Week 8 - Neurodegenerative Disorders Flashcards
(28 cards)
What is dementia
abnormal, progressive and disabling decline in cognitive functions – distinct from normal aging.
A general term for a group of symptoms that affect memory, thinking, behaviour and the ability to perform everyday tasks. It is not a specific disease but rather a syndrome caused by various brain disorders.
What does dementia affect
- Memory and cognition (calculations, problem solving)
- Language skills
- Ability to learn new sills
- Visuospatial ability and motor skills
- Changes in personality, mood and behaviour
What is alzheimer’s disease
a neurological disorder that involves irreversible worsening changes in the ability to think and remember. – it’s the loss of the ability to reason, learn new skills and plan and prioritise to the point where it interferes with a person’s daily life and activities.
- Type of dementia
- Most common neurodegenerative disease worldwide
- Chronic, progressive disorder of unknown cause
- Occurs in middle to late life risk doubling every 5 years beyond age of 65
- Mainly cognitive dysfunction but also mental symptoms e.g. hallucinations or behavioural abnormalities
- Psychological and economic burden on patients and families
what does the initial memory loss and confusion in alzheimer’s disease lead to
- Behaviour and personality changes
- Decline in cognitive abilities such as decision making and language skills
- Problem recognising family and friends
What are the 4 principle signs and symptoms of Alzheimer’s Disease
- Amnesia – loss of ability to recall one’s memories
- Aphasia – loss of ability to comprehend and express speech
- Apraxia – loss of ability to execute motor movements
- Agnosia – loss of ability to process sensory information (visual, auditory, tactile, or olfactory senses)
What is amnesia
loss of ability to recall one’s memories
what is aphasia
loss of ability to comprehend and express speech
what is apraxia
loss of ability to execute motor movements
what is agnosia
loss of ability to process sensory information (visual, auditory, tactile, or olfactory senses)
What is the mild or early stage of ALzheimer’s
- Symptoms may not be obvious but can be detected by close friends and family
- May be unable to remember a word or name
- Possible changes in mood or personality
- Show diminished judgement
- Still capable of living their lives independently
Symptoms - Problems can include wandering and getting lost, trouble handling money and paying bills, repeating questions, taking longer to complete normal daily task and personality and behaviour changes
What is the moderate of middle stage of Alzheimer’s
- Symptoms more pronounced
- Unable to remember events in personal history or learn new information
- Changes in behaviour and personability – agitated, aggressive or confused
- Lost or wandering aimlessly
- Require some assistance in daily lives but can handle simple tasks
Symptoms
- Unable to learn new things
- Unable to carry out multistep tasks such as getting dressed or cope with new situations
- May have hallucinations, delusions and paranoia and may behave impulsively
What is the severe or late stage of Alzheimer’s
- Extreme disruptions in cognitive functions
- May lose control over movement or other physical abilities such as holding objects or swallowing
- Communication may be difficult or impossible
- May be bedridden and require continuous assistance and long term care
Symptoms
- Cannot communicate
- Bed ridden near the end of life
What are potential causes of Alzheimer’s
- genetic predisposition
- down syndrome - early onset - overexpression of the APP gene on chromosome 21
- potential link with high fat and ultra processed food diets - trigger neuroinflammation in the brain which is linked to neuronal damage
What are the macroscopic changes which occur during Alzheimer’s Disease
- Cerebral atrophy associated with neuronal loss, particularly in hippocampus and cortex regions
- Irreversible, progressive brain degeneration, impairing memory and reasoning
Cerebral atrophy = loss or shrinkage of brain tissue, reduction in size and number of neurons and connections between them
What are the main microscopic changes that occur during Alzheimer’s disease
- Amyloid beta plaques
- Neurofibrillary tangles
what is the function of the hippocampus
- Crucial to information processing, acquired new memories and retrieving old ones
- This is compromised in Alzheimer’s
What are amyloid -beta plaques
Abnormal clumps of a protein called beta-amyloid that accumulates between neurons.
The plaques disrupt communication between neurons contributing to brain damage and cognitive decline.
patches of degenerating nerve terminals clustering around a core of amyloid beta peptide
- formed from the breakdown of larger protein amyloid precursor protein (APP)
- APP has a neurogenic and neuro regenerative role
- AB plaques lead to synaptic dysfunction, neuronal death, and cognitive decline
- Number and distribution of plaques and tangles appear to be important in the development of AD
What are beta-amyloid proteins derived from
Beta-amyloid is derived from a larger proteins called the amyloid precursor protein (APP). In healthy brains this protein is broken down and cleared but in Alzheimer’s it accumulates and forms clumps.
what is tau
microtubule stabiliser that regulates microtubule assembly, dynamics and stability; normally found in axons
What are neurofibrillary tangles (NFTs)
Abnormal accumulations of a protein called tau that collect inside neurons.
In healthy neurons tau helps stabilize microtubules, however in Alzheimer’s tau is hyperphosphorylated causing it to detach from microtubules and clump together, forming tangles. These tangles disrupt the neuron’s transport system and can lead to neuronal dysfunction and cell death.
- Neurofibrillary tangles are made of hyperphosphorylated tau inside abnormal neurons
- They harm synaptic communication between neurons
- Phosphorylation at certain tau residues promotes dislocation to soma and dendrites
- Synaptic loss principal correlate of disease progression
In healthy neurons, tau normally binds to and stabilises microtubules. In AD however, abnormal chemical changes (hyperphosphorylation) cause tau to detach from microtubules and stick to other tau molecules, forming threads that eventually join to form tangles inside neurons. These tangles block the neuron’s transport system, which harms the synaptic communication between neurons.
what circuitry is disrupted in Alzheimer’s
Cholinergic Circuitry
- Disruption of cholinergic neurons involved in learning, memory and attention
- Loss of choline acetyltransferase – enzyme required for the synthesis of acetylcholine
- Also: reduced acetylcholine levels due to deterioration of neurons -> memory loss and difficulty forming new memories
- Drugs increasing the availability of acetylcholine shown to be effective in slowing progression of AD
AcH = An important neurotransmitter for learning, developing memories
What circuitry is disrupted in Alzheimer’s
Cholinergic circuit
What is the cholinergic circuit
neuronal pathway in the brain that uses ACh as their primary neurotransmitter.
Circuit is crucial for learning, memory, attention and motor control.
Composed of cholinergic neurons that release ACh which binds to specific receptors on other neurons, triggering a response.
In Alzhiemer’s what are the changes to the cholinergic circuit
- Decrease in ACh synthesis - due to loss of choline acetyltransferase (ChAT) – enzyme required for the synthesis of acetylcholine
- loss of cholinergic neurons (in basal forebrain)
