Overview 3 Flashcards
Most common form of dementia is?
AD
Four non-modifiable risk factors for dementia are?
Age
Genetics
Family history
Down syndrome
Greatest risk factor for onset of dementia is?
Age
Four modifiable risk factors leading to dementia?
Vascular - cholesterol, hypertension
Cognitive inactivity
Environment - head injury
Depression
Two protein components that are characteristic of AD are?
Beta-amyloid plaques
Neurofibrillary tangles of protein Tau
Significant loss of what cells occurs in the brain of someone with AD?
Loss of cholinergic cells
Genes causing early onset AD? x3
APP
PSEN1
PSEN2
APP is on which chromosome?
21
PSEN1 is on which chromosome?
4
PSEN2 is on which chromosome?
1
Why are those with Downs syndrome more susceptible to the development of AD?
Three lots of chromosome 21 - more chance of mutation of APP gene
Function of PSEN proteins?
Cleavage of APP
APP stands for?
Amyloid precursor protein
APP expressed in which cells? x4
Neurones
Glial cells
Endothelial cells
Smooth muscle cells
Number of mutations in APP that are possible?
29
APP mutation that is protective of AD is?
A673T
PSEN1 and PSEN2 are subunits of what?
Gamma-secretase
PSEN1 and PSEN2 - which is common and which is rare?
PSEN1 - common
PSEN2 - rare
What is the type of mutation that occurs in PSEN2?
Missense
What are the three different secretase enzymes that can cleave APP protein?
Alpha-secretase
Beta-secretase
Gamma-secretase
Two possible amyloid pathways are?
Amyloidogenic
Non-amyloidogenic
Which of the amyloidogenic pathways are pathological?
Amyloidogenic
Secretase enzymes involved in the non-amyloidogenic pathway is? x2
Alpha-secretase
Gamma-secretase
Secretase enzymes involved in the amyloidogenic pathway is? x2
Beta-secretase
Gamma-secretase
Toxic species generated from the amyloidogenic pathway is?
Oligomers
Why are oligomers dangerous?
These are neurotoxic
Inflammatory response occurs in AD - what cells are activated?
Microglia
Activated microglia release what component?
TNF-alpha
Why are oligomers toxic?
Can signal to normal beta-amyloid protein to misfold itself and adopt the mutated form of beta-amyloid that is formed from the amyloidogenic pathway
Gene resulting in development of late onset AD is?
Apolipoprotein E
Apolopoprotein E found on which chromosome?
19
Early onset AD occurs at what age?
40-50 years
Late onset AD occurs at what age?
60+ years
Three isoforms of ApoE are?
ApoE2
ApoE3
ApoE4
Isoform of ApoE causing development of late onset AD is?
ApoE4
Isoform of ApoE that is protective to the development of AD is?
ApoE2
Tangles of what form in AD?
Neurofibrillary tangles of the protein Tau
Normal function of Tau is?
Stabilisation of microtubules to ensure neurones receive the correct components e.g. ATP required for their function
Consequence of hyperphosphorylation of Tau?
Causes Tau to dissociate off of the microtubules
What is the gene that encodes the protein Tau?
MAPT
Are mutations in the MAPT gene associated with the development of AD?
No
Looking at CSF - what will be seen in someone with AD?
Less amyloid present in the CSF
Amyloid is accumulating in the brain as plaques
MRI scan for diagnosis for AD will show?
Neuronal loss - cortex and hippocampus
Enlarged ventricles
Loss of what neurones in AD?
Cholinergic
How can the cholinergic effects of AD be treated?
Administer acetylcholinesterase inhibitors
Name three acetylcholinesterase inhibitors
Donepezil
Rivastigmine
Galantamine
Don’t Rivers Galantamine
Contraindication of AChE inhibitors in patient - what drug might be used?
NMDA receptor antagonists
Indication for use of AChE inhibitors vs. NMDA receptor antagonists?
AChE inhibitors - mild to moderate AD
NMDA receptor antagonists - moderate to late disease
NMDA receptor antagonist main one used is?
Memantine
Why are NMDA receptor antagonists used to treat AD?
Some form of excitotoxicity occurs in AD and this prevents htis
Nucleus that controls the sleep wake cycle i.e. circadian rhythm is?
Suprachiasmatic nucleus
Suprachiasmatic nucleus is located where?
Hypothalamus
Two neuronal systems involved in wakefulness are?
Cholinergic systems
Monoaminergic systems
Neuronal system involved in sleep is?
GABA
One sleep cycle lasts how long?
90 minutes
What are the three stages of the sleep-wake cycle?
REM
NMREM
SWS
What is SWS in the sleep-wake cycle?
Slow wave sleep
Function of sleep on memories?
Consolidation of memories
Three forms of insomnia are?
Transient - jet lag
Short term - illness
Chronic - underlying cause
Two drugs used to treat insomnia are?
Benzodiazepines
Z-drugs
Main difference between benzodiazepines and z-drugs?
