Degenerative Diseases of the CNS

Question 1

What are the common features of neurodegenerative diseases?

Answer 1

Aetiology is largely unknown, usually later onset, gradual progression, neuronal loss and structural imagining is often normal

Question 2

What is dementia?

Answer 2

Progressive impairment of multiple domains of cognitive function in alert patient
Leads to loss of acquired skills and interference of occupational and social role

Question 3

What is the incidence and prevalence of dementia?

Answer 3

Incidence is 200 pre 100000
Prevalence is 1500 pre 100000

Question 4

Why is dementia important?

Answer 4

High incidence and prevalence
Devastating impact on patient and family
Is expensive for the NHS - esp. care homes

Question 5

What are the causes of later onset dementia?

Answer 5

Alzheimer’s, vascular, Lewy body and others
Often mixed pathology

Question 6

What are the causes of young onset dementia?

Answer 6

Alzheimer’s, vascular, frontotemporal and other - alcohol, Huntington’s, HIV, CJD and MS

Question 7

What are treatable causes of dementia?

Answer 7

Vitamin B12 deficiency
Thyroid disease
HIV and syphilis

Question 8

What are mimics of dementia?

Answer 8

Hydrocephalus, tumour and depression - pseudodementia

Question 9

How is dementia diagnosed?

Answer 9

History - type of deficit, progression, risk factors, FH
Exam - cognitive function, neurological and vascular
Investigations - Bloods, CT/MRI, CSF, EEG, functional imaging and genetics

Question 10

How is cognitive function examined?

Answer 10

Screening testes - Mini-mental MMSE and Montreal MOCA
Neuropsychological assessment
Examine memory, attention, language, visuospatial, behaviour, emotion…

Question 11

What are some clues to diagnosis of dementia?

Answer 11

Type of cognitive deficit, speed of progression - rapid (CJD) and stepwise (vascular)
Other neurological signs - abnormal movements (Huntington’s), parkinsonism (Lewy body) and myoclonus (CJD)

Question 12

Describe Alzheimer’s disease

Answer 12

Commonest neuro-divergent condition - mean onset is 70 years old
Tempero-parietal dementia - early memory disturbance, language + visuospatial problems and personality is persevered until later

Question 13

What is the pathology of Alzheimer’s disease?

Answer 13

B amyloid plaques and neurofibrillary tangles

Question 14

What are the risks of Alzheimer’s disease?

Answer 14

Genetic - APOE, APP, PSEN1+2
Environmental
Increase risk - smoking, obesity, diabetes and hypertension
Decrease risk - cognitive reserve, exercise and diet

Question 15

Describe frontotemporal dementia

Answer 15

Tau pathology
Early change in personality/ behaviour
Early dysphasia and often change in eating habits
Memory and visuospatial is relatively persevered

Question 16

Describe dementia with Lewy bodies

Answer 16

Early visuospatial and executive dysfunction
Prominent fluctuation
Parkinsonism and visual hallucinations common

Question 17

Describe vascular dementia

Answer 17

Mixed picture (parts of brain affected)
Stepwise decline

Question 18

What is non pharmacological treatment of dementia?

Answer 18

Occupational therapy, social work, support, and voluntary organisations

Question 19

What symptoms can be treated in dementia?

Answer 19

Insomnia, behaviour (care with antipsychotics) and depression

Question 20

What is specific treatment for Alzheimer’s disease (also Lewy body)?

Answer 20

Cholinesterase inhibitors - donepezil, rivastigmine, galantamine. Small symptomatic improvement of cognition
NDMA antagonist - memantine

Question 21

What is the frontotemporal specific treatment?

Answer 21

None

Question 22

What is the specific treatment for vascular dementia?

Answer 22

No robust evidence for decreased vascular risk factors

Question 23

Describe parkinsonism

Answer 23

Clinical syndrome with more than 2 of - bradykinesia, rigidity, tremor, and postural instability

Question 24

Describe the pathology of parkinsonism

Answer 24

Predominantly dopamine loss
Lewy bodies

Question 25

What are causes of Parkinson’s disease?

Answer 25

Idiopathic - dementia with Lewy bodies
Drug induced (dopamine antagonists)
Vascular parkinsonism
Parkinson’s plus syndromes - multiple system atrophy and progressive supranuclear palsy

Question 26

What are the risk factors of PD?

Answer 26

Genetic - LRRK2, Parkin, GBA
Environmental - pesticides, smoking and caffeine

Question 27

How is Parkinson’s disease clinically diagnosed?

Answer 27

Bradykinesia + more than 1 - rigidity, tremor, instability
Slowly progressive
Supported by asymmetric rest tremor and good response to dopamine replacement treatment

Question 28

What are some cardinal signs of parkinsonism?

Answer 28

Tremor - unilateral and at rest
Bradykinesia - progressive decrement and asymmetry
Postural instability

Question 29

What are some non-motor symptoms of PD?

Answer 29

Anosmia, REM sleep behaviour disorder, autonomic (constipation, urinary), neuropsychiatric (hallucinations, cognitive) and depression

Question 30

How can PD look on functional imaging?

Answer 30

Dopamine transporter SPECT
Dopamine will be strongly in basal ganglia
Decreases in PD

Question 31

What is the early treatment of PD?

Answer 31

Levodopa
With carbidopa or benserazide
Also with COMT inhibitor - entacapone, tolcapone and opicapone
Dopamine agonists
MOAB inhibitor

Question 32

What are later complications of PD?

Answer 32

Drug induced - motor fluctuations as levodopa wears off, dyskinesis and psychiatric
Also falls, balance, dementia, speech, swallow and gait freezing

Question 33

What is the late treatment for PD?

Answer 33

Prolong levodopa half life - MAOB and COMT inhibitors, and slow release levodopa
Add oral dopamine agonist
Continuous infusion
Functional neurosurgery
Allied health professionals