Module 4: The Pathology Of Neurological Disorders And Mental Health Flashcards
Central Nervous System
Consists of brain and spinal cord
Peripheral Nervous System
all the nerve tissue outside the CNS
Cells of Nervous System
Neuron
Glial Cells - regulate environment around the neurons, maintain the position of the neuron and repair the neuron if damaged
Structure of a Neuron
Cell Body
contains a nucleus, mitochondria, and
other important organelles.
Dendrites
Protrusions of membrane act as connections for receiving incoming signals.
Some neurons have many dendrites, whereas others may not have any at all.
Axon
An extension from the cell body transmits outgoing signals away from the cell body
Myelin Sheath
Some axons coated in a fatty coating called myelin. This myelin sheath acts
as insulation for neuronal signals, increasing the speed of signal transmission along the axon.
Axon Terminals
Signals that travel down to reach the axon terminal and is transmitted to adjacent neurons.
Signalling Across the Nervous System
Reception – A signal from outside the neuron is received by its dendrites.
Action Potential – The signal turns into an electrical impulse, traveling through the neuron down the axon.
Synapse – The impulse triggers the release of neurotransmitters (chemicals) at the axon terminals into synapse cleft.
Transmission – The neurotransmitters pass the signal to the next neuron, continuing the process until the message reaches its destination.
Neurotransmission
Resting State – Neurotransmitters are stored in vesicles in the axon terminal.
Signal Arrival – When an electrical signal (action potential) reaches the axon terminal, neurotransmitters are released.
Signal Transfer – Neurotransmitters bind to receptors on the next neuron, triggering a new action potential.
Reset – Once signaling is complete, neurotransmitters detach, vesicles are recycled, and neurons return to rest, ready for the next signal.
Glial Cells
Schwann Cells – Insulate and support neurons in the PNS, forming myelin sheaths around axons.
Oligodendrocytes – Perform a similar role in the CNS, myelinating multiple axons at once.
Microglial Cells – Act as the brain’s immune system, clearing debris, damaged neurons, prune unnecessary synapses during brain development, and harmful substances.
Astrocytes – Star-shaped cells that provide nutrients, support the blood-brain barrier, and aid in tissue repair. They also help regulate blood flow, remove excess neurotransmitters, and maintain the chemical environment needed for neurons to function properly.
Mental Health and Mental Illness
Mental Health – Your emotional and psychological well-being. Good mental health is essential for overall health, while poor mental health can lead to illness. Maintaining mental health may involve therapy, wellness techniques, and medication.
Mental Illness – A diagnosable and treatable medical condition, like diabetes or heart disease. It affects thinking, mood, or behavior and can make daily life difficult. Common causes include stress, loneliness, and sadness. Examples include anxiety, depression, eating disorders, and schizophrenia.
Adverse Childhood Experiences
ACEs are traumatic events like neglect, abuse, or an unstable home before age 18. They can negatively impact long-term health.
Higher ACE scores increase the risk of diseases and other health challenges.
Building resilience in children through support programs can help reduce these risks.
Factors to Prevent ACEs
Individual Factors
1. Strong Cultural Identity
2. Self-Regulation – Ability to control actions, behaviours, and emotional responses
3. Sense of Meaning and/or Purpose
4. Effective Coping Skills – Ability to react appropriately to adverse experiences
5. Problem Solving Skills
Family and Relational Factors
1. Stable and Supportive Relationships
2. Adequate Housing and Income
3. Stimulating Home Environment
4. Role Modelling
5. Connection to Positive Social Network
Community Factors
1. Safe & Connected Communities
2. Access to Services
3. Mentorship
4. Positive Relationships with Peers
5. Access to Extracurricular Activities
6. Positive School Environments
7. Quality Child Care
Neurodegenerative Disorders
Alzheimer’s Disease (AD) – Primarily affects the hippocampus and cerebral cortex.
Parkinson’s & Huntington’s Disease – Both affect neurons in the basal ganglia.
Spinocerebellar Ataxias – A group of disorders affecting the spinal cord and/or cerebellum, causing problems with balance and coordination (ataxia).
