Degenerative Diseases of the CNS

Question 1

What are common features of neurodegenerative diseases?

Answer 1

aetiology largely unknown (mendelian genetic cases rare, often younger onset)

usually late onset

gradual progression

neuronal loss (specific neuropathology)

structural imaging often normal (atrophy)

Question 2

What is dementia?

Answer 2

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

Question 3

Why is dementia important?

Answer 3

Common and increasing:

^{- incidence 200 per 100,000}

^{- prevalence 1,500 per 100,000}

^{- >850,000 patients in UK ( 1.6M by 2040)}

Devastating impact on patient + family

Costly: ~£35 billion/yr (15% NHS, 40% social, 45% unpaid)

Projected £94 billion by 2040

66% of those in care homes

Question 4

What are the causes on late onset dementia? (more common)

Answer 4

Late onset (65+ yrs):

Alzheimer’s (55%)

Vascular (20%)

Lewy body (20%)

Others (5%)

Question 5

What are the causes on younge onset dementia? (rarer)

Answer 5

Young onset (<65 yrs):

Alzheimer’s (33%)

Vascular (15%)

Frontotemporal (15%)

Other (33%):

^{Toxic (alcohol)}

^{Genetic (Huntington’s)}

^{Infection (HIV, CJD)}

^{Inflammatory (MS)}

Question 6

What are the treatable causes of dementia?

Answer 6

Vitamin deficiency - B12

Endocrine - thyroid disease

Infective - HIV, syphilis

Question 7

What are mimics of dementia?

Answer 7

Hydrocephalus

Tumour

Depression: “pseudodementia”

Question 8

How do you diagnose dementia?

(clinical diagnosis)

Answer 8

History (independent witness) - type of deficit, progression, risk factors, FH

Examination: cognitive function, neurological, vascular

Investigations:

routine - bloods, CT / MRI

others - CSF, EEG, functional imaging, genetics (biopsy)

Question 9

WHat is the most important part of diagnosing dementia?

Answer 9

history!

Question 10

How is the examination of cognitive function carried out?

Answer 10

Various domains: Memory, attention, language, visuospatial,

Behaviour, emotion, executive function, Apraxias, agnosias

Screening tests - Mini-mental (MMSE), Montreal (MOCA) - more common one

Neuropsychological assessment

Question 11

What are some clues for diagnosis?

Answer 11

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)}

Question 12

If the dementia is a step wise progression what is the more likley cause?

Answer 12

Vascular

Question 13

What is the mommonest neurodegenerative condition?

Answer 13

Alzheimer’s disease

Question 14

What is the mean age onset of alzheimers disease?

Answer 14

mean age onset 70 yr (25% <65yrs)

Question 15

What are the risk factors for alzheimer’s disease?

Answer 15

genetic

lifestyle (smoking, exercise, diet, alcohol)

Question 16

What type of dementia can alzheimer’s disease cause and what is it?

Answer 16

Temporo-parietal dementia

– Early memory disturbance

– Language and visuospatial problems

– Personality preserved until later

Question 17

What does Frontotemporal dementia cause?

Answer 17

Early change in personality/behaviour

Often change in eating habits

Early dysphasia

Memory/visuospatial relatively preserved

Question 18

What does vascular dementia cause?

Answer 18

Mixed picture

Stepwise decline

Question 19

What are the 2 types of symptomatic treatment for dementia?

Answer 19

Non pharmacological

Pharmacological

Question 20

What are the non pharmacological treatments for symptomatic dementia?

Answer 20

Information & support, dementia services

Occupational therapy

Social work/support/respite/placement

Voluntary organisations

Question 21

What is the pharmacological treatment of symptomatic dementia?

Answer 21

Insomnia

Behaviour (care with antipsychotics)

Depression

Question 22

What is specific treatment for alzheimers disease (+/- Lewy body dementia)?

Answer 22

Cholinesterase inhibitors (cholinergic deficit)

^{• Donepezil, rivastigmine, galantamine}

^{• Small symptomatic improvement in cognition (wash-out)}

^{• No delay in institutionalisation}

NMDA antagonist (memantine)

Question 23

What is the specific treatment for frontotemporal dementia?

Answer 23

none

Question 24

What is the specific treatment for vascular dementia?

Answer 24

No robust evidence for ↓ vascular risk factors

Question 25

Does any treatment for dementia chance the progression of the disease?

Answer 25

no

Question 26

What is Parkinsonism?

Answer 26

A clinical syndrome with 2 or more of the following:

• Bradykinesia (slowness of movement)
• Rigidity (stiffness)
• Tremor (shakiness)
• Postural instability (unsteadiness/falls)

Question 27

Parkinsonism is a pathology where?

Answer 27

Pathology in basal ganglia - predominantly dopamine loss

Question 28

What are the causes of parkinsonism?

Answer 28

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}

Question 29

What is the epidemiology of PD?

Answer 29

2nd commonest neurodegenerative 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

Cost in UK: ~£2 billion/year (most indirect)

60-90% dead or disabled at 10 yrs

Question 30

What is the 2nd commonest neurodegenerative disease?

Answer 30

Parkinsons disease

Question 31

What is the Incidence of PD by age?

Answer 31

Question 32

How do you diagnose parkinsons disease?

Answer 32

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

Less likely if rapid progression, symmetrical, lack of rest tremor, poor response to treatment, early falls, early dementia, other abnormal neurological signs

Question 33

The dignosis of parkinsons is based on what kind of features?

Answer 33

clinical features

Question 34

What is the early medical treatment of PD?

Answer 34

dopamine effecting the neurone synapses

Question 35

What are some later drug induced complications of parkinsons disease?

Answer 35

Motor fluctuations - levodopa wears off

Dyskinesias - involuntary movements (levodopa)

Psychiatric - hallucinations, impulse control

Question 36

What are some later non-drug induced complications of parkinsons disease?

Answer 36

Depression (20%)

Dementia (~50% after 10 yrs)

Autonomic: BP, bladder, bowel

Speech, swallow

Balance

Question 37

What is the late treatment of parkinsons disease?

Answer 37

Drugs:

• Prolong levodopa half life
• Add oral dopamine agonist
• Continuous infusion (apomorphine, Duodopa)

NB PD medications are time critical (hospital admissions)

Functional neurosurgery (deep brain stimulation)

Allied health professionals +/- care package

Question 38

Neurodegenerative conditions are common and ________

Main chronic health burden with ______ society and improvements in treating vascular disease & cancer

Need effective ________/_______ strategies

Answer 38

Neurodegenerative conditions are common and increasing

Main chronic health burden with ageing society and improvements in treating vascular disease & cancer

Need effective neuroprotective/restorative strategies