US researchers found that people with memory problems who are depressed are at higher risk of developing Alzheimer’s disease than people who are not depressed, and that the popular Alzheimer’s drug donepezil (brand name Aricept) may delay progress to Alzheimer’s in depressed people who have memory problems or mild cognitive impairment (MCI).

The research was the work of lead author Dr Po H Lu, assistant professor of neurology with the David Geffen School of Medicine at University of California Los Angeles (UCLA), and colleagues, and is published online in the 16 June issue of Neurology, the medical journal of the American Academy of Neurology.

Lu said in a statement that:

“Our longer term findings add to the body of evidence that suggests depression is a major risk factor for Alzheimer’s disease.”

“Since the drug donepezil has been shown to improve the behavioral symptoms of Alzheimer’s disease, our study also tested whether the drug would delay the progression to Alzheimer’s disease in people with memory problems,” he added.

A person with Mild Cognitive Impairment (MCI) has problems with memory that are greater than those brought on by normal aging, but they don’t show symptoms of Alzheimer’s such as difficulty completing every day activities.

For the study, Lu and colleagues followed the progress of 756 people between 55 and 91 years of age who had MCI and were taking part in a three-year, double-blind, placebo-controlled Alzheimer’s Disease Cooperative Study trial of donepezil and vitamin E.

A double blind trial is one where neither the participants nor the health professionals who give them the drugs know whether they are taking the active drug or a placebo.

At the start of the study the participants underwent a test that measured depression severity and intensity (the Beck Depression Inventory, BDI), and 208 were diagnosed with depression using the BDI.

The main outcome measure was progression to possible or probable Alzheimer’s disease, which was diagnosed either during or at the end of the trial.

The participants were in three goups: one group was given vitamin E, another donepezil and the third a placebo.

The results showed that:

  • A participant’s risk of developing Alzheimer’s went up by 3 per cent for each point increase on the depression test.

  • At 1.7 years into the study, among depressed-diagnosed participants with MCI, 11 per cent of those given donepezil developed Alzheimer’s disease compared to 25 per cent of those who were given vitamin E or placebo.

  • At 2.2 years into the study, these figures went up to 14 per cent and 29 per cent respectively.

  • Donepezil had little effect in the participants who were not diangosed with depression.

The authors concluded that:

“Results suggest that depression is predictive of progression from amnestic mild cognitive impairment (aMCI) to Alzheimer disease (AD) and treatment with donepezil delayed progression to AD among depressed subjects with aMCI. Donepezil appears to modulate the increased risk of AD conferred by the presence of depressive symptoms.”

Lu said:

“If we can delay the progression of this disease for even two years, it could significantly improve the quality of life for many people dealing with memory loss.”

The FDA has not approved donepezil (Aricept) for the treatment of MCI but only for mild to moderate and severe Alzheimer’s.

Alzheimer’s disease, which is named after the German physician Alois Alzheimer who first described it in 1906, is the most common form of dementia, accounting for 50 to 70 per cent of cases. It is a progressive and fatal brain disease with no cure and the 7th leading cause of death in the US.

Alzheimer’s destroys brain cells, causing problems with memory, thinking and behavior that impair ability to work, relate to others, enjoy hobbies and get on with every day life. The National Institute on Aging reports that according to recent estimates, as many as 2.4 to 4.5 million Americans are living with Alzheimer’s.

“Donepezil delays progression to AD in MCI subjects with depressive symptoms.”
Lu, P. H., Edland, S. D., Teng, E., Tingus, K., Petersen, R. C., Cummings, J. L., On behalf of The Alzheimer’s Disease Cooperative Study Group.
Neurology, 2009 72: 2115-2121.
Published online 16 June 2009.

Additional sources: American Academy of Neurology, Alzheimer’s Association, NIA.

Written by: Catharine Paddock, PhD