dementia diagnosis and treatment Flashcards
what happens if examination meets the criteria for dementia
-doctors have to work out what type
e.g is it degenerative cause like alzheimers or frontotemporal dementia
is it vascular (immediate onset e.g from stroke)
what are the 4 steps to assessing dementia
- patient history (including next of kin collaboration with GP)
- cognitive tests at memory clinic
- physical examination to identify other issues e.g vitamin B12 deficiency can lead to signs of dementia so ackowledging this as a cause means the vitamin can be given to remove symptoms quite easily
- MRI examination
what happens if examination doesnt meet criteria for dementia
-doctors have to work out what else could be causing the symptoms
e.g depression, anxiety, delerium, learning disability, MCI etc
how does Fjell et al 2014 define the disease process
it will be difficult to understand AD without understanding why it preferably affects older brains
is dementia extreme ageing or fundamentally different to ageing
-we know ageing is linked as it is the no1 risk factor for dementia
-maybe AD cannot be understood until we understand ageing better
-we need to establish whether AD and advanced healthy ageing can be seen as qualitatively or quantitatively different things
what is the quantitative approach
we go from young adulthood to ageing in our 60s, dementia is a progression from that
why might the quantitative approach not be true
bc not everyone develops dementia
what is the qualitative approach
we go from young adulthood to ageing, then advanced ageing in a healthy capacity or an abnormal capacity
(there is a different process driving healthy/abnormal advanced ageing e.g amyloid)
what is the typical progression of the AD pathology
-progression of amyloid plaques and neurofibrillary tau tangles (NFT)
what are the 3 stages of amyloid deposits in the brains of AD patients
stage A: deposit in temporal and orbitofrontal regions
stage B: deposit in medial temporal lobe and neo cortex
stage C: brain stem and cerebellum and parietal cortex impacted, most severe regions are those from stage A
why is memory loss one of the first symptoms of AD
as amyloid effects the temporal lobe first which is key for episodic memory formation
what are the stages of NFT in AD patients
stage I and II: small region of medial temporal lobe effected (forms STM traces)
stage III and IV: rest of medial temporal lobe effected
stage V and VI: medial lobe impacted and spreads through neocortex
why are there more severe deposits of amyloid in AD brains than tau tangles
bc amyloid develops first in the amyloid cascade hypothesis
how long does it take for AD symptoms to fully develop
20yrs
typical progression of AD symptoms
- SCC: subjective complaints of memory loss, language problems, personality changes, mood disturbance
- MCI: objective signs due to neuropsychological tests
- mild AD: functional loss and objective signs from neuropsychological tests
- moderate: marked behavioural changes e.g unable to learn/recall new info, LTM effected, wandering, agitation, assisted daily living
5.severe: sufficient changes, constant care required, unable to recall family, unstable, incontinent, speech loss, aggression, swallowing problems
what order do biological, behavioural and cognitive aspects of AD occur
1.amyloid deposits
2.tau tangles
3.changes to brain structure
4.memory difficulties
5.observable clinical function from neuropsychological tests
what does the order of these biological, behavioural and cognitive aspects imply
-behavioural signs are very late after onset of amyloid
-amyloid deposits form at beginning of disease when it is asymptomatic
-at the moment diagnosis relies so much on clinical function so we only get an insight into amyloid plaques when the behavioural signs are also present
(questions whether clinical tests are the best way to diagnose dementia or is this too late and should we look to biological biomarkers)
what are the 4 biological biomarkers
CSF measures of amyloid and tau
PET measures of amyloid
FDG - PET imaging of brain metabolism
structural MRI of brain atrophy (loss in grey matter)
strength and weakness of CSF measures of amyloid and tau
+amyloid is earliest detectable biomarker of AD
- very invasive, involves taking CSF from spine with needle
strength and weakness of PET measures of amyloid
+ flags amyloid hotspots specifically
- expensive and limited availability
strength and weakness of FDG - PET imaging of brain metabolism
+ indicates synaptic activity, neural function and neuronal metabolic activity
- expensive, limited availability, cannot directly identify location of amyloid, rather it looks at metabolic activity
strength and weakness of structural MRI of brain atrophy
+ measure of cerebral atrophy which is a core feature of neurodegeneration
- brain structural deficits are not as early onset as amyloid or tau so relatively late diagnosis if aiming to prevent cog damage
- cannot directly detect the core pathological features of AD
is there a cure for dementia
what is the aim
no
aim is to alleviate symptoms or delay progression
what helps minimise the effect of AD
-lifestyle interventions e.g increasing physical, mental and social activity
-maintaining and restoring plasticity e.g by modifying neurotransmission or increasing Brain Derived Neurotrophic Factor (BDNF)
–BDNF = protein implicated in plasticity, exercise can help increase BDNF to restore plasticity loss
-reducing pathology eg clearing amyloid/tau burdens with drug treatments
what are traditional and alternative treatments for AD
traditional: attempt to keep memory function by targeting cholinergic and glutamatergic systems
alternative therapeutic treatments aim to reduce protein deposits (amyloid and tau) found in brains (Panza et al 2016)
evidence of one unsuccessful and one successful drug for treating AD
verubecestat
-reached stage 3 out of 4 of clinical trials
-deemed to have no chance of finding a positive clinical effect
aducanumab
-approved and slows cog decline by 40% by reducing presence of brain plaques
when do drugs work best
in preclinical/mild AD patients
anti-inflammatory measures for treating AD
(Heneka et al 2015)
-protein build up causes inflammation
-naproxene helps reduce pathology and had a protective role in patients who had been asymptomatic at baseline
-links with obesity
lecanemab (drug)
-potential breakthough drug
-slower decline in patients symptoms
-those getting drug were 0.45 points better off
what are the 2 distinctions of disease modifying drugs
- beta secretase (BACE) inhibitors: inhibit amyloid precursor protein e,g verubecestat
- amyloid immunisation: clears build up of amyloid beta peptides which are neurotoxic e.g lecanemab
are interventions worthwhile
range of interventions could lower prevalence of dementia
-alzheimers society say delaying onset of AD by 5 yrs could reduce attributable deaths by 30,000
projected prevalence of dementia
-dem seems to be increasing in prevalence, especially past age 85
-although, Cognitive Function and Ageing Study CFAS shows prevalence is dropping
prevalence of dementia in china
as china is becoming more westernised, dementia prevalence is increasing (chan et al 2013)
-prevalence of AD almost tripled between 1990 and 2010
