Dementia Flashcards
What is dementia?
Acquired cognitive impairment that interferes with normal activities and function
What are the four common types of dementia?
Alzheimer’s disease
Vascular dementia
Lewy body/Parkinson dementia
Frontotemporal dementia
Which illness is dementia a complication of?
Parkinson Disease
Dementias are almost always __________, deteriorating illnesses
progressive
As dementia progresses, __________ behaviours may develop.
responsive
What are some examples of behavioural and psychological symptoms of dementia (BPSD)?
Depression, anxiety, apathy, agitation, delusion, and hallucination
What is the pathophysiology of Alzheimer’s Disease?
Protein buildup and plaque development -> eventual neuronal degeneration
What is the pathophysiology of frontotemporal lobe dementia?
Atrophy in frontotemporal lobe
What is the pathophysiology of vascular dementia?
Acute and/or chronic reduction of blood flow to the brain
What’s a common cause of other vascular dementia?
Stroke or other CV events
What is the pathophysiology of Lewy Body/Parkinson’s dementia?
Development of Lewy bodies in nerve cells
What is the typical progression of the four types of dementia?
Alzheimer’s= gradual onset and progressive
Frontotemporal lobe= more progressive
Vascular= more sudden and can be stepwise decline after a CV event
Lewy body= gradual and progressive
What are the symptoms of Alzheimer’s Disease?
Begins with cognitive decline and progresses to motor impairment
What are the symptoms of frontotemporal lobe dementia?
Socially inappropriate behaviours and disinhibition
What are the symptoms of vascular dementia?
Stepwise decline in cognition after CV events (memory, executive function, language and attention)
What are the symptoms of Lewy Body/Parkinson’s dementia?
Hallucinations and motor impairments are common
What are the stages of dementia?
Preclinical= functioning is unimpaired. May just be normal aging and may not progress to dementia
Mild= impaired instrumental activities of daily living (driving, medications, finance, cooking, shopping, electronic devices, and housekeeping)
Moderate= impaired IADL and personal activities of daily living (bathing, grooming, dressing, toileting, and feeding). Require assistance or prompting
Severe= personal ADL cannot be done independently, even with prompting
Terminal= patient is immobile and non-verbal. Must be fed
Which screening tool is ideal for mild cognitive impairment or early dementia?
Montreal Cognitive Assessment (MoCA)
Which screening tool is ideal for moderate stage dementia?
Mini-Mental Status Exam (MMSE) alone or in combo with the clock drawing test
How is functional disability measured?
-Disability Assessment for Dementia (DAD)
-Functional Assessment Staging Tool (FAST)
What reversible medical illnesses can have cognitive impairment symptoms that mimic dementia?
Hypothyroidism, Vitamin B12 deficiency
Neuroimaging is recommended for most older adults with cognitive impairment. IS CT or MRI preferred?
MRI
If imaging resources are limited, what characteristics would prioritize the need for imaging?
<60 years of age
New onset (less than 2 months)
Rapid progression (1-2 months)
Unexpected and unexplained decline in cognition in patients with known dementia
Head trauma or history of head trauma
Use of anticoagulants or history of bleeding disorder
Unexplained neurological symptoms
Early urinary incontinence and gait disorder
Significant vascular risk factors
History of cancer (particularly brain)
What medications class can contribute to potentially reversible cognitive impairment in someone without dementia or aggravate pre-existing dementia?
Anticholinergics
Do anticholinergics impact mortality?
Yes, it’s associated with increased mortality
What are the 6 drug classes that have anticholinergic effects?
- Antidepressants (Amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline, paroxetine)
- Antiemetic/antivertigo (dimenhydrinate, promethazine, scopolamine)
- Antihistamine (diphenhydramine, hydroxyzine)
- Antimuscarinic (darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine)
- Antipsychotic (chlorpromazine, clozapine, olanzapine)
- Hypnotics (BZDs, zolpidem, zopiclone)
Which of the drug classes above are also risk factor for dementia?
Antimuscarinic and benzodiazepines
What non-pharm can older adults with dementia benefit from?
Ongoing exercise, cognitive stimulation, and social engagement
What’s the mainstay of FTD management?
Non-pharm approach with emphasis on family and caregiver support
- speech and language therapists is also good for prominent language
How is the effectiveness of medications measured?
Either improvement or no deterioration of target symptoms as measured at regular intervals
What’s a common goal for patients with mild to moderate AD?
Reduction in repetitive questioning
How often do we monitor treatment after initiating therapy or increasing dose
2-4 weeks
Which screening tool can be used to monitor therapy effectiveness?
Mini-Mental Status Exam (MMSE)
- annual decline of less than 2 points while on drug therapy indicated a beneficial effect
Is the MMSE a good measure for treatment response?
No, it’s now recognized as a poor measure. However, it’s a required measure for reimbursement of cholinesterase inhibitors in some Canadian provinces.
What are the two drug classes used to treat dementia?
