LAUSR

Hyperphagia is characterized by increased food intake, active searching for food in between meals, and loss of satiety. It has been observed in patients with impaired cognitive function. In this case series, we describe four patients with Alzheimer’s disease (AD) who presented at our clinic with disturbing eating behaviour. A 91-year-old man was admitted after having a poor appetite for 2 weeks. He was known to have diabetes mellitus type 2 and had recently been prescribed gliclazide and metformin. He also presented with a 6-month history of anterograde episodic memory impairment with apraxia, temporal and spatial disorientation, and an inability to bathe. There was no clinical evidence of depression. Physical examination was unremarkable. Thyroid function test, vitamin B12 level, and folate level were within normal range. Brain computed tomography showed bilateral medial temporal lobe atrophy. He was clinically diagnosed with AD according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association diagnostic criteria. Neither an active infection nor another identifiable secondary cause was found to have caused the patient’s lack of appetite. Metformin was stopped in view of the limited oral intake. Off-label use of oral megestrol acetate 40 mg twice daily was started, and the patient was discharged with marked improvement of appetite. The patient was admitted for one week. However, he was readmitted with hyperphagia 2 weeks after discharge. His relatives noted an absence of satiety, with frequent inappropriate requests for food. He was found searching for food in the kitchen late at night and, on a few occasions, had consumed his dog’s canned food. In the absence of any organic causes based on clinical examination and laboratory tests, megestrol acetate was stopped. Hyperphagia gradually subsided a few days later. At our follow-up clinic 8 weeks later, there was no evidence of hyperphagia. Our encounter with the first patient prompted us to review the case records of 94 AD patients (14 with cerebrospinal biomarkers support, 80 with F-fluorodeoxyglucose-positron emission tomography support, and 18 with amyloid load confirmed on C-Pittsburgh compound B positron emission tomography). From these 94 cases, we identified three more AD patients with hyperphagia (Table 1, Appendix S1), meaning the prevalence of hyperphagia was 4.2% (4/95). There was a predominance of male patients (75%). Hyperphagia developed between 2 weeks and 5 years after the diagnosis of AD and lasted transiently for 2 weeks to 5 months. All cases resulted in an increase in bodyweight. The relatives of these three patients were taught behavioural management techniques, including keeping food out of sight, using distraction techniques, and eating low-calorie snacks. One patient was managed by stopping the causative medication. To the best of our knowledge, medication has not been previously regarded as a potential cause of hyperphagia, and there have been no reported cases of hyperphagia due to the administration of megestrol. Megestrol is a progestin with anti-androgen activity that is marketed for use as an appetite stimulant in patients with cancer-related cachexia. Occasionally, it has been used off-label in elderly patients with poor appetite due to various causes. Our case demonstrated the drastic effect of megestrol on appetite stimulation, to the extent of hyperphagia or even pica. Previously, 5-hydroxytryptamine receptor 4 was reported to mediate anorexia. Decreased 5-hydroxytryptamine receptor 4 density in the temporal cortex was associated with a higher incidence of hyperphagia in patients with AD. Our case series further suggested that hyperphagia in AD is mostly a transient problem that lasts for months. The