Dementia Flashcards by alice Sawka

What is the rate per year of someone with mild cog impairment converting to Alzheimers disease?

5-10% (compared with 1-2% normal)

Need to have significant cog decline from previous level in one or more domain but the deficits do NOT interfere with the capacity for independence in every day activities (i.e. compensatory strategies for complex ADLs)

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True or false- can get prominent parkinsonian features in vascular dementia?

True

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What are the synucleopathies and why are they called that?

DLB
MSA
Parkinson’s disease

See accumulation of alpha synuclein

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What are the tauopathies and why are they called that?

Alzheimer’s disease
PSNP
Frontotemporal dementia

Tau protein is deposited within neurons in the form of neurofibrillary tangles (NFTs)

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What do you see on SPECT and PET in DLB?

Occipital hypoperfusion

On MRI the mesio temporal region is spared.

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What is the classic presentation in vascular dementia?

Memory loss can be spared early improve by prompting; not rapid forgetters
Poor attention
Gait affected- looks like PD but more apraxic
Language usually ok, just some dysarthria
Executive dysfunction may be prominent

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What are the three core features and what are some other features suggestive of DLB?

Fluctuating cognitiosn
Recurrent visual hallucinations
Spontaneous features of parkinsonism a year post onset (truncal, slowed gait, less tremor, less L dopa response)

Suggestive:
REM sleep behaviour
Severe neuroleptic sensitivity- Quetiapine if must fFTD
Low DA uptake in basal ganglia on SPECT or PET
Falls, autonomic dysfunction
Depressions
Executive dysfunction
Unexplained black outs
RELATIVELY PRESERVED MEMORY
Marked attention and visuospatial difficulties

OFTEN RESPOND VERY WELL TO CHOLINESTERASE INHIBITORS- but can lead to worse tremor and drooling

Rapid onset with progressive decline compared with AD

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What areas to cholinesterase inhibitors improve?

donepezil
galantamine
rivastigmine

Attention, concentration, anxiety, apathy, depression

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MOA Donepeil

Prevent breakdown of Acetylcholine by inhibiting acetylcholinesterase

Note slows or prevents decline with NNT of 10 but not disease modifying. May improve adverse behavious and delay onset of adverse behavior. Might delay admission to nursing home. Retain ADLs

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MOA glantamine

Allosteric potentiator of human nicotinic ACh receptors

Also weak body wide reversible cholinesterase inhibitors

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MOA rivastigmine

Inhibits butylcholinesterase

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Doneepezil side effect profile

GI upset
AV block
Syncope OR 1.5
Asthma
Peptic ulcer disease
Insomnia with vivid dreams 
Increase frequency urination

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Memantine MOA

In AD there is increased glutamate with XS activation of NMDA with increased intracellular calcium

Memantine is an NMDA antagonist

Benefits on agitation and aggression
Used in mod-severe AD and VD
Can use with donepezil

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When people talk about “cortical” features of dementia, what do they mean?

Apraxia
Aphasia
Amnesia
Agnosia

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Where is amyloid?

between cells

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Where is tau?

inside cells

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What are the main risk factors for AD (hint unmodifiable)

Female
Age
Family history
APOE4

What is thought to be the defect in Alzhimers disease familial?

AD in under 1%
Associated mutations: 
-APP
-presenilin  1
-presenilin 2

Presinilin proteins make up part of gamma secretase which cleave APP to give amyloidogenic Amyloid beta protein 42. (alpha secretase is ok)

What is the role of amyloid precursor protein?

Cleaved pathologically by secretase–>increase in beta amyloid. APOE4 interacts with beta amyloid in some way.

What does functional imaging and imaging in general show in FTD?

Asymmetrical frontal/temporal atrophy but can be bilateral

Hypometabolism and hypoperfusion in same areas

What are the motor syndromes associated with FTD?

Motor neuron disease (upper and lower limbs, but more prominent bulbar dysfunction- facial, tongue weakness, dysphagia)

Corticobasal degeneration

PSNP

Corticobasal degeneration clin picture

Asymmetric parkinsonism, apraxia, myoclonus, dystonia, alien limb syndrome

HypER reflexic
Axial rigidity
abnormal eye movement- slow pursuit, saccadic

What do you see pathologically in DLB?

Lewy bodies- eosinophilic intracytoplasmic accumulations of alpha-synuclein revealed by ubiquitin and alpha synuclein staining techniques

Treatment of DLB?

Levodopa for falls risk
Cholinesterase inhibitors work
For psych symptoms use agents that do not block dopamine receptors- eg clozapine

Most common dementia?

AD or AD/VaD

Prevalence of AD as per age?

1-2% in 65-74 25% over 85 doubles every 5 years

DSM 5 defining dementia now called MAJOR NEUROCOGNITIVE DISORDER

Evidence of significant cognitive decline from prev level performatnce ``` One or more areas: learning and memory language exec dysfunction complex attention social cognition perceptual-motor ``` not exclusively during delirium Not better explained by another mental disorder

What are the limitations of MMSE?

Not sensitive for AD - but specific not good for frontal or executive dysfunction depend on age, language, education level not good for tracking change over time

Strongest RF for AD?

Age Also FH, female, head injury, MCI, vascular disease, low B12 or folate, apolipoprotein E e4 allele, Down's

4 types of AD

amnestic (usual type) logopenic aphasia - early non fluent aphasia posterior cortical atrophy with aprasxia, prominent visuospatial deficits Frontal varient looks like FTD with early behavioural sx

What possibly reduces risk AD?

Physical exercise current (not in youth)

How does aplipoprotein E on chromosome 19 predispose to AD?

controversial E4 allele is strong RF for AD, especially with head injury - mean onset in 60s rather than 80s >50% late sporadic AD have E4 Around 20% have at least one E4 DO NOT check someones ApoE4

Types of FTD?

Behavioural Semantic dementia (fluent but jibberish) Primary progressive aphasia (nonfluent- stuttering) Motor subtypes (MDN, CBD, PSNP) MND is associated with chromosome 17 Recent progranulin mutation identified Also TDP 43

Does FTD run in family?

About half have FH

What are the neuropathologies that you see in AD?

Tau-->tangles- inside cells Lewy bodies -->alpha synuclein Plaques (amyloid) -outside cells

How is PET useful in AD?

useful to rule IN AD

What CSF biomarkers do you see?

Amyloid beta 42 decreased p-tau increased in AD

MRI findings in AD

generalised atrophy volume loss hippocampi PET shows hypometabolism of precuneus and lateral parietotemporal cortex

Mainstay of treatment of behavioural disturbance in dementia?

behavioural mx carer education/support Otherwise, evidence for risperidone in aggressive or psychotic nursing home patients Evidence for olanzapine No evidence for quetiapine or newer agents

What increases risk of MCI converting?

``` FH AD Imaging changes consistent with AD (pet shows amyloid) CSF biomarkers increase age rapid forgetting on neuropsych testing ```

lewy body imaging

occipital hypoperfusion on SPECT and PET | MRI shows mesiotemporal SPARING!