clinical ad Flashcards
what is dementia
an illness of brain resulting in impairments in multiple spheres of cognition
what is the #1 risk factor for dementia
age
T/F : dementia implies an etiology or diagnosis
FALSE
what are some diagnosis barriers for dementia
- patient is typically unaware of symptoms
- evaluation may be time consuming and not well compensated financially
- belief that memory loss and cognitive decline are part of normal aging
- belief by physicians and public that AD is not treatable
about how long is the delay between symptoms and diagnosis with AD
about 2 years
what’s the general path of symptoms that a patient with AD may experience as their disease progresses?
starts with cognitive symptoms, then diagnosis, then loss of function and independence, then behvaior issues, and then potential nursing home placement, then death
give an example of an ability that someone with a 20 MMSE score may start to lose or show signs of having difficulty with.
keeping appointments, using phone, obtaining meal or snack, traveling alone
most alzheimer’s patients die from what? what does not typically cause death with AD?
- being bed-bound/bed sores
- not typically caused by cognitive decline or mental impariments
what is the typical medical causes doctors rule out prior to diagnosing dementia?
alcoholic dementia, vitamin deficiencies, tumors, seizures, MS, infections, brain lesions
approximately what percent of the US population +65 is demented?
13.1 - 5.8million people
Decline in _____ causes someone to go from normal to mild cognitive impairment (MCI). Decline in _______ causes someone to go from MCI to dementia.
- cognition
- function
approximately what percent of the US population 65+ has MCI or dementia
29% - over 12 million people
AD8 screening is used to assess what? what kinds of questions are asked?
-used to assess cognitive impairment by asking family members questions as a checklist that identify if a person could have AD based on how many answers are NO to questions.
- ex. “does your family member have trouble remembering appointments”
Montreal Cognitive Assessment is used for what?
a bedside cognitive screening where patients answer questions of a wide range to test cognitive function and is sensitive to early decline
what’s one downside to the Montreal Cognitive Assessment?
takes about 15 minutes so may be better to break up into pieces
the ROS identifies what main groups to assess dementia?
mood, behavior, psychosis, sleep, physical/motor skillsw
what are some common behaviors with dementia?
- hallucinations/delusions
-abusive/combative behavior
-short term memory loss/repetition - wandering/pacing
- agitation
- wanting to go home
- lethargy/lack of initiative
-rummaging/hoarding
why is behavior a problem with ADRD?
memory is a part of the limbic symstem which is hit early and hard in every neurodegenerative disorder
how early can behavioral symptoms occur? depression? agitation?
-behavioral symptoms occur 3 years before diagnosis in 40%
-depression occurs 2 years before diagnosis in 60%
-agitation occurs 1 year before diagnosis in 80%
what differences do we see in hippocampal size in normal aging vs MCI vs AD at same age (75yr old) compared to a 25yr old
- normal is slightly shrunk but not much
- MCI is significantly shrunk but still has right shape
- AD is warped and almost completed depleted
on a FDG-PET (fluorodeoxyglucose) what do we see different between normal and AD brain scans?
the normal scan lights up but the AD brain does not
what test is typically used to assess AD in the clinical setting?
Montreal Cognitive Assessment (MoCA)
how does an FDG-PET scan work
you are injected a sugary substance that your brain absorbs and activates various parts of the brain where high activity is
regular pet scans utilize what kind of substance to measure pathology in the brain?
radioactive compounds that bind to neurofibrillary tangles and plaques
can amyloid plaques be present in the brain and symptoms of AD not present themselves?
YES – plaques form years prior to any symptoms arising
what is the delay (years) between plaques appearing in HPC and AD diagnosis
15 years
what is one way csf is utilized in AD diagnosis
spinal taps can help to measure abnormal tau proteins in csf to diagnose AD
how are blood markers utilized in AD diagnosis
they measure for abnormal tau proteins in the blood
the Preclivity test using what to identify AD?
blood tests
which two tests can diagnose AD the earliest, and which two tests are only able to detect more severely progressed cases of AD?
earliest- amyloid imaging and CSF amyloid-beta 42 spinal tap
latest- cognitive performance tests and functional decline testing
what takes someone from a prodromal phase to a dementia phase?
functional impairment
describe the 6 step algorithm for dementia and what side steps are taken if signs are shown for alternate causes of symptoms
- memory complaint or other impetus for consult
- neuro exam with “bedside” cognitive eval (if shown normal complete neurophysch eval)
- medical with imaging and lab testing (if medically reversible cause of decline found treat as needed)
- establish diagnosis of dementia
- define type (use additional biomarkers to confirm diagnosis)
- treat type of dementia & related symptoms
describe the 3 main identifiers in AD pathology and if/how they impact nerve cell
-neurofibrillary tangles - kill nerve cell inside out
-neuritic plaque - amyloid build up kills nerve cell from outside in
-cerebral atrophy
describe the process of beta amyloid plaque formation in 3 steps
- APP (membrane-bound glycoprotein) serves as a growth factor in injury and repair but is the amyloid precursor
- APP normally cleaved by alpha-secretase and beta-secretase, but in AD gamma-secretase is active
- b-amylois is toxic to cells and accumulates in brain tissue as amyloid plaques
describe how tau protein causes tangle formation in AD pathology
tau stabilizes microtubules, but when neuron is diseased, microtubules become destabilized and fall apart causing tangled clumps of hyperphosphorylated tau to float in the cell
T/F : neurofibrillary degeneration spreads from nerve cell to nerve cell in all neurodegenerative diseases
true
what was the significance of the study done by De calignon and Liu in 2012?
