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Cognitive Decline Rapid and not Regained Following Discontinuation of Acetylecholinesterase Inhibitors: Presented at IADRD

By Patrice Olson
Special to DG News

STOCKHOLM, SWEDEN -- July 22, 2002 -- Two separate studies have confirmed that a rapid decline in cognition occurs following discontinuation of treatment with acetylcholinesterase inhibitors (AChEI) in patients with Alzheimer's disease (AD) as well as those with dementia with Lewy bodies (DLB) and Parkinson's disease (PD).

Cognition also declined following discontinuation of AChEI therapy in patients with DLB without PD, but cognitive deterioration was less pronounced. Findings from the two studies were presented here July 21 during the 8^th International Conference on Alzheimer's Diseases and Related Disorders.

Dr. Gregor Steiger-Baechler and colleagues from the Memory Clinic, in Basel, Switzerland, evaluated the consequences of discontinuing relatively long-term AChEI therapy in seven patients, mean age 71.9 years. Patients discontinued treatment because they or their caregivers were not satisfied with the observed therapeutic effect.

Two of the patients had taken rivastigmine, and five had taken donepezil, over a treatment interval ranging from nine to 26 months (average 16.7 months). Patients were tested with the Mini-Mental State Examination (MMSE) at treatment discontinuation and 23.7 days later.

Prior to discontinuation, MMSE scores for the seven patients ranged from 14 to 24, or an average of 17.3. Approximately 23 days after AChEI therapy had been discontinued, MMSE scores decreased between 0 and 4 points, to an average of 15.3 -- a statistically significant difference (p<0.05).

In two patients, treatment with galantamine was re-introduced, but their scores remained at the same level as they were at their second MMSE test-even when re-tested up to 137 days after initial test.

"These results provide further support to the notion that discontinuation of AChEI therapy may lead to a decline of cognitive functioning that might be difficult to regain," Dr. Steiger-Baechler and colleagues concluded.

A second study was also done in nine patients with DLB and 11 patients with DLB and PD, all of whom had received up to 10 mg of donepezil a day for 20 weeks.

In this study, Dr. Lucy Wilkinson and colleagues from the Institute for Ageing and Health, in Newcastle General Hospital, Newcastle-upon-Tyne, United Kingdom, noted that "DLB patients taking donepezil showed significant improvements in cognition by week 20 [at] a mean increase in MMSE of 4.6."

Following withdrawal of AChEI therapy in the same group of patients, there was a significant decline in MMSE scores at 26-week after discontinuation, although scores remained significantly better than they had been before treatment with donepezil had been initiated. Patients with PD plus DLB also showed a mean increase in MMSE scores of 3.3 on introduction of donepezil therapy.

Once treatment was discontinued, cognitive performance in patients with PD and DLB declined back to baseline levels, the authors found. Behavioral changes as reflected by scores on the Neuropsychiatric Inventory (NPI) also declined significantly in PD plus DLB patients following discontinuation of treatment, as did scores on the Clinicians' Interview-Based Impression of Change.

"Clinicians need to be aware of the potential for deterioration following withdrawal of cholinesterase inhibitors and to monitor patients for evidence of decline," the researchers concluded.

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