Lecture 9.1 Flashcards
(101 cards)
1
Q
What are nootropics?
A
Nootropics are drugs that are used to improve attention, memory, mental alertness, concentration, energy levels, and wakefulness.
2
Q
What are some other names for nootropics?
A
Some other names for nootropics are smart drugs, brain boosters, memory boosters, and neuroenhancers.
3
Q
What are cognitive enhancers used to improve?
A
Cognitive enhancers are used to improve attention, memory, mental alertness, concentration, energy levels, and wakefulness.
4
Q
Besides being prescribed for specific disorders, how else are cognitive enhancers used?
A
Besides being prescribed for specific disorders, cognitive enhancers are also used recreationally by people without a diagnosis to improve cognitive performance.
5
Q
In what ways do cognitive enhancers work?
A
Enhancers work in several different ways and act on multiple body systems, and can sometimes affect multiple systems simultaneously; a key factor is neurotransmitters.
6
Q
What does the research say about how cognitive enhancers work?
A
Research is still inconclusive about how many cognitive enhancers actually work.
7
Q
What are the two broad categories of cognitive enhancement discussed?
A
The two broad categories of cognitive enhancement discussed are enhancing attention with stimulants and enhancing memory with cholinesterase inhibitors.
8
Q
What is 3,4-dihydroxyphenethylamine?
A
3,4-dihydroxyphenethylamine is an inhibitory and excitatory neurotransmitter and hormone.
9
Q
What is dopamine, and where is it produced in the brain?
A
Dopamine is a catecholamine that is produced in the substantia nigra, VTA, and arcuate nucleus.
10
Q
What are the central nervous system (CNS) functions of dopamine?
A
The central nervous system functions of dopamine include reward-mediated behaviour, movement, appetite, mood, and memory.
11
Q
How does dopamine mediate attention?
A
Dopamine mediates verbal fluency, serial learning, sustained and focused attention, and impulse control.
12
Q
What is norepinephrine, and where is it produced?
A
Norepinephrine is a catecholamine that is produced in the pons and medulla, with projections to the hypothalamus and limbic system.
13
Q
What are the CNS functions of norepinephrine?
A
The central nervous system functions of norepinephrine include attention, emotions, sleeping, dreaming, and learning.
14
Q
How does norepinephrine affect attention, energy, and motivation?
A
Norepinephrine affects sustained and focused attention, energy, fatigue, motivation, and interest.
15
Q
Which pathways are implicated in disorders of inattention?
A
Dopaminergic and noradrenergic pathways are implicated in disorders of inattention, such as Attention Deficit Hyperactivity Disorder (ADHD), and also in disorders where stress/cognition is affected, for example, Alzheimer’s disease, depression, and anxiety.
16
Q
How are arousal/focus and inattention related to dopamine/norepinephrine levels?
A
Arousal/focus is related to increased dopamine/norepinephrine, and inattention is related to decreased dopamine/norepinephrine.
17
Q
Can too much dopamine/norepinephrine enhance attention?
A
More dopamine/norepinephrine will enhance attention, but only to a certain extent; too much can lead to a deterioration in cognitive performance.
18
Q
Where does dopamine project to in the brainstem concerning attention pathways?
A
Dopamine projects from the ventral tegmental area in the brainstem to the mesocortical and dorsolateral prefrontal cortex.
19
Q
Where does norepinephrine project to in the brainstem concerning attention pathways?
A
Norepinephrine projects from the locus coeruleus in the brainstem to the prefrontal cortex.
20
Q
What is Attention Deficit Hyperactivity Disorder (ADHD), and when did it first appear in the DSM?
A
Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder of attention that first appeared in the DSM-II in 1968.
21
Q
What is the estimated prevalence of ADHD in Australia and globally for children under 18?
A
The estimated prevalence of ADHD in Australia is 5% of children under 18, and globally, it is estimated to be 2.2% of children under 18.
22
Q
Does ADHD affect boys or girls more?
A
ADHD tends to affect boys more than girls.
23
Q
What are the three main characteristics of ADHD?
A
The three main characteristics of ADHD are inattention, hyperactivity, and impulsivity.
24
Q
What are some examples of inattention symptoms in ADHD?
