Alzheimer/Dementia tx Flashcards
Neurocognitive disorders
-dementia
-delirium
-amnestic
-others
-major or mild
-primary deficit is cognitive function and are aquired not developmental
-must represent decline from previously attained level of functioning
Neurocognitive domains
-basis for diagnostic criteria
-complex attention
-learning and memory
-perceptual/motor (hand-eye coordination)(praxis)
-executive function (planning)
-language
-social cognition (recognize emotions)
mild neurocognitive disorders
-modest cognitive decline from previous level of performance
-does NOT interfere with independence
-not attributed to delirium episode or other explanation
Major neurocognitive disorder
-significant decline
-interferes with independence
-also not delirium episode or anything else
Subtypes of neurocognitive disorders
-alzheimers
-vascular dementia
-lewy body disease
-also: HIV, Huntington’s, frontotemporal lobar degeneration, traumatic brain injury, prion disease, parkinsons, drug-induced
Evaluation of NCD
-fam hx
-head injuries
-alc/substance use
-depression
-acute illness
-meds
-language impairment
-focal weakness,gait
Differential diagnosis of NCD
-CV
Reversible cognitive decline
-reversible labs
-B12/folate deficiency
-hypothyroidism
-CBC
-electrolytes
-LFTs
-infection (UTI)
-depression (psuedodementia)
-RPR/VDRL - syphilis
-rarely explains sx
-infection may cause delirium presentation w or wo underlying dementia
Drug-induced cognitive impairment
-Drugs with ACB score of 2 and 3
-anticholinergics
-most often: skeletal muscle relaxants, tricyclic antidepressants, bladder antispasmodics, antihistamines (OTC allergy, rx antiemetics)
Alzheimer’s Cognitive decline
-steady decline over time
Vascular dementia cognitive decline
-stepwise decline
-represent cognitive impairment by CV event (stroke)
Lewy Body cognitive decline
-oscillating decline and improvement over time that trends down
Rating scales
-MMSE
-ADAS
-MoCA
-SLUMS
MMSE
-screening exam
-orientation, memory, attention, naming, comprehension, spatial orientation
-change in 3-4 points over 1 year = decline
-max: 30 points
-mild: 26-18
-moderate: 17-10
-severe: 9-0
Alzheimer’s Disease Assessment Scale (ADAS)
-eval severity over time
-11 cognitive items, 10 non-cognitive behavioral items
-scale: 0-70 (high is worse)
-avg decline in alzheimers is 6-11 dec per year
-not used often bc it takes long time
MoCA
SLUMS
Progression of Alzheimer’s type dementia
-cognitive sx
-diagnosis
-loss of independence
-behavior probs
-nursing home placement
-death
-9 years?
Treatment goals
-slow sx and preserve function as long as possible
-newer drugs maybe removing patho but still being studied (not full reversal but reduction of sx)
-tx of psychiatric and behavioral probs may maintain ability to live in one’s own home as long as possible
Options for alzheimer’s tx
-cholinesterase inhibitors
-NMDA receptor antagonist
Cholinesterase inhbitor drugs
-donepezil (Aricept)
-Rivastigmine (Exelon)
-Galantamine (Razadyne)
-donezapil easiest to titrate and qd dosing
cholinesterase inhibitors
-1st line tx
-mild to mod dementia
-donezapil approved for severe and usually preferred
-rivastigmine horrible side effects
NMDA receptor antagonist drugs
-Memantine (Namenda)
-Donepazil/Memantine (Namzaric)
NMDA receptor antagonists
-does not slow or prevent degeneration
-mod to severe only
-not useful in mild
-marginal benefit in alzheimer’s
-usually combo w cholinesterase inhibitors
Tx effect in alzheimers
-similar rate of progression but delayed
Donezapil dosing
-start 5mg qd at bedtime
-inc to 10mg after 4-6 weeks
Donezapil side effects
-GI bleeding (caution w NSAIDs)
-NVD
-bradycardia
-syncope
-insomnia
-weight loss
-P450 2D6 and 3A3/4 substrate
Galantamine dosing
-4mg NID for 4 weeks w breakfast and dinner
-DO NOT give dose > 16mg/day in renal/hepatic impairment
Galantamine side effects
-GI bleeding
-weight loss (warnings)
-NVD
-bradycardia
-syncope
-insomnia
-P4502D6 and 3A4 substrate
Rivastigmine dosing
-BID
-take w meal to minimize GI effects
Rivastagmine side effects
-GI bleeding, weight loss
-toxicity due to not removing previous patch qd (bad NVD)
-esophageal ruptue in one case (restart lower dose therapy if interupted)
-bradycardia
-syncope
-EPS
-insomnia
-no P450 interactions
-not really using this bc side effects
Memantine dosing
-IR tablets only generic available (BID)
-adj dose in CrCl 5-29 ml/min: start 5mg qd x 1week then target dose 5mg BID for IR
Memantine side effects
-caution in seizure pt
-dizziness/HA
-hallucination
-insomnia
-confusion
-constipation
-use w carbonic anhydrase inhibitors and sodium bicarbonate – clearance of memantine reduced 80% if urine alkalinized
-no P450 interactions
Memantine/Donepazil dosing
-if donepazil 10mg only, start 7/10mg qd and inc by 7mg up to 28/10mg qd target
-if memantine 10mg or ER 28mg: switch to 28/10 w dinner qd
memantine/donezapil side effects
-warning for bradycardia and heart block
-inc risk of GI ulceration
-NVD
-bladder obstruction
Combo tx
-cholinesterase + NMDA
-start cholinesterase
-consider NMDA if decline at max dose and pt is mod-severe
-decline very common, drugs only hold it off a couple of months
Key concepts of oral agents
-target dose is highest tolerated
-assess risk/benefit
-do NOT stop suddenly
-consider withdrawal of therapy w progressed sx
-behavioral sx not well managed by drug
Chart
chart
Cholinesterase safety
-donezapil best
-galantamine not bad
-rivastigmine pretty bad
tolerability of memantine
chart
chart
mAb drugs for tx of dementia
-aducanumab (Aduhelm)
-Lecanemab (Leqembri)
-reduce volume of amyloid plaques in brain
Aducanumab and lecanemab
-requires presence of amyloid beta patho prior to initiating tx
-fewer than 10% of people w AD and 15% w MCI would be eligible
-costs $28K/year
Aducanumab and lecanemab side effects
-ARIA
-A: up to 40%, MRI within year of tx and before 7th and 12th dose
-L: up to 30%, need MRI within year os starting and before 5,7,14 doses
Non-pharma options
-cognitive stimulation (problem games)
i think only need to know what meds to avoid
damn
