December 22, 2004
Medications commonly given to those with mild to moderate Alzheimer's may have particular benefits in the earliest stages of Alzheimer's disease, a new study suggests. Cognitive functions such as memory, attention, reasoning, language skills, and orientation improved in about 70 percent of men and women with early-stage Alzheimer's disease. In contrast, improvement was noted in less than half of those taking a dummy placebo pill.
"This study demonstrates that initiating therapy early in the progression of the disease can help benefit cognitive ability when it is at its highest level," said study leader Benjamin Seltzer, M.D., director of the Alzheimer's Disease & Memory Disorders Center at Tulane University Health Sciences Center in New Orleans. "Improving memory and thinking may help patients with activities in their daily lives."
The study, conducted at more than a dozen medical centers around the country, examined 153 men and women aged 50 to 92 who were in generally good health except for early symptoms of memory loss. All had been diagnosed with mild Alzheimer's in the previous 12 months, though none were taking medications to treat the disease.
Ninety-six of the study participants were given the drug Aricept (generic name donepezil), one of several so--called "cholinesterase inhibitors" currently approved for the treatment of mild-to-moderate Alzheimer's disease. (Related drugs include Reminyl, or galantamine, and Exelon, or rivastigmine.) The others received the look-alike placebo.
After 24 weeks on the drugs, the participants were screened with tests to measure memory and thinking skills. Those who had been taking Aricept showed measurable improvements in cognitive abilities. They scored higher on tests to measure verbal and visual memory, such as matching a name to a face or recalling someone's first and last name compared to those taking the placebo.
This study is among the first to look at the effects of an Alzheimer's drug exclusively on people in the very early stages of the disease. Most other studies on Aricept and related drugs have included people who have had Alzheimer's for several years and are considered to have "mild to moderate" disease and a range of symptoms.
Consistent with other studies, the side effects of the drug were reasonably well tolerated. About 16 percent of those taking the Aricept dropped out because of side effects, such as digestive upset, nausea, diarrhea, weakness, or troubling dreams. About 9 percent of those taking the placebo complained of these side effects.
Neither group showed significant declines in overall functioning during the six months the study lasted. However, it is not uncommon for those in the very early stages of Alzheimer's disease to show minimal or no decline in mental functioning in the first year or two. As the disease progresses to the more moderate to severe stages over several years, however, symptoms may become rapidly progressive and disabling.
The investigators believe that treatment with an Alzheimer's drug may offer unique benefits for those in the early stages of disease. "Many patients and their families delay seeing a physician about memory problems for several years after symptoms are first noticed," notes Dr. Seltzer. "Based on my clinical experience, I encourage seeking a diagnosis of Alzheimer's disease at the earliest sign of disease so that the appropriate treatment can be initiated as soon as possible."
Nobody is sure how long the benefit of a drug like Aricept may last, although in some cases, doctors recommend that those with Alzheimer's remain on the medication for years. The authors of the current study called for longer-duration studies to further determine whether the benefits of such drugs may be long-lasting for those with Alzheimer's, and ease the burden for their families and caregivers.
Ben Seltzer; Parvaneh Zolnouni; Margarita Nunez; et al; for the Donepezil "402" Study Group: "Efficacy of Donepezil in Early-Stage Alzheimer Disease: A Randomized Placebo-Controlled Trial." Archives of Neurology, December 2004; Vol. 61: pages 1852-1856.