Benzodiazepines - long half life - not good for short period of sleep
Z-drugs - short half life
Benzodiazepines/z-drugs - which is more popular for treatment of insomnia?
Z-drugs (short half life)
Unwanted side effects of benzodiazepines? x5
Change in sleep patterns Daytime sedation Insomnia Tolerance Dependence
Why should prolonged usage of hypnotics be avoided?
Dependence
Treatment for chronic insomnia is?
CBT
What is orexin?
Peptide
Where is orexin produced?
Hypothalamus
Two forms of orexin?
A and B
Orexin is also known as?
Hypocretin (1 and 2)
Three functions of orexin?
Arousal regulation
Appetite regulation
Wakefulness regulation
Deficiency in orexins results in?
Narcolepsy
What is narcolepsy?
Excess sleepiness - falling asleep in the day
Anxiety disorders are more common in m or f?
Female
Two neurotransmitters involved in anxiety are?
GABA
Monoamines
Key region in the brain related to anxiety?
Amygdala
Five genes associated with anxiety development?
COMT CCK Adenosine A2 MAOa 5-HT2
Anxiolytic group that is no longer used is?
Barbituates
Four groups of anxiolytics?
Benzodiazepines
5-HT1a agonists
Beta-adrenoreceptor antagonists
SSRIs
Function of barbituates?
Very strong CNS depressants
Four adverse effects o barbituates?
Major drug dependence
Tolerance
Fatal in overdose
Withdrawal syndrom
Key target of most anxiolytic drugs is?
GABAergic synapse
Function of benzodiazepines at GABAa receptor?
Positive allosteric modulators - causes the channel to open more frequently
Function of barbituates at GABAa receptor?
Positive allosteric modulators - causes the channel to open for longer
Function of benzodiazepines vs. barbituates?
Benzo - increase frequency
Barbituate - increase duration
Drug that should be given in a benzodiazepine overdose is?
Flumazenil
Function of flumazenil?
Antagonist at benzodiazepine receptor
Flumazenil - short or long half life?
Short
What is buspirone?
Anxiolytic
Five issues of benzodiazepine use in the elderly?
Psychomotor impairment Increased risk of falls Daytime drowsiness Intoxication Amnesia Depression
Z drugs bind to which subunits of GABAa receptor?
Alpha subunit
Z drugs bind to which subunits of GABAa receptor for hypnotic purpose?
alpha-1
Z drugs bind to which subunits of GABAa receptor for anxiolytic purpose?
alpha-3
Long term memory involves what region of the brain?
Hippocampus
Two types of long term memory are?
Declarative/explicit
Non-declarative/implicit
Declarative memory is?
Conscious and intentional memory of factual information and experiences
Non-declarative memory is?
Memory acquired unconsciously e.g. skills/behaviours
Two types of declarative memory?
Episodic memory
Semantic memory
Episodic memory is?
Form of declarative memory - going back in time to remember personal events
Semantic memory is?
Recalling general facts and facts about the world e.g. 2+2=?
Is short term memory involved with ‘learning and memory’?
No
Spatial memory is?
Memory responsible fo recording information based on one’s environment and spatial orietnation
Spatial memory involves what part of teh brain?
Hippocampus
Three types of amnesia?
Anterograde
Retrograde
Dissociative
Amnesia is?
Partial or complete loss of memory
Anterograde amnesia is?
Cannot transfer new events into long term memory (Henry M)
Retrograde amnesia is?
Cannot recall events that occurred prior to onset of amnesia
Dissociative amnesia is?
Blocking out critical personal information of a traumatic/stressful nature
Long term potentiation is?
Strengthening of synapses due to repetition
Receptors involved in LTP?
NMDA glutamate
Long term depression is?
Reduction in strength of synapses due to lack of repetition
Definition of consciousness is?
Ability of an individual to react appropriately to a stimuli in the outside world
Consciousness measured via?
Glasgow Coma scale
Part of the brain controlling consciousness is?
Cerebral cortex
EEG shows what?
Activity of neurones in the cerebral cortex
EEG of someone in coma?
No electrical activity
EEG of someone in sleep?
In certain stages - EEG represents that of someone awake and at some points, represents that of someone that is unconscious
Normal sleep is known as which stage of sleep?
Slow wave sleep
Function of slow wave sleep? x3
Increased growth and rejuvenation of the immune system
of the nervous system
of skeletal and muscular systems
REST AND REPAIR
What hormone is secreted during slow wave sleep? x2
Growth hormone
Leptin
Cortisol levels during sleep?
Decreased
Blood pressure during normal/slow wave sleep?
Reduced - nocturnal dipping
Lack/diminished nocturnal dipping indicates what?
Predictor of cardiovascular disease
How many stages are there in sleep?
4 + 1 stage of REM
Stages 1-4 repeat how often?
Every 90 minutes
EEG of REM sleep represents?
EEG of REM is similar to that of someone that is awake
More synchronisation on EEG represents?
Less conscious the individual
Key control centre of sleep located where?
Reticular formation of the PONS
Reticular formation of the pons is regulated by what?
