cognitive neurology

Question 1

what pathophysio are dementias usually due to?

Answer 1

neurodegenerative proteinopathies

Question 2

what domains does cognition encompass?

Answer 2

o Memory
o Executive function – problem solving, decision making
o Social functioning – judgement, evaluation
o Attention
o Visuospatial- perception, spatial awareness
o Language – comprehension + production of language

Question 3

proteinopathy assoc with Alzheimer’s +/- vascular dementia

Answer 3

amyloid

Question 4

proteinopathy assoc with Parkinsons / Lewy body dementia

Answer 4

alpha-synuclein

Question 5

proteinopathy assoc with Creutzfeldt-Jakob Disease (CJD)

Answer 5

prion

Question 6

proteinopathy assoc with frontotemporal dementia

Answer 6

tau

Question 7

proteinopathy assoc with Huntingtons dementia

Answer 7

huntingtin

Question 8

dementia

Answer 8

Evidence of significant cognitive decline in at least 1 cognitive domain, plus both –
- Cognitive deficits interfere with independence in everyday activities
- They are not better explained by another process/do not occur exclusively in the context of delirium

Question 9

stuttering vs gradual onset of cognitive decline

Answer 9

stuttering - vascualr

gradual - proteinopathy

Question 10

dementia investigation

Answer 10

blood screen to exclude reversible causes
- glucose, TFTs, vit B12, folate, Ca, LFTs, ESR/CRP, FBC + U&Es

imaging - subdural haematoma, normal pressure hydroceph, paterns of atrophy

MRI- if young, fast progression
SPECT - most usueful for frontotempotal/clarifying alzheimers

DAT - for DLB/parkinsons if not enough supported features

Question 11

who to refer to?

Answer 11

• > 65 years old gradual onset dementias / no additional neurology = old age psychiatry
• <65 yrs / any unusual features (including speed of onset) / additional neurology = neurology

Question 12

brain insults

Answer 12

Deficits depend on area of brain affected
Viral encephalitis
- E.g. herpes simplex encephalitis
o Loves temporal lobes
o Memory, behaviour, language changes

Head injury
- Subcortical problems
- Attention, memory, executive dysfunction

stroke - depends

Question 13

Transient global amnesia (TGA)

Answer 13

sudden episode of memory loss, during which they cannot form new memories + have difficulty recalling recent memories (can remember old memories, antegrade >retrograde)
- asks repetitive questions

transient - 4-6hrs (always <24hrs)
generally a one off
rare, >50s (most 70)

Question 14

triggers and pathophysio of Transient global amnesia (TGA)

Answer 14

triggers = emotion, changes in temp

pathophysio = transient changes in hippocampus

Question 15

transient epileptic amnesia (TEA)

Answer 15

usually diagnosed with TGA but then have another episode -> TEA
antegrade memory - forgetful, repetitive questions

can carry out complex activities with no recollection of events

short lived - 20-30mins

Assoc with temporal lobe seizures
o 30% seizures not witnessed
*response to anti-epileptic medication should be seen
* Want to be certain be start medication – bit of watching/waiting

Question 16

functional/subjective cognitive impairment

Answer 16

Everyday forgetfulness impacting on function
o Went upstairs + forgot why I was there
o Lost track of conversation

• Fluctuation of symptoms

Mismatch between symptoms + reported function
 can’t remember a thing but are able to run a busy household, can work etc

Question 17

Creutzfeldt-Jakob disease

Answer 17

rapidly progressive neurological condition caused by prion proteins

these protein induce the formation of amyloid fold resulting in tightly packed beta-pleated sheets resistant to proteases

Question 18

prion protein in CJD

Answer 18

prion protein important for brain health

dodgy protein has domino effect on healthy proteins

Question 19

subtypes of CJD

Answer 19

sporadic - 60s, rapid onet dementia, myoclonus, 4months duration

variant - 20s, painful sensory dissturbance, psychiatric decline, 14mnths

iatrogenic - 30s, cerebellar/visual onset, <2yrs

genetic - any age, may mimic sCJD, mutation of PRNP

Question 20

sporadic CJD

Answer 20

• 85% of cases
• 10-15% of cases are familial
• Mean age of onset is 65yrs

duration of illness = 4months

rapid onset dementia + neuro signs + myoclonus

Question 21

hallmark histological sign of CJD

Answer 21

spongiform change (all subtypes)

small round or oval empty spaces in the neuropil. When confluent, they merge to form “morula-like” structures.