- Cholinesterase Inhibitors
- N-methyl-D-aspartate Receptor Antagonists
What are the three drugs under the cholinesterase inhibitors class?
Donepezil
Rivastigmine
Galantamine
How does cholinesterase inhibitors work?
Blocks the breakdown of acetylcholine -> increased acetylcholine levels in synaptic cleft, increased function of neural cells
What types of dementia are cholinesterase inhibitors indicated for?
AD, VD, mixed AD/VD, LBD, PDD
What type of dementia is cholinesterase inhibitors not recommended for? Why?
FTD
They are ineffective and may cause agitation
What type of dementia is donepezil indicated for?
Only cholinesterase inhibitor that is indicated for all severities of Alzheimer’s dementia
Also used in mixed AD/VD, LBD, and PDD
What’s the typical dosing of donepezil? What the advantage with this dosing?
Donepezil 5mg/day showed benefits.
Slightly larger benefit with 10mg/day dose
Advantage is once daily dosing
Were there any additional benefit with doses higher than 10mg/day?
No
What type of dementia is rivastigmine indicated for?
Mild-moderate AD, mild-moderate PDD, LBD
What type of dementia is galantamine indicated for?
Mild to moderate AD, mixed AD/VD
- mild to moderated LBD (only if donepezil or rivastigmine is not tolerated)
Which of the above cholinesterase inhibitors come in a dosage form that is not a pill?
Rivastigmine comes as a patch (Exelon)
- Once daily dosing
- Can be hard to remember to change patch daily (warning from Health Canada from accidental overdoses from failure to remove previous patch)
How does the rivastigmine patch compare with the oral pill?
Modest benefit compared with placebo and fewer side effect compared with the oral formulation.
Patch is more expensive
Can you provide a summary of which cholinesterase inhibitor is indicated for which types of dementia?
AD: Donepezil (all severity), rivastigmine (mild-moderate), galantamine (mild-moderate)
VD: Donepezil (if mixed with AD), galantamine (if mixed with AD)
PD/Lewy Body: Donepezil, rivastigmine (mild-moderate), galantamine (mild-moderate and only if donepezil or rivastigmine is not tolerated)
FTD: None
What’s the effect of cholinesterase inhibitors on Alzheimer’s dementia?
Clinically detectable but typically small to moderate
- More than half of patient with AD have initial period of cognitive stabilization before continuing to decline at the pretreatment rate
- another study found that patients had a modest but persistent reduction in cognitive decline over a 5 year follow-up period
What’s the effect of cholinesterase inhibitors on Lewy Body/PD dementia?
Reduction in visual hallucination and other behavioural symptoms
- effective in treating cognitive impairment but do not affect risk of falls
What’s the effect cholinesterase inhibitors on vascular dementia?
Cholinesterase inhibitors are only used in people with VD and a mixed component of AD, LBD, or PDD
If patient does not respond to one cholinesterase inhibitor, what can we do?
Patient may respond to another
Is it possible for some symptoms to worsen after starting cholinesterase inhibitors?
Yes, it’s normal that some symptoms, some with remain stable, and other will worsen.
For each of the drugs, doses at the _________ end of recommended ranges typically have better outcomes.
Higher
What are common adverse effects of cholinesterase inhibitors?
N/V/D
Anorexia and/or weight loss
Vivid dreams
Tremor
Vertigo
Cholinergic effects (rhinorrhea, increased urinary frequency)
What’s the safety concern with cholinesterase inhibitors?
Health Canada poses a small risk of QT interval prolongation
- Caution recommended in patients with sick sinus syndrome, profound bradycardia, prolonged QT interval or multiple conduction abnormalities
Start cholinesterase inhibitors at _______ dose and increase incrementally every ____ weeks as tolerated.
Lowest
4 weeks
What is the risk of starting cholinesterase inhibitors at high doses without slow titration?
Associated with higher rates of serious events, emergency room visits, and hospitalization
What should we avoid doing if patient is experiencing side effects with cholinesterase inhibitors? What should we do instead?
Avoid treating side effects with new medication (oxybutynin to treat urinary frequency)
Reduce the dose or switch the cholinesterase inhibitor once the side effects have fully resolved after stopping initial agent
When would we consider cardiovascular screening prior to initiation of cholinesterase inhibitor?
Consider baseline EKG if patient is:
- Bradycardic (<60)
- Multiple cardiac rate-limiting agents (beta blockers, non-DHP CCB, amiodarone)
- Unexplained syncope or presyncope
If there is concern about patient’s ability to tolerate side effects, which cholinesterase inhibitor should we pick?
One with a shorter-half life
How do we rank the cholinesterase inhibitors based on half lives?
Donepezil (longest ~70 hrs)
Galantamine (6-8 hrs)
Rivastigmine patch (3 hrs)
Rivastigmine oral (1.5-2 hrs)
When do we consider discontinuing a cholinesterase inhibitor?