Hypothalamus
Effect of ghrelin on sleep?
Inhibitory action on sleep
Effect of CCK on sleep?
Increases sleepiness
Effect of adenosine on sleep?
High adenosine induces sleep
Effect of caffeine on adenosine?
Caffeine - antagonist at A1 adenosine receptor
Reticular formation located where?
Pons
Why does caffeine effect sleep?
Adenosine - induces sleep
Caffeine - antagonist of adenosine at A1 receptor
Histaminergic neurones located in which nucleus?
Tubermamillary nucleus
Histamine neurones during wake/sleep?
Active during wake
Silent during sleep
Effect of antihistamines on wake/sleep?
Cause drowsiness - histamine is silent during sleep
Diurnal rhythms controlled by which nucleus?
Suprachiasmatic
Reticular formation is key control of what?
Sleep
Cause of narcolepsy?
Lack of orexins
Orexins are found where in the brain mainly?
Posterior hypothalamus
Orexins cause release of which four neurotransmitters?
Acetylcholine
Noradrenaline
Serotonin
Dopamine
Pedunculopontine nuclei neurones project to where?
Thalamus
Nucleus basalis/basal forebrain nucleus contains neurones of which neurotransmitter?
Cholinergic neurons
What percentage of AD patients have sleep disorders?
70%
Serotonin - increase or decrease during sleep?
Decrease
Noradrenaline - increase or decrease during sleep?
Decrease
Acetylcholine - increase or decrease during sleep?
Increase
Acetylcholine activates what two areas of the brain?
Thalamus
Cortex
Lack of memory of dreams is due to lack of production of which neurotransmitter?
Noradrenaline
Amphetamine/cocaine - prevents sleep due to the production of which neurotransmitter?
Dopamine
SSRis interfere with which stage of sleep?
REM sleep
TCAs promote sleep how?
Block histamine H1 receptors
Function of REM sleep? x2
Memory consolidation
Removal of junk and defragmentation of memories
Motor cortex - active or inactive during sleep?
Active
What normally prevents e.g. sleep walking during seep?
Inactivation of LMNs
Inactivation of LMNs during sleep is mediated via which two neurotransmitters?
Serotonin
Dopamine
Unconditioned stimulus is?
Stimulus that already elicits a response e.g. food
Unconditioned response is?
A response that does not need to be learned e.g. salivating to food
Conditioned stimulus is?
Previously neutral stimulus which the individual now responds to e.g. bell
Conditioned response?
Learned response e.g. salivating to sound of a bell
What is the Garcia effect?
Avoid eating certain food/drink due to past unpleasant experience
Theory of tolerance (in classical conditioning) is?
Cessation of conditioned stimulus intake does not break the association of the conditioned response from the conditioned stimulus
What is ‘flooding’?
Place client into a situation which is anxiety inducing but where no harm can come to them
Operant conditioning - what is fixed ratio reinforcement?
Positive/negative reinforcement given after every response
Operant conditioning - what is variable ratio reinforcement?
Reinforcement is not stable and is randomised - most effective
Mortality rate of severe head injury?
25%
Munroe-kelly doctorine states what?
Fixed cranial compartment (skull) - if one of the constituents increase then there is a rise in ICP
Three constituents stated by the Munro-kelly doctorine are?
Brain
CSF
Blood
Equation of ICP and cerebral perfusion?
CPP = MAP - ICP
Effect of increased ICP on cerebral perfusion?
Cerebral perfusion will decrease
Uncus is part of what lobe?
Temporal lobe
Two layers of the dura mater are?
Periosteal layer
Meningeal layer
High ICP - good or poor outcome?
Poor
How is the pain tolerance ratio calculated?
Time in trial 1 (experiment) / time in the baseline (control)
How is the pain intensity ratio calculated?
Mean score in trial 1 / mean score in the baseline
What region of the brain is specifically effected in MS?
Medial longitudinal fasciculus (MLF)
Region responsible for memory relay/transmission prior to storage is?
Fornix
Region responsible for memory storage is?
Hippocampus
Region responsible for memory formation is?
Cingulate cortex
Middle meningeal artery enters the cranial cavity via which foramen?
Foramen spinosum
Uncal herniation occurs where?
Lateral to brainstem
Tonsillar herniation occurs where?
Posterior - by the cerebellar tonsils
Subfalcine herniation occurs where?
Posterior by the cerebellum
What passes through the cribriform plate?
CNI
What passes through the optic canal?
CNII
What passes through the superior orbital fissure? x4
CN III
CN IV
CNV1
CNVI
What passes through the sella turcica?
Hypophysis
What passes through the foramen rotundum?
CNV2
What passes through the foramen ovale?
CNV3
What passes through the foramen lacerum?
Petrosal nerve
What passes through the foramen spinosum?
Middle meningeal artery
What passes through the internal auditory meatus? x2
CNVII
CNVIII
What passes through the jugular foramen? x4
Internal jugular vein
CNIX
CNX
CNXI
What passes through the hypoglossal canal?
CNXII