Charcot-Marie-Tooth Disease (CMT) – Affects the peripheral nervous system (PNS), involving various genetic disorders.
Risk Factors of Neurodegenerative Diseases
Age – Aging increases the risk of neurodegenerative diseases, leading to problems like defects in mitochondrial metabolism, increased reactive oxygen species, and cell death.
Protein Misfolding – Abnormal protein folding and clumping (aggregation) play a major role in many neurodegenerative diseases.
Synaptic Dysfunction – Problems with the synapse (where neurons communicate) are an early sign of many neurodegenerative diseases.
Neuronal Cell Death – Neuron death is a key feature of these diseases, often after long periods of stress and maladaptation. Simply preventing neuron death may not fully help in treatment.
What it is: decline in cognitive function that affects memory, thinking, and daily activities
Main causes:
Alzheimer’s disease
Lewy Body dementia
Symptoms: Memory loss, difficulty thinking, and trouble with daily tasks.
Other causes:
Vitamin deficiencies
Stress
Infections
Medication side effects
Rick Factors for Dementia
Health Factors
1. Genetics
2. Diabetes
3. High blood pressure
4. Unhealthy cholesterol levels
Lifestyle/Dietary Factors
1. Smoking
2. Physical inactivity
3. Obesity
4. Drug and alcohol abuse
5. Poor access to good diet
Mental Health
1. Post-traumatic stress disorder (P T S D)
2. Depression
3. Schizophrenia
Indigenous Views on Dementia
- In Indigenous cultures, memory loss is often seen as a natural part of aging.
- Terms for dementia are gentle and humorous, such as “mind changes” or “buried memories.”
- Dementia symptoms are sometimes described as a “second childhood” or being “closer to the Creator.”
- Memory loss is not viewed negatively but as a natural part of the circle of life.
Cognitive Test
used to evaluate judgement, reasoning, memory, problem-solving. to detect cognitive impairment
ex. clock drawing and pattern recognition
Alzheimer’s Disease (AD)
Most common cause of dementia, responsible for 50-75% of cases.
Progressive neurodegenerative disease that worsens over time.
Life expectancy post-diagnosis:
Average: 4-8 years
Rare cases: Up to 20 years
Risk Factors for AD
Genetics:
- 1% of cases are caused by inherited mutations affecting amyloid-β processing.
- Other genetic factors can increase the risk of sporadic (non-inherited) AD.
Sex:
- Women are twice as likely as men to develop AD.
- This may be due to hormones and lifestyle factors, not just longer life expectancy.
Lifestyle:
Modifiable risk factors include:
- Diabetes
- Obesity
- Depression
- Smoking
- Low education levels
Amyloid-B Oligomers and Plaques
What is Aβ?
- A small protein fragment formed by cleavage of a larger protein called amyloid precursor protein (APP) in neuron cell membranes.
How does Aβ cause damage?
- These aggregates (oligomers) gather at synapses, disrupting communication between neurons.
- Outside neurons, oligomers form Aβ plaques, which:
Activate microglia, causing inflammation and neuronal damage.
Damage brain blood vessel walls, leading to Cerebral Amyloid Angiopathy (CAA).
Tau Oligomers and Neurofibrillary Tangles
What is Tau?
- A protein that binds to microtubules, which are key for transporting cargo (vesicles, mitochondria) along axons.
- Helps stabilize microtubules for proper neuron function.
How does Tau cause damage in AD?
- In Alzheimer’s Disease, Tau misfolds and binds less strongly to microtubules.
- This causes microtubules to break down, disrupting neurotransmission.
- Misfolded Tau forms oligomers, which then clump together inside neurons as neurofibrillary tangles (Tau tangles).
Why is this harmful?
- Tau oligomers and tangles are toxic to neurons.
- Misfolded Tau can spread to other neurons, causing more misfolding and worsening brain damage over time.
Amyloid Cascade Hypothesis
The amyloid cascade hypothesis is the leading theory explaining the development of Alzheimer’s disease (AD).
- It proposes that misfolded amyloid-β (Aβ) proteins accumulate in the brain, setting off the disease process.
