Daniel M. Keller, PhD

April 22, 2013

Taipei, Taiwan — The key to maintaining cholinesterase inhibitor drugs in patients with Alzheimer's disease (AD) may be better education about what to expect from these agents, a new study suggests.

A new analysis of patients with AD in a remote rural setting who were taking these medications showed that only years of formal education distinguished those who were still taking their medications at 6 months from those who discontinued treatment, Andrew Kirk, MD, from the Department of Neurology at the University of Saskatchewan in Saskatoon, Canada, told delegates here at the Alzheimer's Disease International (ADI) 28th International Conference.

"While it's possible that people with less education don't benefit as much from the drug, my idea is that it may be more likely that those with more education may put more faith in science and medicine or they may better understand the potential benefits of the drug and weigh that against the potential side effects and be more willing to put up with them," Dr. Kirk speculated.

He said he and his staff always counsel patients and families about expectations, adverse effects, and how to take the drug, "but perhaps we should consider spending more time discussing this with patients who are less educated."

Modest Efficacy

Given the modest efficacy of this class of drugs and the potential adverse effects, including light-headedness, bradycardia, and muscle cramps, some patients may feel that it is not worth continuing therapy with these drugs, the authors note.

In addition, previous studies have shown that women, patients with more severe cognitive impairment, and patients who lack social assistance are more prone to stop taking them. On the other hand, frequent physician visits, a higher burden of chronic diseases, and greater functional impairment predicted better adherence. However, prior studies have generally been population-based and lacking in detailed demographic data.

So Dr. Kirk and colleagues decided to see what predicted discontinuation of anticholinesterase drugs in patients with dementia who live in a very rural and remote area.

Patients come to Saskatoon once for a complete evaluation and work-up by a team of health professionals. If their scores on the Mini-Mental State Examination (MMSE) fall in the 10 to 26 range, they are eligible for public drug coverage for 3 months. They remain eligible if they improve by 2 points or more on the MMSE or by 1 point on the Functional Activities Questionnaire. But Dr. Kirk has seen that very few patients will continue to take the drugs if coverage stops.

The researchers collected demographic data on patients and administered several self-rated scales that covered quality of life, depression, life concerns, activities of daily living, and memory. They also had the patients perform several standard neuropsychological tests.

They began the study in 2004 by looking at the first 318 consecutive patients. After excluding those not treated with a cholinesterase inhibitor or who had already started it before the first visit, they were left with 63 patients for whom 6-month follow-up data were available.

Study patients were an average of 74.6 years old, and 60.3% were women. They had an average of 10.4 years of education, 73% were of European ethnicity, and two thirds were married. Mean (standard deviation) scores were 22.3 ± 3.7 on the MMSE and 13.8 ± 7.3 on the Functional Activities Questionnaire.

Patients mainly had AD (83.6%), and a minority had Lewy body dementia (8.2%), mixed AD/vascular dementia (5.5%), or vascular dementia (2.7%). All but 2 patients were prescribed donepezil; those 2 patients began receiving galantamine.

One Third Discontinued

"Thirty-one percent had discontinued by 6 months — about half just because of inefficacy, about a third because of side effects, and 15% both inefficacy and side effects," Dr. Kirk reported.

"In a bivariate analysis using all of those things that we collected as the potential independent variables — the psychometric, the medical, the demographic data — we found that only years of formal education significantly differed between those who were still on the drug at 6 months and those who weren't," he said. "So people with less formal education are more likely to have discontinued the drug by 6 months. And in a multivariate logistic regression, again, only years of formal education was a significant predictor," he added, with an odds ratio of 0.76 (95% confidence interval, 0.59 - 0.96; P = .02).

Session chair Daisy Acosta, MD, past president of Alzheimer's Disease International and a geriatric psychiatrist in the Dominican Republic, said she was not surprised by the rate of discontinuations.

"[In] cultures with low education there is more chance that people stop the medications they are taking, especially where they don't see any big effects, as it is with their cholinesterase inhibitors," she told Medscape Medical News. "It is interesting that if the government doesn't provide the medications, they stop. So that's very normal."

She explained that the problem with cholinesterase inhibitors is that efficacy is hard to gauge unless one does formal testing and "the patient usually cannot measure that, and the patient can not feel really that the medication is really working."

She agreed with Dr. Kirk's assessment that better patient and family education is critical with prescribing the medications to give them a realistic expectation of outcomes. "They are not going to see any miracles and anything big in terms of effects from the medication itself," she said. They should expect the disease to progress. "It's just slower."

Dr. Kirk and Dr. Acosta have disclosed no relevant financial relationships.

Alzheimer's Disease International (ADI) 28th International Conference. Abstract OC026. Presented: April 19, 2013.