Alzheimers

Definitions:
Aphasia: loss of ability to understand or express speech comprehension/formulation of language)
Apraxia: loss of ability to execute purposeful actions
Agnosia: loss of recognition, sensation
Anomia: inability of naming or recognizing names

How to rule out other condition that can cause new onset of memory loss?
Medications Diseases Labs
Anticholinergics Anemia Thyroid function
Benzodiazepine (sedatives) Trauma Brain trauma/ cancer/ tumor
Antipsychotics Infection Folate level
Digoxin (Antiarrhythmic) Malignancy/tumor Anemia (CBC)
NSAIDs Drug abuse Liver function
Antihypertensive Vitamin Deficiency Infection
Corticosteroid Thyroid disease Vitamin B12 deficiency
(long-term, systemic) Hepatic encephalopathy Electrolytes
H2RA (cimetidine)
Opioids

Mini-Mental Status Exam (MMSE) Max score = 30

MCI Mild 26-28 Moderate 17-10 Severe 9-10

ADAS-Cog:
The higher the score the worse the decline in cognitive function
4 points change in scale = clinically significant

Acetylcholinergics-esterase Inhibitors 1st Line

All agents have similar efficacy
First 6 months expected result
ADAS-Cog: 2.8-4 points improvement
MMSE: 1- 1.5 points improvement
After the first 6 months: efficacy will decline
Considered effective if
ADAS-Cog 7 points decrease per year
MMSE <2 points decrease per year

Adjunctive Agents:
Memantine (Namenda)
Moderate to severe disease
MOA: antagonize NMDA (glutamate) receptor acts like Magnesium
Only systematic relief
Clinical pearls:
NO DDI
Renal adjustment [IR = 5mg BID] [XR = 14mg QD]
Dosing:
IR XR
Initial 5mg QD 7mg QD
Titration by 5mg q week by 7mg q week
Maintenance 10mg BID 28mg QD
 Aspirin [81mg/day]
Always on board (if no CI)
Treat vascular disease (increase oxygen delivery)
Statins (lipid lowering):
Only start if indicated
Make sure on CI (liver function & rhabdomyolysis)
Ginkgo
Blood thinner (reduce blood viscosity) increase blood flow
OK to use if no DDI
Vitamin B
Decrease homocysteine level (high level can cause vascular inflammation)

Agents for Non-cognitive Symptoms:

Antipsychotics Anti-depressant BZD Anticonvulsant
Specific Agents Aripiprazole (Abilify) Citalopram Lorazepam CBZ & VA
Quetiapine (Seroquel) Escitalopram Oxazepam (Better ADR but
Olanzapine (Zyprexa) Temazepam caution in DDI)
Risperidone (Risperdal)
Depression ***
Insomnia/restlessness X ***
Agitation/aggression X X ***
Psychosis ***

NOT recommended for the treatment of Alzheimers

Vitamin E
NOT recommended (lack of efficacy)
>400mg IU = increased risk of mortality
Estrogen
NOT recommended (consider d/c if patient is already on it)
NSAIDs
Can still use for pain on PRN basis

Comparison of Ach-I Agents:

Advantage Disadvantage Comments
Donepezil QD dosing Weight loss Initial: 5mg qPM
(Aricept) ODT formulation DDI (2D6/3A4) Mild-Mod: in 4-6wks, up to 10mg
Selective Less incidence/severity Mod-Severe:
of GI side effects Up to 23mg after 3 months
Rivastigmine No DDI (not CYPs) Severe GI ADR (N/V/D) Oral: 1.5mg BID with meals by
(Exelon) Transdermal (QD) Renal adjustment 1.5mg q wk 306mg BID maintenance
Non-selective Oral BID dosing Patch: 4.6mg/day up to 9.5mg/day in
4-6 weeks (Max: 13.3mg/day)
Galantamine QD dosing (ER) Hepatic/renal adjust
(Razadyne) (avoid in severe cases)
Selective Severe GI ADR
DDI (2D6/3A4)
Increase in mortality in
patients with MCI