WEEK 8 NEUROLOGICAL DISEASES Flashcards
What is the second leading cause of death for Australians?
Dementia
In 2020 how many Australians are living with dementia?
459, 000 Australians, and 50 million worldwide
What is the ADNeT registry?
- the backbone (spine) of the dementia research project
- Clinical quality registry for persons newly diagnosed with dementia or Mild Cognitive Impairment (MCI)
What is the estimated percentage of dementia among people aged 65 and over?
10%
What is the estimated percentage of dementia among people aged 85 years and over?
30%
In which settings might a person receive diagnosis work up and assessments for dementia?
General practice, memory clinics, other Hospital outpatient clinics, hospital inpatient wards, private specialists including geriatricians and neurologists, aged care assessments, residential aged care facility
What are some of the early signs of dementia?
- Confusion
- Forgetfulness
- Memory loss
- Impact language use.
is a dementia diagnosis done with a combination of different assessments or just one?
- Combination of different assessments
- This is to assess cognitive capabilities e.g. mini mental state exam in a memory clinic for example
What does ADNeT mean?
- Australian Dementia Network Registry
What are clinical quality registries (CQR)?
- Organisations which systemically monitor the quality (appropriateness and effectiveness) of healthcare, within specific clinical domains, by routinely collecting, analysing and reporting health – related information.
What are three benefits of clinical quality registries?
- Driving continuous improvements in patient-centred health care and outcomes.
- Improving the value of healthcare.
- Contributing to the sustainability of healthcare systems.
What did the Framework for Australian clinical quality registries develop?
- A prioritised list of clinical domains for clinical quality registry development
What is ADNeT collecting data for, that will hopefully change the standard of care?
- Dementia
What is the vision of ADNeT?
- To incorporate all diagnostic settings and services for dementia in Australia, and register the entire population of persons newly diagnosed with either dementia or MCI, and in doing so, systemically drive improvements and quality of care and patient outcomes.
What is the primary aim of ADNeT?
- To collect and analyse data to monitor and enhance the quality of care and patient outcomes for people diagnosed with dementia or MCI.
What is the secondary aim of ADNeT?
- To facilitate recruitment of participants into research projects, and establish a resource to facilitate further study into the risk factor for, and trajectory of dementia and MCI in Australia
What are the three different types of data collection source for the CQIs?
- Participating sites (Patient demographic information, and baseline and follow-up clinical data)
- Registry participants and carers (if appropriate, and only following recruitment into the registry)
- Linkage with administrative datasets (information on aged care, hospitilisation etc)
What is the primary endpoint from the ASPREE study?
- Death from any cause OR incident dementia OR persistent physical disability
What were some examples of the secondary endpoints for the ASPREE study?
- cancer, cardiovascular events, death from any cause, dementia, depression, major hemorrhage, mild cognitive impairment.
What is a heart failure hospitaliation endpoint defined as for the ASPREE study?
- Unplanned admission to hospital for greater than 24 hours where heart failure was the primary reason for admission
What is the dementia endpoint defined as in terms of the ASPREE study?
- Adjudicated from 3MS, pharmacological and diagnosis data
What % of the body’s energy at rest does the brain use?
- 20%
What is the cerebral cortex responsible for?
Sensing, thinking, learning, emotion, consciousness, and voluntary movement.
What is the amygdala responsible for?
Part of the limbic system involved in emotion and aggression.
What is the cerebellum responsible for?
- Structure that coordinates of thigh muscle movement in balance
What is the hypothalamus responsible for?
Part of the limbic system involved in learning and memory
What is the medulla responsible for?
Regulating largely unconscious functions such as breathing and circulation.
Approximately how many neurones does the adult human brain contains?
- Approximately 86.1 billion with 16.3 billion in the neocortex.
How many synapses are contained in the neocortex, and how many synapses does each neuron receive?
Estimated 164 trillion synapses in neocortex, with each neuron receiving b/w 7,200 and 80,000 synapses
At what time in development does the fetal brain resemble that of an adult brain?
- 9 months (at birth)
What does the ectoderm form?
- Nervous system and skin
What does the mesoderm form?
- Musculoskeletal, vascular and lymphatic systems, kidney and gonads.
What does the endoderm form?
- Gastrointestinal tract, glands, lung, liver, pancreas.
What occurs at the gastrula stage?
- Differentiation of cells information into three germ layers.
What are the three main steps in the formation of the neural tube?
- The notochord forms from mesoderm cells soon after gastrulation is complete.
- Signals from notochord cause inward folding of ectoderm at neural plate.
- Ends of the neural plate fuse and disconnect to form an autonomous neural tube.
What is the notochord?
- A rod like structure in the middle of the embryo that secretes factors that provide position and fate information.
What occurs at the end of week 3 of gestation in terms of the notochord?
