Neurological Diseases - Degenerative disorders - Dementia and Parkinson's Flashcards
what are common features of neurodegenrative 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)
what is dementia?
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
> 850,000 patients in UK ( 1.6M by 2040)
47M worldwide 2015 (131M by 2050)
what are causes of late onset dementia (65+ years)?
Alzheimer’s (55%)
Vascular (20%)
Lewy body (20%)
Others (5%)
what are the causes of young onset dementia?
Alzheimer’s (33%)
Vascular (15%)
Frontotemporal (15%)
Other (33%)
what are other causes of dementia?
Toxic (alcohol)
Genetic (Huntington’s)
Infection (HIV, CJD)
Inflammatory (MS)
what are treatable causes / mimics of dementia?
Vitamin deficiency - B12
Endocrine - thyroid disease (hypothyroidism)
Infective - HIV, syphilis
Mimics: Hydrocephalus
Tumour
Depression: “pseudodementia”
what should be asked in the history for dementia?
type of deficit, progression, risk factors, FH
what should be examined in diagnosis of dementia?
cognitive function, neurological, vascular
what investigations are done to diagnose dementia?
routine - bloods, CT / MRI
others - CSF, EEG, functional imaging, genetics
what various domains should be covered in examination of cognitive function?
Memory, attention, language, visuospatial,
Behaviour, emotion, executive function
Apraxias, agnosias
what screening tests can assess cognitive function?
Mini-mental (MMSE), Montreal (MOCA)
what is mini-mental test?
The mini mental state examination (MMSE) is a commonly used set of questions for screening cognitive function.[1] This examination is not suitable for making a diagnosis but can be used to indicate the presence of cognitive impairment, such as in a person with suspected dementia or following a head injury
The examination has been validated in a number of populations. Scores of 25-30 out of 30 are considered normal, 21-24 as mild, 10-20 as moderate and below 10 as severe impairment.
what assessment is used to examine cognitive function?
Neuropsychological assessment
what is Montreal (MOCA)?
The Montreal Cognitive Assessment (MoCA) was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation
what would rapid progression of disease suggest?
CJD
what is CJD?
Creutzfeldt-Jakob disease (CJD) is a rare and fatal condition that affects the brain. It causes brain damage that worsens rapidly over time.
what would stepwise progression of disease suggest?
vascular dementia
which disease is indicated from abnormal movements?
Huntington’s
which disease is indicated from parkinsonism?
Lewy body
which disease is indicated from myoclonus?
CJD
what is the commonest neurodegenerative condition?
Alzheimer’s disease
when is the mean age onset for alzheimers disease?
mean age onset 70 yr (25% <65yrs)
what is the pathology of alzeimers disease?
β-amyloid plaques and neurofibrillary tangles
what increases risk of alzeimers disease?
smoking, obesity, diabetes, hypertension
what decreases the risk of alzheimers disease?
cognitive reserve, exercise, diet (medditeranian)
what genes increase risk of alzheimers disease?
APOE, APP, PSEN1, PSEN2
how does temporo-parietal dementia present clinically?
Early memory disturbance
Language and visuospatial problems
Personality preserved until later
how does frontotemporal dementia present clinically?
Tau pathology
Early change in personality / behaviour
Often change in eating habits
Early dysphasia
Memory / visuospatial relatively preserved
what is the pathology of dementia wirh lewy bodies?
Lewy bodies (accumulations of abnormal α synuclein)
what are the clinical features of dementia with lewy bodies?
Early visuospatial and executive dysfunction
Prominent fluctuation
Parkinsonism and visual hallucinations common
how does vascular dementia present clinically?
Mixed picture
Stepwise decline
what is non pharmacological symptomatic treatment for dementia?
Information & support, dementia services
Occupational therapy
Social work / support / respite / placement
Voluntary organisations
what is pharmacological symptomatic treatment for dementia?
Insomnia
Behaviour (care with antipsychotics)
Depression
what is specific treatment for alzheimers (+/- lewy body dementia)?
Cholinesterase inhibitors (cholinergic deficit)
Donepezil, rivastigmine, galantamine
Small symptomatic improvement in cognition (wash-out)
No delay in institutionalisation
NMDA antagonist (memantine)
what are the effects of cholinesterase inhibitors on alzheimers?
Small symptomatic improvement in cognition (wash-out)
No delay in institutionalisation
what are examples of cholinesterase inhibitors?
Donepezil, rivastigmine, galantamine
what specific treatments are there for frontotemporal dementia?
none
what are specific treatments for vascular dementia?
none
what is parkonsonism?
A clinical syndrome with ≥ 2 of:
Bradykinesia (slowness of movement)
Rigidity (stiffness)
Tremor (shakiness)
Postural instability (unsteadiness / falls)
what is the pathology of parkinosonism?
predominantly dopamine loss
Lewy bodies (α synuclein)
what are four different 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 2nd commonest neurodegenerative disease?
parkinsons disease
what is the incidence of parkinsons disease?
Incidence: 15-20 per 100,000 per year
- age dependent, 1.5 M : F
Crude prevalence: 150-300 per 100,000
~150,000 in UK
what are risk factors for parkinsons disease?
Genetic (LRRK2, Parkin, GBA)
Environmental (pesticides, smoking, caffeine)
how is parkinsons definitevly diagnosed?
post-mortem
what is the clinical presentation of parkinsons disease?
Bradykinesia + ≥1 tremor, rigidity, postural instability
No other cause / atypical features
Slowly progressive (> 5-10 yrs)
Supported by asymmetric rest tremor
what does parkinsons asymmetric rest tremor respond well to?
dopamine replacement treatment
when does symptoms of parkinsons disease have a poor response to treatment?
Less likely if rapid progression, symmetrical, lack of rest tremor, poor response to treatment, early falls, early dementia, other abnormal neurological signs
what are cardinal signs of parkinsonism?
Tremor
Unilateral
At rest
Bradykinesia
Progressive decrement
(asymmetry, expressionless face)
postural instability
what are non-motor symptoms?
Anosmia
REM sleep behaviour disorder
Autonomic (constipation, urinary, bowel sexual)
Neuropsychiatric (hallucinations, cognitive)
Depression, fatigue, pain
what functional imaging can be done for parkinsons disease?
Dopamine transporter SPECT
what medical treatments are available for PD?
COMT inhibitor
MAO-B inhibitor
Dopamine agonists
Levadopa
what are examples of COMT inhibitors?
entacapone
tolcapone
opicapone
what are examples of dopamine agonists?
ropinirole
pramipexole
rotigotine
what are examples of MAO-B inhibitors?
selegiline
rasagiline
safinamide
what are later drug induced complications of PD?
Motor fluctuations - levodopa wears off
Dyskinesias - involuntary movements (levodopa)
Psychiatric - hallucinations, impulse control
what are later complications of PD?
Balance/falls/fractures
Dementia (~50% after 10 yrs)
Speech, swallow
Gait freezing
what pharmalogical treatment can be given late into PD?
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
