Dementia and Movement Disorders Flashcards
what is dementia?
a syndrome in which there is a deterioration in memory, thinking, behaviour and the ability to perform everyday activities
what is Alzheimers disease?
commonest type of dementia
caused by ageing with a complex interaction of genetic and environmental risk factors
what is vascular dementia?
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
what is dementia with lewy bodies?
dementia associated with the development of abnormal protein clumps in the brain
what is front-temporal dementia?
dementia caused by selective neurodegeneration of frontal and temporal lobes
how does front-tempotal dementia present?
personality change, social inhibition, loss of language
how does Alzheimers disease present?
initially problems with memory (recent/ new memories)
may develop- dysphasia, apraxia (difficulty with motor tasks), disorientation, impairment in planning/problem solving
what are the diagnostic features of Alzheimers?
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
what are the investigations used in Alzheimers?
cognitive testing- verbal episodic memory structural brain imaging- CT/MRI may have patterns of cortical atrophy functional imaging (PET)
what are the core clinical features of Lewy body dementia?
- fluctuating cognition
- visual hallucinations
- parkonsinism
- REM sleep behaviour disorder
what are the investigations for dementia with Lewy bodies?
- cognitive testing- attentional and executive function, visuospatial/visual perception
- structural imaging- exclude other causes
- SPECT/PET scan- can show low dopamine uptake in basal ganglia (DaT scan)
- 123 iodine- MIBG myocardial scintigraphy- reduced cardiac uptake of 123iodine-MIBG in DLB
- polysomnography- REM sleep disorder
how can cognition be assessed?
mini mental state exam
addenbrookes cognitive examination
which brain pathway and brain areas are involved in object recognition?
the ventral visual pathway
temporal lobe
what are the neuropathological features of Alzheimers disease?
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
what are the neuropathological features of Lewy body diseases?
macroscopic changes- depigmentation of substantia nigra
microscopic changes- misfolded alpha-synuclein forms inclusions in cell bodies (Lewy bodies) and axons (lewy neurites)
what are the clinical features of Huntington’s disease?
triad of motor, behavioural and cognitive deficits
what are the neuropathological features of huntigtons disease?
macroscopic- cerebral atrophy, atrophy of neostriatum, globus pallidus, thalamus s.nigra and cerebellum
microscopic- loss of neurones, neostriatal dark neurones, intracellular huntingtin protein inclusions
what are the effects of damage to the basal ganglia?
tremors, involuntary muscle movements, abnormal increase in tone, difficulty initiating movements, abnormal posture
what are the symptoms of Parkinson’s disease?
motor symptoms- pill rolling terror, increased muscle tone, Bradykinesia (slow movement), postural instability
non-motor symptoms- sleep disorders, dementia, depression, fatigue
what are the cardinal pathological features of Parkinson’s disease?
formation of Lewy bodies and lewy neurites
progressive neuronal loss particularly in the substantia nigra pars compacta- decreased dopamine
what are the investigations for Parkinson’s disease?
DaT scan- type of SPECT scan which shows the function of the dopamine terminals
what are the main treatments for Parkinson’s disease?
dopamine replacement therapy- levodopa, dopamine agonists
reduction of dopamine/levodopa breakdown- catechol-O-methyltransferase (COMT) inhibitor, monoamine oxidase isoenzyme type B (MAO-B) inhibitor
what is the mechanism of action and side effects of levodopa?
MOA- it is converted to dopamine and exerts its effects
side effects- nausea/vomiting, tiredness, dizziness
what is the mechanism of action and side effects of dopamine agonists (pergolide)?
MOA- agonist at D2 receptor
side effects- nausea/vomiting, dizziness, tiredness
what is the mechanism of action and clinical use of catechol-O- methyltransferase inhibitors?
MOA- reduces the breakdown of levodopa, extending its half life and prolonging its action
clinical use- given with levodopa
what is the mechanism of action of monoamine oxidase-B inhibitors (selegiline)?
MOA- prevents the breakdown of dopamine leading to greater dopamine availability
what are the movement disorders seen in Huntington’s disease?
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
what are the behavioural and cognitive problems associated with Huntington’s disease?
behavioural- apathy, dysphoria (dissatisfaction), irritability, agitation, aggression, poor self care, inflexibility
cognitive- affects planning, abstract thinking and inhibition of inappropriate actions
how is Huntington’s diagnosed?
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
how is dementia treated?
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
what is the mechanism of action of donepezil hydrochloride, rivastigmine and galantamine?
inhibits acetylcholinesterase and choline acetyl transferase activity to reduce cholingeric deficit
what is the mechanism of action and side effects of memantine hydrochloride?
MOA- weak glutamate receptor antagonist (NMDA receptor), prevents excessive pathological NMDA receptor activation
side effects- headache, impaired balance, dizziness, drowsiness, dyspnoea, hypertension
