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Pharmacotherapy for Mild Cognitive Impairment: Are We There Yet?

Pharmacotherapy for Mild Cognitive Impairment: Are We There Yet?

Memory complaints are ubiquitous in our aging population. Vexing as it can be to misplace one's keys temporarily or to forget the motivation for a trip to the basement, a more fundamental fear of many older adults is that today's forgetfulness will usher in tomorrow's dementia. In some settings, medications indicated for treatment of mild to severe Alzheimer disease (AD) are offered to persons with more subtle cognitive lapses.

One recent survey found that more than 1 in 4 patients who have mild cognitive impairment (MCI) were receiving cholinesterase inhibitors in Italian AD treatment centers even though these medications were being used "off-label."1 In the United States, the FDA has not approved any medication for use in treating MCI. Should we consider this syndrome amenable to pharmacotherapy? What is the evidence that medications might relieve present symptoms or reduce future decline? What are the potential harms associated with such treatment? The following composite and anonymized vignette addresses some of the issues that are increasingly brought to physicians who prescribe neuropsychiatric medications.

Case Vignette
Mrs Keyes, a youthful 72-year-old piano teacher, has been urged by her concerned children to have a memory evaluation. She continues to give music lessons, manage her household, and perform activities of daily living with no major difficulty. During the past 2 years, however, she has noted greater difficulty in recalling the names of acquaintances and learning new names. On one occasion, she attended a friend's birthday party but several weeks later could not recall having done so. She has more trouble finding an unfamiliar location than previously. She takes longer to balance her checkbook, although she still does it correctly. At times, she has felt "blue" for more than a few days in a row, and she has wondered whether she is depressed.

Her medical history is notable for hypertension, appropriately medicated, but otherwise she appears to enjoy good health. Laboratory studies (complete blood cell count, metabolic panel, fasting lipid profile, and levels of thyroid-stimulating hormone, B12, folate, and homocysteine) show no abnormalities. Ultrasound studies show no significant carotid stenosis or plaque formation. MRI shows mild periventricular white matter disease. Neuropsychological testing results do not support a diagnosis of dementia, but her score on a test of delayed recall is significantly lower than would be expected for her age and educational level. Her executive dysfunction is clinically insignificant. She and her family ask what the future holds for her and whether medication might improve her memory or her prognosis.

Mrs Keyes' forgetfulness, preserved activities of daily living, demonstrable impairment of delayed recall, and lack of dementia are consistent with a diagnosis of MCI.2 Subtyping of MCI, which may have etiologic and prognostic significance, is based on identification of the affected cognitive areas and whether one or more have declined. Mrs Keyes' syndrome of impaired delayed recall with little executive dysfunction would be classified as amnestic, single-domain MCI.3




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