Cholinesterase inhibitor delays nursing home admission in late-stage AD

By Lucy Piper, Senior medwireNews Reporter

The withdrawal of donepezil from patients with Alzheimer’s disease (AD) as they reach the moderate-to-severe stages of the disease doubles their risk of being placed in a nursing home within the first 12 months, secondary analysis of the DOMINO-AD trial indicates.

The findings, which appear in The Lancet Neurology, demonstrate a real-world benefit to continuing the cholinesterase inhibitor beyond the early stages of the disease for which it is licensed.

They also complement the earlier findings for the primary outcomes, reported in the NEJM in 2012, of improved cognition and function with continued donepezil treatment compared with withdrawal or starting memantine.

Among 295 community-living patients who had transitioned to moderate-to-severe disease and had been taking donepezil for at least 3 months, withdrawal of the drug in 73 increased the risk of being permanently admitted to a nursing home during the first 12 months from 20% with continued treatment to 37%, giving a hazard ratio of 2.09.

Speaking to the press, lead researcher Robert Howard, from University College London in the UK, said that his team’s results demonstrate that “[donepezil] is continuing to improve symptoms in a way that helps patients to maintain independence and it’s doing that for longer and later into the illness than we previously had evidence of.”

They calculate that for every six patients treated with the drug for 12 months, one nursing home placement could be prevented.

“It is a modest effect but an effect that is very important if it is your mother or your wife or someone close to you”, Howard pointed out. He therefore encourages physicians to think against stopping the treatment when patients progress to the moderate-to-severe stages of the disease.

The benefit seen in the first 12 months was not sustained at further follow-up sessions during the remaining 3 years of the trial, however, when the patients were treated at the discretion of their physicians.

The four treatment options studied were continuing donepezil 10 mg/day in 73 patients, discontinuing the drug in 73, stopping donepezil and starting memantine 20 mg/day in 76 and both continuing donepezil and starting memantine in 73 patients.

The introduction of memantine, which is approved for moderate-to-severe AD, did not have a significant effect on nursing home admission, either with or without donepezil, the researchers note.

Howard stressed that the findings are exploratory, adding: “We’re not saying that the treatment is actually slowing down Alzheimer’s disease; these drugs are symptomatic treatments, they improve the symptoms of Alzheimer’s disease.”

But he stressed that by delaying dependence on residential care, donepezil is helping to reduce public spending and improve quality of life.

“We are all impatient for the advent of true disease-modifying drugs that can slow or halt the Alzheimer process, but donepezil is available right now and at modest cost”, he concluded.

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