A
Examples of inattention symptoms in ADHD include often failing to give close attention to details or making careless mistakes, often having difficulty sustaining attention in tasks or play activities, often not seeming to listen when spoken to directly (mind seems elsewhere), often not following through on instructions or failing to finish tasks, often having difficulty organizing tasks and activities (poor time management), often avoiding, disliking, or being reluctant to engage in tasks requiring sustained mental effort, often losing things necessary for tasks, often being easily distracted by extraneous stimuli, and often being forgetful in daily activities.
25
What are some examples of hyperactivity/impulsivity symptoms in ADHD?
Examples of hyperactivity/impulsivity symptoms in ADHD include often fidgeting with or tapping hands/feet or squirming in seat, often leaving seat in situations where remaining seated is expected, often running around or climbing where it would be inappropriate, often being unable to play or take part in activities quietly, often being 'on the go' as if 'being driven by a motor', often blurting out an answer before a question is finished, often talking excessively, often having trouble waiting their turn, and often interrupting or intruding on others.
26
How many symptoms of inattention are needed for a diagnosis of ADHD in children and adults, and for how long must they be present?
For a diagnosis of ADHD, 6 or more symptoms of inattention are needed for children, and 5 or more for adults; these symptoms must be present for at least 6 months.
27
How many symptoms of hyperactivity/impulsivity are needed for a diagnosis of ADHD in children and adults, and for how long must they be present?
For a diagnosis of ADHD, 6 or more symptoms of hyperactivity and impulsivity are needed for children, and 5 or more for adults; these symptoms must be present for at least 6 months and be disruptive.
28
What other criteria must be met for an ADHD diagnosis?
In addition to the symptom counts and duration, several symptoms must be present in two or more settings, all symptoms must be inappropriate for the developmental age, several symptoms must be present before age 12 years, symptoms are not better explained by another disorder, and symptoms interfere with social, school, or work functioning.
29
How does heterogeneity present itself in ADHD?
Heterogeneity in ADHD presents as inattentive (easily distractible or inattentive, but isn't hyperactive or impulsive), hyperactive-impulsive (symptoms of impulsivity and hyperactivity), and combined (mixture of symptoms including hyperactivity, inattention, and impulsivity); symptom presentations can change with age.
30
What is the Dynamic Developmental Theory of ADHD?
The Dynamic Developmental Theory of ADHD posits that dopaminergic transmission is impaired in frontal and limbic circuits, a steeper delay of reinforcement gradient is associated with lower levels of dopamine, less dopamine means it is harder for stimuli to be rewarding, the critical window where reinforcement by dopamine is possible (i.e., while still in the synapse) is narrower, resulting in stimuli losing value quicker, which leads to more stimulus sensation seeking to compensate, and ultimately manifests as inattentive/hyperactive behaviours.
31
What is the Dopamine Transfer Deficit Theory?
The Dopamine Transfer Deficit Theory of ADHD suggests that the dopaminergic system uses previous instances of reinforcement to produce anticipatory dopamine release, baseline levels of dopamine are normal, but the amount of dopamine used in response to reinforcement is altered to the point of being ineffective.
32
What type of medication is most commonly used for ADHD?
Stimulant medication is most commonly used for ADHD.
33
What are some common stimulant medications for ADHD?
Common stimulant medications for ADHD include methylphenidate (Ritalin), dexamphetamine, and mixed amphetamine salts.
34
According to international guidelines, which medication is typically trialed first for ADHD?
According to international guidelines, methylphenidate is typically the first medication trialed.
35
What is the goal of ADHD medication treatment?
The goal of ADHD medication treatment is to provide an effective way to treat symptoms; current medications do not offer a "cure" for ADHD.
36
How do stimulant medications work to treat ADHD?
Stimulant medications work by increasing the availability of synaptic dopamine and norepinephrine.
37
What is the mechanism of action of methylphenidate?
Methylphenidate is a dopamine (DA) and norepinephrine (NE) reuptake inhibitor, blocking DAT and NET, which increases the availability of DA and NE in synapses.
38
What is the mechanism of action of amphetamine?
Amphetamine is a dopamine (DA), norepinephrine (NE), and 5-HT reuptake inhibitor, increasing concentrations by inhibiting VMAT2 and inhibiting MAO; the net result is increased dopamine in the synaptic cleft and reuptake inhibition.
39
What are the administration forms of stimulants?
Stimulants are always administered orally as tablets, and can be short (4h) or long (8h) forms.
40
What are some examples of stimulant medications available in Australia?
