Alzheimers

Question 1

Is there a genetic cause to AD?

Answer 1

form of AD known as ‘familial Alzheimer’s disease’
Very rare but more common in early onset cases.
The effects on the brain are almost indistinguishable from ‘normal’ AD - tangles and beta amyloid plaque
Changes happen rapidly, show signs in 40s-50s

Question 2

What causes AD? - genetics

Answer 2

Mutations occur when a gene is copied incorrectly. If the mutant gene is dominant, its effects will be seen in the organism (‘phenotype’).
If the gene is recessive, its effects will only be seen in a person who inherits two copies of the faulty gene, one from each parent. People with one copy are healthy “carriers”

Question 3

Familial AD inheritance

Answer 3

The genes responsible for familial AD are found on 3 different chromosomes.
Each of these mutations causes a build-up of amyloid plaques in the brains of affected individuals.
Genetic testing can identify whether an individual is carrying a mutant form of one of the genes responsible for familial AD (and will therefore develop AD).
An individual carrying a mutation knows that if they have children, each child has a 50% chance of inheriting familial AD.

Question 4

Some evidence that late onset AD is inherited - APOE4

Answer 4

Having other family members with AD increases the probability of developing the disease, but only by a small amount.
One copy of APOE4 increases the risk of late onset AD by about 4 times.
Two copies increase the risk about 10-20 times.
But many people with even 2 copies of APOE4 do not develop AD.
Only 35% of people with AD have the APOE4 gene

Question 5

Hoe diet can act as a protective factor to AD

Answer 5

60000+ people in UK Biobank over 9 years, large sample size
Scored for adherence to “Mediterranean diet”, higher in chicken, fish, salad, nuts, pulses, olive oil, fruits and vegetables, lower in red meat, high fat dairy and added sugar.

Highest adherence had 23% lower risk of developing dementia, compared with lowest adherence.

Many confounds, these foods are more expensive so may have a higher income, may be younger or more educated, many variables which may have caused results

Question 6

Other environmental factors that may increase risk of developing AD

Answer 6

Smoking may increase the risk in carriers of APOE4.

Bad gut microbes (high fat and sugar diet) can trigger a systemic inflammatory response – inflammatory markers which can cause brain inflammation, may be a risk factor for dementia

Question 7

Modifiable risk factors to reduce chances of developing AD

Answer 7

45% of cases of dementia are potentially preventable by addressing 14 modifiable risk factors during the life course.

These are lower levels of education in early life (5%); hearing impairment (7%), high levels of LDL cholesterol (7%), depression (3%), traumatic brain injury (3%), physical inactivity, diabetes, smoking, high blood pressure, obesity, and excessive alcohol consumption in midlife; social isolation (5%), air pollution (3%) and vision loss in later life.

Question 8

How early can AD be detected and what are the warning signs?

Answer 8

Dementia has an insidious onset – hardly noticed at first
MCI can be a sign of early dementia

Question 9

What are the symptoms of mild cognitive impairment (MCI)?

Answer 9

Forgetting appointments and recent events
Losing train of thought or thread of conversations
Misplacing everyday items, or putting them in strange places
Failing to recognise familiar people and places
Problems with ‘word finding’ (e.g., remembering the names of people or things)
Problems with planning complex tasks like making meals
Impaired judgement and decision making

Question 10

What is needed for an AD diagnosis?

Answer 10

Increasing deficits in at least two areas of cognitive function (e.g. memory and language)
Severe problems that interfere with everyday activities

Question 11

MCI figures

Answer 11

May reflect the earliest stages of dementia
Could also be due to depression, bereavement, side-effects of medications can produce reversible MCI
Repeated testing every 6 months to identify dementia
Only 12% of people with MCI aged 65+ develop AD every year
50% after 5 years
Not a solid prediction of AD

Question 12

Brain imaging in people with MCI

Answer 12

Show degeneration of hippocampus and other memory structures in MCI patients 3 years before diagnosis of AD.
Temporal lobes and ventral surface lost the most mass in people with AD
Same pattern in MCI but less extreme

Question 13

Benefits of cognitive reserve

Answer 13

High levels of intelligence and education may allow a person to continue to function relatively normally through the early stages of AD.

Question 14

The nun study - how cognitive reserve helps to prevent symptoms of AD

Answer 14

Analysed their autobiographies for grammatical complexity and density of ideas.
Nuns who had developed dementia by the mid 1990s showed lower scores in their early autobiographies than nuns who had not developed dementia.
Education may be a protective factor against AD - they were teachers who had been educated
At post moretom it was revealed that many nuns had alzheimer’s pathology but were still functioning normally
May be due to brain activity daily, puzzles, reading, community

Question 15

How do education levels impact a persons likelihood of being diagnosed with AD?

Answer 15

No effect of years of education on signs of AD pathology in brain (e.g. plaques, tangles)

But more educated participants were less likely to have been diagnosed with AD – they could still function adequately despite pathology.

Question 16

What are the treatments for AD?

Answer 16

Cognitive stimulation (‘brain training’), exercise and improved nutrition can boost performance (in short-term) and improve mood.

‘Reminiscence therapy’ may allow patients to make the best use of early memories and knowledge and promote social interaction and well-being.

No evidence that these change progression of disease.

Question 17

Which drugs are used for mild to moderate AD and why are they used?

Answer 17

‘Cholinesterase inhibitors’
Drugs which boost acetylcholine levels by inhibiting enzymes which break it down.
About half of AD patients show benefits for a limited time.

