dementia diagnosis and treatment

Question 1

what happens if examination meets the criteria for dementia

Answer 1

-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)

Question 2

what are the 4 steps to assessing dementia

Answer 2

1. patient history (including next of kin collaboration with GP)
2. cognitive tests at memory clinic
3. 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
4. MRI examination

Question 3

what happens if examination doesnt meet criteria for dementia

Answer 3

-doctors have to work out what else could be causing the symptoms
e.g depression, anxiety, delerium, learning disability, MCI etc

Question 4

how does Fjell et al 2014 define the disease process

Answer 4

it will be difficult to understand AD without understanding why it preferably affects older brains

Question 5

is dementia extreme ageing or fundamentally different to ageing

Answer 5

-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

Question 6

what is the quantitative approach

Answer 6

we go from young adulthood to ageing in our 60s, dementia is a progression from that

Question 7

why might the quantitative approach not be true

Answer 7

bc not everyone develops dementia

Question 8

what is the qualitative approach

Answer 8

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)

Question 9

what is the typical progression of the AD pathology

Answer 9

-progression of amyloid plaques and neurofibrillary tau tangles (NFT)

Question 10

what are the 3 stages of amyloid deposits in the brains of AD patients

Answer 10

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

Question 11

why is memory loss one of the first symptoms of AD

Answer 11

as amyloid effects the temporal lobe first which is key for episodic memory formation

Question 12

what are the stages of NFT in AD patients

Answer 12

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

Question 13

why are there more severe deposits of amyloid in AD brains than tau tangles

Answer 13

bc amyloid develops first in the amyloid cascade hypothesis

Question 14

how long does it take for AD symptoms to fully develop

Answer 14

20yrs

Question 15

typical progression of AD symptoms

Answer 15

1. SCC: subjective complaints of memory loss, language problems, personality changes, mood disturbance
2. MCI: objective signs due to neuropsychological tests
3. mild AD: functional loss and objective signs from neuropsychological tests
4. 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

Question 16

what order do biological, behavioural and cognitive aspects of AD occur

Answer 16

1.amyloid deposits
2.tau tangles
3.changes to brain structure
4.memory difficulties
5.observable clinical function from neuropsychological tests

Question 17

what does the order of these biological, behavioural and cognitive aspects imply

Answer 17

-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)

Question 18

what are the 4 biological biomarkers

Answer 18

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)

Question 19

strength and weakness of CSF measures of amyloid and tau

Answer 19

+amyloid is earliest detectable biomarker of AD
- very invasive, involves taking CSF from spine with needle

Question 20

strength and weakness of PET measures of amyloid

Answer 20

+ flags amyloid hotspots specifically
- expensive and limited availability

Question 21

strength and weakness of FDG - PET imaging of brain metabolism

Answer 21

+ indicates synaptic activity, neural function and neuronal metabolic activity
- expensive, limited availability, cannot directly identify location of amyloid, rather it looks at metabolic activity

Question 22

strength and weakness of structural MRI of brain atrophy

Answer 22

+ 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

Question 23

is there a cure for dementia
what is the aim

Answer 23

no
aim is to alleviate symptoms or delay progression

Question 24

what helps minimise the effect of AD

Answer 24

-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

Question 25

what are traditional and alternative treatments for AD

Answer 25

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)

Question 26

evidence of one unsuccessful and one successful drug for treating AD

Answer 26

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

Question 27

when do drugs work best

Answer 27

in preclinical/mild AD patients

Question 28

anti-inflammatory measures for treating AD

Answer 28

(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

Question 29

lecanemab (drug)

Answer 29

-potential breakthough drug
-slower decline in patients symptoms
-those getting drug were 0.45 points better off

Question 30

what are the 2 distinctions of disease modifying drugs

Answer 30

1. beta secretase (BACE) inhibitors: inhibit amyloid precursor protein e,g verubecestat
2. amyloid immunisation: clears build up of amyloid beta peptides which are neurotoxic e.g lecanemab

Question 31

are interventions worthwhile

Answer 31

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

Question 32

projected prevalence of dementia

Answer 32

-dem seems to be increasing in prevalence, especially past age 85
-although, Cognitive Function and Ageing Study CFAS shows prevalence is dropping

Question 33

prevalence of dementia in china

Answer 33

as china is becoming more westernised, dementia prevalence is increasing (chan et al 2013)
-prevalence of AD almost tripled between 1990 and 2010