Rivastigmine Dermal Patch Solves Eating Problems in an Individual with Advanced Alzheimer's Disease

Abstract

To the Editor: Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder and a leading cause of dementia in elderly adults.1 In 2003, AD was the fifth leading cause of death in individuals aged 65 and older in the United States. The best current estimates indicate that median survival after the onset of symptoms of dementia ranges from 3 to 6 years, shorter than previously estimated.2 Swallowing dysfunction with or without aspiration pneumonia is a major cause of morbidity and mortality in individuals with end-stage AD.3, 4 Herein is reported an individual with advanced AD with swallowing problems and recurrent pneumonias who was successfully treated with a rivastigmine transdermal patch. An 81-year-old woman was diagnosed with AD in 2005, manifesting as gradually progressive short-term memory loss, with a sharper decline during the past 3 years despite vigorous treatment with donepezil. Magnetic resonance imaging revealed brain atrophy, especially in the hippocampus. She had repeated episodes of aspiration pneumonia, malnutrition, dehydration, falls and femoral neck fracture, and sarcopenia. In February 2011, she was hospitalized for recurrent aspiration pneumonia and unresponsiveness. On admission, she was diagnosed as having AD according to the Functional Assessment Staging Scale, spending the entire day in a wheelchair, speaking only several words, and requiring complete support for eating and toileting. She was successfully treated using intravenous antibiotics and hydration. After pneumonia treatment, her oral intake was poor, and she occasionally refused to eat. She was taking just one or two spoonfuls of food or some juice. A bedside swallowing evaluation revealed mild oral dysphagia with delayed swallowing latency (4.2 ± 0.2 seconds).3, 4 Although a mechanically altered diet or nutritional supplements were ordered, her weight declined from 42 to 35 kg, and she developed a pressure ulcer on her hip over the next 3 months. It took a long time to hand feed and deliver oral medications, but her son did not agree to placement of a long-term feeding tube. In June 2011, she was discharged home to be cared for by her son. Her family physician and nurses provided intravenous hydration three times a week. In October 2011, her family physician decided to use a rivastigmine transdermal patch (Rivastach patch) instead of donepezil, and she was titrated from an initial dose (4.5 mg in a 2.5-cm2 patch per day) to a maintenance dose (18 mg in a 10-cm2 patch per day) by 2.5 cm2 at 4-week intervals over 16 weeks. At a dose of 9 mg (5 cm2) per day, her oral intake improved dramatically, and she gained weight. A bedside test revealed that her swallowing function had improved and that the swallowing latency had shortened (3.1 ± 0.3 seconds).3, 4 Her unresponsiveness was partially resolved, and the pressure ulcer resolved. Her clinical condition has been maintained under treatment with rivastigmine patch until now (May 2012). AD is characterized by progressive cholinergic failure with an extensive loss of cholinergic neurons.5 It has previously been shown that cholinergic neurons might be involved in the regulation of normal swallowing function,6 indicating that cholinergic dysfunction might impair swallowing reflex in individuals with advanced AD.5, 6 Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) can regulate the action of acetylcholine in the human brain, and BuChE is capable of compensating for low AChE activity.7, 8 Thus BuChE may become more important as AD progresses, and there is growing evidence that BuChE, as well as AChE, is a clinically relevant treatment target in AD.7, 8 Rivastigmine is the first approved transdermal patch for individuals with AD and has a dual inhibitory action of AChE and BuChE.7, 8 A clinical study demonstrated that rivastigmine dose-dependently inhibited BuChE activity.7 Rivastigmine might therefore improve swallowing function by slowing the degradation of acetylcholine in the cholinergic nervous system in individuals with advanced AD. In addition to a better tolerability profile than oral rivastigmine, transdermal delivery may allow better delivery for individuals with AD with swallowing disorders. Rivastigmine transdermal patch may enable individuals with advanced AD with eating problems take meals orally. Conflict of Interest: Takashi Ohrui is employed at the Division of Geriatric Pharmacotherapy, Tohoku University, which receives research funding support from Ono Pharmaceutical Company, Japan. Ono Pharmaceutical Company manufactures a rivastigmine dermal patch. Author Contributions: Uwano C, Suzuki M, Aikawa T, Ebihara T, Une K, Tomita N, Kosaka Y, Furukawa K, Arai H, and Ohrui T: Acquisition of subjects and data. Uwano C and Ohrui T: Analysis and interpretation of data and preparation of manuscript. Sponsor's Role: None.