Pharmacotherapeutics of Geriatric Dementias Flashcards
True or False: Alzheimer’s dementia (AD) is the most common cause of dementia.
True
What is the second most common type of dementia?
Vascular dementia
True or False: the prevalence of vascular dementia increases linearly with age.
True
What are the four major anatomical changes that occur in Alzheimer’s Dementia?
- Neurofibrillary tangles
- Amyloid plaques
- cortical atrophy
- Degeneration of cholinergic and other neurons
Describe Acetylcholine imbalance in Alzheimer’s disease
Normal Pt: balanced Ach and Dopamine
Alzheimer’s Pt: loss of choline-acetyl transferase (synthesizes Ach) and loss of cholinergic neurons
What are the risk factors of Alzheimer’s Dementia?
-age: young (15-19) or old (>40), small head/brain, head trauma, family history, low level of education, vascular disease risk factors (smoking), mild cognitive impairment
What is Mild Cognitive Impairment (MCI)?
Categorizes people with cognitive issue insufficient to warrant dementia diagnosis.
-can possibly develop into AD
What does MMSE stand for? What are the categories for it?
- Mini Mental State Exam
- mild, moderate, severe
Mild MMSE
- score 21-26
- difficulty remembering events
- Can still complete ADLs and even IADLs
- may get lost while driving
Moderate MMSE
- score 10-20
- Requires assistance with ADLs
- severe impairment of event recall
- functional fluctuation, may be suspicious
Severe MMSE
- score 0-9
- lost ability to speak, walk and feed self
- incontinence of urine and feces
- needs 24/7 care
True or False: Genetic link of AD accounts for a majority of cases
False, it accounts for a minority of cases
Which proteins are involved in the AD genetic link?
- Beta-amyloid
- Apolipoprotein E (Apo E2, 3, 4)
- Tau
How does Beta-amyloid function in AD?
overproduction linked to alterations in chromosomes 1, 21, or 14
-associated with early onset and senile plaques
How does Apolipoprotein E function in AD?
Mutations associated with chromosome 19
-associated with neurofibrillary tangles and late onset AD
How does Tau function in AD?
- soluble protein that supports microtubule function
- mutations in chromosome 17 associated with PD (not with AD)
- hyperphosphorylated tau associated with neurofibrillary tangles
AD presents as _____ deficits that occur ______ over time
- cognitive deficits
- progressively over time
What are the major symptoms of AD?
cognition: memory loss, apraxia (diff. motor movements), agnosia(can’t identify objects or people), disorientation, impaired executive function
Neuropsychiatric: depression, psychotic symptoms, behavioral disturbances
Functional: impaired ADLS and IADLs
What is used for AD diagnosis?
- DSM-5 criteria
- extensive neuropsychiatric testing to indicate progressive cognitive decline
- neuroimaging and serological testing to rule out other causes of cognitive decline
What are the pharmacological options for AD?
- Cholinesterase inhibitors (Donepezil, Rivastigmine, Galantamine)
- NMDA antagonist (Memantine)
- Biogen’s Aducanumab (new therapy)
MOA, dosage forms, and administration of Donepezil (Aricept)
- inhibits AChE
- oral tablets, ODT
- Administer at bedtime without regard to meals
- used for mild, moderate, and severe AD
MOA, dosage forms, and administration of Rivastigmine (Exelon)
- inhibits both AChE and BChE (butyrylcholinestrase)
- available in capsule or patch
- Used for mild, moderate and severe AD
- In severe cases, use patch; dosing of patch is the same as in mild to moderate case
- administer with meals; place patch on upper or lower back
- starting dose not clinically effective
- conversion: if oral dose is less than 6 mg, use 4.6 mg patch; if greater than or to 6 mg, use 9.5 mg patch the next day
- Cautious titration for CrCl less than 50 ml/min
MOA, dosage forms, and administration of Galantamine (Razadyne)
- AChE inhibitor; also stimulates nicotininc acetylcholine receptors (nAChRs); may increase glutamate and serotonin
- used for mild to moderate AD
- IR tablets, ER capsules, oral solution
- starting dose not clinically effective
- can be used off-label for severe AD
- renal adjustment for CrCl 9-59 ml/min; don’t use if less than 9 ml/min
- IR or solution with breakfast and dinner; ER with breakfast
MOA, dosage forms, and administration if Memantine (Namenda)
- NMDA antagonist/modulator (not complete antagonist; type of glutamate receptor)
- Used for moderate to severe AD
- tablet, ER capsule, oral solution, combination package
- admin without regard to meals; ER swallowed whole or contents sprinkled in applesauce
What is the current state of approval of Biogen’s Aducanumab (Aduhelm)?
