Older Age Predicts Better Response to Alzheimer's Drugs

Daniel M. Keller, PhD

April 25, 2013

Taipei, Taiwan — Cholinesterase inhibitor drugs were most effective in a real-world clinical setting the older the patients were and the higher the cognitive functioning at baseline, a Taiwanese study of patients with Alzheimer's disease (AD) presented here shows.

Chi-Ying Lin, MD, from the Department of Neurology at the Taipei Veterans General Hospital in Taipei, Taiwan, said his study results suggest that early diagnosis and prompt initiation of drug therapy can give better outcomes.

The findings were presented here at the Alzheimer's Disease International (ADI) 28th International Conference.

No Annual Decline

The study involved 827 elderly patients with AD (average age, 76.9 years) receiving cholinesterase inhibitors for at least 3 months. Effectiveness outcomes were no annual change on the Mini-Mental State Examination (MMSE) or an annual decline of 2 or fewer points.

About half the patients were men, the average educational level was 8.98 years, and the average baseline MMSE score was 18.90 ± 4.49 (range, 10 to 26), with an average annual decline of 0.26 ± 0.20. Most patients were taking donepezil, 6.3% were receiving rivastigmine, and 7.2% were taking galantamine.

Most of the patients had good responses out to 5 years, as measured by a decline of 2 points or less on the MMSE, and some patients experienced no decline.

Table. Percentage of AD Patients With Good Response to Cholinesterase Inhibitors

MMSE Score <1 Year (n = 157) 1 to 2 Years (n = 191) 2 to 3 Years (n = 172) 3 to 4 Years (n = 173) 4 to 5 Years (n = 134)
Annual decline ≤2 78.3 92.7 94.8 99.4 100
Annual change >0* 25.5 23.6 21.5 17.9 18.7

*Denotes improvement.

Referring to a goal of no annual decline on the MMSE, Dr. Lin said, "We can see the patients with the use of cholinesterase [inhibitors] within 1 year, there were 25.5% of patients to reach this goal. And the longer we used the drug, the less the patient can achieve or [stay at] this goal. However, even in those who use the drug more than 5 years there was 18.7% of patients who can maintain this goal."

But 78.3% of patients taking these drugs for less than a year achieved the goal of an MMSE decline of 2 points or less. "And as time goes by the longer we use the drug, the higher percentage of patients can achieve this goal," he reported.

Older age correlated with good responses to the drugs. The 769 patients for whom the drugs were effective were on average about 2.7 years older than the 58 patients without good responses (77.09 vs 74.38 years, respectively; P < .05).

Baseline MMSE scores trended higher for the better responder group compared with those for whom the drugs were not effective (18.98 vs 17.83; P = .059). "The P value was a little higher than .05, so we postulated that the baseline MMSE plays a marginal role," Dr. Lin said.

Interestingly, there was an association between vascular disease and better effectiveness of the cholinesterase inhibitors. For patients with hypertension, 87 (95.6%) of 91 had good responses (P = .001), as did 51 (96.2%) of 53 patients with ischemic heart disease (P = .023).

"Our results support the hypothesis... that if the patient has vascular risk factors or vascular disease, less AD pathology is required to show the same severity compared to the pure AD people," Dr. Lin said. "So that might be the reason why better response to a cholinesterase [inhibitor] will be seen in the patient with vascular disease or vascular risk factors."

There did not appear to be any effect of diabetes, stroke, lung or liver disease, cancer, chronic infection, or foods or nutritional supplements of almonds, fish oil, or vitamins B, C, or E complex. Sex, education, mental health, or other cognitive domains on different neuropsychological tests also had no effect.

Session chair Daisy Acosta, MD, past president of Alzheimer's Disease International and a geriatric psychiatrist in the Dominican Republic, said it is possible that the older the patient, the more there is a vascular component to the dementia. Because vascular pathology accrues with age, this may help explain the better responses in the older patients.

When asked if at some point patients may be too old to treat for their AD, she said that regardless of age, her advice is to do a trial of treatment to alleviate whatever burden of disease that may be possible.

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

Alzheimer's Disease International (ADI) 28th International Conference. Abstract #OC029. Presented: April 19, 2013.