- The notochord induces the formation of the neural plate from the ectoderm, which then folds and fuses to form the neural tube
Which week of gestation does the neural tube separate from the ectoderm?
- By the end of week 4
Which two main areas of the brain does the forebrain form at 5 weeks, and which brain structures are these as an adult?
- Forebrain forms the Telencephalon and Diencephalon at week 5
- Telencephalon forms the Cerebrum (hemispheres, cortex, white matter, basal nuclei) at adult
- Diencephalon forms the diencephalon (thalamus, hypothalamus, epithalamus) at adult
Which two main areas of the brain does the midbrain form at 5 weeks, and which brain structures are these as an adult?
- Midbrain forms Mesencephalon at 5 weeks.
- Mesencephalon forms the midbrain (part of brainstem) at adult –> this is a confusing one haha
Which two main areas of the brain does the hindbrain form at 5 weeks, and which brain structures are these as an adult?
- Hindbrian forms the Metencephalon and Myelencephalon at 5 weeks
- Metencephalon forms the Pons and cerebellum at adult
- Myelencephalon forms Medulla oblongata (part of brainstem)
Does layer 1 of the cortex have lots of neurons?
- NO
- Does not have many neurons
What is the organisation of layer 2 and 3 of the human cortex?
- These are packed with neurons!
- Contain small sized neurons which are mainly inhibitory
Are the small sized neurons in the cortex inhibitory or excitatory?
- They are inhibitory
- Exert an inhibitory tone on the excitatory neurons
What do the inhibitory neurons play an important role in?
- Brain development
Which type of neurons are present in layers 4 and 5 of the cortex?
- Excitatory neurons (larger neurons)
What are the 6 general steps of the cellular and molecular processes occurring in neural development?
- Proliferation
- Migration
- Aggregation
- Differentiation
- Circuit formation
- Pruning and programmed cell death.
What occurs in step 1 of the cellular and molecular processes occurring in neural development; Proliferation?
- Cell division to form billions of neurones.
What occurs in step 2 of the cellular and molecular processes occurring in neural development; Migration?
- Movement of neurones from site of birth to Final Destination the brain.
What occurs in step 3 of the cellular and molecular processes occurring in neural development; Aggregation?
- Adhesion of similar cells into specific brain structures.
What occurs in step 4 of the cellular and molecular processes occurring in neural development; Differentiation?
- Neuronal commitment to become a particular type of new one for example inhibitory or excitatory neurones.
What occurs in step 5 of the cellular and molecular processes occurring in neural development; Circuit formation?
- Growth of axons and dendrites followed by synapse formation (synaptogenesis)
What occurs in step 6 of the cellular and molecular processes occurring in neural development; Pruning and Programmed cell death?
- Loss of extra synapses on neurones.
When does pruning and cell death occur, and which condition does this NOT occur in?
- When the synapses are no longer used
- This doesn’t occur in conditions like Autism
What is symmetrical division in terms of neuronal proliferation, differentiation and migration?
- Symmetrical cell division: Progenitor cells are like the parent cells. Neuronal precursor cells can continue to produce many more precursor cells, or they can go and create glial cells (cell proliferation at the ventricular zone).
What is asymmetrical division in terms of neuronal proliferation, differentiation and migration?
Asymmetrical division: two daughter cells produced with different cell fates.
- In this context: Can produce more progenitor cells of neuronal lineage or generate percursor cells that are astrocyte lineage or precursor cells that go onto become oligodendrocytes.
What can neural epithelial cells go onto form?
- Radial glial cells or intermediate progenitor cells that can then go onto form astrocytes, oligodendrocytes or neurones.
What is meant by the “inside out” way of cellular distribution in terms of neuronal proliferation, differentiation and migration?
- Cells that are born first are packed into the deeper layers of the cortex and those that are born last are packed to the dorsal surface of the brain. This is what happens to the excitatory neurons- to form the different layers of the cortex.
Are neuronal progenitors that are born first packed into the deeper layers or the surface?
- The cells that are born first are packed into the deeper layers of the cortex. This is known as the “inside out” way of cellular distribution.
Which type of neuronal cells undergo symmetric cell division and why ?
- NPCs (Neuroepithelial cells)
- This is to produce initial pool of cortical progenitors that will later be ventricular radial glia cells (vRGCs).
Which type of cells undergo asymetrical division?
- vRGCs (ventral radial glia cells)
- This is to generate another vRGC and nascent projection neuron. This will then migrate from VZ radially along the basal process of RGC into cortical plate.
As neurogenesis occurs, what form of cell division are diverse subtypes of neurons generated?
- Through successive asymmetric division of RGCs.
In which areas of the neocortex is tengential migration of interneurons observed?
- MZ (marginal zone), IZ (intermediate zone), SVZ (subventricular zone)
What does the radial scaffold do after the neurogenic stages in the neocortex?
- Radial scaffold detaches from apical surface and vRGCs become gliogenic
- This means they generate astrocytes, or transform into ependymal cells.
