Alzheimers Flashcards

1
Q

Neurodegeneration

A

‘Progressive damage or death of neurons leading to a gradual deterioration of the bodily functions controlled by the affected part of the nervous system.’

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2
Q

Acute neurodegeneration

A

Stroke

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3
Q

Chronic neurodegeneration

A

Alzheimers, parkinsons etc.

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4
Q

Natural degeneration

A

ageing

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5
Q

Dementia

A

An ‘umbrella’ term for a particular group of symptoms

Characteristic symptoms of dementia = memory, language, problem-solving, other cognitive abilities

Dementia has many causes

Alzheimer’s disease = most common cause of dementia

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6
Q

Prevalence

A
  • 50 million worldwide
  • 1 million UK
  • 1 in 14 people aged over 65
  • At current rate – over 1.5 million people in the UK by 2040
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7
Q

Non-modifiable risk factors

A
  • Age
    • Most important risk factor
    • Ageing DOES NOT = Alzheimer’s disease
    • 65-74 yrs – 3%; 75-84 yrs – 17%; over 85 – 32% of population

Biological sex
* x2 as many women over 65 with AD versus men
* Why? Women live longer than men? Links with loss of the hormone oestrogen post-menopause?

Genetics

Family history

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8
Q

Modifiable risk factors

A
  • Cardiovascular disease risk factors – smoking, diabetes, obesity, hypertension, high cholesterol

Relationship between cardiovascular system and brain function
* Brain – consumes 20% of the blood’s oxygen and energy supplies
* Brain function – reliant on healthy heart and blood vessels
* Impaired blood flow = increases risk of dementia/AD
* Fatty plaques – cholesterol, salt, age, lack of exercise

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9
Q

Preventative factors/recommendations?

A
  • Physical activity
    • Healthy diet
    • Social and cognitive engagement
      ○ Data support a relationship
      Biological explanation?
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10
Q

Early stages symptoms

A

Changes in brain function aren’t sufficient to = symptoms
Compensatory mechanisms activated?
Some changes in brain function (e.g. beta-amyloid levels) may occur up to 20 years before symptoms

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11
Q

Early signs

A
  • Normal ageing?
    • ‘Blunting of emotional responses’
    • Social withdrawal
  • Memory Impairment
    • Progressive memory loss (initially episodic and declarative)
  • Impairment in function
    • Memory, insight, judgement, language
  • Changes in personality
    Apathy, indifference, depression
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12
Q

Early Stage AD

A

Temporary memory lapses

Forgetting words/names

Difficulty performing complex tasks (e.g. at work)

Misplacing valuable objects

Difficulties with planning/organising

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13
Q

Middle-Stage AD

A

Forgetful of events/personal history

Confuse words

Unable to recall personal information

Frustration/anger

Confusion – surroundings/time

Sleep disturbances

Bladder/bowel problems

Personality/behavioural changes – delusions, paranoia, repetitive (stereotyped) behaviours.

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14
Q

Late Stage AD

A

Lose awareness – surroundings, time

Difficulties in communicating

Changes in physical abilities – walking, swallowing

Vulnerable to infections (especially pneumonia)

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15
Q

Presentation of symptoms dependent on;

A
  • Stage of disease
    • Age of individual
    • Sex of individual
    • Other underlying conditions/medication
    • Patient vs carer reporting
    • Access (real or perceived) to diagnosis
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16
Q

Advanced stages presentation of symptoms

A
  • Gross disorientation in time and place
    • Total dependence on carer for ‘everyday’ tasks
    • Inability to comprehend/communicate
    • Little awareness of past or future
    • Little movement – difficulty in swallowing – infections (e.g. sepsis, pneumonia)
17
Q

AD causes

A
  • There is (most probably) not a single cause of Alzheimer’s disease.
    ○ Most likely develops from multiple factors - genetics, lifestyle and environment.
    Majority of cases (99%) of Alzheimer’s disease are NOT hereditary
18
Q
  • What causes brain dysfunction associated with Alzheimer’s?
A
  • The accumulation of the protein fragment beta‐amyloid (called beta‐amyloid plaques) outside neurons
    • and the accumulation of an abnormal form of the protein tau (called tau tangles) inside neurons are the most prominent brain changes associated with Alzheimer’s.
19
Q

Early onset AD

A
  • Caused by gene mutations on chromosomes;
    Chromosome Gene
    1 Presenelin 1 (PS-1)
    14 Presenelin 2 (PS-2)
    21 Amyloid precursor protein (APP)

