Alzheimers Dementia Flashcards
What are the diff severity of Alzheimer’s dementia?
Mild cognitive impairment
Mild Alzheimers
Moderate Alzheimers
Severe Alzheimers
Where do these types of alzheimers dementia spread to?
Mild cognitive imapriment: medial temporal lobe of the brain
Mild Alzheimer’s = L temporal and parietal lobes
Moderate Alzheimers = Frontal lobe
Severe Alzheimers = Occipital lobe
What are the symptoms of these types of Alzheimers dementia?
Mild cognitive impairment = short-term memory loss
Mild alzheimers = reading probs, poor object recognitiion, poor direction sense
Moderate alzheimers = poor judgement, impulsitivity, short attention span
Severe alzheimers = visual problems
What is the most common form of dementia?
Alzheimers dementia
What are other types of dementia?
Frontotemporal dementia
Dementia with Lewy bodies
Vascular dementia
What are 2 important proteins in ALzheimers?
Beta-Amyloid proteins
Tau proteins
What protein fragment has toxic effect on the neurons if clustered togther disrupting cell-to-cell communication?
Beta-amyloid proteins
What are clusters from larger deposits found in Beta amyloid proteins?
Amyloid plaques
What are proteins found in alzheimers dementia that play a part in internal suport to neurons & transport system?
Tau proteins
Tau proteins change shape and organize themselves into what?
Neurofibrillary tangles
What are lesions in ALzheimers dis?
Neuritic plaques
Neurofibrillary tangles
What are other mechanisms involved in Alzheimers dis?
Inflammatory processes
Dysfunction of neurovasculature
Mitochindtrial dysfunction
Oxidative stress
What is the most essential NT for processing of memory & learning found to be DEC in alzheimers?
Acetylcholine
What are extracellular lesions found in brain & cerebral vasculature?
Neuritic plaques/amyloid/senile plaques
What is the amyloid cascade hypothesis?
Altered apolipoprotein processing —> overproduction of BAP —> plaque formation —> INC neurodegeneration -> neuronal loss -> dementia
What is the glutamatergic hypothesis?
Overactivation of N-methyl-d-aspartate receptors by glutamate, sustained low-level activation of NMDA receptors?
What are the 10 warning signs of alzheimers?
- Memory loss that disrupts daily life
- Challenges in planning/solving problems
- Difficulty completing familiar tasks at home, work, or leisure
- Consution w/ time or place
- Trouble undestanding visual images/spatial relations
- New problems with words in speaking or writing
- Misplacing things and losign the ability to retrace steps
- Decreased or poor judgement
- Withdrawal from work or social activities
- Changes in mood & personality
What are the different symptoms of alzheimers?
Memory impairment
One or more of the ff cognitive disturbances:
- aphasia
- apraxia
- agnosia
- anosmia
- amnesia
What are the diff scoring in mini mental status exam?
25-30: Qnably significant
- clin signs of cog impairments are present, formal assesssment of cog may be valuable
- clin significant but mild eficit likely most demanding activigties of daily living
20-25: Mild
- formal assessment may be helpful to better determine patten & extent of deficits
- signifcant effect may require some supervision, suport, and assistance
10-20: Moderate
- formal assessment may be helpful if there aer other specific clin indications
- clear impariment
- may require 24H supervision
0-10: Severe
- Px not likely to be testable
- marked impairment
- likely to require 24H supervision & assistance
What are potentially safety issues of dementia?
Ambulation
Dizziness
Independence
Wandering behavior
Agitation
Manage finances
Driving
Level of superision
What are therapeutic objectives in txing dementia?
To delay the progession of the disease
To improve behavioral symptoms
To identify supportive measures applciable to the px
What are non-pharmacological measures of dementia?
Px and caregiver support
Psychotherapy => behaioral, reality orientation, interpersonal
Alternative therapies => aromatherapy, art activities, gardening, dance/music, pets
What are diff pharmacolgoical tx for dementia?
Cholinesterase inhibitors
- RIvastigmine oral or patch
- Donepezil oral
- Galantamine
NMDA receptor antagonist
- Memantine
What are the diff management of non-cognitive symptoms of dementia?
