Neurodegenerative disorders Flashcards
(34 cards)
what are neurodegenerative diseases
ensemble of conditions primarily affecting the neurons in the human brain
frequently culminate in neuronal cell death
what are neurons prone to
o2 lack- 3 mins to death (VASCULAR)
degenerative triggers
-stress
-immuno-sensitive
-toxic aggregates
-trauma
-age
POOR REGENERATIVE POWERS
when is dementia conventionally diagnosed
when progressive cognitive decline has occurs
this has had a noticeable impact upon a persons ability to carry out important everyday activities
defined according to the EXTENT of brain failure
when do the pathological changes of dementia start
likely commenced well in advance to symptoms presenting
(15-30 years)
therefore how do you reverse cell death that has already occurred
define cognition in relation to brain function
what are the 5 DOMAINS of cognition
the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses
- learning and memory
- language
- visuo-spatial function
- executive function
- psychomotor abilities
what are 10 signs of dementia
poor/ decreased judgement
difficulty with simple tasks
problems communicating
misplacing things
dat-to-day forgetfulness
problems with language
difficulty solving problems
confusion of time/place
changes in personality
what is dementia
diagnosis
treatment
chronic
often global
irreversible deterioration of cognition
rule out vascular/tumour cause
but cant differentiate between different kinds of dementia
-lab and imaging
POST MORTEM ONLY DEFINITICE DIAGNOSTIC
lack reliable biomarkers
SUPPORTIVE treatment (no cure/reversing treatment)
CHOLINESTERASE INHIBITORS- temporarily improve cognition
what is dementia
diagnosis
treatment
chronic
often global
irreversible deterioration of cognition
rule out vascular/tumour cause
but cant differentiate between different kinds of dementia
-lab and imaging
POST MORTEM ONLY DEFINITICE DIAGNOSTIC
lack reliable biomarkers
SUPPORTIVE treatment (no cure/reversing treatment)
CHOLINESTERASE INHIBITORS- temporarily improve cognition
what test do you do for frontal lobe
-sequencing, verbal fluency
luria hand sequencing task
verbal fluency 1 minute words
what test do you do for temporal lobes
-memory, speech
address test
object recall
serial 7s (100-7)
what test do you do for parietal lobes
-spatial awareness (R)
-language (L)
clock face
naming objects
drawing cube, interlocking infinity
agnosia (name object with closed eye)
what screening tests are there for detecting dementia
- MINI-MENTAL STATE EXAMINATION (MMSE)
-not good at discriminating (have to be very demented) - ADDENBROOKE’S COGNITIVE EXAMINATION III
-good differentiation between dementia, MCI and controls but not dementia subtypes
what is the difference between sensitivity and specificity
AND MMSE vs ACE III
sensitivity- TRUE POSITIVE
specificity- TRUE NEGATIVE
ace has higher sensitivity and specificity
what is mild cognitive impairment
(grey zone)
cognitive impairment greater than age related impairment
decline in function of 1 or more of the 5 cognitive domains
no ADL impairment
it might progress to dementia
is alzheimers predominant in female or men
and how does it present
female
early memory disturbance
progress to dyspraxia and dysphasia
eventually immobile and mute
what are the signature proteins of AD
(aggregates)
INTRACELLULAR in cytoplasm
-phosphorylated TAU proteins
-neurofibrillary tangles
EXTRACELLULAR
-amyloid plaques
-AB peptides
what are the risk factors of dementia
less education
hypertension
hearing impairment
smoking
obesity
depression
physical inactivity
diabetes
infrequent social contact
(xs alcohol, TBI, air pollution)
12 modifiable risk factors account for 40% of worldwide dementias
–could theoretically be prevented or delayed
what are specific recommended actions to reduce risk of dementia
maintain BP (130 or less)
use of hearing aids- reduce noise induced hearing loss
reduce air pollution exposure, second hand tobacco smoke
reduce head injury
limit alcohol use <21 units a week
avoid smoking
provide primary and secondary education
how do amyloid precursor peptide cleavage patterns determine plaque formation
-Membrane protein processed
in secretory pathway
-Cleaved by secretases
-If beta secretase acts Abeta
fragments with 38-42 amino
acids generated
-Less soluble and aggregate
extracellularly to make
fibrils/plaques
what are some major risk genes associated with AD
in particular familial alzheimers
ApoE4- membrane trafficking
TREM2- recycling
SORL1-sorting
ENDOSOMAL MEMBRAINE TRAFFICKING PROBLEMS
familial forms:
changes in amyloid precursor protein
and presemilin gene
what is the retromer complex
and what happens in AD patients
involved in endosomal protein sorting back to surface for reuse
key components of retromer are depressed in hippocampus of AD patients
–causes mixing of B secretase and APP, aberrant trafficking
this causes AB production and TAU increases
what are some biomarkers
structure:
CT, MRI
functional PET
amyloid PET
tau PET
EXPENSIVE, DONT PROVIDE A SCREENING TOOL
CSF studies- why if cant differentiate and cant treat, why put patient through that
peripheral blood samples- more accessible, promising
MAINLY CLINICAL
Ach and dementia
what drug can you use
marked loss of Ach (mainly responsible for memory and learning defect)
-related to neuronal loss from nucleus basalis of Meynert
DONEPEZIL (most affective in mild-moderate)
MEMANTINE (moderate to severe)
what does MEMANTINE target
glutamate is off target from astrocytes
on extra-synaptic NMDA (glutamate receptors)
stimulate death pathways
so block flow though glutamate channels
affect function of receptors and block death pathways
NMDA receptor antagonists
