Degenerative Diseases of the CNS Flashcards
What are some common features of neurodegenerative diseases?
- Aetiology largely unknown
- Mendelian genetic cases are rare, often younger onset
- Usually late onset
- Gradual progression
- Neuronal loss (specific neuropathology)
- Structural imaging often normal
What is 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
Describe the epidemiology of dementia?
- Incidence 200/100,000
- Prevalence 1500/100000
- Very costly, about £35 billion per year (NH, social and unpaid work)
- Projected to increase to £94 billion by 2040
How does the incidence of dementia change with age?
Increases with age
What are some causes of dementia?
- Late onset (over 65 years old)
- Alzheimer’s (55%)
- Vascular (20%)
- Lewy body (20%)
- Other (5%)
- Young onset (younger than 65 years old)
- Alzheimer’s (33%)
- Vascular (15%)
- Frontotemporal (15%)
- Other (30%)
When is dementia onset considered to be young and late onset?
Young onset <65 years old
Late onset > 65 years old
What are the most common causes of late onset dementia?
- Alzheimer’s (55%)
- Vascular (20%)
- Lewy body (20%)
- Other (5%)
What are the most common causes of young onset dementia?
- Alzheimer’s (33%)
- Vascular (15%)
- Frontotemporal (15%)
- Other (30%)
What are some treatable causes of dementia?
- Vitamin B12 deficiency
- Endocrine
- Thyroid disease
- Infective
- HIV, syphilis
What are some other diseases that dementia mimics?
- Hydrocephalus
- Tumour
- Depression (psudodementia)
What parts of the history are important for diagnosing dementia?
- Type of deficit, progression, risk factors, family history
What parts of the examination are important for diagnosing dementia?
- Cognitive function, neurological, vascular
What investigations are important for diagnosing dementia?
- Routine
- Bloods, CT/MRI
- Others
- CSF, EEG, functional imaging, genetics
Why is imaging used to diagnose dementia?
Imaging is done to rule out other things that can cause cognitive deficit such as tumour, other investigations are rarely done
What different parts of cognition can be examined?
- Memory, attention, language, visuospatial, behaviour, emotion, executive function, apraxias (difficulty with the motor planning to perform tasks when asked) agnosias (inability to process sensory information)
What is apraxias?
Difficulty with the motor planning to perform tasks when asked
What is agnosias?
Inability to process sensory information
What are different ways of examining cognitive function?
- Screening tests
- Mini-mental (MMSE), Montreal (MOCA)
- Neuropsychological assessment
Which of MOCA and MMSE is better?
MOCA due to testing more domains
What is the only way that a definitive diagnosis of dementia can be made?
Definitive diagnosis of type of dementia can only be made post-mortem, but there are clues to diagnosis:
- 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)
Although definitive diagnosis of the type of dementia can only be made post-mortem, what are some clues to diagnosis when alive?
What is the most common neurological condition?
Alzheimer’s dementia
What is the mean onset of Alzheimer’s dementia?
Mean age onset is 70 years, 25% are younger than 65
What are some risk factors for Alzheimer’s dementia?
- Genetic
- Lifestyle
- Smoking
- Exercise
- Diet
- Alcohol
What are some different dementias based on location?
- Temporo-parietal dementia
- Early memory disturbance
- Language and visuospatial problems
- Personality preserved until later
- Frontotemporal dementia
- Early change in personality/behaviour
- Often change in eating habits
- Early dysphasia
- Memory/visuospatial relatively preserved
What is the clinical presentation of temporo-parietal dementia?
- Early memory disturbance
- Language and visuospatial problems
- Personality preserved until later
What is the clinical presentation of fontotemporal dementia?
- Early change in personality/behaviour
- Often change in eating habits
- Early dysphasia
- Memory/visuospatial relatively preserved
What is vascular dementia caused by?
Caused by brain damage from impaired blood flow to the brain
Describe the progression of the decline due to vascular dementia?
Stepwise decline
What is the symptomatic treatment for dementia?
- Non-pharmacological
- Information and support, dementia services
- Occupational therapy
- Social work/support/respite/placement
- Voluntary organisations
- Pharmacological
- Insomnia
- Behaviour (care with antipsychotics)
- Depression
What is the specific treatment for dementia?
- Alzheimer’s (with or without Lewy body dementia)
- Cholinesterase inhibitors (cholinergic deficit)
- Donepezil, rivastigmine, galantamine
- Small symptomatic improvement in cognition (wash out)
- No delay in institutionalisation
- NMDA antagonist (memantine)
- Cholinesterase inhibitors (cholinergic deficit)
- Frontotemporal
- None
- Vascular dementia
- No robust evidence for decreasing vascular risk factors
Are there any medicines that stop the decline due to dementia?
There are no neuroprotective medicines that stop the decline of the disease, we can provide symptomatic relief
What is 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 located that causes parkinsonism?
Pathology is in the basal ganglia, predominantly dopamine loss
What are some causes of parkinsonism?
- Idiopathic PD
- Dementia with lewy bodies
- Drug induced
- Such as dopamine antagonists
- Vascular parkinsonism (lower half)
- PD plus syndromes
- Multiple system atrphy
- Progressive supranuclear palsy/corticobasal degeneration
What is the epidemiology of PD?
- Incidence is 15-20/100000 per year
- Age dependent
- 1.5 M:F
- Crude prevalence 150-300/100000
What is the M:F ratio of PD?
1.5 M:F
What is the incidence of PD?
- Incidence is 15-20/100000 per year
- Age dependent
How does the incidence of PD change with age?
Increases
What is the clinical presentation of PD?
- Bradykinesia plus one or more of tremor, rigidity or postural instability
- No other cause/atypical features
- Slowly progressive, possibly more than 5 to 10 years
Why would functioning imaging be used to make a PD diagnosis?
Functioning imaging is occasionally used to make diagnosis (dopamine transporter SPECT) due to not being able to image dopamine neurons on MRI, but can with this label as it binds to dopamine transporter
What is the first line treatment of PD?
Levodopa
What is treatment of PD based on?
Neuropharmacology of dopaminergic neurons
What are some late treatments for PD?
- Drugs
- Prolong levodopa half life
- MAO-B inhibitors
- COMT inhibitor
- Slow release levodopa
- Add oral dopamine agonist
- Continuous infusion (apomorphine, duodopa)
- Prolong levodopa half life
- Functional neurosurgery (deep brain stimulation)
- Allied health professionals
What are some later complications of PD that are drug-induced?
- Motor fluctuations
- Levodopa wears off
- Dyskinesias
- Involuntary movements (due to levodopa)
- Psychiatric
- Hallucinations, impulse control
What is dyskinesias?
What are some later complications of PD that are not drug-induced?
- Depression (20%)
- Dementia (about 50% after 10 years)
- Autonomic problems
- BP, bladder, bowel
- Speech, swallowing
- Balance
- 5-10% of people with PD get a fracture each year due to falling
Why can treatment for PD lead to patients being sexually inappropriate, going to the casino or excessive shopping?
Dopamine drives reward system so treatment can overstimulate it and they can start doing things overcompulsary such as being sexually inappropriate, casino, shopping
