Degenerative Diseases of the CNS Flashcards
What common features are there of neurodegenerative diseases?
- Aetiology largely unknown (mendelian genetic cases rare, often younger onset)
- Usually late onset
- Gradual progression
- Neuronal loss (specific neuropathology)
- Structural imaging often normal (atrophy)
Define dementia
A syndrome consisting of:
Progressive impairment of multiple domains of cognitive function in alert patient leading to loss of acquired skills and interference in occupational and social role
What is the incidence and prevalence of dementia?
- Incidence 200 per 100,000
- Prevalence 1,500 per 100,000
- > 750,000 patients in UK
What is the financial cost of dementia?
- £20 billion/year (£6 billion by carers)
- 66% of those in care homes
How does dementia incidence vary with age?
Increases with age from around age 60 with steep increases after 80 years and 90 years
What is the demarcation between early and late onset dementia?
- Early onset <65 years old
- Late onset >65 years old
What are the types of late onset dementia
- Alzheimers (55%)
- Vascular (20%)
- Lewy body (20%)
- Others
What are the types of early onset dementia?
-Alzheimers (33%)
-Vascular (15%)
-Frontotemporal (15%)
-Other (33%)
What
What are treatable causes of dementia?
- Vitamin deficiency: B12
- Endocrine: thyroid disease
- Infective: HIV, syphilis
What dementia mimics are there?
- Hydrocephalus
- Tumour
- Depression:’pseudodementia’
How is dementia diagnosed?
History
-Type of deficit, progression, risk factors, FH
Examination
-Cognitive function, neurological, vascular
Investigations
- Routine: bloods, CT/MRI
- Other: CSF, EEG, functional imaging, genetics (biopsy)
What domains are examined when assessing cognitive function?
- Memory
- Attention
- language
- Visuospatial
- Behaviour
- Emotion
- Executive function
- Apraxia’s
- Agnosias
What screening tests can be used to examine cognitive function?
- Mini mental state examination (MMSE)
- Montreal (MOCA)
- Neuropsychological assessment
When is a definitive dementia diagnosis made?
Post-mortem
What clues are there in the diagnosis of dementia?
Type of cognitive deficit
Speed of progression
- Rapid progression (CJD)
- Stepwise progression (vascular)
Other neurological signs
- Abnormal movements (Huntington’s)
- Parkinsonism (Lewy body)
- Myoclonus (CJD)
What is the commonest neurodegenerative condition?
Alzheimer’s disease
What is the mean age onset for Alzheimer’s disease?
70 years
How does temporo-parietal dementia present?
- Early memory disturbance
- Language and visuospatial problems
- Personality preserved until later
How does frontotemporal dementia present?
- Early change in personality / behaviour
- Often change in eating habits
- Early dysphasia
- Memory / visuospatial relatively preserved
How does vascular dementia present?
- Mixed picture
- Stepwise decline
How can dementia symptoms be managed/eased?
Non pharmacological:
- Information & support, dementia services
- Occupational therapy
- Social work / support / respite / placement
- Voluntary organisations
Pharmacological:
- Insomnia
- Behaviour (care with antipsychotics)
- Depression
What specific treatment is there for Alzheimer’s (+/- Lewy body dementia)?
Cholinesterase inhibitors
- Donepezil, rivastigmine, glantamine
- Small symptomatic improvement in cognition (wash-out)
- No delay in institutionalisation
NMDA antagonist
-Memantine
What specific treatment is there for frontotemporal dementia?
None
How effective is decreasing vascular risk factors in the treatment of vascular dementia?
No good evidence
Define Parkinsonism
A clinical syndrome with 2 or more of:
- Bradykinesia (slowness of movement)
- Rigidity (stiffness)
- Tremor (shakiness)
- Postural instability (unsteadiness / falls)
Where is the pathology in Parkinsonism?
- Predominantly dopamine loss in the basal ganglia
- Associated with substantia nigricans
What are the causes of Parkinsonism?
Idiopathic Parkinson’s disease
-Dementia with Lewy bodies
Drug-induced (e.g. dopamine antagonists)
Vascular parkinsonism (lower-half)
Parkinson’s plus syndromes
- Multiple system atrophy
- Progressive supranuclear palsy / corticobasal degen
What is the epidemiology of Parkinsonism?
- 2nd commonest neurodegenerative disease
- Incidence 15-20 per 100,000 per year
- Crude prevalence 150-300 per 100,000
How does the incidence of Parkinsonism differ with age?
- Increases with age
- Decreases 80-90
When is definitive diagnosis of Parkinsonism made?
Post-mortem
How is a diagnosis od Parkinsonism made clinically?
- Bradykinesia + ≥1 tremor, rigidity, postural instability
- No other cause / atypical features
- Slowly progressive (> 5-10 yrs)
-Supported by asymmetric rest tremor, good response to dopamine replacement treatment
How can Parkinsonism be imaged?
Functional imaging: Dopamine transporter SPECT
What early medical treatment is there for Parkinsonism?
Dopamine agonists
- Ropinirole
- Pramipexole
- Rotigotine
MAO-B inhibitor
- Selegiline
- Rasagiline
- Safinamide
COMT inhibitor
- Levodopa
- Entacapone
What drug induced complications may there be with Parkinsonism?
- Motor fluctuations: levodopa wears off
- Dyskinesias: involuntary movements (levodopa)
- Psychiatric: hallucinations, impulse control
What non-drug induced complications may there be with Parkinsonism?
- Depression (20%)
- Dementia (~50% after 10 yrs)
- Autonomic: BP, bladder, bowel
- Speech, swallow
- Balance
What late treatment is there for Parkinsonism?
Drugs:
- Prolong levodopa half life: MAO-B inhibitors, COMT inhibitor, slow release levodopa
- Add oral dopamine agonist
- Continuous infusion (apomorphine, Duodopa)
Functional neurosurgery (deep brain stimulation)
Allied health professionals +/- care package
