Cholinesterase-inhibiting drugs have been associated with slowed disease progression in mild to moderate Alzheimer’s dementia; however, the drugs do not prevent eventual deterioration. Although studies have been limited and had inconsistent results, many subspecialists recommend discontinuing these drugs in patients with severe symptoms. Winblad and colleagues studied the effectiveness of donepezil (Aricept) in nursing home residents with severe Alzheimer’s disease.
The double-blind, parallel-group, placebo-controlled study included residents of 50 nursing homes in Sweden. Eligible patients were 50 years or older, met the criteria for Alzheimer’s disease in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed.; had Mini-Mental State Examination (MMSE) scores of 1 to 10; and had functional assessment stages ratings of 5 (i.e., requires assistance in selecting proper clothing) or higher. Patients also were required to have cerebral imaging study results consistent with Alzheimer’s disease and no clinical or laboratory evidence of an alternative etiology for dementia.
The 128 patients randomly assigned to receive donepezil were comparable with the 120 assigned to receive placebo in all significant variables. All but one participant were white, 80 percent were women, and the average age was 85 years. The average MMSE score was 6. All participants in the donepezil group and 99 percent of the placebo group were taking other medications; more than 80 percent of participants were taking psychoactive drugs. Each participant had his or her own room in a unit that housed five to 15 patients and had an established nursing assistant who cared for the patient for at least four hours per day for three days per week for at least 12 weeks. Study participants in the intervention group received 5 mg oral donepezil daily for 30 days followed by 10 mg daily for six months if well tolerated.
Primary outcomes were change in the Severe Impairment Battery and the modified Alzheimer’s Disease Cooperative Study activities of daily living for severe disease (ADCS-ADL-severe) inventories. The Severe Impairment Battery includes 40 items to assess cognitive function in nine domains: memory, language, orientation, attention, praxis, visuospatial, construction, name orientation, and social interaction. The modified ADCS-ADL-severe includes 19 items to assess basic (e.g., eating, bathing) and complex (e.g., using light switches and faucets) activities of daily living. Other study outcomes included clinical global impression of improvement, MMSE score, vital signs, and adverse effects. Physical examinations, laboratory testing, and electrocardiography were performed at baseline and at six months.
Ninety-five patients in the donepezil group completed the study compared with 99 in the placebo group. The median duration of donepezil therapy was 176 days, and 91 percent of patients received the 10-mg dosage. Patients treated with donepezil showed greater improvement in Severe Impairment Battery and MMSE scores with less decline in ADCS-ADL-severe scores compared with those treated with placebo. These results were statistically significant; however, they were not reflected in the clinical caretaker assessment ratings. Although adverse effects were common, most were transient and mild. Sixteen percent of patients in the donepezil group discontinued therapy because of adverse effects compared with 7 percent in the placebo group.
The authors conclude that donepezil improved and preserved function in patients with severe Alzheimer’s disease.