Evidence-Based Reviews

Mild cognitive impairment: How can you be sure?

Current Psychiatry. 2008 April;7(4):37-49

References

1. Gauthier S, Reisberg B, Zaudig M, et al. Mild cognitive impairment. Lancet 2006;367:1262-70.

2. Lopez OL, Jagust WJ, DeKosky ST, et al. Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1. Arch Neurol 2003;60:1385-9.

3. Petersen RC. Conceptual review. In: Petersen RC, ed. Mild cognitive impairment: aging to Alzheimer’s disease. New York, NY: Oxford University Press; 2003:1-14.

4. Petersen RC, Morris JC. Mild cognitive impairment as a clinical entity and treatment target. Arch Neurol 2005;62:1160-3.

5. O’Brien JT. Vascular cognitive impairment. Am J Geriatr Psychiatry 2006;14:724-33.

6. Janvin CC, Larsen JP, Aarsland D, et al. Subtypes of mild cognitive impairment in Parkinson’s disease: progression to dementia. Mov Disord 2006;21:1343-9.

7. Farlow MR, He Y, Tekin S, et al. Impact of APOE in mild cognitive impairment. Neurology 2004;63:1898-1901.

8. Winblad B, Palmer K, Kivipelto M, et al. Mild cognitive impairment—beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 2004;256:240-6.

9. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 2004;256:183-94.

10. Geda YE, Smith GE, Knopman DS, et al. De novo genesis of neuropsychiatric symptoms in mild cognitive impairment (MCI). Int Psychogeriatr 2004;16:51-60.

11. Robert PH, Berr C, Volteau M, et al. Apathy in patients with mild cognitive impairment and the risk of developing dementia of Alzheimer’s disease: a one-year follow-up study. Clin Neurol Neurosurg 2006;108:733-6.

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18. Gabryelewicz T, Styczynska M, Pfeffer A, et al. Prevalence of major and minor depression in elderly persons with mild cognitive impairment: MADRS factor analysis. Int J Geriatr Psychiatry 2004;19:1168-72.

19. Geda YE, Knopman DS, Mrazek DA, et al. Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment: a prospective cohort study. Arch Neurol 2006;63:435-40.

20. Devanand DP, Pelton GH, Marston K, et al. Sertraline treatment of elderly patients with depression and cognitive impairment. Int J Geriatr Psychiatry 2003;18:123-30.

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Monitoring. The American Academy of Neurology recommends monitoring patients diagnosed with MCI every 6 to 12 months for cognitive and functional decline.

In these visits, include:

repeat office-based cognitive assessment, especially the modified MMSE, clock-drawing test, and MoCA
careful history-taking from the patient and reliable informant
repeat neuropsychological testing annually or when dementia is suspected
assessment of the caregiver for distress.

Compensating for memory loss. Many individuals with MCI have insight into their cognitive deficits and are interested in making lifestyle changes. Experts recommend:

moderate exercise (at least 30 minutes per session, 3 times a week)
cognitively stimulating activities that involve language and psychomotor coordination, such as dancing, crossword puzzles, and volunteer work.

Potentially helpful tools include calendars, reminder notes, electronic cuing devices, pill boxes, and “speed-dial” telephones. Encourage patients to participate in local senior organizations and to use community resources.¹

Medications—yes or no? Cholinesterase inhibitors, rofecoxib, and vitamin E have not been shown to prevent MCI from progressing to AD. Thus, insufficient evidence exists to recommend medications for patients with MCI.

Donepezil has shown possible short-term benefits, however, and patients may choose to try this medication. Some find comfort in seeking this “extra time” to make decisions about advanced directives, attend to estate and will issues, and optimize relationships while they have only mild cognitive deficits and possess decision-making capacity.

Donepezil. The Alzheimer’s Disease Cooperative Study—supported by the National Institute on Aging—was designed to determine whether daily doses of donepezil or vitamin E can delay or prevent progression of aMCI to AD.²⁵ In the double-blind, placebo-controlled, parallel group study, 769 patients with aMCI were randomly assigned to receive donepezil, 10 mg/d; vitamin E, 1,000 IU bid; or placebo for 3 years.

Overall progression to AD was 16% per year, and the 3-year risk of progression was the same in all 3 groups. Donepezil therapy was associated with a reduced rate of progression to AD compared with placebo during the first year of treatment. Donepezil’s benefit was evident among ApoE e4 carriers at 2-year follow-up, but none of the 3 groups showed statistically significant differences after 3 years. Vitamin E showed no effect on AD progression throughout the study.

Rivastigmine. A randomized, placebo-controlled trial in which 1,018 MCI patients received rivastigmine or placebo for 4 years found no statistically significant benefit of rivastigmine on AD progression.²⁶

Galantamine. Two international randomized, double-blind, placebo-controlled trials failed to show a statistically significant benefit of galantamine in slowing progression from aMCI to AD. MRI data from one of these studies suggested that galantamine may have reduced the rate of brain atrophy over a 2-year period.²⁷

Rofecoxib. Epidemiologic studies indicate that anti-inflammatory drugs may reduce the risk of developing AD, but the COX-2 inhibitor rofecoxib did not delay progression to AD among aMCI patients in a large, placebo-controlled trial.²⁸

Educate patients and family members about supportive nonpharmacologic treatments and cholinesterase inhibitors. The Alzheimer’s Association, National Institute on Aging, and local department of aging agencies offer useful resources (see Related Resources).

CASE CONTINUED: Dealing with uncertainty

Mr. R and his wife are unsettled by his MCI diagnosis. They prefer to take a “wait and watch” approach, decline initiation of a cholinesterase inhibitor, and agree to adhere to nonpharmacologic interventions you discussed. You schedule a follow-up visit in 6 months and encourage them to call you with questions.

Related resources

Rosenberg PB, Johnston D, Lyketsos CG. A clinical approach to mild cognitive impairment. Am J Psychiatry 2006;163: 1884-90.
Montreal Cognitive Assessment (MoCA). 10-minute screening test designed to help clinicians detect mild cognitive impairment. www.mocatest.org.
Alzheimer’s Association. www.alz.org.
National Institute on Aging. www.nia.nih.gov.

Drug brand name

Benztropine • Cogentin
Cyclobenzaprine • Flexeril
Donepezil • Aricept
Galantamine • Razadyne
Oxybutynin • Ditropan
Rivastigmine • Exelon
Rofecoxib • Vioxx
Sertraline • Zoloft

Disclosure

Dr. Goveas and Dr. Dixon-Holbrook report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Kerwin is a consultant to Pfizer and a speaker for Pfizer and Novartis.

Dr. Antuono receives research support from Eisai, Pfizer, and Elan and is a speaker for Pfizer and Forest Pharmaceuticals.