they added a promotor to abnormal tau to over-express it and better understand the pathology of how it worked in the hpc
what are some main genetic markers that increase toxic amyloid in the brain?
- APP
- ApoE
- PS1
- PS2
APP is linked to familial AD. what kind of genetic effect does it have and how is it passed thru generations
it is an autosomal dominant form of ad and it has a risk of 60% chance of developing AD for those who inherit it
how early can AD arise in familial AD cases?
40s
what is the gene that makes you more likely to develop AD
ApoE E4
whats the chance difference between having one vs two copies of ApoE E4?
one copy -4x more likely than someone without a copy
two copy- 10x more likely than someone without a copy
what are some other potential genetic markers that could impact AD risk outside of the normal pathology?
- cholesterol - APOE, SORL1
- inflammation - CR1, MS4A
- synapse function - PICALM, BIN1
- brain development - EPHA1
what are the 4 main types of dementia? does someone only have just one in every case?
lewy body dementia, vascular dementia, frontotemporal dementia, and alzheimer’s - NO, majority of the time its a mixed bag of all of them
which type of dementia is most prevalent of the 4?
AD - 60%
what pathology do we see in vascular dementia
strokes
what pathology do we see in frontotemporal dementia
tau accumulation tangles
what pathology do we see in alzheimer’s
neurofibrillary tangles, and neuritic proteins
what pathology do we see in lewy body dementia
lewy body bundles form
frontotemporal dementia is associated with what main symptoms
loss of interpersonal skills and language issues
ad is associated with what main symptoms
memory loss and slow progressing symptom appearance
lewy body dementia is associated with what main symptoms
hallucinations and mild parkinsonism
vascular dementia is associated with what main symptom
stroke
what do we see in symptom category impact as the diseases of each types of dementia progress
they start out having higher prevalence in their specific areas, but by the end stages, all categories are equally as impactful
T/F : QMP (quadruple misfolded proteins) are seen in stages prior to dementia
FALSE
T/F : shared mechanisms can cause multiple neurodegenerative disease pathologies to be present in a patient
TRUE
T/F : 1/5 of dementia patients have every form of dementia
TRUE
the __(more/less)__ pathologies accumulated, the greater the risk and severity of cognitive decline
more
final clinical stages of dementia present themselves in what symptom form
mute, fetal-like posture, bedridden, loss of ability to walk, rigidity, seizures, urinary and fecal incontinence
AD is treated based on what?
main symptoms
treating cognitive impairments as the main problem of AD can use what kinds of drugs?
cholinesterase inhibitors or memantine
treating behavioral issues/psychiatric as the main problem of AD can use what kinds of drugs?
SSRI, antipsychotic, mood stabilizing anti-epileptic
treating motor issues as the main problem of AD can use what kinds of drugs?
carbidopa levodopa, DA agonist
what happens with acetylcholine production in severe stages of AD
production decreases
how does the cholinergic pathway relate to dementia treatment
some cases can be treated via neurotransmitter replacement therapy in the cholinergic pathway to increase acetylcholine production
memantine acts via ________ receptors found widespread through the _______
glutamate, cortex
how does memantine work to enhance cognition?
it silences the background noise of receptors and neurotransmitters binding to all for the signal to be heard/identified for memory formation
T/F : Treatments of AD can improve symptoms and longevity
FALSE - treatments currently can not impact longevity, all AD patients still die
which treatment of the following improves symptoms most efficiently:
a. no treatment
b. AChEI’s
c. AChEI + memantine
C. AChEI + memantine
what drug was pulled from the market despite being FDA approved and why?
ENGAGE and EMERGE was pulled bc no one would pay for it and it had 41% of subjects develop swelling/strokes/bleeding and 25% had worsening AD symptoms
what drug was created at UK and impacts clinical outcomes currently? What is the downside of this medication
Lecanemab - only removes amyloid so for cases when amyloid isn’t the only pathology causing the disease progression
lecanemab impacts CDR-SB which leads to potentially ________?
buying patients 1.5 more years of life for every 4 years of treatment
how can antibodies catch amyloid and impact levels of risk?
- they may recognize monomers - safest
- they may recognize oligomers - increase risk but increase benefit
- recognize plaque - highest risk but most likely to remove plaque
amyloid from plaques impact blood vessels in what way?
they can clog vessels