What is a reason for tangenial migration?
- There are no RGCs to help the new cells with migration so they migrate in a tangient direction
Does the cerebral cortex contain BOTH inhibitory and excitatory neurons?
- YES
Where are the excitatory neurons of the cerebral cortex born, and where do they end up?
- Born in Ventricular zone (VZ)
- Generate excitatory neurons which migrate to dorsal surface to then be packed down
Where are the inhibitory neurons of the cerebral cortex generated and where do they end up?
- Born in the ganglionic eminence (different migration pattern- migrate to L2 and L3 of cortex- they SWIM!)
- They move tangiently up the cortex from layers 2 and 3
Which type of neurons swim and move tangiently up the cortex from layers two and 3 (inhibitory or excitatory)?
- Inhibitory
Does brain development stop after birth?
- NO
When do synaptogenesis and synaptic pruning mainly occur (before or after birth)?
- Mainly after birth
What are the two main processes of neural development?
- Prenatal development
- Postnatal development
What are the two sub areas of prenatal development?
- Embryonic
2. Fetal
What is characteristic of the embryonic stage of prenatal development in terms of:
- when in pregnancy it occurs
- what arises in that time?
- Occurs within the first 8 weeks of pregnancy
- The primordium of the CNS arises–> development of the neural tube and formation of 3 vesicles
- majority of the congenital abnormalities occur during this period
What is characteristic of the fetal phase of prenatal development?
- Characterised by growth (40x increase in brain weight)
- Appearance of sulci and gyri on cerebral surface
What are the two sub areas of postnatal development?
- At birth
2. Infant
At birth, what does the gross anatomy of the CNS resemble?
- An adult
At birth, are the repertoire of neurons of the neocortex largely established?
- YES
Which three main events occur at the infant stage of postnatal development?
- Massive outgrowth of dendrites and axons
- Synaptogenesis, gliogenesis , myelination.
- Neurogenesis in cerebellum still occurring. I seriously
What are the structural changes that occur in the adolescent brain? (3 things)
- Reduction in grey matter of neocortex- pruning of synapses.
- Increases in white matter- increased myelination and connectivity.
- Axonal sprouting and growth in circuits in the amygdala and cortex.
What are the behavioural changes in the adolescent brain? (6 things)
- Increase social behaviour.
- Novelty in sensation seeking.
- Tendencies toward risk taking.
- Emotional instability
- Impulsivity
- Dominance of peer relationships.
What is the critical period in neural development defined as?
- A period in brain development when neural circuits responsible for a particular process can be sculpted or changed radically by experience or by the environment.
When do the critical periods for cortical regions devoted to vision and other senses open and close in?
- They open in infancy (technically birth but peaks at infancy) and close tightly in mid childhood
When do the critical periods for cortical regions devoted to language and higher concentration open and close?
- Open later than senses (late infancy) and never close entirely
What are the successive waves for sensitivity to learning ideal for?
- Aquiring increasingly complex skills
What is a good example of the critical period?
- If the child has a lazy eye, then you can patch the good eye and try to enhance the stimulation to the lazy eye. BUT once the critical period is over, then you can no longer do this. If children are exposed to new languages in infancy, then they are much more able to pick up languages easily (this closes in childhood). Cognitive function opens up much later in childhood.
What is the definition of NDD?
- Neurodevelopmental disorders
- A group of psychiatric illnesses that is the result of abnormal brain development.
What are the causes of NDDs?
- Deficits in neurogenesis, progenitor cell proliferation, migration, synapse formation and myelination during embryogenesis.
What do symptoms of an NDDs include?
- Disabilities in cognitive, social, motor and affective function.
When is impairment of an NDDs usually detected?
- At birth, during infancy and sometimes adolescence.
Is there both a genetic and environmental components NDDs?
- YES
Are most and NDDs highly heritable?
- YES
- Generally polygenic (de novo mutations of multiple genes)
What are two examples of monogenic NDDs?
- Angelman’s (ubiquitin ligase UBE3A) and Fragile X syndromes (FMRP)
During embryonic and early postnatal development, What does GABA excite (depolarise) postsynaptic targets due to?
- This is due to the HIGH intracellular [Cl-] in the developing brain
What is the GABA induced current crucial for?
- Crucial for generating synchronised patterns of activity of developing networks that are fundamental to the maturation of neuronal circuits.
TRUE OR FALSE: The day synchronisation in spontaneous network activity coincides with increasing influence of sensory experience whereby external signals compete with internally generated activity to shape synaptic connectivity.
- TRUE
Doe GABAergic neurons switch from excitatory to inhibitory at birth, and if so, why is this thought to occur?
- YES
- Thought to PROTECT neurons from hypoxia and ischaemic damage during delivery
What may contribute to NDDs?
- Alterations in the ratio of excitatory to inhibitory cortical activity.