Evalute for sleep disturbanec if present
Treat psychosis and agitation
Assess and tx depressio
What is lola G’s tx?
Mild: AChEIs
Moderate: Combination of cholinesterase inhibitors (ChEIs) + Memantine
Severe: Memantine, add an approved ChEI as needed
What hypothesis says that there is progressive loss of neurons resulting in marked DEC in choline acetyltransferase & other markers of cholinergic activity?
Cholinergic deficiency hypothesis
What is the first-line agent for tx of mild-moderate Alzheimers dis?
Acetylcholinesterase Inhibitors
What are significant AEs of Cholinesterase Inhibitors?
Common: Nausea, vomiting, diarrhea, anorexia
INC risk of falls & fracutres
What is a long-acting CjEI and muscarinic modulator that is the 1st drug shown to have benefit in ALzheimers?
Tacrine
Why is Tacrine no longer used and is now replaced by newer ChEIs?
Hepatic toxicity
WHat are newer ChEIs?
Donepezil
Rivastigmine
Galantamine
What are the diff AEs of newer ChEIs?
Nausea
Vomitng
Diarrhea
Weight loss
Loss of appetite
Muscle weakness
What is the PD of Donepezil?
Selective reversible non-competitve inhibitor of AChE
What is a significant AE of Donepezil?
Vivid dreams or nightmares
What is the PD of RIvastigmine?
Pseudoirreversible inhibitor of AChE & BChE
What is the meaning of pseudo-irreversible?
No covalent bond formed by mimics action of the other drugs
WHat is the PD of Galantamine?
Reversible inhibitor of AChE
Presynaptic modulator of nicotinic AChE
What is the diff betw R & irreversible inhibitors in terms of type of bonds with enzyme, removal, activitity restoration?
Irreversible inhibitors
- Type of bonds w/ E: inhibitors bind COVALENTLY with enzyme
- Removal: CANNOT BE REMOVED by dialysis or other way
- Activity of restoration: PERMANENTLY MODIFY active sitre residues -> enzymes becomes inactive
REversible Is
- Type of bonds w/ enzyme: inhibitors bind NONCOVALENTLY
- removal: removed by dialysis
- Activity restoration: removal of inhibitor RESTORES enzyme activity
What are common drug interactions of diff drugs & its effects w/ DONEPEZIL?
Ketoconazole = inhibit metab of Donepezil
Risperidone = worsening of extrapyramidal symptoms
B blocker = protentiate bradycardia
What are common drug interactions of diff drugs & its effects w/ Rivastigmine ?
Haloperidol = exacerbation of EPS
Tobacco = INC clearance of rivastigmine by 23%
What are other precautions of cholinergic agents?
- can reduce seizure threshold (those w/ hx)
- msucle cramps & weakness
- taking NSAIDs is no no
- Asthma & COPD can be exacerbated
What drugs are given for moderatre to severe cases?
NMDA antagonist
What is the Glutamate hypothesis of cognitive deficiency
NMDA receptor is coincidence detector and allows inflow of ions
What are NMDA receptor antagonists?
Memantine - main
Ketamine
AMantadine
What are soluble forms of Abeta & Tau working idnependtly & accumulate into plaques & tangles?
NMDA rceptors
WHat are factors that afffect NMDA receptor signalling?
Glutamate availability
Modulaltion of channel
What are important AEs of NMDA receptor antagonist?
Dizziness
Headache
What NMDA antagonist reduces abnormal activation of glutamate neurotransmission?
Memantine
What is the PD of Memantine?
Inhibits prolonged influx of Ca ions
What re comon side effects of ChEIs?
Nausea
Vomiting
Diarrhea
Weight loss
Loss of appetite
Muscle weakness
Vivid dreams/nightmares
What are common symptoms of NMDA receptor antagonist/Memantine?
Dizziness
HEadaches
Cosntipation
COnfusion
What are other issues of treatment?
Vitamin E = harmful in higher doses
NSAIDs
Statins & insulin sensitizers
Lecithin or Acetyl L-carnitine