Question 22

CJD presentation

Answer 22

• Dementia – rapid onset
• Myoclonus = sudden, brief involuntary twitching/jerking of muscle(s)
• New variant CJD
  o Psychological symptoms
   Anxiety
   Withdrawals
   Dysphonia

Question 23

new variant CJD

Answer 23

younger -25yrs

psychological symptoms such as anxiety, withdrawal and dysphonia are the most common presenting features

median survival 13months

Question 24

CJD investigations

Answer 24

• CSF is usually normal
• EEG – biphasic, high amplitude sharp waves (only in sporadic CJD)
• MRI – hyperintense signals in the basal ganglia + thalamus

Question 25

who needs a scan?

Answer 25

CT - standard - No if over 80 with typical Alzheimer’s history - Helpful excluding tumour/bleed/large stroke, vascular or structural changes MRI o If young, fast progression or other atypical features SPECT o Most useful for frontotemporal, may also be used if trying to clarify Alzheimers diagnosis DAT o For suspected DLB/DPD when patient doesn’t have enough supporting features to be sure of a diagnosis

Question 26

Alzheimer's disease

Answer 26

Progressive degenerative disease of the brain accounting for most dementia in UK <65yrs = early onset o Genetic influences o May be atypical presentation >65yrs = sporadic o Environmental > genetic influences o Usually typical forgetful

Question 27

risk factors for alzheimers

Answer 27

increasing age more common in women fam history 5% inherited as autosomal dominant caucasion downs - onset in 3rd or 4th decade

Question 28

atypical presentation of alzheimers (15% of cases)

Answer 28

younger more likely posterior cortical atrophy - visuospatial disturbance, commonly referred from ophth progressive primary aphasia - semantic(naming) - can describe all around word but not word - logophenic (repeating) - non-fluent (effortful)

Question 29

pathophysio of Alzheimers

Answer 29

1. loss of cortical neurones -> cortical atrophy, widening of sulci, compensatory dilation of ventricles -> 2nd degree hydroceph 2. neurofibrillary tangles 3. senile plaques - extracellular protein deposits containing amyloid beta-protein degeneration of medial hippocampus + lateral parietal lobes -> forgetfulness -> apraxia/visuospatial

Question 30

genetic influences in Alzheimers

Answer 30

autosomal dominant traits Mutations in the – - amyloid precursor protein (chromosome 21) – downs - presenilin 1 (chromosome 14) - presenilin 2 (chromosome 1) ->presenilin 1+2 are components of gamma-secretase, an enzyme that normally cleaves the APP protein apoprotein E allele E4 – encodes for cholesterol transport protein o boxer hit on head with more likely to get if have this allelle

Question 31

alzheimers on imaging

Answer 31

MRI – atrophy of temporal / parietal lobes SPECT – temporoparietal decreased metabolism CSF – decrease amyloid:increased tau ratio !!!!!!!!!!*** Research – amyloid ligand imaging Shrinkage of hippocampus + cerebral cortex Severely enlarged ventricles wide sulci, narrow gyri

Question 32

alzheimers presentation

Answer 32

- Gradual onset, decline of particularly short-term memory - Autobiographical and political memory often well preserved - Poor concentration, poor sleep, low mood - Personality change - disinhibited, aggression, lack of self-care - In end stages - hallucinations, poor dentition, skin ulcers, loss of verbal communication - Atypical presentations: - Posterior cortical atrophy - visuospatial disturbance - Progressive primary aphasia

Question 33

alzheimers management

Answer 33

Address vascular risk factors ACh boosting treatments - Cholinersterase inhibitors - rivastigmine, donepezil, galantamine ---(**not with active peptic ulcer or severe asthma/COPD) - Mematine - NMDA receptor blocker used in moderate or severe AD or where cholinesterase inhibitors are not tolerated

Question 34

amyloid angiopathy

Answer 34

extracellular eosinophilic accumulation polymerized beta pleated sheets formed from A-beta stain CONGO RED disrupts blood brain barrier - serum leaking, oedema, local hypoxia

Question 35

vascular dementia presentation

Answer 35

majority >65yrs post-stroke Hx of hypertension or stroke sudden stepwise deterioration of cognitive function and not regained insight preserved** can include visual, sensory/motor, seizures, concentration

Question 36

vascular dementia investigation + management

Answer 36

CT - vascular changes - white matter change, white fluffy patches in subcortical manage vascular RF potential cholinesterase inhibitors CPN(community psychiatric nurse)

Question 37

core criteria of vascular dementia

Answer 37

1. Prescence of cerebrovascular disease plus 2. A clear temporal relationship between the onset of dementia + cerebrovascular disease Multi-infarct o Abrupt onset o Stepwise progression o History of hypertension/stroke o Evidence of stroke on CT or MRI

Question 38

dementia with Lewy bodies

Answer 38

progressive dementia, along with hallucinations + fluctuation levels of attention/cognition late onset - most >65yrs assoc with parkinsons