Question 18

Which drugs are used for severe AD and why are they used?

Answer 18

‘NMDA inhibitors’
Drugs which block glutamate. This is released in large quantities by damaged cells and is toxic to surrounding cells.
Main excitatory neurotransmitter in the brain
Help sufferers to function at a better level

Question 19

Are drugs used to treat AD cost effective?

Answer 19

No
Anti-Alzheimer drugs do not stop the progression of AD
They only work for some patients
Expensive
Have significant side-effects

Question 20

Why could immunotherapy be useful for treating AD?

Answer 20

Using the immune system to reduce amyloid plaques
New drugs involve monoclonal antibodies that target beta amyloid

Question 21

How effective was Immunotherapy when used to treat AD?

Answer 21

Treated with anti-amyloid antibody
Infusions twice a week over 18 months vs. placebo.
Reduced amyloid plaques supports “amyloid hypothesis”
Cognition declined 27% slower in participants taking drug than in placebo
Only delaying progression by 6 months - is it worthwhile?

Very serious side effects in 3% - brain swelling and small brain bleeds. Requires expensive monitoring.
Need for regular infusions is unpleasant and expensive.
Eligibility for the drug requires levels of amyloid in the brain to be measured – involves PET scan or lumbar puncture which only 2% of Alzheimer’s patients have currently.
Drug is not prescribed by NHS

Question 22

Which areas of the brain are responsible for each aspect of AD?
- episodic memory and language
- controlling thoughts and behavior
- memory and navigation

Answer 22

Episodic memory (remembering recent events) - Atrophy in medial temporal lobe

Semantic memory and language (understanding and producing words) - Atrophy in anterior temporal and inferior frontal cortex

Controlling thought and behaviour - Atrophy in frontal cortex

Memory and navigation skills reduce- Hippocampus starts to deteriorate

Question 23

Where is the hippocampus found?

Answer 23

embedded within the temporal lobes, one in each hemisphere

Question 24

WHat causes memory issues in AD?

Answer 24

Recall - you have to find a way of accessing the relevant memory traces
Recognition - seeing the item again acts as a potential cue
Deficit for both recall and recognition in early AD
AD damages formation of memory traces themselves; it is not just a problem with retrieval

Question 25

How are free recall and recognition impacted before being diagnosed with AD?

Answer 25

Impairment can be seen even 6 years before diagnosis
Episodic memory is poorer in patients even before they develop AD
Not much change in performance between 3 and 6 years before diagnosis

Question 26

Changes in brain structure in people with MCI

Answer 26

Shrinkage in anterior, Inferior and medial temporal lobes (including hippocampus) before diagnosis

Pattern of atrophy and neuropsychology both suggest episodic memory deficits at early stages of AD

Question 27

What does medial mean?

Answer 27

deep inside the brain, towards the midline

Question 28

Which areas of the brain are responsible for semantic memory and language?

Answer 28

The left hemisphere is dominant for most aspects of language processing (in most people).

Anterior temporal lobe (front part) and the inferior frontal lobe (lower part) are important for understanding and producing words. Atrophy here produces semantic and language deficits in AD.

Question 29

How does AD affect functioning?

Answer 29

Category fluency task - Vocabulary shrinkage, with greater loss of harder words – i.e., words that are used less often, and that are learned later in life.
Impaired object naming correlates with cortical thinning in the left anterior temporal lobe in AD.
May struggle with showing how an object e.g scissors are used as it still requires general knowledge of what the object is and how to use it

Question 30

How does Transcranial Magnetic Stimulation (TMS) help us understand AD?

Answer 30

Coil held on the scalp, produces a strong magnetic field, can generate a virtual lesion on a healthy brain temporarily which can stop a function
Inhibitory TMS to the anterior temporal lobes disrupts semantic tasks, in line with the deficits of patients with dementia – e.g., specific object naming but not reading numbers

Question 31

Why do people with AD have difficulty controlling thoughts and behaviour?

Answer 31

The frontal lobes are especially important for controlling thought and behaviour (“executive function”).

AD patients have atrophy in these areas causing trouble concentrating, making decisions and planning complex actions

Question 32

Describe executive dysfunction in AD patients - dual tasks

Answer 32

Problems coordinating multiple activities at once as it requires attention to be flexibly allocated to each task

e.g a digit span test and eye tracking test simultaneously

Over time, digit span and tracking individually remain stable but dual task combination declines in AD

Suggests executive dysfunction deficits in AD patients

Question 33

Describe the personality changes that may occur in people with AD and why they may occur

Answer 33

Behavioural symptoms include:
Irritability, agitation, outbursts, shouting, restlessness, pacing, fidgeting, repetitive behaviours (perseverations)
May be related to lack of cognitive control (following frontal lobe atrophy)
Harder to suppress actions as it requires executive function, e.g shouting when you’re angry
Apathy in moderate stages of AD - Lack of interest in life; failure to initiate actions and thoughts

Associated with atrophy in orbitofrontal cortex (linked to processing reward value e.g people we love, food we like, earning money) and frontal pole (linked to high level goals)

Question 34

Why may people with AD experience hallucinations?

Answer 34

Patients in the later stages of AD remain able to see (without recognizing what they see), hear (without understanding what they hear), and move (but without clear purpose).

Primary sensory and motor areas of the brain remain relatively unaffected in AD.

Seeing without understanding may give rise to misperceptions (hallucinations) e.g misinterpreting shaddows, holes in the floor, thinking people on the TV are in the room with them