alzheimers and dementia Flashcards
(22 cards)
Dementia definition
the loss of mental processing ability, communication, abstract thinking, judgment and physical abilities, such that it interferes with daily living
- chronic,progressive disorder
symptoms of alzheimers
- memory lapses of increasing
frequancy - language deficits - word
finding - comprehension -
paraphasia - disturbed/repetitive behaviour
- visuo-spatial deficits
- impaired judgement and
executive functions - effects on social function e.g
confusion, lack of memory,
mood swings, loss of
confidence, loss of life skills
Gross pathology of alzheimer - what parts of brain effected
- loss of nerve cells - brain
appears to shrink - regions affected: frontal
cortex and temporal lobe
(hippocampus, amygdala)
What are the two types of key pathology for AD?
- Extracellular: amyloid plaques,
contain amyloid beta (Ab) - Intracellular: neurofibrillary
tangles (NFTs), contain tau
What is Amyloid hypothesis?
Abeta is a small peptide and monomeric (does around by itself)
This can begin to oligomerise which means it is still soluble but also toxic
These oligomers become bigger and insoluble forming beta-sheets to fibrils - which eventually get deposited as plaques
Where does abeta come from and how
Abeta is cleaved from Amyloid precursor protein (APP)
APP sits in the membrane of the cell and at some point in the lifecycle the Abeta is cleaved from the protein by two enzymes: beta-secretase and gamma-secretase
What ate NFTs?
Build up of Abeta can lead to NFTs
They come from tau proteins - naturally occuring
They are in axons on microproteins and help microtubule stability
These proteins can become abnormally phosphorylated in AD which inhibits tau-tau and tau-tubulin connections
This leads to cytoskeletal disruption and therefore alter protein transport to and from dendrites - leads to neuronal cell death
- strong correletion between sevrity of dementia and number of NFTs in brain
What are the genetic causes of AD?
Two presentations:
- early onset/familial - strong genetic components (as early as 40)
rare and autosomal dominant
- Late onset - sporadic (>65)
mutations in APP
mutations in presenilins (gamma-secretase components)
Environmental causes of AD?
age
Lancet:
- hearing loss
- head injury
- hypertension
- alcohol consumption
- smoking
- social isolation
- physical inactivity
- air pollution
- diabetes
What are the two ways of treating AD?
Only symptomatic treatment
- Acetylcholinerase inhitiors
- NMDA receptor antagonist
Name 3 Acetylcholinesterase inhibitors
- Donepezil: selective AChE inhibition
- Galantamine: selective AChE inhibition
- Rivastigmine: AChE/BuChE inhibition
No delay in disease progression and no change in Abeta
How do NMDA receptors work and give a example
Excessive glutamate release activates NMDA receptors and results in calcium influx
This leads to reactive oxygen species and mitochondrial damage
Can contribute to cell death
NMDA receptor antagonist e.g Memantine - uncompetitive antagonist, no effect on normal NMDA activity
Information about dementia with lewy bodies
Alpha synucleinopathy (as is PD)
- Lewy bodies – round inclusion
bodies in cytoplasm of
neurons
- Substantia nigra and cortex
- Lewy bodies contain alpha
synuclein
- May see amyloid beta
deposits as well (not in
Lewy bodies)
Loss of dopamine and acetyl choline (more so than in AD)
Symptoms
- Fluctuating cognitive functions
- Hallucinations
- Features of parkinsonism –
rigidity and slowness of
movement
- May respond better to
cholinesterase inhibitors than
AD (rivastigmine)
- Movement disorders treated
in similar way to PD
- levodopa for rigidity and
loss of spontaneous
movement
- Severe neuroleptic sensitivity
- Neuroleptic (antipsychotic)
sensitivity could worsen the
motor symptoms
Information about frontotemporal dementia (FTD)
Younger onset (50s)
- Frontal / temporal lobe
affected
- Behavioural variant
- Early decline in social
interpersonal and personal
conduct
- Disinhibitions and
executive functioning
- Semantic (speech) variant
- Gradual and progressive
loss of words and
comprehension
- Recent memory typically
preserved
Pathology
- Pick cells/bodies – swollen
neurons
- Protein inclusions
- Tau / TDP-43
- No Abeta
- Litte benefit of
cholinesterase inhibitors
(relative sparing of
cholinergic neurons)
List the cognitive and non-cognitive symptoms of dementia
Cognitive Symptoms:
- Memory loss
- Lack of concentration
- Disorientated
- Difficulty with speech
Non-Cognitive Symptoms:
- Agitation
- Aggression
- Distress
- Psychosis
What are the most important clinical features for each dementia and AD?
Alzheimers:
- develops after 60
- main symptom is memory loss
Vascular dementia
- cognitive impairment
- patient should be screened for
depression and signs of
psychomotor retardation
Lewy Body dementia
- main symptoms visual
hallucinations and PD like
symptoms
Frontotemporal dementia
- Develops <65
- behavioural (decline in
interpersonal changes in food
preferences)
- semantic and non-fluent
How to talk to a patient with dementia?
V - validate
E - emotional connection
R - reassurence
A - activity
What to use to assess capacity of consent to treatment?
Use the Abbreviated Mental Test Score (AMTS)
- If patient gets 6/10 or less - suggests delirium or dementia
non- pharmacological management of mild-moderate dementia
- Structured group cognitive
stimulation programme - group reminiscene therapy
- cognitive rehabilitation or
occupational therapy to
support daily functional ability
Managment of Alzheimers 1st line
Donepezil
- caution: cardiac conduction
disorders, asthma, COPD…
Galantamine
- Avoid GI obstruction,
urinary outflow obstruction
- severe cutaneous adverse
reactions (SCARs)
Rivastigmine
- stop if patient dehydrated
from prolonged
vomiting/diarrhoea
- less side effects with
transdermal administration
- monitor body weight (if
patient <50kg - more prone to
ADRs)
Management of non-alzheimer dementia (pharmacological) 1st line
Donepezil or rivastigmine
- to patients with mild-to-
moderate dementia with lewy
bodies
Donepezil or Memantine
- to patients with vascular
dementia, if suspected co-
morbid AD, PD dementia, or
dementia with lewy bodies
*Glutamate receptor antagonist : Memantine - caution: epilepsy, history of convulsions
managment of non-cognitive symptoms
Agitation, aggression, distress and psychosis
- Antipsychotics: increased risk
of stroke amd small increase
of death when used in elderly
dementia patients
use at lowest effective dose
for shortest time possible
Depression and anxiety
- Cognitive behavioural therapy
(CBT)
Sleep distubances
- sleep hygiene education,
exposure to daylight,
increasing excersice and
activity
