dementias Flashcards
what defines dementia?
Syndrome which refers to progressive decline in intellectual functioning (COGNITION), severe enough to interfere with person’s normal daily activities and social relationships.
Dementia mainly affects people over the age of ___________and the likelihood increases with age
Dementia mainly affects people over the age of 65 and the likelihood increases with age
what are the most prevalent forms of dementia?
Alzheimer’s Disease
Vascular Dementia
Lewy Body Dementia
Frontotemporal
what are the rarer forms of demetia
Pre-senile Dementia
Picks Disease
Korsakov Dementia*
Pseudo-dementia*
Endocrine related Dementia*
Parkinson’s Disease
Huntington’s chorea
Posterior cortical atrophy
Normal Pressure Hydrocephalus*
Neurosyphilis*
* are reversible
features of vascular dementia?
Refers to the____________
Early symptoms are ___________ and _________
Often a history of ____________
Stepwise progression
Vascular risk factors usually present (_______, _________, __________)
Refers to the pathology – many different types
Early symptoms are memory difficulties and executive difficulties
Often history of stroke / falls
Stepwise progression
Vascular risk factors usually present (High blood pressure, high cholesterol, diabetes)
features of Lewy body dementia?
Under the umbrella of disease related to _______________
Early symptoms include ________________
Under the umbrella of disease related to Parkinson’s disease
Early symptoms include executive difficulties
Visuospatial problems
Hallucinations
features of frontotemporal demetia?
______frontotemporal______variant
Umbrella term – may different variants including ____picks____, ____semantic ____, _primary progressive aphasia________
The main cognitive deficits are in executive ______difficulties______ and____attention________
____Visuospatial______and _____memory_____abilities mostly spared
what are the Changes in Cognitive Symptoms with Dementia? in relation to perception
PERCEPTION 🡺 the process of making sense of information externally (environment) and internally (your body)
Unable to recognize objects
Unable to judge the position/ location of people/ objects.
Ignoring one side of the world (including oneself, environment)
what are the Changes in Cognitive Symptoms with Dementia? in relation to EXECUTIVE FUNCTIONING
EXECUTIVE FUNCTIONING 🡺 processing of information in order to plan, sequence, make decisions, prioritize, problem-solve and self-monitor
Difficulties with initiating tasks
Getting stuck on tasks/ repeating actions
Not thinking through the consequences of actions
what are the Changes in Cognitive Symptoms with Dementia? in relation to LANGUAGE
LANGUAGE 🡺 understanding information said by others (receptive language) and the process of expressing information (expressive language)
Difficulties understanding (e.g. words, concepts, complex sentences)
Difficulties finding the word
Reduced vocabulary
symptoms of Non-cognitive dementia?
Apathy / Indifference
Disinhibition
Irritability / lability / aggression
Aberrant motor behaviour
Night-time behaviour
Appetite / Eating change
Delusions
Hallucination
Agitation / wandering
Depression / dysphoria
Anxiety
Euphoria/elation
For complete diagnosis of dementia, patients need to show?
Memory impairment
Impairment in one or more of the following cognitive domains (language; motor activity; recognition; executive function)
Continuing cognitive decline
Clinically, one cannot conclusively determine the subtype of Dementia
A range of diagnostic criteria involving different healthcare practitioners
what are they?
Mini Mental State Exam (MMSE)
A series of questions and tests
Tests a number of different mental abilities (memory, attention and language).
what happens in alzheimer’s pathology
Neurofibrillary tangles: rich in cytoskeletal proteins, especially the microtubule-associated protein, “tau”.
In the tangles: heavily phosphorylated proteins,
which may cause aggregation and precipitation of the cytoskeleton.
what are the two major hypotheses for AD
β amyloid protein (BAP) v. tau
BAPtists: The accumulation of a fragment of the amyloid precursor protein or APP (the amyloid beta 42 residue fragment or
Ab-42) leads to the formation of plaques that kills neurons.
TAUists: Abnormal phosphorylation of tau proteins makes them “sticky,” leading to the break up of microtubules. The resulting
loss of axonal transport causes cell death.
DESCRIBE THE AMYLOID HYPOTHESIS?
The amyloid precursor protein (APP) is broken down by a series of secretases.
During this process, a non-soluble fragment of the APP protein (called Aβ-42) accumulates and is deposited outside the cell.
The non-soluble or “sticky” nature of Aβ-42 helps other protein fragments
(including apoE) to gather into plaques.
