - makes up 50% of all dementias, v common)

Question 17

Describe the main neuropathology seen in Alzheimer’s disease.

Answer 17

Neuronal synaptic loss (leads to cholinergic deficit)
Symmetrical cortical atrophy
Senile plaques (core of B-amyloid)
Neurofibrillary tangles (Tau protein - which is also seen in Pick bodies)

Question 18

What is the role of the cholinergic system in Alzheimer’s disease?

Answer 18

Acetylcholine (ACh) is an NT found in the autonomic nervous system (symp/parasymp, all parasympathetic organs), PNS at the NMJ (between motor neurons and skeletal muscle), and in the CNS.

In Alzheimer’s disease, there is a marked decrease in ACh concentration in the cerebral cortex and caudate nucleus. The deterioration of cholinergic innervation of the neocortex is associated with the memory loss in AD (muscarinic receptors are important mediators of behaviour in the CNS).

Question 19

What are the risk factors for Alzheimer’s disease?

Answer 19

Age (up to 90), female (2:1), FHx (4x risk), Down’s syndrome, Dialysis, head injury.

Question 20

Why is Down’s syndrome a risk factor for Alzheimer’s disease?

Answer 20

Three copies of chromosome 21, which contains the B-amyloid precursor protein (APP) gene.

Question 21

What are the 4 genes associated with Alzheimer’s disease?

Answer 21

Inheritance: e4 allele of apolipoprotein E (ch 19) (e2 is protective).
Ass. w/ late onset.

Mutations:
APP gene (B-amyloid precursor protein) and Presenilin 1
Presenilin 2
Ass. w/ rarer early onset.

Question 22

What are the main clinical features of Alzheimer’s disease?

Answer 22

MEMORY LOSS and PERSONALITY CHANGES

Memory:
Short term impairment > long term
Leads to disorientation in TTP.

Personality:
Euphoric/labile OR irritable/apathy
Disinhibition, aggression, socially inappropriate
Inattention, distractibility 
Obsessive and stereotyped behaviours

Question 23

What is the neuropathology of dementia with Lewy Bodies?

Answer 23

Lewy bodies present. Intracellular eosinophilic inclusions - consisting of abnormally phosphorylated neurofilament proteins, and aggregated with ubiquitin and ALPHA-SYNUCLEIN.
Cortical and subcortical structures affected.

This leads to neuronal loss and cholinergic deficit

Question 24

What are the symptoms of the EARLY STAGES of Alzheimer’s disease?

Answer 24

Memory lapses
Forgetting names of people and places
Difficulty finding words for things
Inability to remember recent events
Forgetting appointments

Question 25

What are the symptoms of the LATER STAGES of Alzheimer's disease?

Answer 25

Wandering, disorientation Apathy Psychiatric symptoms - depression, hallucinations, delusions Behavioural problems - disinhibition, aggression, agitation Altered eating habits Incontinence

Question 26

What are the symptoms of Alzheimer's disease AS IT PROGRESSES?

Answer 26

Difficulties with language Apraxia Problems with planning and decision making Confusion

Question 27

What is the criteria for diagnosing DLB? (presentation)

Answer 27

Presence of dementia. Plus, two of the three core features: 1. Fluctuating attention and concentration. 2. Recurrent well-formed visual hallucinations. 3. Spontaneous Parkinsonism.

Question 28

What is Diogenes syndrome?

Answer 28

Severe senile self-neglect. Often accompanied with syllogomania.

Question 29

What is the neuropathology of Vascular Dementia?

Answer 29

Focal disease/Stroke related VaD - from single (big stroke)/more commonly multiple infarcts (lots of little strokes - sometimes unnoticed). Diffuse disease/Subcortical VaD - small vessel disease leads to diffuse disease (Binswanger's disease and Lacunar state) ``` Often coexist (Mixed type can also have these changescoexisting with AD) ```

Question 30

What is a Lacunar state? (VaD)

Answer 30

Appearance of small, smooth-walled cavities in the brain

Question 31

What is Binswanger's disease? (VaD)

Answer 31

Small vessel vascular dementia

Question 32

What are the RFs for Vascular Dementia?

Answer 32

``` Hx of stroke/TIA Older age M>F DM Hypercholesterolaemia Hypercoaguable states CVD (including AF) Obesity / smoking / alcohol FHx of stroke/CVD ```

Question 33

What is the presentation of Vascular Dementia (and how is a diagnosis made?)?

Answer 33

Presence of dementia (cognitive decline from higher level of functioning) AND Cardiovascular disease Relationship between the two, inferred by: - onset of dementia within 3/12 of recognised stroke - abrupt deterioration in cognitive function - fluctuating, stepwise progression of cognitive deficits

Question 34

What is the neuropathology of Frontotemporal Lobe dementia/Pick's disease?

Answer 34

Selective, asymmetrical, 'knife blade' atrophy Get atrophy, neuronal loss and gliosis affecting frontal and temporal lobes. Characteristic features: - Pick cells = ballooned neurons - Pick bodies = Tau-protein positive neuronal inclusions N.B. no senile plaques/NF tangles as in AD.

Question 35

What is the presentation of FTL/Pick's disease?

Answer 35

Insidious and progressive dementia. Px at 45-60y Early and prominent behavioural/personality changes and disinhibition Executive functioning Spatial orientation preserved

Question 36

Summarise the aetiology of the main 4 types of dementia.

Answer 36

AD - degeneration of cerebral cortex, senile plaques (B-amyloid), NF tangles (Tau), cortical atrophy, decreased ACh production from affected neurons. DLB - Lewy bodies (alpha-synuclein) Picks - Pick's bodies (Tau) VaD - single/multiple infarcts

Question 37

Summarise the aetiology of Huntington's disease.

Answer 37

Autosomal dominant neurodegenerative disorder - ≥36 CAG repeats encoding glutamine in Huntington's protein (ch 4) Anticipation - as number of repeats increases, age of onset decreases (progressively lower w/in generations), Abn Huntington's protein leads to degeneration of neurons: - caudate nucleus & putamen - movement disorders - cerebral cortex - dementia

Question 38

What is the presentation of Huntington's disease?

Answer 38

Choreiform movements (dance-like repeated movements) Progressive dementia Psychiatric disturbances (notable early depression) Behavioural disturbances

Question 39

What is the diagnostic criteria for ALL types of dementia? (NICE)

Answer 39

Affect ability to function in normal activities. Represent a decline from a previous level of function. Cannot be explained by delirium or other major psychiatric disorder. Have been established by history-taking from patient and informant, and formal cognitive assessment. Involve impairment of at least two of the following domains: - Ability to acquire and remember new information - Judgement, ability to reason or handle complex tasks - Visuospatial ability - Language functions - Personality and behaviour

Question 40

Which class of drugs can be used to treat AD/DLB?

Answer 40

``` Cholinesterase inhibitors (these dementias have an acetylcholine deficiency) eg donepezil, rivastigmine ```

Question 41

How often should a prescription for donepezil/rivastigmine be assessed?

Answer 41

Reassess after 2-4/12, and only continue if a demonstratable improvement or lack of decline. Then reassess 6/12.

Question 42

What is the main difference between delirium and dementia?

Answer 42

Delirium has clouding of consciousness, dementia does not.

Question 43

Lesions in the dominant temporal lobe can lead to ...

Answer 43

Verbal agnosia, visual agnosia, receptive aphasia, hallucinations