Alzheimer dementia: Starting, stopping drug therapy

Article Figures & Data

TABLE 1

Cognitive enhancers approved for Alzheimer disease

Drug	Proprietary name (date approved)	Indications	Formulations
Cholinesterase inhibitors
Donepezil	Aricept (1996), generics available	Mild to moderate disease (5–10 mg), moderate to severe disease (10–23 mg)	Tablets, disintegrating tablets
Rivastigmine	Exelon (2000), generics available	Mild to moderate disease	Tablets, oral solution, transdermal patch
Galantamine	Razadyne (2001), generics available	Mild to moderate disease	Immediate-release tablets, oral solution, extended-release tablets
N-methyl-d-aspartate receptor antagonist
Memantine	Namenda (2003), generics available	Moderate to severe disease	Tablets, oral solution
Combination drug
Donepezil + memantine	Namzaric (2014), generics available	Moderate to severe disease	Extended-release capsules

TABLE 2

Alzheimer disease: Severity, associated symptoms, and recommended treatment

Dementia category	Global Deterioration Scale (stages 1–7)	Medications
Not demented	1 No cognitive impairment 2 Very mild decline: age-associated cognitive impairment 3 Mild cognitive impairment, minor neurocognitive decline	No indication for cognitive enhancers
Mild dementia	4 Decreased knowledge of current and recent events Decreased ability to travel, handle finances, and manage basic activities of daily living	Cholinesterase inhibitors
Moderate dementia	5 Unable to recall a major relevant aspect of their current life, an address or telephone number of many years, or the names of close family members Basic activities of daily living begin to be impaired	Cholinesterase inhibitors with or without an NMDA receptor antagonist
Severe dementia	6 Occasionally forgets the name of the spouse or caregiver on whom he or she is entirely dependent Unaware of all recent events and experiences in their lives Most basic activities of daily living impaired	Cholinesterase inhibitor (donepezil) with or without an NMDA receptor antagonist
Advanced dementia	7 Cannot speak or walk, has incontinence and difficulty swallowing	No randomized controlled trials in stage 7

TABLE 3

Adverse effects of cognitive enhancers: Percent of patients affected

	Cholinesterase inhibitors				NMDA receptor antagonist
	Donepezil	Galantamine	Rivastigmine	Rivastigmine transdermal	Memantine
Nausea	3%–19%^a	21%	17%–47%	2%–4%	Not available
Diarrhea	5%–15%^a	7%	5%–19%	≤ 7%	5%
Constipation					3%–5%
Anorexia	2%–8%	7% (decreased appetite)	≥ 17% 3%–26% (weight loss)	≤ 3%	< 1% 3% (weight gain) (extended-release formulation)
Vomiting	3%–9%^a	11%	13%–31%	3%–9%	2%–3%
Insomnia	2%–14%	Not available	1%–9%	Not available	Not available
Headache	3%–10%	7%	4%–17%	≤ 4%	6%
Dizziness	2%–8%	8%	6%–21%	≤ 6%	5%–7%
Fatigue	1%–8%	4%	4%–9%	2%–4%	2%
Syncope	2%	1%	3% (falling) 6%–12%	Not available	Not available
Bradycardia	≥ 1%	1%	< 1%	< 1%	< 1%
Infection	11%	< 1%	1%–10% (urinary tract infections)	Not available	4% (influenza)