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MKSAP Quiz: gradual memory loss

Prior aspirin use a marker for recurrent events post-ACS, but not mortalityDental procedures may pose transient, minimal cardiovascular risk


An 84-year-old man is evaluated for the gradual onset of progressive memory loss over the past 2 years. In the past 4 months, he has twice been unable to find his way home after going to the local supermarket; his wife now goes with him whenever he leaves the house. His wife also has assumed responsibility for the household finances after the patient overdrew their checking account for the third time because of subtraction errors in their checkbook. He has hypertension treated with hydrochlorothiazide and hypothyroidism treated with levothyroxine. His mother had onset of Alzheimer dementia at age 79 years and died at age 86 years. His only other medication is a daily multivitamin.

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On physical examination, temperature is 36.9 °C (98.4 °F), blood pressure is 130/80 mm Hg, pulse rate is 72/min, respiration rate is 14/min, and BMI is 25. His level of alertness, speech, and gait are normal. His score on the Folstein Mini–Mental State Examination is 24/30, including 0/3 on the recall portion.

Results of laboratory studies, including a complete blood count, serum vitamin B12 measurement, thyroid function tests, and a basic metabolic panel, are normal.

An unenhanced MRI of the brain shows no abnormalities.

Which of the following is the most appropriate treatment at this time?

A. Donepezil
B. Memantine
C. Quetiapine
D. Sertraline
E. Discontinuation of all current medications

Reveal the Answer

MKSAP Answer and Critique

The correct answer is A) Donepezil. This item is available to MKSAP 15 subscribers as item 11 in the Neurology module.

This patient should receive donepezil. The Folstein Mini–Mental State Examination (MMSE) discriminates well between the major stages of dementia used for prognosis and management purposes. The MMSE score range of 21 to 25 corresponds to mild dementia, 11 to 20 to moderate dementia, and 0 to 10 to severe dementia. This patient has Alzheimer dementia and is at a mild to moderate stage of impairment. The most appropriate medication with which to begin treatment is an acetylcholinesterase inhibitor of which there are currently three: donepezil, rivastigmine, and galantamine. Multiple large, prospective, randomized, double-blind, placebo-controlled studies have shown in patients with mild, moderate, or severe Alzheimer dementia the efficacy of donepezil (and its superiority to placebo) in the preservation of instrumental and functional activities of daily living and in the reduction of caregiver stress. Other studies have found that patients treated with donepezil have improved cognitive function compared with those treated with placebo. Donepezil was safe and well tolerated in this patient group.

Memantine is also used to treat Alzheimer dementia, but only in patients with moderate to severe impairment. There is no evidence that memantine has any effect in earlier stages of Alzheimer dementia or that it alters the course of the disease. With a score of 24/30 on the MMSE, this patient has mild dementia, which makes memantine an inappropriate treatment. In patients with severe dementia, memantine can be used alone or added to an acetylcholinesterase inhibitor.

Quetiapine is an antipsychotic drug, and sertraline is an antidepressant agent. Although both can be used in patients with Alzheimer dementia, their use is limited to treatment of behavioral symptoms of psychosis and depression, respectively, neither of which this patient has exhibited. However, if these medications are to be used in such patients, the risks must first be carefully weighed against the benefits. The U.S. Food and Drug Administration has reported that the use of second-generation antipsychotic medications (aripiprazole, olanzapine, quetiapine, and risperidone) in elderly patients with dementia is associated with increased mortality.

Although it is important to consider the potential cognitive side effects of prescription (and nonprescription) medications, those taken by this patient are not associated with such effects. Therefore, there is no need to risk potential harm to this patient by discontinuing his blood pressure and thyroid medications.

Key Point

  • First-line pharmacotherapy for mild Alzheimer dementia is an acetylcholinesterase inhibitor.