cognitive neurology Flashcards
what pathophysio are dementias usually due to?
neurodegenerative proteinopathies
what domains does cognition encompass?
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
proteinopathy assoc with Alzheimer’s +/- vascular dementia
amyloid
proteinopathy assoc with Parkinsons / Lewy body dementia
alpha-synuclein
proteinopathy assoc with Creutzfeldt-Jakob Disease (CJD)
prion
proteinopathy assoc with frontotemporal dementia
tau
proteinopathy assoc with Huntingtons dementia
huntingtin
dementia
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
stuttering vs gradual onset of cognitive decline
stuttering - vascualr
gradual - proteinopathy
dementia investigation
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
who to refer to?
- > 65 years old gradual onset dementias / no additional neurology = old age psychiatry
- <65 yrs / any unusual features (including speed of onset) / additional neurology = neurology
brain insults
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
Transient global amnesia (TGA)
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)
triggers and pathophysio of Transient global amnesia (TGA)
triggers = emotion, changes in temp
pathophysio = transient changes in hippocampus
transient epileptic amnesia (TEA)
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
functional/subjective cognitive impairment
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
Creutzfeldt-Jakob disease
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
prion protein in CJD
prion protein important for brain health
dodgy protein has domino effect on healthy proteins
subtypes of CJD
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
sporadic CJD
- 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
hallmark histological sign of CJD
spongiform change (all subtypes)
small round or oval empty spaces in the neuropil. When confluent, they merge to form “morula-like” structures.
CJD presentation
- Dementia – rapid onset
- Myoclonus = sudden, brief involuntary twitching/jerking of muscle(s)
- New variant CJD
o Psychological symptoms
Anxiety
Withdrawals
Dysphonia
new variant CJD
younger -25yrs
psychological symptoms such as anxiety, withdrawal and dysphonia are the most common presenting features
median survival 13months
CJD investigations
- CSF is usually normal
- EEG – biphasic, high amplitude sharp waves (only in sporadic CJD)
- MRI – hyperintense signals in the basal ganglia + thalamus
who needs a scan?
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
Alzheimer’s disease
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
risk factors for alzheimers
increasing age
more common in women
fam history
5% inherited as autosomal dominant
caucasion
downs - onset in 3rd or 4th decade
atypical presentation of alzheimers (15% of cases)
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)
pathophysio of Alzheimers
- loss of cortical neurones -> cortical atrophy, widening of sulci, compensatory dilation of ventricles -> 2nd degree hydroceph
- neurofibrillary tangles
- senile plaques - extracellular protein deposits containing amyloid beta-protein
degeneration of medial hippocampus + lateral parietal lobes -> forgetfulness -> apraxia/visuospatial
genetic influences in Alzheimers
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
alzheimers on imaging
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
alzheimers presentation
- 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
alzheimers management
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
amyloid angiopathy
extracellular eosinophilic accumulation
polymerized beta pleated sheets formed from A-beta
stain CONGO RED
disrupts blood brain barrier - serum leaking, oedema, local hypoxia
vascular dementia presentation
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
vascular dementia investigation + management
CT - vascular changes
- white matter change, white fluffy patches in subcortical
manage vascular RF
potential cholinesterase inhibitors
CPN(community psychiatric nurse)
core criteria of vascular dementia
- Prescence of cerebrovascular disease plus
- 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
dementia with Lewy bodies
progressive dementia, along with hallucinations + fluctuation levels of attention/cognition
late onset - most >65yrs
assoc with parkinsons
dementia with Lewy bodies pathophysio
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
dementia lewy bodies core criteria
- Fluctuating cognition plus
- Recurrent well-formed visual hallucinations
a. Feeling someone’s behind you - +/- presence of extrapyramidal features (seen in 75%)
a. Motor features (parkinsons vibes)
dementia with Lewy bodies presentation
visual hallucinations
fluctuating cognition - delirium like
REM sleep behavioural disorder
parkinsonism - not more than 1yr prior to onset of dementia
neuroleptic association in dementia with Lewy bodies
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
investigation dementia with lewy bodies
clinical diagnosis but
DaT -> reduced dopaminergic activity within the basal ganglia
dementia with lewy bodies management
small dose levodopa
acetylcholinesterase inhibitors - donepsil, rivatigimine
*avoid neuroleptics (antipsychotics)
frontotemporal dementia
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
frontotemporal dementia pathophysio
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
histological hallmarks of frontotemporal dementia
Pick’s cells -> swollen neurons
intracytoplasmic filamentous inclusion (Pick’s bodies)
frontotemporl dementia presentation
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
frontotemporal dementia investigation
MRI - atrophy of frontotemporal lobes
SPECT - decreased frontotemporal metabolism
CSF - INCREASED tau:normal amyloid
management of frontotemporal dementia
trazadone
antipsychotics to help behavioural features
power of attorney
controlled access to food/money
MND support?
differentiation between parkinsons + Lewy body dementia
DLB dementia <1yr of presentation
PDD >1yr presentation
alcohol related dementia
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
huntingtons disease
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
huntingtons pathophysio
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
huntingtons presentation
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
huntingtons investigation + management
genetic testing
MRI - atrophy of basal ganglia, loss of caudate heads -> butterfly appearance
mood stabilisers
drugs for chorea
HD nurse specialist
