Correspondence
Transient Memory Impairment and Hallucinations Associated with Tolterodine Use
N Engl J Med 2003; 349:2274-2275December 4, 2003
- Article
To the Editor:
Although anticholinergic medications are widely used to treat urinary incontinence in the elderly, the fact that their use may be associated with memory loss and visual hallucinations has not been well recognized, and these complications may therefore be incorrectly attributed to a degenerative dementia (e.g., Lewy body dementia).1 We report the case of a 73-year-old woman who presented with a two-year history of decreased short-term memory and vivid hallucinations of deceased relatives that occurred only during nighttime sleep; she awoke regularly to converse with these relatives. The symptoms began several weeks after she began to take tolterodine (2 mg twice daily) for urinary incontinence. These hallucinations did not distress the patient and resolved after three months of donepezil therapy, which was initiated by her primary physician, who suspected dementia. The patient did not take tolterodine for several months and her memory improved, but she had begun taking it again two weeks before our evaluation and her memory loss recurred.
Examination revealed no dysfunction of the frontal lobe or basal ganglia. Her scores on the Mini–Mental State Examination (28 out of 30), the Controlled Oral Word Association test, and the Boston Naming Test were normal, but the Hopkins Verbal Learning Test–Revised (HVLT-R) Form 1 (a 12-word list presented in three sequential trials) revealed abnormal immediate learning (score, 8 of 36, <1st percentile) and delayed recall (score, 0 of 12, <1st percentile).2 Brain imaging and laboratory studies were normal.
Because the patient's memory had improved when she was not taking tolterodine, treatment was discontinued again. Retesting, with the use of HVLT-R Forms 2 and 3, revealed continued memory impairment after one month but dramatic improvement after two months, with an immediate-learning score of 29 of 36 (75th percentile) and a delayed-recall score of 9 of 12 (50th percentile).
Anticholinergic medications can impair verbal learning and delayed free recall and induce visual hallucinations by reducing cerebral acetylcholine levels.3 The resolution of the patient's hypnopompic hallucinations with donepezil therapy (which increases acetylcholine levels) and the improvement in verbal memory after the discontinuation of tolterodine therapy are consistent with the anticholinergic properties of tolterodine. Tolterodine-associated memory impairment, without the presence of hallucinations, has been reported only once previously.4 Amnesia may be more common, but in the absence of cognitive testing, it remains underdiagnosed.4 The half-life of tolterodine is less than 10 hours, but in this case, memory normalized long after its use was discontinued, suggesting that the medication altered gene regulation or protein expression. Furthermore, increased rates of pathological findings similar to those in Alzheimer's disease have recently been correlated with the use of anticholinergic agents.5 Thus, we recommend the judicious use of anticholinergic medications, together with the formal assessment of verbal memory (e.g., the learning of word lists with the HVLT-R), in all older patients who are susceptible to memory loss and dementia. We also recommend discontinuing treatment with anticholinergic medications in patients with memory loss, hallucinations, or both.
5 ReferencesJack W. Tsao, M.D., D.Phil.
Naval Hospital Jacksonville, Jacksonville, FL 32214-5005
jwtsao@bellsouth.net Kenneth M. Heilman, M.D.
Veterans Affairs Medical Center, Gainesville, FL 326081
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