Neurological Diseases - Degenerative disorders - Dementia and Parkinson's

Question 1

what are common features of neurodegenrative 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

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

what is the incidence and prevalence of dementia?

Answer 3

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)

Question 4

what are causes of late onset dementia (65+ years)?

Answer 4

Alzheimer’s (55%)
Vascular (20%)
Lewy body (20%)
Others (5%)

Question 5

what are the causes of young onset dementia?

Answer 5

Alzheimer’s (33%)
Vascular (15%)
Frontotemporal (15%)
Other (33%)

Question 6

what are other causes of dementia?

Answer 6

Toxic (alcohol)
Genetic (Huntington’s)
Infection (HIV, CJD)
Inflammatory (MS)

Question 7

what are treatable causes / mimics of dementia?

Answer 7

Vitamin deficiency - B12
Endocrine - thyroid disease (hypothyroidism)
Infective - HIV, syphilis

Mimics: Hydrocephalus
Tumour
Depression: “pseudodementia”

Question 8

what should be asked in the history for dementia?

Answer 8

type of deficit, progression, risk factors, FH

Question 9

what should be examined in diagnosis of dementia?

Answer 9

cognitive function, neurological, vascular

Question 10

what investigations are done to diagnose dementia?

Answer 10

routine - bloods, CT / MRI

others - CSF, EEG, functional imaging, genetics

Question 11

what various domains should be covered in examination of cognitive function?

Answer 11

Memory, attention, language, visuospatial,
Behaviour, emotion, executive function
Apraxias, agnosias

Question 12

what screening tests can assess cognitive function?

Answer 12

Mini-mental (MMSE), Montreal (MOCA)

Question 13

what is mini-mental test?

Answer 13

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.

Question 14

what assessment is used to examine cognitive function?

Answer 14

Neuropsychological assessment

Question 15

what is Montreal (MOCA)?

Answer 15

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

Question 16

what would rapid progression of disease suggest?

Answer 16

CJD

Question 17

what is CJD?

Answer 17

Creutzfeldt-Jakob disease (CJD) is a rare and fatal condition that affects the brain. It causes brain damage that worsens rapidly over time.

Question 18

what would stepwise progression of disease suggest?

Answer 18

vascular dementia

Question 19

which disease is indicated from abnormal movements?

Answer 19

Huntington’s

Question 20

which disease is indicated from parkinsonism?

Answer 20

Lewy body

Question 20

which disease is indicated from myoclonus?

Answer 20

CJD

Question 21

what is the commonest neurodegenerative condition?

Answer 21

Alzheimer’s disease

Question 22

when is the mean age onset for alzheimers disease?

Answer 22

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

Question 23

what is the pathology of alzeimers disease?

Answer 23

β-amyloid plaques and neurofibrillary tangles

Question 24

what increases risk of alzeimers disease?

Answer 24

smoking, obesity, diabetes, hypertension

Question 25

what decreases the risk of alzheimers disease?

Answer 25

cognitive reserve, exercise, diet (medditeranian)

Question 26

what genes increase risk of alzheimers disease?

Answer 26

APOE, APP, PSEN1, PSEN2

Question 27

how does temporo-parietal dementia present clinically?

Answer 27

Early memory disturbance Language and visuospatial problems Personality preserved until later

Question 28

how does frontotemporal dementia present clinically?

Answer 28

Tau pathology Early change in personality / behaviour Often change in eating habits Early dysphasia Memory / visuospatial relatively preserved

Question 29

what is the pathology of dementia wirh lewy bodies?

Answer 29

Lewy bodies (accumulations of abnormal α synuclein)

Question 30

what are the clinical features of dementia with lewy bodies?

Answer 30

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

Question 31

how does vascular dementia present clinically?

Answer 31

Mixed picture Stepwise decline

Question 32

what is non pharmacological symptomatic treatment for dementia?

Answer 32

Information & support, dementia services Occupational therapy Social work / support / respite / placement Voluntary organisations

Question 33

what is pharmacological symptomatic treatment for dementia?

Answer 33

Insomnia Behaviour (care with antipsychotics) Depression

Question 34

what is specific treatment for alzheimers (+/- lewy body dementia)?

Answer 34

Cholinesterase inhibitors (cholinergic deficit) Donepezil, rivastigmine, galantamine Small symptomatic improvement in cognition (wash-out) No delay in institutionalisation NMDA antagonist (memantine)

Question 35

what are the effects of cholinesterase inhibitors on alzheimers?

Answer 35

Small symptomatic improvement in cognition (wash-out) No delay in institutionalisation

Question 36

what are examples of cholinesterase inhibitors?

Answer 36

Donepezil, rivastigmine, galantamine

Question 37

what specific treatments are there for frontotemporal dementia?

Answer 37

none

Question 38

what are specific treatments for vascular dementia?

Answer 38

none

Question 39

what is parkonsonism?

Answer 39

A clinical syndrome with ≥ 2 of: Bradykinesia (slowness of movement) Rigidity (stiffness) Tremor (shakiness) Postural instability (unsteadiness / falls)

Question 40

what is the pathology of parkinosonism?

Answer 40

predominantly dopamine loss Lewy bodies (α synuclein)

Question 41

what are four different causes of parkinsonism?

Answer 41

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 42

what is the 2nd commonest neurodegenerative disease?

Answer 42

parkinsons disease

Question 43

what is the incidence of parkinsons disease?

Answer 43

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

Question 44

what are risk factors for parkinsons disease?

Answer 44

Genetic (LRRK2, Parkin, GBA) Environmental (pesticides, smoking, caffeine)

Question 45

how is parkinsons definitevly diagnosed?

Answer 45

post-mortem

Question 46

what is the clinical presentation of parkinsons disease?

Answer 46

Bradykinesia + ≥1 tremor, rigidity, postural instability No other cause / atypical features Slowly progressive (> 5-10 yrs) Supported by asymmetric rest tremor

Question 47

what does parkinsons asymmetric rest tremor respond well to?

Answer 47

dopamine replacement treatment

Question 48

when does symptoms of parkinsons disease have a poor response to treatment?

Answer 48

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

Question 49

what are cardinal signs of parkinsonism?

Answer 49

Tremor Unilateral At rest Bradykinesia Progressive decrement (asymmetry, expressionless face) postural instability

Question 50

what are non-motor symptoms?

Answer 50

Anosmia REM sleep behaviour disorder Autonomic (constipation, urinary, bowel sexual) Neuropsychiatric (hallucinations, cognitive) Depression, fatigue, pain

Question 51

what functional imaging can be done for parkinsons disease?

Answer 51

Dopamine transporter SPECT

Question 52

what medical treatments are available for PD?

Answer 52

COMT inhibitor MAO-B inhibitor Dopamine agonists Levadopa

Question 53

what are examples of COMT inhibitors?

Answer 53

entacapone tolcapone opicapone

Question 54

what are examples of dopamine agonists?

Answer 54

ropinirole pramipexole rotigotine

Question 55

what are examples of MAO-B inhibitors?

Answer 55

selegiline rasagiline safinamide

Question 56

what are later drug induced complications of PD?

Answer 56

Motor fluctuations - levodopa wears off Dyskinesias - involuntary movements (levodopa) Psychiatric - hallucinations, impulse control

Question 57

what are later complications of PD?

Answer 57

Balance/falls/fractures Dementia (~50% after 10 yrs) Speech, swallow Gait freezing

Question 58

what pharmalogical treatment can be given late into PD?

Answer 58

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