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Michele A. Faulkner, Pharm.D., FASHP

Professor of Pharmacy Practice and Medicine

Creighton University

Copyright M. Faulkner, 2018

FACTS AND STATS

Most common form of dementia

Prevalence of AD doubles for every 5 year interval beyond age 65 74.1 million in the US by 2030

Sixth leading cause of death in the US Deaths increased by 123% from 2000-2015

No proven method of prevention

No cure

Inadequate treatment modalities

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WHO IS AT RISK?

Advanced age

Atherosclerosis

Down’s Syndrome

Family History

Head injury

Hypercholesterolemia

Hyperglycemia/Diabetes Mellitus

Hypertension

Amyloid beta (Aß) in the brain Clumps of protein that stick together and build up between

nerve cells

Tau proteins Forms neurofibrillary tangles in the brain of AD patients

preventing transmission of necessary substances from one part of a cell to another

Cellular damage Cell death

Brain shrinkage

Decreased in neurotransmittersNeurofibrillary Tangles

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MEDICATION MIMICS

Anticholinergics Antihistamines

Skeletal muscle relaxants

Tricyclic (and other) antidepressants

Psychoactive agents Antipsychotics

Benzodiazepines

Corticosteroids

Sedative hypnotics

H2-receptor antagonists

Antihistamines Chlorpheniramine Clemastine Diphenhydramine

Antidepressants Tricyclics (amitriptyline, nortriptyline,

desipramine, imipramine, etc.) Paroxetine

Antipsychotics Clozapine Olanzapine Perphenazine Quetiapine Thioridazine Trifluoperazine

Central anticholinergics Amantadine Benztropine Trihexyphenidyl Orphenadrine

Bladder and GI antispasmotics Darifenacin Dicyclomine Flavoxate Oxybutynin Tolterodine

Antiemetics Hydroxyzine Meclizine Promethazine Scopolamine

Drugs with high anticholinergic properties (Anticholinergic Cognitive Burden scale score 3)

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ACB score 1

Alprazolam

Atenolol

Bupropion

Captopril

Codeine

Colchicine

Fentanyl

Metoprolol

Nifedipine

Prednisone

Triamterene

ACB score 2

Carbamazepine

Cyclobenzaprine

Meperidine

Oxcarbazepine

Cholinesterase Inhibitors

• Donepezil• Galantamine• Rivastigmine

Mild-moderate

Alzheimer’s disease

• Cholinesterase Inhibitors• Donepezil

• NMDA Receptor Antagonist

• Memantine

Moderate-severe

Alzheimer’s disease

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Medications must be titrated to a minimum effective dose in order to receive the maximum benefit

Counsel patients and caregivers to take as prescribed, and don’t discontinue without discussion with the prescriber

Discuss side-effects in detail, and provide strategies for mitigation

It may be necessary to switch medications due to lack of effectiveness

Patients may respond differently to on cholinesterase inhibitor compared with another

Effectiveness may wane over time

Combination therapy in moderate-severe AD demonstrates minimal benefit

No recommendations can currently be made on the basis of pharmacogenomics

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• Even mild depression may impair a patient’s ability to function• Recurrent depression has been linked to development of

dementia• Avoid anticholinergics• Consider positive aspects of side-effect profile (sedative

properties, influence on weight)

Depression

• Use sedative agents with caution and utilize shorter acting agents• Consider antidepressants with anti-anxiolytic properties

Anxiety

• Best data with risperidone• Quetiapine has not been shown to positively affect

neuropsychiatric symptoms in AD patients• Use of antipsychotics in dementia patients has been linked to an

increase in stroke and overall mortality• Non-antipsychotic options

• Citalopram and dextromethorphan-quinidine have demonstrated the ability to decrease agitation in AD patients

• Consider whether agitation might be due to another cause (e.g. uncontrolled pain)

Psychosis

Over 50% of institutionalized patients with advanced dementia receive at least one medication deemed of questionable benefit 90-day expenditure for unnecessary

medications is >$800 on average

Feeding tube placement increases the likelihood of inappropriate medication use

Cholinesterase inhibitors and memantine are often continued

Non-essential medications unrelated to AD should be discontinued e.g. lipid lowering agents, agents for

osteoporosis

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Cholinesterase 

Inhibitors

Inidcation Dosage Form(s) Dosing  Titration

Donepezil Mild‐moderate AD

Moderate‐severe AD

Immediate release tablets/ 

orally disintegrating tablets

5mg/day (minimum 

maintenance dose)

10mg/day

Increase to 10mg/day after 4 weeks

May increase to 23mg/day after at 

least three months at 10mg/day dose

Galantamine Mild‐moderate AD Immediate release tablets/ oral 

solution

Extended release capsules

4mg twice daily

4mg/day

Increase by 4mg twice daily every 4 

weeks up to 24mg/day (minimum 

maintenance dose is 16mg/day)

Increase by 4mg/day every 4 weeks 

(same parameters as above)

Rivastigmine Mild‐moderate AD

Moderate‐severe AD

Immediate release 

capsules/oral solution

Topical patch

Topical patch

1.5mg twice daily

4.6mg/24h applied daily

Increase to 3mg twice daily every 2 

weeks up to 12mg/day (minimum 

maintenance dose is 6mg/day)

Increase to 9.5mg/24h after 4 weeks 

(minimum maintenance dose), and 

then to 13.3mg/24h if therapeutic 

benefit from lower dose wanes

13.3mg/24h (minimum maintenance 

dose) titrated as per mild‐moderate AD

NMDA 

Receptor 

Antagonists

Indication Dosage Form(s) Dosing Titration

Memantine Moderate‐

severe AD

Immediate release 

tablets/oral solution

Extended release 

capsules

5mg/day

7mg/day

Increase to 5mg 

twice daily, and then 

by 5mg/day weekly 

alternating between 

AM and PM doses to 

a dose of 20mg/day 

(minimum 

maintenance dose)

Increase by 7mg/day 

weekly to a dose of 

28mg (minimum 

maintenance dose)

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JAMA Intern Med. 2014;174(11):1763-71

J Neurol Neurosurg Psychiatry. 2007;78(12):1298–1303.

Alzheimer’s Association Facts and Figures. Available at: https://www.alz.org/alzheimers-dementia/facts-figures

BMJ 2018 25;361:k1315.

Cur Alzheimer Res. 2018;15:964-74.

J Neurol. 2018;265:2162-3.

BMC Geriatrics. 2018;18:168.

Age Ageing. 2018.1;47(1):88-94.

Expert Rev Neurother. 2018;18(6):461-7.