Examples of stimulant medications available in Australia include methylphenidate (Ritalin, Concerta) and dexamphetamine (Adderall, Vyvanse, Dexedrine).
41
How long does it take for stimulant medication to take effect, and how long do the effects last?
Effects from stimulant medication are seen within approximately 30-60 minutes of administration and last 4-8 hours.
42
What are some common side effects of stimulant medications?
Common side effects of stimulant medications include appetite/weight loss, gastrointestinal upset, trouble sleeping, headaches, worsening of latent MDD/ANX, and, rarely, delayed growth in the first 2 years of treatment (which normalizes afterwards); effects are dose-related, have individual differences, and resolve when treatment is discontinued or the dose is adjusted.
43
According to Faraone & Buitelaar (2010), how effective are amphetamine-based medications compared to placebo for ADHD in children and adolescents?
According to Faraone & Buitelaar (2010), amphetamine-based medications have robust effects compared to placebo in children and adolescents.
44
According to Faraone & Buitelaar (2010), how effective are methylphenidate-based medications compared to placebo for ADHD in children and adolescents?
According to Faraone & Buitelaar (2010), methylphenidate-based medications have robust effects compared to placebo in children and adolescents.
45
What did parents, teachers, and doctors report regarding the efficacy of stimulant medications?
Parents, teachers, and doctors reported improvement in symptoms with stimulant medications.
46
According to Faraone & Buitelaar (2010), are amphetamine-based medications more or less effective than methylphenidate in treating ADHD in children and adolescents?
According to Faraone & Buitelaar (2010), effect sizes for amphetamine-based medications are statistically, but moderately, greater than those for methylphenidate in children and adolescents.
47
According to Fararone & Buitelaar (2010), what is the Number Needed to Treat (NNT) for amphetamine and methylphenidate?
According to Fararone & Buitelaar (2010), the NNT for amphetamine is 2, and the NNT for methylphenidate is 2.6.
48
What does the NNT of 2-3 for amphetamine and 2.6 for methylphenidate mean in practical terms?
Translated, 2-3 children/adolescents need to take amphetamine, and 2.6 need to take methylphenidate to experience a benefit in improving ADHD-related symptoms.
49
What is the failure probability for amphetamines and methylphenidate in treating ADHD?
The failure probability for amphetamines is 50%, and for methylphenidate, it is 62%.
50
Out of 100,000 treatments, how many amphetamine and methylphenidate treatments are estimated to be wasted?
For every 100,000 treatments, 50,000 of amphetamines and 62,000 of methylphenidate are estimated to be wasted.
51
What does the research say about the efficacy of psychological interventions for ADHD?
There is a relative lack of RCT trials for psychological interventions, with few studies able to investigate the efficacy of psychological treatments in non-medicated children with ADHD.
52
According to international clinical practice guidelines, are non-pharmacological interventions a necessary component to ADHD treatment?
According to international clinical practice guidelines, non-pharmacological interventions are a necessary component to ADHD treatment.
53
What are some examples of non-pharmacological interventions for ADHD?
Examples of non-pharmacological interventions for ADHD include parent training, CBT, social skills training, school-based interventions, and academic interventions.
54
When are psychological interventions useful for ADHD?
Psychological interventions are useful when needing to address environmental/situational factors, when symptoms don't improve with medication, when there are adverse reactions to medications, or when the child is under 7 years of age.
55
What are some key aspects of moving forward with ADHD care and treatment?
Key aspects of moving forward with ADHD care and treatment include ongoing care and treatment monitoring, with the type or extent of treatment likely to change over time.
56
In what circumstances might children no longer require treatment for ADHD?
Children may no longer require treatment as they grow into late adolescence and adulthood if they are symptom-free for more than a year while on medication, are doing better but their dosage has not changed, demonstrate behaviour appropriate despite missing an occasional dose, or have developed a newfound ability to concentrate.
57
What is the best practice for trialing and evaluating interventions in children under 7 years old with ADHD?
The best practice is for psychological, environmental, and family interventions to be trialed and evaluated before pharmacological treatment in children under 7 years old.
58
What is the ultimate goal of ADHD treatment, according to the document?
The goal is to provide an effective way to treat symptoms; current medications do not offer a "cure" for ADHD.
59
What is acetylcholine?
Acetylcholine is an excitatory neurotransmitter.
60
Where is acetylcholine produced in the brain?
Acetylcholine is produced in the basal forebrain, diencephalon, and medulla.
