Neurodegenerative ETC Flashcards by Clara Sage

Memory loss over months or years

Dementia

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Memory loss over weeks

Depression

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Memory loss over days

Infection or stroke

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Prevalence of Dementia

Rare if 65 years
20% if >80 years
79% if >100 years

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Associated symptoms of dementia

Agitation, aggression, wandering, hallucinations, slow repetitious speech, apathy

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Ameliorable metabolic causes of dementia

Hypothyroidism
B12/folate deficiency
Pellegra (tryptophan/nicotinic acid - vit B3 deficit)

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Infective causes of dementia

Neurocystericosis
HIV
Syphilis
Whipple’s disease

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CNS causes of dementia

PD
Alzheimer’s Disease
Subdural haematoma
Tumours - meningioma

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What % of dementia is vascular dementia

25%

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What causes vascular dementia

Cumulative effects of many mini-strokes

Sudden onset and stepwise progression are features

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3rd most common cause of dementia?

Lewy Body Dementia
Fluctuating cognitive impairment
with visual hallucinations
Followed by parkinsonism

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Signs of fronto-temporal dementia

Executive impairment
Behavioural/personality changes early on
Early preservation of episodic memory
Disinhibition and emotional unconcern

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Medication for disinhibition/altered behaviour in dementia

Trazodone (antipsychotic) or lorazepam

If worse - quetiapine, risperidone, olanzapine - but will worsen cognition

Haloperidol used short-term

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Medication for depression in dementia

SSRI eg. citalopram

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Drugs to avoid in dementia

Neuroleptics/antipsychotics, sedatives, tricyclics

These all impair cognition

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Main features of AD

Progressive global cognitive impairment
Visuo-spatial skill decrease
Memory loss
Decreased verbal abilities
Executive function (planning)

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What is anosognosia?

Lack of insight into the problems engendered by the disease

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Pathology of AD

B-amyloid accumulation in amyloid plaques
Neurofibrillary tangles
Decreased acetylcholine

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Risk factors for AD

1st degree relative with AD
Down’s syndrome (AD inevitable)
ApoE E4 allele homozygote
Vascular risk factors - vascular dementia in 95% of AD patients

Low physical or cognitive activity
Depression
Loneliness
Smoking >20 cigarettes a day accelerates onset by 2.3years

Prognosis of AD

Mean survival is 7 years from onset of unequivocal symptoms

Medication in AD

Acetylcholinesterase inhibitors
Appear to help more with laying down of new memories than the conservation of old memories
Seem to help in dementia of PD and LB dementia

Eg. Donepezil, Rivastigmine, Galantamine

Side effects of acetylcholinesterase inhibitors

Worsen peptic ulcer disease and heart block
D&V, cramps
Incontinence
Headaches , dizziness, insomnia

Another non-Ach medication in AD

Memantine
NMDA antagonist
Reasonably effective in late stage disease

3 primary features of Parkinsonism

Tremor - resting tremor, pill-rolling
Rigidity - Cogwheel rigidity
Bradykinesia - slow to initiate movement and slow movement

Therefore festinating gait (decreased arm swing)
Micrographia
Expressionless face
Monotonous hypophonic speech

Typical age of onset of PD

65 years

Pathology of PD

Mitochondrial DNA dysfunction leads to degeneration of dopaminergic neurons in the SN of the BG

Features of bradykinesia in PD

Progressive fatiguing - decrement in amplitude of repetitive movement Upper limb usually affected first and is unilateral

Features of tremor in PD

Unilateral in upper limb then to lower limb on that side and then to other arm Made worse by emotion or stress Unmasking - overflow - count backwards from 10

Features of rigidity of PD

Unmasked - synkinesis - get to move other arm | Also called reinforcement

Features of posture and gait in PD

Postural instability and hypotension - not usually present in first 5 years of disease

Feature which may lead to death in PD

Speech and swallowing difficulties - therefore aspiration pneumonia as terminal event

Sleep in PD

REM Behaviour Disorder Talking and thrashing out in sleep with no recollection Treat with clozapine or quetiapine

Main medication in PD

L-DOPA Given with domperidone to prevent nausea and vomiting Also Carbidopa or Benserazide to prevent peripheral conversion

Levodopa extender

Entacapone | COMT inhibitor

DA agonists

Ropinirole and pramipexole Rotigotine patches Bromocriptine/pergolide and cabergoline - not really used because can cause heart problems and lung fibrosis

Preventing breakdown of dopamine at synapse

Selegeline and rasagiline | MAOinhibitors

Management of LDOPA induced dyskinesia

Amantadine | Anticholinergics - Benzhexol and Orphenadrine

Treatment of ON-OFF

Apomorphine - short-acting DA agonist L-Dopa intestinal gel infusion pump Avoid protein rich meals - prevents levodopa absorption

Features of Progressive Supranuclear Palsy

Postural instability early on Pseudobulbar palsy Vertical supranuclear gaze palsy (can't look up or down) Also dementia and parkinsonism Little response to L-DOPA (but parkinsonian features may respond)

Features of Multi-System Atrophy

Parkinsonism is more symmetrical and WITHOUT TREMOR Autonomic failure - severe Olivopontocerebellar atrophy - cerebellar signs PD features may respond but Ldopa

Cortico basal degeneration features

Alien limb phenomenon Myoclonus PD signs and dementia LDOPA has no effect

What type of tremor caused by cerebellar problems?

Intention tremor

What is a essential tremor, two types and what causes it?

Postural - when limb held out against gravity Kinetic - present on movement ``` eg. Benign essential tremor Thyrotoxicosis Anxiety B-agonists ``` Essential - improves with alcohol

Causes of chorea | and treatment

``` Huntingtons Sydenhams chorea (strep) ``` Thyrotoxicosis SLE Dopamine blocking drugs or treat underlying disorder

Egs of Tics | and treatment

Tourettes (motor and vocal) Physical tics Clonazepam and clonidine if severe

Dystonia examples

Primary dystonia - children/young adult, usually starts with foot and then spreads - treat with DBS Focal dystonias - torticollis - writers cramp, blepharospasm - worsened by stress - treat with BOTOX