Dementia Treatment Flashcards
Positive clinical outcomes with CHEI in Alzheimer’s
- Cognitive function (MMSE +1)
- ADLs (1 pt on ADCS-ADL sev)
- Clinician rated global clinical state
Negative outcomes, no improvement in:
1. BPSD
2. QOL
3. Healthcare utilization
NNT for ACHEI in AD
7 (Additional benefit)
12 (min improvement)
42 (marked improvement)
CHEI contraindications and side effects
Absolute CI = hypersensitivity to drug
Relative CI = high degree heart block (except RBBB), symptomatic bradycardia, seizure disorder, COPD/bronchospasm, active PUD, unexplained syncopal episodes
Side Effects
1. GI - N/V/D, appetite loss, weight loss
2. Leg cramps
3. Vivid dreams
4. Increased urinary incontinence
5. CV - bradycardia, syncope
List 5 AD experimental drugs and why they have not been proven effective
- Amyloid clearance - aducanamab, lecanumab
- Tau clearance - zagotenemab
- BACE-1 inhibitor - verubecestat
- Tau aggregation inhibitor - nilotinib
- Microglial activation inhibitor - neflamapimod
Not effective because…
1. Inconsistent outcome measures across studies
2. Heterogeneity of AD population
3. Duration of study trials
5. Costly drugs
6. Small effect size on AD research cognitive scales
7. Severe complications like ARIA-E and H
Barriers to success of adacanumab
- Only intended for those with MCI or early stages of dementia
- Significant side effects including ARIA-H and ARIA-E
- Significant costs
- Requirement for regular MRI imaging to look for side effects
- Minimal benefit on cognitive testing
- Lack of consistent cognitive testing amongst studies
- Communications between FDA and Biogen found to be inappropriate and atypical (requiring further study to prove efficacy in the USA)
Reasons to discontinue CHEI as per CCCDTD-5
Patients taking for >12 mos
1. Clinically meaningful worsening of dementia (cognition, function, global assessment) over last 6 mos (not due to medical or environmental factors)
2. No clinically meaningful benefit observed at any time
3. Pt has severe or end stage dementia
4. Intolerable side effects
5. Med adherence poor and precludes safe ongoing use or inability to assess effectiveness
What non neurologic manifestations of dementia are medications helpful for?
- Global function
- ADL
- Behavioural disturbance
- Caregiver burden
- Apathy
4 reasons there might be lack of persistence of CHEI use
- Poor tolerance
- Lack of familiarity amongst PCPs
- Unrealistic expectations of patients, physicians and caregivers
- Cognitive issues resulting in compliance issues
What conditions can memantine be used for?
Moderate stages
1. AD
2. PDD
3. LBD
4. Vascular dementia
Contraindications to using memantine
- Known hypersensitivity
- Caution in severe hepatic impairment
- Renal impairment GFR <15
- Seizure disorder
- CVD - cardiac failure, bradycardia, HTN/HOTN
Two adverse outcomes for patient when informal caregiver distress
- Abuse
- Decrease in QOL, physical and psychological health deterioration
Evidence for use of gingko biloba
No real strong evidence, it is quite mixed
It has been deemed to be safe but has inconsistent and unconvincing evidence of benefit
Two indications for switching between cholinesterase inhibitors and how would you do it
- Intolerance
- Lack of efficacy in first year of treatment (MMSE 2 point drop, functional decline within 6 months)
If intolerance, wait until complete resolution of side effects after stopping initial agent. Then start second at normal starting dose and inc q4 weeks.
In lack of efficacy then can switch overnight.
What are 4 evidence based outcomes/benefits of donepezil?
ADAS – Cog 3 – 4 points over 24 weeks
CIBIC - less than 1 point difference
If medication is stopped and then restarted, some patients may not return to baseline.
NNT 12 - 42
According to CCCD5, what are three individual level psychosocial interventions, and two community level psychosocial interventions recommended in the management of dementia
Individual Level
a. Exercise (group or individual) for people living with dementia.
b. Group cognitive stimulation therapy for persons living with mild to moderate stage dementia.
c. Psychosocial and psychoeducational interventions for caregivers of people living with dementia.
Community Level:
d. Development of dementia friendly organizations/communities for people living with dementia.
e. Use of case management for people living with dementia.