61
What are the CNS functions of acetylcholine?
The central nervous system functions of acetylcholine include motivation, arousal, and attention.
62
How does acetylcholine affect memory?
Acetylcholine affects memory by encoding working and spatial memories by attenuating towards sensory features of stimuli, increases LTP, and modulates hippocampal neurons.
63
From where does acetylcholine project to in the brain concerning memory pathways?
Acetylcholine projects from the basal forebrain and brain stem to the prefrontal cortex (PFC), basal forebrain (BF), thalamus (T), hypothalamus (Hy), amygdala (A), and hippocampus (H).
64
What is dementia?
Dementia is an umbrella term for heterogeneous and progressive neurocognitive disorders.
65
What are the symptoms of dementia as described in the DSM-5 (Major Neurocognitive Disorder)?
Symptoms of dementia, referred to as Major Neurocognitive Disorder in the DSM-5, include significant decline in complex attention (sustained, divided, selective, speed), executive function (planning, decision making, working memory, inhibition, cognitive flexibility), learning and memory (free and cued recall, recognition, semantic and long-term memory), language (object recognition, verbal fluency, grammar), perceptual motor function (visual perception, visuoconstructional reasoning, coordination), and social cognition (recognition of emotions, Theory of Mind).
66
What is the criteria for decline in cognitive ability in dementia?
The criteria for decline in cognitive ability in dementia are that the decline must be a change from a previously higher level of cognitive ability, the deficits must be sufficient to interfere with independence in everyday activities requiring some assistance with activities of daily living, and the cognitive deficits cannot be solely attributed to delirium or another mental disorder (e.g., MDD, SZ).
67
What are the estimated prevalence rates of Alzheimer's Disease in Australia and globally?
The estimated prevalence rates of Alzheimer's Disease are 330,000 individuals affected in Australia and 24 million individuals affected globally.
68
At what age do symptoms of Alzheimer's typically start?
Symptoms of Alzheimer's typically start around 65 years old.
69
What are the neurological symptoms of Alzheimer's Disease?
Neurological symptoms of Alzheimer's Disease include neurodegeneration in the hippocampus, amygdala, hypothalamus, and cortex.
70
What are the cognitive symptoms of Alzheimer's Disease?
Cognitive symptoms of Alzheimer's Disease include forgetfulness, memory loss, and impairment in speech, thought, problem-solving, judgement, and confusion.
71
What are the psychological symptoms of Alzheimer's Disease?
Psychological symptoms of Alzheimer's Disease include irritability, depression, anxiety, anhedonia, and delusions.
72
What are the behavioural symptoms of Alzheimer's Disease?
Behavioural symptoms of Alzheimer's Disease include appetite/weight changes, sleep impairments, and psychomotor changes.
73
What are amyloid-beta plaques, and what role are they implicated in?
Amyloid-beta plaques (AB) are implicated in enzymatic, anti-oxidant, and anti-inflammatory roles.
74
How do amyloid-beta plaques affect neurons?
Levels of amyloid-beta plaques build to toxicity, causing a chain reaction that results in dendritic spine death; the loss of dendritic spines means neurons cannot communicate effectively, and without messages, they cease being functional. 'Use it or lose it' – if neurons have no purpose, they degenerate and die.
75
What are neurofibrillary (Tau) tangles, and what is the function of Tau?
Tau provides flexibility and stability to axons and aids in nutrient transport.
76
How do Tau tangles affect axons?
Levels of Tau build and reach saturation, and the excess forms strands of insoluble, twisted fibres that 'strangle' axons, causing nutrient transport pathways to collapse; without nutrients, the cell dies.
77
What is the Cholinergic Hypothesis of Alzheimer's Disease?
The Cholinergic Hypothesis of Alzheimer's Disease centers around the acetylcholine cycle.
78
How is acetylcholine formed?
Acetylcholine forms when precursors choline and acetyl coenzyme A (AcCoA) interact with the enzyme choline acetyl-transferase (CAT).
79
How is acetylcholine action terminated?
Acetylcholine action is terminated by the enzymes acetylcholinesterase and/or butyrylcholinesterase, which convert acetylcholine back to choline; choline is transported out of the synaptic cleft and into the pre-synaptic neuron via a choline transporter and can be re-used to re-synthesize acetylcholine.
80
How does Alzheimer's Disease affect acetylcholine production and function?