- Patient or caregivers decide to stop or nonadherence
- No clinically meaningful benefit
- Intolerable adverse effects
- Clinically meaningful progression of dementia over the 6 months unexplained by anything else
- Progression to severe stage or terminal illness.
When should be avoid discontinuing cholinesterase inhibitors?
- Patients with active psychotic symptoms, agitation, or aggression (unless worsened after initiation or dose change)
- those with clinically meaningful reduction in neuropsychiatric symptoms
How do we stop the treatment of cholinesterase inhibitors?
Taper slowly by reducing the dose to half of the previous dose every 4 weeks
What do we need to monitor for during deprescribing??
Responsive behaviours (rapid decline in cognition or function)
When should we restart the cholinesterase inhibitor following discontinuation?
If emergent symptoms or significant deterioration in patient’s condition occurs within 1-3 months of discontinuation
What’s the drug in the N-methyl-D-aspartate receptor antagonist class?
Memantine
What’s the mechanism of action of memantine?
Blocks glutamate-induced neuronal excitotoxicity, a process that is a common pathway in neuronal death
Where does memantine come into play in dementia?
- Memantine monotherapy recommended in moderate AD only if patients are intolerant or have CI to cholinesterase inhibitor
- Adjunct in moderate-severe disease in those who already achieved response with cholinesterase inhibitor
Which types of dementia can memantine not be used in?
PDD (yes to LBD though)
FTD
Is there a supplement that is recommended for dementia?
Supplementation remains controversial:
- Vit D 2000 IU (high dose) appeared to show slowing of dementia. New study showed risk of harm and no benefit so not recommended
- Vit B (high dose) no benefit
Are statins recommended for dementia treatment?
No
Are anti-inflammatories recommended for dementia treatment?
No
Are stimulants recommended for dementia treatment?
No
Is Ginkgo biloba recommended for treatment dementia?
No
As dementia progresses, responsive behaviours may develop. It is unusual for ________ or ______________ to occur in early dementia. When this happens, the person is likely suffering from ___________ dementia.
delusions or hallucinations
Lewy body dementia
What is first line for responsive behaviours?
Non-pharms (psychosocial and environmental interventions)
- Depression and anxiety= CBT and counselling
- Agitation= recreation therapy, sensory stimulation
- Making the physical environment/home more safe in general
If starting pharmacologic therapy, should we continue non-pharms?
Yes
What drug classes are used for responsive behaviours?
- Antidepressants for depression
- do not recommend routine use
- depression indication
- SSRIs (with the exception of paroxetine) are less likely than TCAs to cause anticholinergic side effects
- TCA typically avoided but if lack of response from SSRI, choose desipramine or nortriptyline
- sertraline and citalopram good for agitation (watch for prolonged QTc interval)
- takes 6-8 weeks at therapeutic dose to know if treatment effective
- avoid mirtazapine - Antipsychotic
- agitation or psychosis indication
- significant risk of adverse effects, so limit to when symptoms are severe, dangerous or cause significant distress
- risperidone and olanzapine preferred
- avoid first gen antipsychotics
- avoid haloperidol
- elderly at greater risk of EPS (including tardive dyskinesia which can be irreversible)
- may worsen psychosis in Lewy body dementia
- increased risk of stroke and death
- risk of cerebrovascular events with these medications, especially in patients with mixed and vascular dementia
- Use quetiapine in patients with LBD/PDD if an antipsychotic agent is required
- evaluate for need every 3-6 months. If symptoms subside, taper - Cholinesterase inhibitors and memantine
- mainstay - Trazodone
- for disrupted sleep/wake cycles and sundowning - BZD
- sometimes indicated for severe agitation if other agents fail
- risk of oversedation, falls, and worsening cognition
- use low doses of short acting agents (lorazepam 0.5-1mg, oxazepam 5-10mg, temazepam 15mg)
- in acute severely agitated patients, lorazepam 0.5-1mg + haloperidol given IM q8h for max of 3 days
What drug may be effective in management of apathy in AD patients?
Methylphenidate but more evidence is needed before routine practice can be implemented
Beta blockers (particularly __________), carbamazepine, divalproex, lithium, buspirone, gabapentin, and pregabalin seems to work best when the problem behaviour ______ the psychiatric syndrome for which the drug is efficacious.
pindolol
mimics
What are 12 potentially modifiable risk factors that may impact dementia development?
- Less education
- Social isolation
- Late-life depression
- Mid-life obesity
- Physical inactivity
- Hearing impairment
- Diabetes
- Mid-life hypertension
- Smoking
- Air pollution
- Traumatic brain injury
- Alcohol consumption
Is routine screening for cognitive impairment in asymptomatic older adults recommended for prevention of dementia?
No
What are some non-pharms we can recommend as prevention for dementia?
30 min of exercise more vigorous than a brisk walk at least 3 times per week
Mediterranean diet
Mentally stimulating activities
Avoid severe sleep deprivation
Note to self to review drug chart and algorithm in dementia CPS chapter
