Donepezil in the Prevention of Post-Operative Cognitive Decline

Up to 65% of elderly patients undergoing hip or knee surgery suffer from declining brain function known as post-operative cognitive decline (POCD). These individuals often stay in the hospital longer, have more complications, and are more likely to die. Recent clinical studies have shown the potential benefit of enhancing the cholinergic system among patients with both Alzheimer's disease and / or vascular dementia. Donepezil is currently being used to treat memory loss in patients with Alzheimer's disease.

This study will recruit 30 cognitively impaired adults aged 65 or older who are scheduled to have elective hip or knee replacement surgery at University Hospital. Participants will be randomized to receive either a three to six week supply of Donepezil or a matching placebo approximately 4 weeks prior to surgery. This study will evaluate the effect of Donepezil on delirium incidence and severity during hospitalization, global cognitive function, length of hospitalization, site of discharge, and adverse drug effects.

All material to be collected will be from interviews, questionnaires, and medical chart review. Some will be at baseline, during hospitalization, and 12 weeks post hospitalization and others will be daily during hospitalization. The International Study of Post-Operative Cognitive Decline battery of tests will be used in assessment, as will the CogHealth computerized battery.

• Postoperative Complications
• Delirium

• Dodds C, Allison J. Postoperative cognitive deficit in the elderly surgical patient. Br J Anaesth. 1998 Sep;81(3):449-62. Review.
• Rasmussen LS. Defining postoperative cognitive dysfunction. Eur J Anaesthesiol. 1998 Nov;15(6):761-4.
• Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K, Hanning CD, Langeron O, Johnson T, Lauven PM, Kristensen PA, Biedler A, van Beem H, Fraidakis O, Silverstein JH, Beneken JE, Gravenstein JS. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet. 1998 Mar 21;351(9106):857-61. Erratum in: Lancet 1998 Jun 6;351(9117):1742.
• Abildstrom H, Rasmussen LS, Rentowl P, Hanning CD, Rasmussen H, Kristensen PA, Moller JT. Cognitive dysfunction 1-2 years after non-cardiac surgery in the elderly. ISPOCD group. International Study of Post-Operative Cognitive Dysfunction. Acta Anaesthesiol Scand. 2000 Nov;44(10):1246-51.
• Johnson T, Monk T, Rasmussen LS, Abildstrom H, Houx P, Korttila K, Kuipers HM, Hanning CD, Siersma VD, Kristensen D, Canet J, Ibañaz MT, Moller JT; ISPOCD2 Investigators. Postoperative cognitive dysfunction in middle-aged patients. Anesthesiology. 2002 Jun;96(6):1351-7.

Inclusion Criteria:

• Community-dwelling individuals aged 65 or older
• Scheduled for elective hip or knee replacement at University Hospital

• Mild cognitive impairment, defined as:

  • MMSE total score of 27 or less;
  • normal performance of the activities of daily living tasks of the Bristol scale after excluding mobility related difficulties;
  • no chart-based dementia diagnosis; and
  • no history of ever being on dementia medications such as Memantine or any cholinesterase inhibitors
• Consent to participate in the study

Exclusion Criteria:

• Chart-based dementia diagnosis
• MMSE score greater than 27
• Difficulty performing the activities of daily living not related to mobility as measured by the Bristol scale
• Current or past history of receiving dementia medications such as Memantine or any cholinesterase inhibitors (Tacrine, Donepezil, Rivastigmine, or Galantamine)
• Metastatic cancer or other comorbid illnesses likely to reduce life expectancy to under 6 months
• Multiple trauma or pathological fractures requiring acute hip or knee replacement
• Aphasic, blind, or deaf
• Use of neuroleptics one month prior to surgery
• Allergy to donepezil
• Inability to read and complete study tests and forms
• Alcohol or drug dependence, defined as intake of more than 5 units of alcohol daily during the past 3 months
• Not expected to be discharged from hospital or able to complete the 3-month postoperative test
• Not competent to make medical decisions