- These Aβ deposits disrupt neuron function and trigger inflammation, leading to brain damage.
- Over time, tau proteins misfold, forming neurofibrillary tangles that further harm neurons and worsen the condition.
Progression of Amyloid - B Oligomer and Plaque Formation
- Aβ Production – Amyloid-β (Aβ) is produced when amyloid precursor protein (APP) is cleaved in neuron membranes.
- Synapse Disruption – Aβ oligomers accumulate between neurons and interfere with synaptic function.
- Plaque Formation – Aβ oligomers clump together into plaques outside neurons, further disrupting their function.
- Inflammation Activation – Aβ plaques trigger microglial cells, causing an inflammatory response that damages neurons.
- Tau Tangles Develop – Inside neurons, misfolded tau proteins form neurofibrillary tangles, displacing cell structures.
- Tau Spreads – Misfolded tau spreads to neighboring neurons through synapses, causing more tau misfolding and worsening the disease.
Progression of AD
Early Stage:
- A D starts in or near the hippocampus, a brain region crucial for memory and spatial navigation.
- Memory loss and difficulty recalling recent events are common early symptoms.
Middle Stage:
- The disease spreads to larger areas of the cerebral cortex, leading to more extensive neuron damage.
- Amyloid-β plaques and tau tangles increase, causing cognitive decline, confusion, and difficulty with daily tasks.
Late Stage:
- Progression from mild to severe A D takes several years.
- Extensive brain damage results in severe memory loss, loss of communication abilities, and complete dependence on caregivers.
Cognitive Function Decline in AD
By the time symptoms of Alzheimer’s disease (A D) are noticeable, significant pathological changes have already occurred in the brain.
- Amyloid-β plaques begin accumulating early, often 10-15 years before diagnosis, signaling the start of disease progression.
- Tau tangles typically develop later, closer to the onset of cognitive symptoms and neurodegeneration.
- When noticeable cognitive decline occurs, it is referred to as mild cognitive impairment (M C I), which often precedes
Neurodegeneration With AD
- Cerebral Cortical Atrophy: The outer layer of brain cells, known as the cerebral cortex, shrinks due to neuronal damage, leading to a decrease in the brain’s overall size and weight.
- Enlarged Ventricles: The brain’s fluid-filled spaces, called ventricles, expand as brain tissue degenerates. This process is known as ex-vacuo hydrocephalus.
- Hippocampal Atrophy: The hippocampus, the region where early Alzheimer’s changes begin, progressively shrinks as the disease advances, due to neuronal death.
Neurological Examination
Nerve Conduction Study:
- Measures how well electrical signals travel through nerves using electrodes on the skin.
- A weak response may indicate nerve signal transmission issues.
Electromyography (EMG):
- Involves inserting a needle into a muscle to measure electrical activity during movement and rest.
- Helps assess muscle and nerve function.
Genetic Testing:
- Uses a blood sample to check for hereditary neuropathies through DNA analysis.
Charcot-Marie-Tooth Disease (CMT)
Cause: Genetic Disease that affects the PNS.
Onset & Symptoms: Typically begins in childhood with progressive muscle weakness and atrophy, starting in the legs and causing difficulty running.
Progression: Leads to reduced or absent muscle reflexes and mild sensory deficits.
Prognosis: Slowly progresses but does not affect lifespan.
CMT Type 1
Also Known As: Demyelinating neuropathy.
Cause: Mutation affecting Schwann cells, leading to impaired myelination.
Effects on Nerve Conduction: Slower signal transmission due to demyelination.
Symptoms:
Begins in childhood with weakness and atrophy in the lower legs.
Progresses to hand weakness and sensory loss later in life.
Can cause foot and leg deformities.
Progression: Slowly worsening over time.
CMT Type 2
Also Known As: Axonal neuropathy.
Cause: Mutation leading to degeneration of neuronal axons.
Effects on Nerves: Loss of nerve supply to muscles, causing muscle atrophy.
Symptoms:
Similar to CMT1 but often milder.
Progressive weakness and atrophy, primarily in the legs.
Less severe sensory loss and disability.
Onset: Typically begins in childhood or adolescence.
