Alzheimer Disease: Pharmacologic and Nonpharmacologic Therapies for Cognitive and Functional Symptoms

 

Alzheimer disease comprises a syndrome of progressive cognitive and functional decline. Treatments should target cognitive and functional symptoms. Cholinesterase inhibitors, memantine, and a combination of a cholinesterase inhibitor and memantine have produced statistically significant but clinically small delays in various domains of cognitive and functional decline in select patients with Alzheimer disease. Vitamin E has been shown to delay functional decline in patients with mild to moderate Alzheimer disease, especially when taken in combination with a cholinesterase inhibitor. Structured programs of physical exercise improve physical function and reduce rates of neuropsychiatric symptoms in patients with mild to severe Alzheimer disease. Cognitive stimulation programs show benefit in maintenance of cognitive function and improved self-reported quality of life in patients with mild to moderate Alzheimer disease.

Dementia is a heterogeneous syndrome resulting in impairment in at least one cognitive domain severe enough to limit daily functioning.1 The most common etiologies of dementia in developed nations are Alzheimer disease, vascular dementia, mixed dementia (in which symptoms arise from a combination of multiple etiologies, most often Alzheimer disease and vascular dementia), Lewy body dementia/Parkinson disease dementia, and frontotemporal dementia.25

WHAT IS NEW ON THIS TOPIC: ALZHEIMER DISEASE

A 2014 randomized controlled trial in veterans with mild to moderate Alzheimer disease who were already receiving a cholinesterase inhibitor found that vitamin E slowed functional status decline (3.15 points less than placebo on a 78-point assessment scale over 4 years), with a delay in progression of about 6 months.

A 2012 Cochrane meta-analysis of 15 randomized controlled trials concluded that cognitive stimulation programs are beneficial for maintenance of cognitive function and self-reported quality of life in patients with mild to moderate dementia from Alzheimer disease. However, cognitive stimulation techniques are highly variable and lack standardization, and no effects were noted on functional status, behavior, or mood.

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

Cholinesterase inhibitors, including donepezil (Aricept, 5 to 10 mg per day), galantamine (Razadyne, at least 16 mg per day), or rivastigmine (Exelon, 6 to 12 mg per day orally or 9.5 mg per day transdermally), should be considered for treatment of cognitive and functional decline in patients with mild to moderate Alzheimer disease.

A

1115

Memantine (Namenda, 20 mg per day) should be considered for treatment of cognitive and functional decline in patients with moderate to severe Alzheimer disease.

A

1621

The addition of memantine should be considered for treatment of cognitive and functional symptoms in patients with moderate to severe Alzheimer disease or mixed dementia who are already receiving a cholinesterase inhibitor.

B

19, 20

The addition of vitamin E (2,000 IU per day) should be considered for treatment of mild to moderate Alzheimer disease in patients who are already receiving a cholinesterase inhibitor.

B

22

A structured physical exercise program should be recommended for patients with Alzheimer disease of any severity.

A

3236

Cognitive stimulation programs should be recommended for patients with mild to moderate cognitive impairment.

B

37


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

Cholinesterase inhibitors, including donepezil (Aricept, 5 to 10 mg per day), galantamine (Razadyne, at least 16 mg per day), or rivastigmine (Exelon, 6 to 12 mg per day orally or 9.5 mg per day transdermally), should be considered for treatment of cognitive and functional decline in patients with mild to moderate Alzheimer disease.

A

1115

Memantine (Namenda, 20 mg per day) should be considered for treatment of cognitive and functional decline in patients with moderate to severe Alzheimer disease.

A

1621

The addition of memantine should be considered for treatment of cognitive and functional symptoms in patients with moderate to severe Alzheimer disease or mixed dementia who are already receiving a cholinesterase inhibitor.

B

19, 20

The addition of vitamin E (2,000 IU per day) should be considered for treatment of mild to moderate Alzheimer disease in patients who are already receiving a cholinesterase inhibitor.

B

22

A structured physical exercise program should be recommended for patients with Alzheimer disease of any severity.

A

3236

Cognitive stimulation programs should be rec

The Authors

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TED EPPERLY, MD, is president and chief executive officer of the Family Medicine Residency of Idaho, Boise. Dr. Epperly is past president and board chair of the American Academy of Family Physicians....

MEGAN A. DUNAY, MD, MPH, is an academic geriatrician at the Boise Veterans Affairs Medical Center and is affiliated with the University of Washington Internal Medicine Residency of Boise.

JACK L. BOICE, MD, is an academic geriatrician at the Boise Veterans Affairs Medical Center and is affiliated with the University of Washington Internal Medicine Residency.

Author disclosure: No relevant financial affiliations.

Address correspondence to Ted Epperly, MD, Family Medicine Residency of Idaho, 777 N. Raymond St., Boise, ID 83704 (e-mail: ted.epperly@fmridaho.org). Reprints are not available from the authors.

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