Dunedin-Geriatrics Flashcards
What are the types of mild cognitive impairment?
amnestic subtype
non-amnestic subtype
Does amnestic MCI convert to alzheimers?
yes, 5-16% of them
Does MCI ever reverse?
Yes, 30-50%
factors associated with conversion
- single cognitive domain
- normal hippocampal volume
- depression
- anticholinergic burgen
- higher cognitive scores
- absence of apolipoprotein
What is the relationship between anticholinergic drugs and cognitive disorders?
Anticholinergic drug exposure associated with risk of dementia development OR 1.50
associated with increased cortical atrophy
Is there a role of cholinesterase inhibitors in MCI?
No
How to manage Mild cognitive impairment?
*blood pressure control
*dietary intervention- mediterranean *diet/DASH/vitamin B supplementation
*Cognitive training- inconclusive results
Describe the amyloid cascade hypothesis
Describe the genetics of alzheimers
Familial AD:
- autosomal dominant, <65 years
- APP (CH21), PSEN1, PSEN2 mutation account
Late-Onset AD
- APOE4 allele most common genetic risk factor
Is amyloid B burden associated with dementia severity?
no, but neurofibrillary tangles are
Describe biomarkers in alzeihmers
Core: Alpha Beta Proteinopathy, Tau
Biomarkers of non specific processes in AD: NFL, GFAP
What should you ALWAYS do before prescribing a cholinesterase inhibitor?
Get an ECG
Describe the role of cholinesterase inhibitor in Alzheimers disease
types: donepezil, galantamine, rivastimgine
Efficacy: symptomatic benefit only.
Adverse effects: contraindicated in bradycardia/conduction issues, long QTc
risk with syncope, falls, fractures
GI s/e common
What is the MOA of Memantine?
NMDA receptor blocker
block neurotoxicity from excess glutamine
may worsen delusions and hallucinations
What is Aducanumab? lecanemab? Donanemab?
Aducanumab: it is a amyloid beta-directed monoclonal antibody that were used in mild cognitive impairment (MCI) and early dementia
questionable benefit however caused amyloid-related imaging abnormalities (ARIA)
Lecanemab: Humanised IgG1 monoclonal Ab- binds to Alpha beta soluble protofils
Donaneman: monoclonal antibody that targets a modified form of deposited alpha beta
Solanezumab
what is post-stroke dementia?
10% develop new dementia soon after 1st stroke
>30% have dementia following recurrent stroke
increased risk of post-stroke dementia with:
- age
- previous stroke
- large volume stroke
- aphasia
- left hemisphere lesion
- hemorrhagic stroke
What is Binswanger disease?
extensive white matter lesion seen in cerebral small vessel disease
What is the characteristic of memory loss in cerebral small vessel disease?
Memory often relatively intact – problem with retrieval rather than encoding i.e recall improves with prompt
apathy often misinterpreted as depression
pseudobulbar affect - inappropriée invpluntary laughing and crying
often gait disorder
What is the role of anti-platelet therapy or statins in vascular cognitive impairment?
no evidence
some role of cholinesterase inhibitors in improvement
BP control however hypotension can accelerate cognitive decline in established small vessel disease
What is a big risk with cerebral amyloid angiopathy?
antiplatelets and anticoagulation can increase bleeding risk
you can also get micro bleeds and cortical superficial siderosis
What is the histology of cerebral amyloid angiopathy?
AB protein in cortical and leptomeningeal blood vessel walls
What is CADASIL?
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy
What are the MRI findings in CADASIL?
Lacunes, white matter changes (especially anterior temporal lobe), atrophy
What are the pathological findings in CADASIL?
Granuloma osimophilic material in blood vessel walls, muscles and skin.
skin biopsy 100% specificity
What is the genetic problem in CADASIL?
Frameshift mutation in NOTCH gene on chromosome 19 coding for transmembrane receptor
What are Lewy bodies?
abnormal aggregation alpha- synuclein and eosinophilic inclusions found in
* basal ganglia in Parkinson’s disease
* cortex, brainstem and limbic system in Lewy Body dementia
What are core clinical features of Lewy body dementia?
- fluctuating cognitive impairment
- Visual hallucinations
- REM sleep behaviour disorder
*Parkinsonism: at least 1 of rigidity, bradykinesia or tremor
What are biomarkers in Lewy body dementia?
- reduced dopamine transport uptake basal ganglia SPECT/PET
- low uptake 1231-MIBG myocardial scintigraphy
*Polysomnographic confirmation REM sleep without atonia
What is the mean age of Frontotemporal dementia?
62 years
What dementia is motor neuron disease associated with?
frontotemporal dementia
What is the pathology of frontotemporal dementia?
Pick bodies- argyrophilic inclusions- 3 Tau repeat
IS there a role for cholinesterase inhibitors in FTD?
nope, can worsen behaviour
What is a physical manifestation of corticobasal degeneration?
alien limb- progressive asymetric rigidity and apraxia
What is the most common cause of rapidly progressive dementia?
Creutzfeldt Jacob disease
- 14-3-3 CSF
- 2nd generation RT-QuLc
- Ribbon sign MRI
What is the greatest factor in prevention of dementia?
hearing
Describe some markers of delirium
Too much: glutamate, dopamine, noradrenaline
Too little: melatonin, Ash
Change: serotonin, histamine, GABA
What is the major risk factor for injurious fall?
history of previous fall > fall associated with syncope > decreased executive functioning
Medications associated with falls?
(1) antidepressants
(2) neuroleptics/antipsychotics
(3) benzodiazepines
(4) sedatives/hypnotics
(5) anti-hypertensives
(6) diuretics
(7) b-blockers
What is the best Prevention for falls in the community?
certified exercise program
Is there a role for multifactorial intervention in minimising falls risk?
no
Is there a role for vitamin D in reducing falls?
no
What does the SARC-F screen?
Strength
assistance in walking
Rise from a chair
Climb stairs
falls
Sarcopenia if score >4
What are muscle change with ageing?
*Loss of fast twitch fibres and fast motor units (Type II fibres)
*loss of cross-sectional area muscles
*anabolic resistance
* increased adiposity
*Decrease in muscle quality (reduction in velocity shortening
Which two proteins paired together are responsible for the pathological process of Alzheimer’s disease?
A) Alpha synuclein and Lewy Body fibrils
B) Beta amyloid and tau protein
C) Fibrillin and CRP
D) Alpha synuclein and CRP
E) Huntingtin protein and lewy body fibrils
B) Beta amyloid and tau protein
A 63 year old lady with cancer is still independent with all her activities of daily living. She is unable to do housework, but is able to walk around in her back yard. She is currently spending about 40 % of her waking hours in bed. What is her ECOG?
A. 1
B. 2
C. 3
D. 4
B.2
Match the cognitive domain with screening tools:
A) Repetition of sentence
B) Trail making
C) Months of the year backwards
D) Cube drawing
E) Naming three pictures-
F) Design fluency
G) Digit span forward
H) Sentence writing
A) Repetition of sentence- verbal memory and language abilities
B) Trail making- visual attention and task switching
C) Months of the year backwards- attention, working memory, mental flexibility
D) Cube drawing- visuospacial function
E) Naming three pictures- language function, assess anomia or language deficits
F) Design fluency- executive function and creativity
G) Digit span forward- working memory
H) Sentence writing- language production