Question 39

dementia with Lewy bodies pathophysio

Answer 39

alpha-synuclein cytoplasmic inclusions (Lewy bodies) in substantia nigra, paralimbic + neocortical areas - pallor in substantia nigra where pigmented dopaminergic neurons run reactive gliosis remaining neurons may show Lewy bodies -> eosinophilic, elongated bodes that have dense core + surrounding pale halo spread of Lewy bodies from brainstem to cortex critical

Question 40

dementia lewy bodies core criteria

Answer 40

1. Fluctuating cognition plus 2. Recurrent well-formed visual hallucinations a. Feeling someone’s behind you 3. +/- presence of extrapyramidal features (seen in 75%) a. Motor features (parkinsons vibes)

Question 41

dementia with Lewy bodies presentation

Answer 41

visual hallucinations fluctuating cognition - delirium like REM sleep behavioural disorder parkinsonism - not more than 1yr prior to onset of dementia

Question 42

neuroleptic association in dementia with Lewy bodies

Answer 42

Neuroleptic sensitivity – give them haloperidol (for delirium) will make them much worse -> history of a patient who has deteriorated following the introduction of an antipsychotic agent

Question 43

investigation dementia with lewy bodies

Answer 43

clinical diagnosis but DaT -> reduced dopaminergic activity within the basal ganglia

Question 44

dementia with lewy bodies management

Answer 44

small dose levodopa acetylcholinesterase inhibitors - donepsil, rivatigimine *avoid neuroleptics (antipsychotics)

Question 45

frontotemporal dementia

Answer 45

characterised by progressive changes in character + social deterioration leading to impairment of intellect, memory + language early onset dementia - most <65yrs early onset dementa - most <65yrs 25% genetic cause rapidly progressive -> mean length of illness = 7yrs (between 2-10) assoc with MND

Question 46

frontotemporal dementia pathophysio

Answer 46

neurodegen proteinopathy tau > TDP-43 > ubiquitin protein aggregation ->cell damage extreme atrophy in cerebral cortex in frontal + later in temporal lobes brain weight <1kg neuronal loss + gliosis

Question 47

histological hallmarks of frontotemporal dementia

Answer 47

Pick's cells -> swollen neurons intracytoplasmic filamentous inclusion (Pick's bodies)

Question 48

frontotemporl dementia presentation

Answer 48

behavioral variant (60%) > primary progressive aphasia disinhibition (impulsivity), apathy, compulsive behaviour hyperorality - put things in mouth, may gain weight decreased attention early loss of insight -> collateral history important symptoms related to damage to frontal + temporal lobes

Question 49

frontotemporal dementia investigation

Answer 49

MRI - atrophy of frontotemporal lobes SPECT - decreased frontotemporal metabolism CSF - INCREASED tau:normal amyloid

Question 50

management of frontotemporal dementia

Answer 50

trazadone antipsychotics to help behavioural features power of attorney controlled access to food/money MND support?

Question 51

differentiation between parkinsons + Lewy body dementia

Answer 51

DLB dementia <1yr of presentation PDD >1yr presentation

Question 52

alcohol related dementia

Answer 52

Damage secondary to long term, excessive alcohol consumption - Predominantly affects the frontal lobes - Severe = alcohol related brain injuries (ARBI) o If remain abstinent from 9-12 months then some degree of damage may be reversed -> Allow this period of abstinence before considering cognitive impairments

Question 53

huntingtons disease

Answer 53

early onset dementia 30-50yrs autosomal dominant trait progression to severe dependency + death over 15-20yrs - Genetic anticipation = the phenomenon in which each generation develops a genetic disease at an earlier age

Question 54

huntingtons pathophysio

Answer 54

expasion of the CAG trinucleotide repeat on huntingtin gene - produces neurodegenerative protein - CAG codes for glutamine, expansion means a long string of glutamine that is toxic to soe cells within the brain - age of onset is assoc with repeat size

Question 55

huntingtons presentation

Answer 55

involuntary movements - gait, writhing movements, probs chewing/swallowing/speaking depression, blunted affect, compulsions, aggresion Dementia (later) o Dysexecutive syndrome – difficulty planning o Slowed speed of processing o Eventual involvement of memory o Associated changes in mood/personality o Chorea = abnormal involuntary movement o +/- later psychosis Later clinical signs o Rigidity o Bradykinesia – difficulty initiating + continuing movements o Severe chorea o Weight loss o Inability to walk, speak

Question 56

huntingtons investigation + management

Answer 56

genetic testing MRI - atrophy of basal ganglia, loss of caudate heads -> butterfly appearance mood stabilisers drugs for chorea HD nurse specialist