In Alzheimer's Disease, the build-up of neurofibrillary tangles and amyloid-beta plaques interferes with cholinergic neuron function along brain stem and basal forebrain pathways, ultimately resulting in cell death and not enough acetylcholine being produced to be used effectively in cognitive circuits, which impacts memory and cognition.
81
How do most current treatments for Alzheimer's Disease work?
Most current treatments for Alzheimer's Disease boost the availability of acetylcholine by inhibiting its breakdown by relevant enzymes.
82
What are some examples of 2nd generation cholinesterase inhibitors used to treat Alzheimer's Disease?
Examples of 2nd generation cholinesterase inhibitors typically used include Donepezil, Rivastigmine, and Galantamine.
83
Can cholinesterase inhibitors halt or reverse the cell damage caused by Alzheimer's Disease?
There is no evidence that cholinesterase inhibitors can halt or reverse the process of cell damage that causes Alzheimer's Disease.
84
What is the goal of pharmacological treatment for Alzheimer's Disease?
The goal is to provide an effective way to improve memory or at least slow the rate of memory loss; current medications do not offer a "cure".
85
What are acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and what do they do?
Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) are enzymes that break down acetylcholine into choline.
86
How do cholinesterase inhibitors work?
Cholinesterase inhibitors inhibit the breakdown of acetylcholine into choline by AChE and BuChE by binding to either AChE or BuChE, which increases the amount of acetylcholine available in the synapses for neural function.
87
How does Donepezil work?
Donepezil is a selective inhibitor of AChE, and is reversible and long-acting without inhibition of BuChE.
88
How does Rivastigmine work?
Rivastigmine is a selective inhibitor of AChE over BuChE, and is reversible and long-acting in the cortex and hippocampus.
89
How does Galantamine work?
Galantamine inhibits AChE and is also a positive allosteric modulator of nicotinic cholinergic receptors.
90
How are cholinesterase inhibitors administered?
Cholinesterase inhibitors are primarily administered orally as tablets, but sometimes as patches.
91
What are some examples of cholinesterase inhibitors available in Australia?
Australian examples of cholinesterase inhibitors include Donepezil (Aricept), Rivastigmine (Exelon Patch), and Galantamine (Reminyl).
92
When do the effects of cholinesterase inhibitors appear, and how long do they last?
Effects from cholinesterase inhibitors are seen within approximately 4 weeks of administration and last 6-12 months before dosage or medication adjustment.
93
What are some common side effects of cholinesterase inhibitors?
Common side effects of cholinesterase inhibitors include gastrointestinal upset, muscle cramps, lowered blood pressure, insomnia, fatigue, appetite/weight loss, increased risk of falls, and dizziness.
94
According to Lanctot et al. (2003), how effective are cholinesterase inhibitors compared to placebo?
According to Lanctot et al. (2003), cholinesterase inhibitors show robust improvements (9%) compared to placebo.
95
According to Blanco-Silvente et al. (2017), what improvements were seen with cholinesterase inhibitors compared to placebo?
According to Blanco-Silvente et al. (2017), cholinesterase inhibitors showed robust improvements in cognitive function, global symptomology, and functional capacity compared to placebo.
96
According to Blanco-Silvente et al. (2017), were there any differences in neuropsychiatric symptoms between cholinesterase inhibitors and placebo?
According to Blanco-Silvente et al. (2017), there was no difference in neuropsychiatric symptoms between cholinesterase inhibitors and placebo.
97
What did Blanco-Silvente et al. (2017) find regarding all-cause discontinuation and mortality in the active condition?
Blanco-Silvente et al. (2017) found that all-cause discontinuation was higher in the active condition, but mortality was lower too.
98
According to Lanctot et al. (2003), what is the NNT for cholinesterase inhibitors?
According to Lanctot et al. (2003), the NNT for cholinesterase inhibitors is 12.
99
How does the NNT for cholinesterase inhibitors compare to antipsychotics in schizophrenia, antidepressants in major depressive disorder, and interventions to prevent cardiovascular events?
Comparatively, the NNT is 3 for antipsychotics in schizophrenia, 3 for antidepressants in major depressive disorder, and 29-86 to prevent one cardiovascular event.
100
What are the key aspects of moving forward with dementia care and treatment?
Key aspects of moving forward with dementia care and treatment include ongoing care and treatment monitoring; the best-case scenario is that there is some kind of noticeable improvement.
101