- FDA advisory committee unanimously rejected drug
- accelerated approval granted based on endpoint (reduced amyloid beta plaque) and not clinical efficacy
- post approval trials must demonstrate clinical benefit
Biogen’s Aducanumab MOA, dosage form(s), admin, ADRs, and pricing
- Used for MCI or mild dementia
- IV admin
- diluted in 0.9% sodium chloride and infused over 1 hour every 4 weeks for a year
- $56,000 per year
- ADRs: brain edema, headache, cerebral hemorrhage
What is the truth regarding managing expectations for AD treatment?
- medications are not curative
- changes in MMSE are variable
- possible slight improvement in MMSE (1 or 2 Points)
- over time MMSE scores will decline despite treatment
When should AD therapy be discontinued?
- no clear recommendations on when to d/c
- patients that can’t speak, ambulate, or provide self-care have little reason to continue medication; risks exceed benefits
Which agents used for neuropsychiatric symptoms in dementia should be avoided in elderly?
- Select SSRIs (paroxetine and fluoxetine): paroxetine is highly anticholinergic; fluoxetine has long half-life–>excess CNS stimulation, sleep disturbance, agitation, falls
- Psychosis-Antipsychotics (clozapine and olanzapine)–>CVD and death
What is the extent and time frame of improvement of pharmacological intervention in AD?
- 4-6 weeks for observable benefit
- benefits may last 1-2 years
When should a patient switch to another AChE-I in AD?
- if there’s no improvement after 12-24 weeks of treatment
- No need to try a third
True or False: Memantine may be used in combo with an AChE-I in moderate to severe AD for added benefit.
True
What should be done if AChE-I therapy is interrupted for more than a few days in AD?
Re-titration from starting dose is recommended
True or False: AM dosing is an option with donepezil for alleviation of insomnia and vivid dreams/nightmares in AD
True
True or False: start low and go slow… but go!
True
What is Vascular Dementia (VaD)?
cognitive disorder caused by vascular disease
- most common cause is occlusion of cerebral blood vessels by thrombus or embolus leading to ischemic brain injury
- hemorrhagic brain lesions responsible for some VaD cases
Risk factors for VaD
advanced age, diabetes mellitus, small vessel cerebrovascular disease, hypertension, heart disease, hyperlipidemia, cigarette smoke, alcohol use, more common in males
What is the clinical presentation of VaD?
- stepwise cognitive decline (stability followed by rapid decline due to cerebrovascular insults)
- personality and mood changes, depression, psychomotor retardation
- gait disturbance, unsteadiness, unprovoked falls
- urinary incontinence and frequency
Can AChE-Is be used in VaD treatment?
deficits in cholinergic transmission and nicotinic binding abnormalities have been observed
-some data indicates improvement in cognition and daily function
What are secondary prevention methods for VaD?
-Bp regulation, cholesterol control, diabetes control (A1C<7-8%), antiplatelet therapy, smoking cessation, decrease alcohol intake, lifestyle modification
Describe Parkinson’s disease related dementia pathology
- Lewy bodies: abnormal proteinaceous inclusions throughout brain
- Neurofibrillary tau tangles may be present
- brain atrophy
What are the two subtypes of Parkinson’s disease related dementias?
- Lewy Body Dementia (DLB): cognitive symptoms develop less than 1 year after PD diagnosis
- Parkinson’s Disease Dementia (PDD): cognitive symptoms develop >1 year after PD diagnosis
True or False having MCI at PD diagnosis increases risk of conversion to dementia
True: risk of conversion increases 6 fold
What are the risk factors of Parkinson’s disease related dementias?
MCI, advanced age, gait dysfunction, presence of hallucinations
What pharmacological treatments can be used for PDD and DLB?
- cholinesterase inhibitors for cognition and memory
- donepezil and rivastigmine
- rivastigmine has higher efficacy but more adverse events
- donepezil used more off label while rivastigmine is FDA approved for PDD
Why should anticholinergic agents be avoided in PDD?
anticholinergics are indicated in early PD but worsen PDD