Somehow the plaques (or possible the migration of Aβ-42 outside the
cell) cause neuronal death.
in TAU hypothesis:
Neurons have an _________structure partly made up of microtubules. A protein called ________ helps stabilize microtubules. In AD, _________ changes, causing microtubules to _______, and ________ proteins clump together to form neurofibrillary tangles.
Neurons have an internal support structure partly made up of microtubules. A protein called tau helps stabilize microtubules. In AD, tau changes, causing microtubules to collapse, and tau proteins clump together to form neurofibrillary tangles.
describe the TAU hypothesis?
Ordinarily, the τ (tau) protein is a microtubule-associated protein that
acts as a three-dimensional “railroad tie” for the microtubule. The microtubule is responsible for axonal transport.
Accumulation of phosphate on the tau proteins cause “paired helical
filaments” or PHFs (like two ropes twisted around each other) that accumulate and lead to the neurofibrillary tangles (NFT). PHFs are the
main component in NFTs.
Impaired axonal transport is the probable cause of cell death.
what are the current theories for AD
Multifactorial, involving several pathways and dependent on life experience 🡺 not all old people get AD
Protein accumulation 🡺 plaques & tangles 🡺 does not explain all the pathology
Inflammation🡺 overactive brain immune cells (microglia)
Oxidative stress 🡺 development of free radicles 🡺 cellular death
what is the features of the first stage of Alzheimer’s disease
Synapse loss occurs first, then neurons die
Changes can begin 10-20 years before symptoms
appear.
Primary early symptom 🡺 deficit in recent memory
Intellectual deficits confirmed by neuropsychological
testing
Some awareness of their symptoms, so the person
may become anxious, depressed and may be in denial
No distinguishing features on physical examination
state features of the second stage of Alzheimer’s disease?
AD pathology (Tau and Aβ) spreads through the brain.
The cerebral cortex begins to shrink as more neurons die.
Significant memory loss (forget close family members
well known routes/places)
🡺 Personality and behavioural changes (self-neglect
🡺 Disorientation in time and space
Inability to undertake simple tasks i.e. dressing
🡺 Reduced range of thinking (intellectual deficits)
🡺 Language problems start
state features of the 3rd stage of Alzheimer’s disease?
Extreme shrinkage occurs in the brain
Patients are completely dependent on others for care.
🡺Dysphasia with disordered and fragmented
speech
🡺Aggression, restlessness and wandering
🡺Hallucinations and delusions
🡺Incontinence
🡺Immobility, rigidity and recurrent falls
🡺General physical deterioration
Death usually occurs from aspiration
pneumonia or other infections.
what are the pharmacotherapeutic approaches for treating AD?
Acetylcholinesterase inhibitors
Glutamate NMDA receptor antagonist
explain why Acetylcholinesterase inhibitors
are used for AD, and what are the examples
Cholinergic basal forebrain neurons are among the first to die in AD resulting in decreased brain levels of Ach
🡺 Tacrine, Donepezil, Rivastigimine, Galantamine
explain why Glutamate NMDA receptor antagonist
are used for AD, and what are the examples
Excitotoxicity (overactvity of glutamatergic synapses) proposed to be part of AD pathology)
🡺 Memantine
what DRUG CLASS is the first line treatment for AD and what does it improve?
Acetylcholinesterase inhibitors
🡺Cognitive function
🡺Behavioural symptoms
🡺Daily activities
which Acetylcholinesterase inhibitor was the first drug to have any therapeutic effect
Tacrine
what is the moa for Tacrine and what are the side effects?
MOA
Long acting AchEI
Blocks M1, M2 and nicotinic receptors
Increases the release of Ach from nerve endings
Inhibit MAO
Increase release of NA, 5HT and DA from nerve endings
SIDE EFFECTS (SIGNIFICANT)
Nausea and vomiting - increased peripheral Ach levels
Hepatic toxicity - life threatening
- Largely superseded by newer AchEIs
what are the Acetylcholinesterase inhibitors for AD treatment?
Donepezil, Tacrine, Rivastigimine, Galantamine
what is the moa for donepezil and what are the indication and side effects ?
Indicated for the treatment of mild-to-moderate AD, but can be used for moderate-to-severe AD
Modest improvements in cognitive and behavioural scores in AD patients
MOA
Reversible centrally active AchEI
SIDE EFFECTS
Nausea and vomiting
Hallucinations, Aggression, Agitation
Urinary incontinence
Gastric and duodenal ulcers
