Alzheimer's Disease Flashcards
what is neurodegeneration?
Progressive damage or death of neurons leading to a gradual deterioration of the bodily functions controlled by the affected part of the nervous system
what is are some examples of chronic neurodegeneration?
- Alzheimers disease
- Parkinsons disease
- Huntington’s chorea
what is dementia?
- 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
what is an example of a acute neurodegernation?
a stroke
what is Alzheimer’s?
- a disease first identified over 100 years ago
- a degenerative brain disorder of unknown origin that causes progressive memory loss, motor deficits, and eventual death
- incidence is high as population ages
what is the prevalence of Alzheimer’s?
- 50 million people affected wordwide
- 1 million UK
- 1 in 14 people aged over 65
- at current rate - over 1.5 million people in the UK by 2024
- access to diagnosis/treatment/support
Age as a risk factor of Alzheimers disease
- most important risk factor
- ageing does not mean you have alzheimer’s disease
- ages 65-74 3% of the population are affected
- ages 75-84, 17% are affected
- ages 85 and over, 32% are affected
Biological sex as a risk factor for Alzheimers
- x2 as many women over 65 with AD versus men
- why? Women live longer than men? Links with the loss of the hormone oestrogen post-menopause
Prevelance of Alzheimers between females and males between the ages of 65-69
0.7% female: 0.6% male
Prevelance of Alzheimers between females and males between the ages of 85-89
14.2% female
8.8% male
cardiovascular disease as a risk factor for Alzheimer’s disease
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
what are some things suggested to try to prevent Alzheimers?
- physical activity
- healthy diet
- social and cognitive engagement
estimated total cost of dementia care in the UK
total cost of dementia care (UK) - £26.3 billion per annum (NHS, private social care, local authority care)
stages of Alzheimers disease (AD)
Preclinical AD (no symptoms) → MCI due to AD (very mild symptoms that do not interfere with everyday activities) → Mild (symptoms interfere with everyday activities) → Moderate (symptoms interfere with many everyday activities) → Severe )symptoms interfere with most everyday activities
- length of each phase of the continuum is influence by age, genetics, gender and other factors
Early symptoms of Alzheimers
- 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
- can be seen as normal ages
- ‘Blunting of emotional responses’
- Social withdrawal
what are early stage symptoms of AD?
- Temporary memory lapses
- Forgetting words/names
- Difficulty performing complex tasks (e.g. at work)
- Misplacing valuable objects
- Difficulties with planning/organising
what are middle stage symptoms of AD?
- 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.
Late stage symptom AD
- Lose awareness – surroundings, time
- Difficulties in communicating
- Changes in physical abilities – walking, swallowing
- Vulnerable to infections (especially pneumonia)
what % of Alzheimers disease are hereditary?
1%
what causes brain dysfunction with Alzheimers disease?
- The accumulation of the protein fragment beta‐amyloid (called beta‐amyloid plaques)outsideneurons
- the accumulation of an abnormal form of the protein tau (called tau tangles)insideneurons are the most prominent brain changes associated with Alzheimer’s.
what are the two main types of Alzheimers?
Early-onset:
- Hereditary
- diagnosed between 60-65 years of age
- makes up less than 5% of cases
Late-Onset:
- majority of cases
- above the age of 60-65 years
what is early onset of AD caused by?
- Caused by gene mutations on chromosomes
- Autosomal dominant inheritance: If one of these mutated genes is inherited from a parent – person will almost always develop early onset AD
causes of late-onset AD
- genetic risk factors involved
- e.g. Apolipoprotein E (apoE)
what is Apolipoprotein E (apoE)?
- gylcoprotein, transports cholesterol in blood, plays a role in cellular repair
- On chromosome 19, the apolipoprotein E (ApoE) gene has three common forms or alleles: E2, E3, and E4. Thus, the possible combinations in one person* are E2/2, E2/3, E2/4, E3/3, E3/4, or E4/4
- E4 = one allele of ApoE
- Presence of E4 = increases risk of developing AD (does not cause AD)
what is brain atrophy?
- Loss of connections between neurones
- severe degeneration of the hippocampus, cerebral cortex and ventricular enlargement of brains in AD patients
what are senile plaques?
- extracellular deposits of the amyloid beta protein mainly in the grey matter of the brain
- Degenerative neuronal elements and an abundance of microglia and astrocytes can be associated with amyloid plaques
How is the amyloid beta protein produced?
by enzymatic reaction between beta and gamma
what are some ‘normal’ functions of amyloid beta peptide?
- mostly short form, soluble, circulate in CSF/blood
- activator of kinase enzymes
- protects against oxidative stress
- regulation of cholesterol transport
- anti-microbial actions
role of amyloid beta peptides in Alzheimers?
- increased portion of long form
- long form – less soluble, more likely to accumulate
- induce synaptic dysfunction, disrupt neuronal connectivity and result in neuronal death
- weak correlation in quantity and distribution + AD
Neurofibrillary tangles (tau tangles) role in Alzheimers
- Non-AD brains – tau binds to and stabilizes microtubules (nutrient transport system)
- AD – tau detaches and sticks to other tau molecules, disrupts cell’s transport system
is synaptic loss extensive in alzheimers disease?
- yes it’s extensive
- Depletion of selective neurotransmitter systems
→Acetylcholine (Ach)
→Glutamate
→Serotonin
→Noradrenaline
what is cholinergic neurotransmission?
- acetylcholine production
acetyl CoA + choline → (with ChAT) Ach and coenzyme A - Acetylcholine destruction
Ach → (with AchE) Choline and acetic acid
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
- Treatment strategy? (see next section on ‘treatments)
what are some types of psychological treatments for AD?
- memory aids e.g. diaries, journals, lists
- CBT: aimed at reducing depression and anxiety
- Music therapy: helps engage and express feelings
- Structured social interaction: allows carer to maintain an activity/contact with a patient for 10-15 mins a day
- Stimulated presence therapy: using reminders of events from their personal life
- helps reduce agitation and restlessness
what are caregivers?
- 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
cholinergic drugs as an example of a pharmacological treatment for Alzheimers
- 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
Glutamate receptor antagonists as a pharmacological treatment for Alzheimers disease
- 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
Strategies to reduce beta amyloid accumulation as an Alzheimers treatment
- Anti-inflammatory agents
- Enzyme inhibitors (decrease production of b-amyloid)
Strategies to reduce tau aggression
Anti-inflammatory agents
what are 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)
What are some biomarkers specific to Alzheimers disease?
- CSF levels/changes of B-amyloid and/or tau
- Blood tests of brain-derived products
- Brain imaging studies: MRI/CT – structural changes in brain
- Amyloid or Tau PET scans – to examine accumulation of amyloid/tau
- Fluorodeoxyglucose PET scans – to examine energy i.e. glucose use in brain