These genes possess the characteristic of Autosomal dominant inheritance
* If one of these mutated genes is inherited from a parent – person will almost always develop early onset AD

20
Q
  • Late onset AD
A
  • Genetic risk factors involved
    • e.g. Apolipoprotein E (apoE)
      ○ gylcoprotein, transports cholesterol in blood, plays a role in cellular repair
      ○ E4 = one allele of ApoE
      Presence of E4 = increases risk of developing AD (does not cause AD)
21
Q
  • ApoE and b-amyloid
A

Normally – b-amyloid is soluble
* BUT… becomes insoluble when ApoE4 attaches to it
* Therefore, more likely to be deposited in plaques
* Presence of ApoE4
Increases deposits of b-amyloid and formation of plaques

22
Q

Pathology

A
  1. Brain atrophy
  2. Cellular level features
    • Senile plaques
    • Neurofibrillary tangles
  3. Synaptic loss
  4. Selective depletion of neurotransmitter systems (e.g. Ach)
23
Q

Brain atrophy

A

Severe degeneration of the hippocampus, cerebral cortex and ventricular enlargement

24
Q

Cellular level features

A

Normal = is usually short form amyloid beta

AD = increase of long form amyloid beta which are less soluble > lead to accumulation of plaques

Normal = tau binds to and stabilizes microtubules

AD = tau detaches and sticks to other tau molecules, disrupts cell’s transport system

25
Synaptic loss
- Extensive - Depletion of selective neurotransmitter systems * Acetylcholine (Ach) * Glutamate * Serotonin * Noradrenaline
26
Cholinergic hypothesis of AD
- Cholinergic neurones * Learning, memory, certain aspects of sleep states * Antagonists (e.g. scopolamine) ○ Deleterious effect on learning and memory - Alzheimer’s Disease * Degeneration of Ach producing neurones in forebrain * Deficit in Ach producing enzyme (affecting learning and memory)
27
Treatment - existing and developing treatment
- Psychological * For example: external memory aids, visual imagery, reality orientation - Pharmacological * Cholinesterase inhibitors * Glutamate receptor antagonists
28
Psychological (non-pharmacological) approaches treatments
Does not stop Alzheimers development but does increase individual's quality of life - Memory Aids * diaries, journals, lists, - Cognitive Behavioural Therapy (CBT) * aimed at reducing depression/anxiety (rather than specifically AD) - Music Therapy * to help engage and express feelings - Structured social interaction * Allows a carer to maintain an activity/contact with a patient for 10-15 mins/day - Stimulated presence therapy * Using reminders of events from their personal life * Helps reduce agitation and restlessness
29
Caregiving
- Attending to another person’s health needs and well-being - Assisting with activities of daily living - Emotional and practical support - Managing medications/health service interactions - Informal/unpaid - 2/3 = women - 1/3 = over 65 yrs - Caregiver wellbeing and burden Reduce carer burden/stress and improve quality of lif
30
Pharmacological approaches
- Cholinergic drugs - Nearly every drug currently licensed for AD = cholinesterase inhibitor (ChEI) - Boosts activity at cholinergic synapses - Examples include Aricept, donezepil, rivastigmine, galantamine - Licensed (in UK) for mild to moderate AD, transiently improves clinical symptoms for 6-12 months
31
- Glutamate receptor antagonists
* E.g. Memantine * NMDA receptor antagonist * Protects brain cells from toxic effects of excessive levels of glutamate * Licensed (in UK) for treatment of moderate-to-severe AD * Shown to temporarily slow the progression of symptoms * Helps behavioural symptoms such as aggression and agitation
32
- Treatment approaches in development
* Strategies to reduce b-amyloid accumulation ○ Anti-inflammatory agents ○ Enzyme inhibitors (decrease production of b-amyloid) * Strategies to reduce tau aggregation ○ Anti-inflammatory agents * Improving cardiovascular health
33
Biomarkers
- A naturally occurring molecule, gene, or characteristic by which a particular pathological or physiological process, disease, etc. can be identified - Found in blood, other body fluids, organs and tissues Can track healthy functioning, diagnosis disease, monitor response to treatment, identify health risks (e.g. high cholesterol/high blood pressure for cardiac disease
34
Biomarkers specific to AD
* CSF levels/changes of B-amyloid and/or tau * Blood tests of brain-derived products * Brain imaging studies ○ MRI/CT – structural changes in brain (*need age comparison) ○ Amyloid or Tau PET scans – to examine accumulation of amyloid/tau ○ Fluorodeoxyglucose PET scans – to examine energy i.e. glucose, use in brain