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    A 76-year-old man with poor memory and concentration

    A 76-year-old man has been brought in for evaluation by his family because of his poor memory and concentration. His family reports a gradual cognitive decline since the patient retired. He often forgets recent events, names, and appointments, and sometimes the family says he cannot find his car.

    A Mini-Mental Status Examination (MMSE) is performed, and the score is 20. He received points off for orientation to time, recall, and calculation.

    After ruling out other potential causes, you make a diagnosis of Alzheimer disease.

    In discussing possible medication therapy with the patient and his family, what should they be counseled to expect with regard to medication effectiveness?

    • cognitive improvement coupled with behavioral worsening
    • decrease in aggression and agitation
    • temporary slowing of cognitive and functional decline
    • 4-point improvement on the MMSE
    • 6-point improvement on the MMSE
    The correct answer is:

    temporary slowing of cognitive and functional decline

     

    Studies of donepezil for moderate to severe Alzheimer disease show statistically significant--but not clinically relevant--modest cognitive and functional improvement. There is a slowing of decline with treatment that may allow a patient to delay institutionalization on a temporary basis. The initiation of memantine therapy is also associated with statistically significantly better cognition and function, although the magnitude of the benefit is smaller than it is with donepezil. Combined treatment with donepezil and memantine is not significantly superior to treatment with donepezil alone.

    Treatment with acetylcholine esterase inhibitors are recommended in patients with mild to moderate Alzheimer disease and either acetylcholine esterase inhibitors or memantine in those with moderate to severe Alzheimer disease to manage cognitive, functional, and behavioral symptoms, despite its benefit being modest.

    Drugs approved by the US Food and Drug Administration for the management of Alzheimer disease provide symptomatic benefit but without any proven impact on clinical progression.

    References:

    Farlow MR, Salloway S, Tariot PN, et al. Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10 mg/d) donepezil in moderate to severe Alzheimer's disease: a 24-week, randomized, double-blind study. Clin Ther. 2010;32:1234-1251.

    Howard R, McShane R, Lindesay J, et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med. 2012;366:893-903.

     

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