10 Jan 2003

A meta-analysis of clinical trials indicates that cholinesterase inhibitors do more than boost cognitive test scores in Alzheimer's patients. As reported in yesterday’s Journal of the American Medical Association, the drugs as a group also improve psychiatric symptoms and enhance daily function.

Cholinesterase inhibitors (ChEIs) clearly have a beneficial effect in mild to moderate Alzheimer's (though whether they do this by inhibiting ChE has recently been questioned; see ARF related news item). There is also evidence that this benefit extends beyond cognitive decline to include effects on symptoms such as hallucinations, paranoia, agitation, and affective disturbances. There also is evidence that ChEIs might improve functional measures-either the early declines in instrumental activities of daily living (IADL), such as use of the telephone or ability to maintain drug regimens, or the later declines in basic activities of daily living (ADL), such as eating or dressing. However, because ChEI clinical trials that evaluated these measures have had conflicting results, Kristine Yaffe of the University of California, San Francisco, Nhi-Ha Trinh of Massachusetts General Hospital in Boston, and colleagues decided to examine some of these trials in a meta-analysis.

The authors included 29 studies of many different ChEIs that met various criteria, including being parallel-group or crossover randomized, double-blind, placebo-controlled trials of outpatients with mild to moderate AD. Among these trials, 16 had neuropsychiatric and 18 had functional measures.

Of the 16 studies measuring neuropsychiatric manifestations, the six trials using the Neuropsychiatric Inventory (NPI) showed a small but statistically significant benefit from ChEIs, whereas the 10 trials using the Alzheimer Disease Assessment Scale, noncognitive (ADAS-noncog) showed a nonsignificant trend toward a benefit. (In the case of three trials that used both instruments, the researchers included only the NPI in their analyses, because the ADAS-noncog does not include measures of aggressiveness and anxiety, and may be less sensitive to change.)

Of the 18 studies measuring daily function, the 14 that measured ADL showed a nonsignificant trend toward benefit from ChEIs, whereas the 13 trials that measured IADL showed a small but statistically significant benefit. "However," the authors note, "because functional impairment is closely linked to cognitive impairment, it is unknown whether the benefit to functional impairment from [ChEIs] is due to reducing cognitive impairment or an independent mechanism."

The authors found that each of the ChEI's had similar beneficial effects, though they acknowledge that their analysis had limited statistical power to make this assessment. "We believe our results are the first attempt to quantitatively synthesize the efficacy of a variety of [ChEIs] for neuropsychiatric symptoms and functional impairment, and to suggest a modest benefit [in these outcomes]," the authors write.—Hakon Heimer

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References

News Citations

1. Revise Mechanism for Alzheimer's Drug? Acetylcholine Increased in Earliest Stage of Disease 22 Nov 2002

Further Reading

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