Alzheimer’s disease (AD) affects approximately 4 million people in the United States. This progressively degenerative brain disease is the leading cause of dementia , accounting for about half of all dementia cases in the US.

AD impairs cognitive function, most notably short-term memory. But the disease also induces troublesome neuropsychiatric behaviors such as hallucinations, paranoia, and agitation, and impairs functional behaviors such as taking medications, eating, and dressing.

Cholinesterase inhibitors (ChIs), such as donepezil (Aricept) and galantamine (Reminyl), are the class of medications most widely used to treat cognitive decline in AD patients. Recent studies that examined the neuropsychiatric and functional impairments associated with AD have suggested that ChIs should be effective in treating these symptoms as well. However, clinical studies examining this relationship have had mixed results.

In a meta-analysis published in the January 8, 2003 Journal of the American Medical Association , scientists from the San Francisco Veterans Affairs Medical Center and the University of California, San Francisco found that ChIs do have a modest, beneficial role in treating neuropsychiatric and functional problems associated with mild to moderate AD.

About the Study

Scientists studied the results of 29 randomized, double-blind, placebo-controlled trials, published between January 1966 and December 2001, which looked at the treatment of AD with ChIs. Of the 29 trials, 16 examined the relationship between ChIs and neuropsychiatric behaviors, and 18 looked at the effect of ChI treatment on functional impairment. Eligible studies enrolled patients with mild to moderate AD who were treated with a cholinesterase inhibitor for at least one month.

Neuropsychiatric and functional impairments were measured using standard assessment tools.

The Findings

Depending on the assessment tool used, ChIs had either a small but statistically significant benefit or a trend toward benefit in the treatment of neuropsychiatric behaviors, compared with placebo.

The benefit on functional behaviors was analyzed by subtype of behavior. Compared with placebo, ChIs displayed a trend in benefit of activities of daily living (ADLs), which include basic activities such as eating, dressing, and bathing independently. The drugs had a small but statistically significant benefit for instrumental activities of daily living (IADLs) such as using the telephone and taking medications, again, compared with placebo.

No particular drug in the ChI class appeared to be more effective than any other.

How Does This Affect You?

Neuropsychiatric problems such as aggression and paranoia are common in AD, causing serious distress for both the patient and the family, and often leading to loss of independence and placement in a nursing home. Functional impairments also lead to dependency and a poor quality of life. Because Alzheimer’s disease takes such a great toll on both patients and caretakers, even a modest improvement of neuropsychiatric and functional behaviors would be welcome.

In this context, and in view of this study’s findings, patients with mild to moderate AD who have neuropsychiatric problems should definitely be considered for treatment with a ChI.

While ChIs also had a positive effect on functional impairments, it is less clear whether this was a direct effect, or whether the drugs improved functional impairments by reducing cognitive impairment. Despite the uncertainty, ChIs are at least worth considering in cases of mild to moderate AD with functional impairment.