Do patients at high risk of Alzheimer’s disease benefit from early treatment?

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Clinical Inquiries

Do patients at high risk of Alzheimer’s disease benefit from early treatment?

J Fam Pract. 2009 June;58(6):320-322

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References

1. Geldmacher DS. Cost-effective recognition and diagnosis of dementia. Semin Neurol. 2002;22:63-70.

2. Balsis S, Carpenter BD, Storandt M. Personality change precedes clinical diagnosis of dementia of the Alzheimer type. J Gerontol B Psychol Sci Soc Sci. 2005;60:P98-P101.

3. Warner J, Butler R, Wuntakal B. What are the effects of treatments on cognitive symptoms of dementia? BMJ Clin Evid. 2008;01:1001-1028.

4. Lopez OL, Jagust WJ, DeKoskey ST, et al. Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1. Arch Neurol. 2003;60:1385-1389.

5. Petersen RC, Smith GE, Waring SC, et al. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56:303-308.

6. Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352:2379-2388.

7. Olazaran J, Muñiz R, Reisberg B, et al. Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer disease. Neurology. 2004;63:2348-2353.

8. Koontz J, Baskys A. Effects of galantamine on working memory and global functioning in patients with mild cognitive impairment: a double-blind placebo-controlled study. Am J Alzheimers Dis Other Demen. 2005;20:295-302.

9. Larson EB, Wang L, Bowen JD, et al. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med. 2006;144:73-81.

10. Ancelin ML, Artero S, Portet F, et al. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ. 2006;332:455-459.

11. Lanctot KL, Herrmann N, Yau KK, et al. Efficacy and safety of cholinesterase inhibitors in Alzheimer’s disease: a meta-analysis. CMAJ. 2003;169:557-564.

12. Santaguida PS, Raina P, Booker L, et al. Pharmacological treatment of dementia. Evidence Report/Technology Assessment No. 97 (prepared by McMaster University Evidence-based Practice Center under Contract No. 290-02-0020). AHRQ Publication No. 04-E019-2. Rockville, MD: Agency for Healthcare Research and Quality; April 2004.

13. Geldmacher DS, Provenzano G, McRae T, et al. Done-pezil is associated with delayed nursing home placement in patients with Alzheimer’s disease. J Am Geriatr Soc. 2003;51:937-944.

14. Boustani M, Peterson B, Hanson L, et al. Screening for dementia in primary care: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2003;138:927-937.

15. Qaseem A, Snow V, Cross JT, Jr, et al. Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2008;148:370-378.

A longitudinal cohort study found that patients taking anticholinergic drugs had an 80% prevalence of MCI, compared with a 35% prevalence in a matched population of patients not using these drugs; yet Alzheimer’s disease hadn’t increased among the anticholinergic drug users at 8-year follow-up. Attributable risk for MCI from anticholinergic drug use was 19%. Stopping anticholinergic medications may reduce the prevalence of MCI.¹⁰

In established Alzheimer’s disease, cholinesterase inhibitors statistically benefit patients with early and moderate disease and probably benefit patients with severe disease.^11,12 The treatment effect is small, however—3 points on a 70-point cognitive scale. Comparison studies show mixed results; no single agent appears to be most effective.¹²

Are cholinesterase inhibitors cost effective?

The relatively modest benefit of cholinesterase inhibitors—especially given their expense—has raised questions about cost effectiveness. When weighing the choice, consider that donepezil may delay nursing home placement,^11,13 and the cholinesterase inhibitors may reduce caregiver burden.¹¹ The medications are likely to be cost effective in patients showing a clinically significant response. More effective treatments would clearly be welcome.

FAST TRACK

For the very elderly, encourage exercise, cognitive stimulation, and increased socialization, which may help prevent functional decline.

Recommendations

The US Preventive Services Task Force (USPSTF) acknowledges that fair to good evidence supports a benefit from treatment of early-stage Alzheimer’s disease. However, routine screening for dementia in older adults receives an I-level recommendation (insufficient evidence), both because it’s unknown whether diagnosis would be as accurate and treatment as effective in primary care practices and because the benefit from screening is uncertain (coupled with a small treatment benefit).¹⁴

The task force reported finding no good data that treating MCI is beneficial. However, the USPSTF recommendation preceded publication of all 4 RCTs on treatment of MCI addressed in this Clinical Inquiry.

The American College of Physicians and American Academy of Family Physicians published a joint clinical practice guideline in March 2008 that questioned whether the slight benefit of cholinesterase inhibitors surpassed the harm of adverse effects and cost. They recommend counseling each patient about the likely benefits and harms.¹⁵

Evidence-based answers from the Family Physicians Inquiries Network