Dementia and Movement Disorders

Question 1

what is dementia?

Answer 1

a syndrome in which there is a deterioration in memory, thinking, behaviour and the ability to perform everyday activities

Question 2

what is Alzheimers disease?

Answer 2

commonest type of dementia

caused by ageing with a complex interaction of genetic and environmental risk factors

Question 3

what is vascular dementia?

Answer 3

dementia associated with cerebral vascular disease
cerebral ischaemia leads to impaired neurological function
classically step wise decline in cognition- each step associated with a vascular event

Question 4

what is dementia with lewy bodies?

Answer 4

dementia associated with the development of abnormal protein clumps in the brain

Question 5

what is front-temporal dementia?

Answer 5

dementia caused by selective neurodegeneration of frontal and temporal lobes

Question 6

how does front-tempotal dementia present?

Answer 6

personality change, social inhibition, loss of language

Question 7

how does Alzheimers disease present?

Answer 7

initially problems with memory (recent/ new memories)

may develop- dysphasia, apraxia (difficulty with motor tasks), disorientation, impairment in planning/problem solving

Question 8

what are the diagnostic features of Alzheimers?

Answer 8

meets criteria for dementia
insidious onset- months/years
clear history of worsening cognition
deficits in one or more of - learning and memory, language, visuospatial, executive function

Question 9

what are the investigations used in Alzheimers?

Answer 9

cognitive testing- verbal episodic memory  
structural brain imaging- CT/MRI may have patterns of cortical atrophy 
functional imaging (PET)

Question 10

what are the core clinical features of Lewy body dementia?

Answer 10

1. fluctuating cognition
2. visual hallucinations
3. parkonsinism
4. REM sleep behaviour disorder

Question 11

what are the investigations for dementia with Lewy bodies?

Answer 11

1. cognitive testing- attentional and executive function, visuospatial/visual perception
2. structural imaging- exclude other causes
3. SPECT/PET scan- can show low dopamine uptake in basal ganglia (DaT scan)
4. 123 iodine- MIBG myocardial scintigraphy- reduced cardiac uptake of 123iodine-MIBG in DLB
5. polysomnography- REM sleep disorder

Question 12

how can cognition be assessed?

Answer 12

mini mental state exam

addenbrookes cognitive examination

Question 13

which brain pathway and brain areas are involved in object recognition?

Answer 13

the ventral visual pathway

temporal lobe

Question 14

what are the neuropathological features of Alzheimers disease?

Answer 14

macroscopic- atrophy of brain, particularly in the medial temporal lobe
microscopic:
hyperphosphorylated Tau- forms neurofibrillary tangles in cell bodies and neuropil threads in axons
extracellular amyloid beta plaques

Question 15

what are the neuropathological features of Lewy body diseases?

Answer 15

macroscopic changes- depigmentation of substantia nigra

microscopic changes- misfolded alpha-synuclein forms inclusions in cell bodies (Lewy bodies) and axons (lewy neurites)

Question 16

what are the clinical features of Huntington’s disease?

Answer 16

triad of motor, behavioural and cognitive deficits

Question 17

what are the neuropathological features of huntigtons disease?

Answer 17

macroscopic- cerebral atrophy, atrophy of neostriatum, globus pallidus, thalamus s.nigra and cerebellum
microscopic- loss of neurones, neostriatal dark neurones, intracellular huntingtin protein inclusions

Question 18

what are the effects of damage to the basal ganglia?

Answer 18

tremors, involuntary muscle movements, abnormal increase in tone, difficulty initiating movements, abnormal posture

Question 19

what are the symptoms of Parkinson’s disease?

Answer 19

motor symptoms- pill rolling terror, increased muscle tone, Bradykinesia (slow movement), postural instability
non-motor symptoms- sleep disorders, dementia, depression, fatigue

Question 20

what are the cardinal pathological features of Parkinson’s disease?

Answer 20

formation of Lewy bodies and lewy neurites

progressive neuronal loss particularly in the substantia nigra pars compacta- decreased dopamine

Question 21

what are the investigations for Parkinson’s disease?

Answer 21

DaT scan- type of SPECT scan which shows the function of the dopamine terminals

Question 22

what are the main treatments for Parkinson’s disease?

Answer 22

dopamine replacement therapy- levodopa, dopamine agonists
reduction of dopamine/levodopa breakdown- catechol-O-methyltransferase (COMT) inhibitor, monoamine oxidase isoenzyme type B (MAO-B) inhibitor

Question 23

what is the mechanism of action and side effects of levodopa?

Answer 23

MOA- it is converted to dopamine and exerts its effects

side effects- nausea/vomiting, tiredness, dizziness

Question 24

what is the mechanism of action and side effects of dopamine agonists (pergolide)?

Answer 24

MOA- agonist at D2 receptor

side effects- nausea/vomiting, dizziness, tiredness

Question 25

what is the mechanism of action and clinical use of catechol-O- methyltransferase inhibitors?

Answer 25

MOA- reduces the breakdown of levodopa, extending its half life and prolonging its action clinical use- given with levodopa

Question 26

what is the mechanism of action of monoamine oxidase-B inhibitors (selegiline)?

Answer 26

MOA- prevents the breakdown of dopamine leading to greater dopamine availability

Question 27

what are the movement disorders seen in Huntington's disease?

Answer 27

chorea- non-rhythmic, brief, irregular movements dystonia- sustained or repetitive muscle contractions resulting in repetitive twisting movements or abnormal fixed postures myoclonus- brief jerking movement of muscle dysarthria- difficulty speaking, poor articulation of words dysphagia abnormal eye movements

Question 28

what are the behavioural and cognitive problems associated with Huntington's disease?

Answer 28

behavioural- apathy, dysphoria (dissatisfaction), irritability, agitation, aggression, poor self care, inflexibility cognitive- affects planning, abstract thinking and inhibition of inappropriate actions

Question 29

how is Huntington's diagnosed?

Answer 29

made by a specialist neurologist mainly based on the presence of specific movement disorders (e.g. chorea), can then be confirmed by gentling testing MRI/CT may show some changes in moderate-severe disease

Question 30

how is dementia treated?

Answer 30

non-pharmacological- structured group cognitive stimulation programme pharmacological: 1st line- acetylcholinesterase inhibitor alternative- mematine hydrochloride both of these drugs only have licensed indication in Alzheimers but are used in DLB

Question 31

what is the mechanism of action of donepezil hydrochloride, rivastigmine and galantamine?

Answer 31

inhibits acetylcholinesterase and choline acetyl transferase activity to reduce cholingeric deficit

Question 32

what is the mechanism of action and side effects of memantine hydrochloride?

Answer 32

MOA- weak glutamate receptor antagonist (NMDA receptor), prevents excessive pathological NMDA receptor activation side effects- headache, impaired balance, dizziness, drowsiness, dyspnoea, hypertension