Donepezil Treatment for Alzheimer’s Disease in Chronic Dialysis Patients

Abstract

Donepezil is one of the cholinesterase inhibitors that are indicated for the treatment of mild to moderate Alzheimer’s disease (AD). Pharmacokinetic analysis has shown that donepezil is primarily eliminated by renal excretion rather than biliary excretion in humans. Therefore, patients with impaired renal function are at high risk of toxicity caused by accumulation of this drug. It is also well known that dialysis patients have very often cholinergic disorders. On the other hand, with the increasing number of long-term chronic dialysis patients, the prevalence of cognitive disorders is increasing in elderly dialysis patients. Because of the above-mentioned special risks of these patients, acetylcholinesterase inhibitors, such as donepezil, are avoided to be prescribed for them. We studied 5 cases of chronic hemodialysis outpatients (3 men [70, 72, and 86 years old] and 2 women [65 and 71 years old]) who were diagnosed as having moderate AD. We administered donepezil at 2.5 mg/day orally to the patients. After 1 month’s treatment, their behavioral symptoms were improved, without them having any adverse events. We enhanced the dose to 5 mg/day without the patients experiencing any episodes of drug toxicity. After 3 months of treatment with the higher dose, their cognitive and executive functions were slightly improved and their behavioral disorders were remarkably milder, without them experiencing any episodes of drug toxicity. The patients’ condition remained stable for 6 months after the initial administration of the drug. All of them were followed for the 10 following years, showing a mild cognitive decline per year for the first 5 years and more severe decline for the remaining years of the follow-up. Our cases indicate that donepezil treatment under prudent use may be well tolerated and have a beneficial impact on chronic hemodialysis patients with AD.

Risk factors for mortality in elderly haemodialysis patients: a systematic review and meta-analysis

“…This review showed that cognitive impairment in older haemodialysis patients is positively correlated to mortality. Older haemodialysis patients are also at potential risk of being befalled with Alzheimer's disease, and receiving this diagnose is associated with an increased mortality [46,47]. Another study found that dementia was associated with an increased risk of death and dialysis drop out in adults aged over 75 years on dialysis [31].…”

Polypharmacy and Mental Health Issues in the Senior Hemodialysis Patient

“…They concluded that cognitive function was improved best when the 5 mg daily dose was used, however, the plasma level came close to reaching a toxic level ( 39 ). Yiannopoulou et al, have reported a case series of five patients on maintenance HD with AD prescribed donepezil ( 40 ). They started with a dose of 2,5 mg daily and increased it after 1 month to 5 mg daily.…”

“…They observed a slight improvement in cognitive and executive functions. During 10 years of follow up, the patients showed a mild cognitive decline per year for the first 5 years, which progressed to severe cognitive decline for the remaining years of follow up ( 40 ).…”

Exercise Training and Cognitive Function in Kidney Disease

“…There is no recommended treatment to prevent cognitive decline in patients with kidney disease, and the few medications available for cognitive impairment have only modest effects (Yiannopoulou et al, 2019). There is a critical need to evaluate therapies to forestall cognitive impairment and maintain or improve cognitive function in older adults with CKD.…”